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Number of 483 issued from the System*

Inspections ending between 10/1/2009 12:00:00 AM and 9/30/2010 12:00:00 AM

Center Name Foods Devices Drugs Incidental text Bioresearch monitoring Veterinary medicine Biologics Parts 1240 and 1250 Human tissue for transplantation Radiological health Special requirements Sum Product Area 483s from System* Actual Total in system 483s**

483 issued 2496 817 646 303 282 232 224 169 111 16 10 5306 4804

Total 483s for Fiscal Year*** Total number of FY10 inspections

6695 17635

* This table does not represent the complete set of 483's issued during the fiscal year as some 483's were manually prepared and not available in this format. The sum of 483's for all Product Areas will be greater than the actual Total 483's issued during the fiscal year since a 483 may include citations related to multiple product areas, and counted more than once, under each relevant product center. ** This is the Actual Total number of 483's issued from this system, and that are represented in this spreadsheet. *** This is the count of the total number of 483's issued in and out of the system during FY2010

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Biologics

Center Name Biologics

Cite Id

Ref No 76 21 CFR 606.100(b)

ShortDesc Maintained and followed

98 21 CFR 606.100(c)

Thorough investigations

160 21 CFR 606.160(a)(1)

Person performing, test results, interpretation

155 21 CFR 606.160(b)

Required records

154 21 CFR 606.160(a)(1)

Concurrent documentation

9225 21 CFR 606.171

Biological product deviation report

31 21 CFR 606.20(b)

Qualifications of responsible personnel

4425 21 CFR 606.60(a)

Equipment observed, standardized, calibrated

159 21 CFR 606.160(a)(1)

Legibility and indelibility

67 21 CFR 606.65(e)

Following manufacturer's instructions

78 21 CFR 606.100(c)

Record review prior to release

57 21 CFR 606.60(a)

Maintain and clean equipment

Page 3

Biologics

12202 21 CFR 606.170(a)

Adverse Reaction - Investigations

15030 21 CFR 606.60(b)

Equipment calibration frequency

41 21 CFR 606.40(a)(1)

Provide space for examination

158 21 CFR 606.160(e)

Unsuitable donors

89 21 CFR 606.100(b)(10)

Controlling storage temperatures

208 21 CFR 640.3(a)(1)

Donor suitability procedures not followed

9044 21 CFR 600.10(b)

Personnel capabilities

9220 21 CFR 606.100(b)(20)

Donor notification

12203 21 CFR 606.170(a)

Adverse Reaction- Reports of Investigations

61 21 CFR 606.60(a)

Provide proper equipment to meet requirements

224 21 CFR 640.4(f)

Arm preparation

9243 21 CFR 630.6(a)

Notification

35 21 CFR 606.40

Clean & orderly

80 21 CFR 606.100(b)(1)

Donor criteria

161 21 CFR 606.160(a)(2)

Determination of lot numbers and supplies

Page 4

Biologics

9234 21 CFR 630.6(c)

Notification w/in 8 weeks

63 21 CFR 606.65

Safe, sanitary, orderly storage

142 21 CFR 606.140(a)

Establishment of spec., standards, and test procedures

150 21 CFR 606.151(e)

Procedures to maintain records of emergency transfusions

157 21 CFR 606.160(d)

Retention period

212 21 CFR 640.3(b)(3)

Qualifications of donor hemoglobin

227 21 CFR 640.4(h)

Storage temperatures after collection

246 21 CFR 640.25(a)

Storage temps./agitation

9089 21 CFR 600.14(c)

When to report

9219 21 CFR 606.100(b)(20)

Donor deferral

42 21 CFR 606.40(a)(2)

Provide space for blood withdrawal

50 21 CFR 606.40(c)

Provide adequate handwashing

51 21 CFR 606.40(c)

Provide adequate toilet facilities

54 21 CFR 606.40(d)(2)

Provide adequate disposal of blood & blood components

77 21 CFR 606.100(b)

Written SOPs available for use by personnel

Page 5

Biologics

88 21 CFR 606.100(b)(9)

Written methods for investigating adverse reactions

93 21 CFR 606.100(b)(14)

QC procedures for supplies and reagents

94 21 CFR 606.100(b)(15)

Schedules and procedures for equipment & calibration

117 21 CFR 606.121(f)

Labeling of blood products unsuitable for transfusion

156 21 CFR 606.160(c)

Assignment of donor number

165 21 CFR 606.170(a)

Adverse reaction - Maintenance of Reports

236 21 CFR 640.5(e)

Testing - inspection

251 21 CFR 640.25(b)

Quality control

333 21 CFR 640.64(e)

Prevention of contamination

376 21 CFR 640.120

Alternative procedures

3244 21 CFR 640.61

Written consent

9052 21 CFR 600.11(b)

Equipment

9227 21 CFR 606.171(a)

BPDR - procedures

9236 21 CFR 630.6(b)(1)

Deferred or not suitable

Page 6

Biologics

9238 21 CFR 630.6(b)(3)

Results of testing

9241 21 CFR 630.6(a)

Supplemental results

43 21 CFR 606.40(a)(3)

Provide space for storage of blood & blood products

45 21 CFR 606.40(a)(5)

Provide space for storage of finished product

49 21 CFR 606.40(a)(9)

Provide space for all packaging, labeling, & finishing ops.

64 21 CFR 606.65(b)

Visual examination

75 21 CFR 606.100(a)

SOP compliance

81 21 CFR 606.100(b)(2)

Donor qualifying tests & measurements

105 21 CFR 606.122

Instruction circular - required information

121 21 CFR 606.121(c)(2)

Name, address, registration number

137 21 CFR 606.121(c)(13)

Unapproved encoded/machine readable information

147 21 CFR 606.151(d)

Crossmatching of donor/recipient cells

162 21 CFR 606.165(a)

Distribution and receipt - recalls

164 21 CFR 606.165(c)

Receipt records - content

Page 7

Biologics

167 21 CFR 606.170(b)

Adverse reaction - fatality

198 21 CFR 640.2(c)(3)

Blood not stored between 1-6 deg / shipped 1-10 deg

205 21 CFR 640.3(f)

Donations in less than eight weeks

215 21 CFR 640.3(b)(6)

Qualifications of donor - disease transmissible by blood

225 21 CFR 640.4(f)

Closed system

233 21 CFR 640.5(b)

Testing - ABO

247 21 CFR 640.24(b)

Storage until removal of platelets

255 21 CFR 640.31

Donor suitability

270 21 CFR 640.34(b)

Fresh Frozen Plasma - preparation

272 21 CFR 640.34(b)

Fresh Frozen Plasma - storage requirements

325 21 CFR 640.63(c)(10)

Narcotics use

335 21 CFR 640.65(b)(1)(i)

Serological test

369 21 CFR 640.72(a)(1)

Shipping temperature requirements

3252 21 CFR 640.63(a)

Determination not made on day of collection

Page 8

Biologics

3258 21 CFR 640.63(d)

Unreliable answers

3443 21 CFR 610.47

Notification of transfusion recipients

9051 21 CFR 600.11(a)

Work areas - temperatures

9076 21 CFR 600.12(a)

Maintenance - concurrence

9077 21 CFR 600.12(a)

Maintenance - completeness

9080 21 CFR 600.12(b)(2)

Retention - Records of Recall

9086 21 CFR 600.14(a)(1)

Who must report - manufacturer

9092 21 CFR 600.80(b)

Review of Adverse Experiences follow up information

9107 21 CFR 600.11(h)

Sterile & pyrogen free

9223 21 CFR 606.160(b)(6)

Required records - transfusion reaction and complaints

9235 21 CFR 630.6(c)

Documentation

9237 21 CFR 630.6(b)(2)

Type of donations

9240 21 CFR 630.6(d)(1)

Physician notification

Page 9

Biologics

9242 21 CFR 630.6(d)(2)

Notification

9271 21 CFR 610.41

Donor Deferral - reentry

9596 21 CFR 640.3(a)

Donor suitability by means of medical history

Page 10

Biologics

LongDesc Written standard operating procedures including all steps to be followed in the [collection] [processing] [compatibility testing] [storage] [distribution] of blood and blood components for [homologous transfusion] [autologous transfusion] [further manufacturing purposes] are not always [maintained] [followed] [maintained on the premises]. Specifically, *** Failure to [perform a thorough investigation] [make a record of the conclusions and follow-up] of [an unexplained discrepancy] [a failure of a lot or unit to meet any of its specifications]. Specifically,*** Records fail to [identify the person performing the work] [include dates of the various entries] [show test results] [include interpretation of the results] [show the expiration date assigned to specific products] [be as detailed as necessary] so as to provide a complete history of the work performed. Specifically, *** Failure to maintain [donor] [processing] [storage and distribution] [compatibility testing] [quality control] [general] records. Specifically, ***

Frqncy 111

37

26

24

Records are not concurrently maintained with the performance of each significant step in the [collection] [processing] [compatibility testing] [storage] [distribution] of each unit of blood and blood components so that all steps can be clearly traced. Specifically, *** Failure to submit a biological product deviation report [within 45 days from the date you acquired information suggesting that a reportable event occurred]. Specifically, *** The personnel responsible for the [collection] [processing] [compatibility testing] [storage] [distribution] of blood or blood components are not adequate in [number] [educational background] [training and experience, including professional training as necessary] to assure competent performance of their assigned functions, and to ensure that the final product has the safety, purity, potency, identity and effectiveness it purports or is represented to possess. Specifically, *** Equipment used in the [collection] [processing] [compatibility testing] [storage and distribution] of blood and blood components is not [observed] [standardized] [calibrated] on a regularly scheduled basis as prescribed in the SOP Manual. Specifically, *** Records are [illegible] [not indelible]. Specifically, ***

23

23

20

15

13

Failure to use supplies and reagents in a manner consistent with instructions provided by the manufacturer. Specifically, ***

12

All records pertinent to a lot or unit were not reviewed before the release or distribution of a lot or unit of final product. Specifically, ***

12

Failure to [maintain] [locate] equipment used in the [collection] [processing] [compatibility testing] [storage] [distribution] of blood and blood products [in a clean and orderly manner] [so as to facilitate cleaning and maintenance]. Specifically, ***

Page 11

Biologics

A thorough investigation of each reported adverse reaction was not made. Specifically,

Equipment used in the [collection][processing][compatibility testing][storage and distribution] of blood and blood components is not observed, standardized and calibrated with at least the frequency required. Specifically, *** Failure to provide adequate space for [private] [accurate] examinations of individuals to determine their suitability as blood donors. Specifically, ***

A record is not available from which unsuitable (deferred) donors may be identified so that products from such individuals will not be distributed. Specifically, *** The standard operating procedure fails to include a written description of the storage temperatures and methods of controlling storage temperatures for all blood products and reagents Specifically, *** Failure to [follow] [maintain] [maintain on the premises] standard procedures and methods for determining the suitability of a donor as a source of blood. Specifically, *** Failure to assure that personnel have [capabilities commensurate with] [the necessary training in] [necessary experience in] [a thorough understanding of] the operations which they perform. Specifically, *** The standard operating procedure fails to include a written description of the [donor notification process] [process for follow-up if the initial attempt at donor notification fails]. Specifically, *** Written reports of investigations of adverse reactions, including conclusions and follow up, are not prepared and maintained. Specifically,

Failure of equipment to perform in the manner for which it was designed so as to assure compliance with the official requirements prescribed in 21 CFR 606. Specifically, *** The phlebotomy site is not prepared by a method that gives maximum assurance of a sterile container of Whole Blood. Specifically, ***

Failure to make reasonable attempts to notify a donor who has been [deferred based on the results of tests for evidence of communicable disease agent(s)] [determined not be to suitable as a donor based on suitability criteria]. Specifically, *** Failure to maintain facilities in a clean and orderly manner. Specifically, ***

The standard operating procedure fails to include written descriptions of criteria used to determine donor suitability, including acceptable medical history criteria. Specifically, *** Appropriate records are not available to determine the lot numbers of [supplies] [reagents] used for specific [lots] [units] of the final product. Specifically, ***

Page 12

Biologics

Failure to make reasonable attempts to notify the donor within 8 weeks after determining that the donor is deferred or determined not to be suitable for donation. Specifically, *** Failure to store all supplies and reagents used in the [collection] [processing] [compatibility testing] [storage] [distribution] of blood and blood components in a safe, sanitary and orderly manner. Specifically, *** Failure to establish scientifically sound and appropriate specifications, standards and test procedures to assure that blood and blood components are safe, pure, potent and effective. Specifically, *** Records [including signature by the physician requesting the procedure] are not maintained of all emergency transfusions [including complete documentation justifying the emergency action]. Specifically, *** Failure to retain records [for 5 years after the records of processing have been completed] [for 6 months after the latest expiration date for the individual product] [indefinitely where there is no expiration date]. Specifically, *** Each donor was not in good health as indicated in part by the blood hemoglobin level which was demonstrated to be less than 12.5 gm. of hemoglobin per 100 ml of blood (38% by microhematocrit). Specifically, *** After collection, blood is not [immediately stored at a temperature between 1 and 6 degrees Celsius] [transported from the donor clinic to the processing laboratory in temporary storage to cool the blood continuously toward a range between 1 and 6 degrees Celsius]. Specifically, *** Failure to store platelets immediately after resuspension [at 20 to 24 degrees Celsius with continuous gentle agitation] [at 1 to 6 degrees Celsius]. Specifically, *** Biological product deviations [were] [are] not reported within the 45 calendar day timeframe. Specifically, ***

The standard operating procedure fails to include a written description of the donor deferral process. Specifically, ***

Failure to provide adequate space for the withdrawal of blood from donors with minimal [risk of contamination] [exposure to activities and equipment unrelated to blood collection]. Specifically, *** Failure to provide [adequate] [clean] [convenient] handwashing facilities for personnel. Specifically, ***

Failure to provide [adequate] [clean] [convenient] toilet facilities for donors and personnel. Specifically, ***

Failure to provide for safe and sanitary disposal for blood and blood components not suitable for use or distribution. Specifically, ***

Failure to make available written procedures for use by personnel in the areas where the procedures are performed. Specifically, ***

Page 13

Biologics

The standard operating procedure fails to include a written description of the procedures for investigating adverse donor and recipient reactions. Specifically, *** The standard operating procedure fails to include a written description of the quality control procedures for supplies and reagents employed in [blood collection] [processing] [pretransfusion testing]. Specifically, *** The standard operating procedure fails to include a written description of schedules and procedures for equipment maintenance and calibration. Specifically, *** Failure to prominently label blood and blood components (except for recovered plasma) determined to be unsuitable for transfusion with ["NOT FOR TRANSFUSION"] [the reason the unit is considered unsuitable]. Specifically, *** Failure of records describing the history and ultimate disposition of blood products to include a donor number [assigned to each accepted donor] [which relates to the unit of blood collected from that donor] [which relates to the donor's medical record] [which relates to any component or blood product from the donor's unit of blood]. Specifically, *** Failure to maintain reports of complaints of adverse reactions regarding each unit of blood or blood product arising as a result of [blood collection] [transfusion]. Specifically, *** Failure to [visually inspect blood during storage and immediately prior to issue for] [prevent issuance of blood found to have] abnormal color, physical appearance, or indication or suspicion of microbial contamination. Specifically, *** Failure to test each month (of manufacture) four units prepared from different donors at the end of the storage period for [platelet count] [pH of not less than 6.0 measured at the storage temperature of the unit] [actual plasma volume]. Specifically, *** The phlebotomy site is not prepared by a method that gives maximum assurance of a sterile container of blood. Specifically, ***

Failure to request from CBER and obtain approval for exceptions or alternatives to requirements regarding [blood] [blood components] [blood products]. Specifically, *** Failure to obtain written consent of prospective Source Plasma donors. Specifically, ***

There is no assurance that equipment is [adequately sterilized] [properly cleaned] [inspected for cleanliness] [suitable for use]. Specifically, ***

Failure to establish a procedure to obtain information about [deviations] [complaints] [adverse events] from your contractor. Specifically, ***

Failure to notify the donor [that the donor is deferred or determined not to be suitable] [of the reason for deferral]. Specifically, ***

Page 14

Biologics

Failure to notify the donor of the results of [tests for evidence of infection due to communicable disease agents that were a basis for deferral] [supplemental tests]. Specifically, *** Failure to [attempt to obtain the results of supplemental testing prior to notifying a donor of a deferral] [notify a donor of the results of supplemental testing]. Specifically, *** Failure to provide adequate space for the storage of blood or blood components pending completion of tests. Specifically, ***

Failure to provide adequate space for the storage of finished products prior to distribution. Specifically, ***

Failure to provide adequate space for the orderly conduction of all [packaging] [labeling] [other finishing] operations. Specifically, ***

Failure to inspect each blood collecting container [and its satellite container(s)] for damage or evidence of contamination including breakage of seals and abnormal discoloration [prior to its use] [immediately after filling]. Specifically, *** Failure of the Standard Operating Procedure to comply with additional standards in 21 CFR 640. Specifically, ***

The standard operating procedure fails to include written descriptions of methods for performing donor qualifying tests and measurements, including minimum and maximum values for a test or procedure when a factor in determining acceptability. Specifically, *** Failure to provide an instruction circular for products intended for transfusion containing adequate directions for use and the information contained in 21 CFR 606.122. Specifically, *** The container label fails to include the [name] [address] [registration number] [the license number of each manufacturer, for a licensed product]. Specifically, ***

The container label bears encoded information in the form of machine-readable symbols which have not been approved for use by the Director, Center for Biologics Evaluation and Research). Specifically, *** Failure of standard operating procedures for compatibility testing to include the testing of the donors cells with the recipients serum (minor crossmatch) by a method that will demonstrate agglutinating, coating and hemolytic antibodies. Specifically, *** Failure of distribution and receipt procedures to include a system by which the distribution or receipt of each unit can be readily determined to facilitate its recall. Specifically, *** Receipt records fail to contain the [name and address of the collecting facility] [date received] [donor or lot number assigned by the collecting facility] [date of expiration or the date of collection, whichever is applicable] Specifically, ***

Page 15

Biologics

A confirmed, fatal complication of [blood collection] [transfusion] was not [reported as soon as possible] [submitted in writing within 7 days after the fatality] to the Director, Office of Compliance, Center for Biologics Evaluation and Research by the [collecting facility in the event of a donor reaction] [facility that performed the compatibility tests in the event of a transfusion reaction]. Specifically, *** Reissued blood has not been [stored continuously at 1 to 6 C] [shipped between 1 and 10 C]. Specifically, ***

A person served as a source of blood more than once in 8 weeks and was not examined at the time of donation and certified by a physician to be in good health as indicated in part in 21 CFR 640.3(b). Specifically, *** Failure to determine whether each donor is free from any disease transmissible by blood as determined by history and examinations. Specifically, ***

The blood is [not collected by aseptic methods in a sterile system] [collected using a vented system which fails to protect the blood against contamination]. Specifically, *** Failure to test blood for determination of ABO blood group [using two blood group tests] [using appropriate reagents] [using appropriate techniques]. Specifically, *** Failure to hold [whole blood] [plasma] immediately after collection between 20 and 24 degrees Celsius until the platelets are separated. Specifically, ***

Failure to ensure that [whole blood] [plasmapheresis] donors meet suitability criteria. Specifically, ***

Failure to prepare Fresh Frozen Plasma [from blood collected by a single uninterrupted venipuncture] [separated from the red blood cells, placed in a freezer within the appropriate time frame, and stored at - 18 degrees Celsius or colder]. Specifically, *** Failure to place plasma, separated from red blood cells and intended to be labeled Fresh Frozen Plasma, in a freezer within eight hours after phlebotomy at a temperature of -18 degrees Celsius or colder. Specifically, *** Each donor was not in good health on the day of donation, as indicated in part by [arms] [forearms] with [skin punctures] [scars] indicative of addiction to selfinjected narcotics. Specifically, *** Failure to draw from each donor [on the day of the first medical exam or plasmapheresis] [at least every 4 months] a sample of blood tested for [syphilis] [total plasma or serum protein determination] [serum protein electrophoresis or equivalent test]. Specifically, *** Failure to maintain documentation establishing that the shipping temperature requirements are being met for Source Plasma intended for manufacture into injectable products. Specifically, *** Determination of the suitability of Source Plasma donors was not made on the day of collection. Specifically, ***

Page 16

Biologics

Failure to consider as unsuitable any donor who does not appear to be providing reliable answers to medical history questions. Specifically, ***

Failure to [notify the attending physician of a recipient of a lookback unit] [make a minimum of three attempts within 8 weeks to notify the recipient of a lookback unit in the event the physician does not inform the recipient] [notify recipient's legal representative or relative] [document notifications of lookback units]. Specifically, *** The [refrigerators] [incubators] [temperature controlled rooms] [are not maintained at the required temperatures] [are not free of extraneous material that may affect the safety of the product]. Specifically, *** Records are not made [concurrently with the performance] of each step in the [manufacture] [distribution] of products. Specifically, ***

The [manufacturing] [distribution] records [are not legible and indelible] [do not detail the various steps of manufacture of the product]. Specifically, ***

Recall records for distributed product [were] [are] not [generated] [retained] [complete]. Specifically, ***

Failure to submit [a] biological deviation [report] [reports]. Specifically, ***

Failure to submit all follow up information on adverse experience reports to FDA, as required. Specifically, ***

There is no assurance that [final containers] [closures] for products intended for use by injection are [sterile] [pyrogen free]. Specifically, ***

Failure to maintain records of transfusion reaction reports and complaints, including investigation and follow up. Specifically, ***

Failure to [document that you have successfully notified a deferred donor] [document that you have made reasonable attempts to notify a deferred donor]. Specifically, *** Failure to notify the donor of the types of donations of blood or blood components that the donor should not donate in the future. Specifically, ***

Failure to provide to an autologous donor's referring physician [information that the autologous donor is deferred based on the results of tests for evidence of infection due to communicable disease agents, and the reason for that decision] [the types of donation of blood and blood components that the autologous donor should not donate in the future] [the results of tests for evidence of infection due to communicable disease agent(s) that were a basis for deferral] [results of any supplemental tests]. Specifically, ***

Page 17

Biologics

Failure to [make] [document] reasonable attempts to notify the autologous donor's referring physician within 8 weeks after determining that the autologous donor is deferred. Specifically, *** The method or process used to requalify deferred donors was not found acceptable for such purposes by FDA. Specifically, ***

Failure to [always] determine donor suitability on the day of collection by means of [medical history] [test for hemoglobin level] [physical examination]. Specifically, ***

Page 18

BIMO

Center Name

Cite Id

Ref No

ShortDesc

Bioresearch monitoring

7560 21 CFR 312.60

FD-1572, protocol compliance

7530 21 CFR 312.62(b)

Case history records- inadequate or inadequate

7281 21 CFR 56.108(a)(1)

Initial and continuing reviews

7526 21 CFR 312.62(a)

Accountability records

7318 21 CFR 56.115(a)(2)

Minutes of IRB meetings

7227 21 CFR 50.27(a)

Consent form not approved/signed/dated

7334 21 CFR 56.115(a)(5)

List of members

7498 21 CFR 312.66

Unanticipated problems

7562 21 CFR 312.60

Informed consent

Page 19

BIMO

7290 21 CFR 56.108(c)

Members present for review

7321 21 CFR 56.110(c)

Method to keep members advised

7482 21 CFR 312.50

General responsibilities of sponsors

7335 21 CFR 56.115(a)(6)

Written procedures per 56.108(a) and (b)

7552 21 CFR 312.66

Changes in research

7520 21 CFR 312.64(b)

Safety reports

7231 21 CFR 50.20

Consent not obtained, exceptions do not apply

7278 21 CFR 56.107(e)

Conflict of interest

7342 21 CFR 56.108(b)(2)

Prompt reporting of noncompliance

7391 21 CFR 50.25(a)(5)

Confidentiality, FDA inspection of records

Page 20

BIMO

7286 21 CFR 56.108(b)(1)

Prompt reporting of unanticipated problems

7293 21 CFR 56.109(f)

Continuing review

7343 21 CFR 56.108(b)(3)

Reporting of suspension/termination

7480 21 CFR 312.50

Ensuring compliance with plan and protocol

7654 21 CFR 56.110(b)

Research not eligible for expedited review

7411 21 CFR 312.53(c)(1)

Investigator statement (FDA 1572)

7517 21 CFR 312.66

Initial and continuing review

7392 21 CFR 50.25(a)(7)

Whom to contact

7209 21 CFR 50.25(a)(1)

Procedures, identification of those which were experimental

7277 21 CFR 56.107(d)

One non-affiliate member

7368 21 CFR 56.108(a)2)

More frequent reviews, verification of no changes

Page 21

BIMO

7459 21 CFR 312.57(a)

Records of receipt, shipment, disposition

3923 21 CFR 58.33(f)

Study director: transfer of data to archives

4007 21 CFR 58.130(a)

Conduct: in accordance with protocol

4025 21 CFR 58.185(a)(9)

Final report: circumstances affecting data qual., integrity

7316 21 CFR 56.115(a)(4)

Copies of IRB/CI correspondence

7333 21 CFR 56.104(c)

Emergency use and IRB approval

7369 21 CFR 56.109(h)

Children as subjects

7371 21 CFR 56.108(a)(1)

Reporting findings and actions to investigator/institution

7666 21 CFR 50.20

Understandable language

3920 21 CFR 58.33(c)

Study director: unforeseen circumstances

3926 21 CFR 58.35(b)(1)

QAU: maintain a master schedule

Page 22

BIMO

3932 21 CFR 58.35(b)(6)

QAU: review final study report

3989 21 CFR 58.107

Test article: handling

4006 21 CFR 58.120(b)

Protocol: approval of changes

7305 21 CFR 56.110(b)(2)

Minor changes

7319 21 CFR 56.115(a)(3)

Records of continuing review

7337 21 CFR 56.115(b)

Retention of records

7339 21 CFR 56.108(a)(4)

Changes in approved research

7340 21 CFR 56.108(a)(3)

Prompt reporting of changes

7388 21 CFR 50.25(a)(2)

Reasonably foreseeable risks or discomforts

7390 21 CFR 50.25(a)(4)

Alternate procedures, courses of treatment

Page 23

BIMO

7393 21 CFR 50.25(a)(8)

Participation; refusal and discontinuance

7657 21 CFR 50.25(b)(5)

Significant new findings

3909 21 CFR 58.31(a)

Management: designating the study director

3918 21 CFR 58.33(a)

Study director: follow study protocol

3919 21 CFR 58.33(b)

Study director: all data recorded and verified

3922 21 CFR 58.33(e)

Study director: follow GLP regulations

3952 21 CFR 58.61

Equipment: appropriate design and adequate capacity

3954 21 CFR 58.63(a)

Equipment: calibration

3958 21 CFR 58.81(a)

SOPs: authorization and documentation of deviations

3959 21 CFR 58.81(a)

SOPs: authorized changes

Page 24

BIMO

3960 21 CFR 58.81(b)

SOPs: required

4016 21 CFR 58.185(a)

Final report: non-existent

7274 21 CFR 56.107(a)

At least five members with varying backgrounds

7279 21 CFR 56.107(f)

Invited individual allowed to vote with IRB

7297 21 CFR 56.109(b)

Information given to subjects

7317 21 CFR 56.115(a)(1)

Copies of all research proposals and related documents

7353 21 CFR 50.52

Factors required for approval

Page 25

BIMO

7363 21 CFR 50.55(f)

Documentation of permission by parents or guardian

7370 21 CFR 56.111(c)

Children as subjects

7384 21 CFR 50.25(b)(1)

Statement of risks

7387 21 CFR 50.25(a)(1)

Statement of research, purpose, duration of participation

7406 21 CFR 56.109(a)

Scope of reviews

7479 21 CFR 312.56(a)

Monitoring investigations

7488 21 CFR 312.59

Records of unused drug disposition

7527 21 CFR 312.62(a)

Unused drug disposition (investigator)

7531 21 CFR 312.62(c)

Record retention

7543 21 CFR 312.61

Unauthorized recipients (investigator)

7656 21 CFR 56.108(c)

Approval from a majority of members present

Page 26

BIMO

7664 21 CFR 50.20

Circumstances of obtaining consent

3900 21 CFR 58.10

Notifying contractor of GLP status

3902 21 CFR 58.29(a)

Personnel: education, training, experience

3911 21 CFR 58.31(c)

Management: assure there is a QAU

3913 21 CFR 58.31(e)

Management: availability of resources

3915 21 CFR 58.31(g)

Management: QAU findings to study director

3925 21 CFR 58.35(a)

QAU: separate and independent

3931 21 CFR 58.35(b)(5)

QAU: authorize deviations from protocols or SOPs

3933 21 CFR 58.35(b)(7)

QAU: signed statement in final report

3935 21 CFR 58.35(d)

QAU: access to SOPs, certify inspections

3945 21 CFR 58.45

Facility: perishable supplies

Page 27

BIMO

3949 21 CFR 58.47(b)

Facility: article storage separate from test system

3955 21 CFR 58.63(b)

Equipment: maintenance SOPs

3957 21 CFR 58.81(a)

SOPs: laboratory methods

3976 21 CFR 58.90(f)

Animal care: cage and equipment cleaning

3977 21 CFR 58.90(g)

Animal care: analysis of feed and water

3983 21 CFR 58.105(a)

Test article: characterization

3996 21 CFR 58.120(a)(3)

Protocol: sponsor name and address

4008 21 CFR 58.130(b)

Conduct: test systems monitoring

4011 21 CFR 58.130(e)

Conduct: recording in ink

4013 21 CFR 58.130(e)

Conduct: changes not obscuring original entries

4018 21 CFR 58.185(a)(2)

Final report: objectives, procedures, changes

4021 21 CFR 58.185(a)(5)

Final report: stability of test and control articles

Page 28

BIMO

4024 21 CFR 58.185(a)(8)

Final report: dosage, regimen, route of admin., duration

4028 21 CFR 58.185(a)(12)

Final report: reports of individual scientists

4039 21 CFR 58.190(c)

Archives: individual responsible

4041 21 CFR 58.190(e)

Archives: indexing, expedient retrieval

4045 21 CFR 58.195(e)

Archives: retention of summaries of training, et. al.

4047 21 CFR 58.195(g)

Archives: records not retained as originals, true copies

7270 21 CFR 56.103(a)

IRB review requirement

7276 21 CFR 56.107(c)

One scientific and one non-scientific member

7292 21 CFR 56.109(g)

Providing publicly-disclosed information to sponsor

7320 21 CFR 56.109(e)

IRB approvals/disapprovals - general

7322 21 CFR 56.111 (a)(2)

Risks to subjects reasonable

7325 21 CFR 56.111(a)(5)

Informed consent documented

Page 29

BIMO

7328 21 CFR 56.111(b)

Vulnerable subject safeguards

7336 21 CFR 56.115(a)(7)

Statements of significant new findings

7354 21 CFR 50.53

Factors required for approval

7374 21 CFR 56.109(c)(2)

Exception from informed consent; emergency research

7389 21 CFR 50.25(a)(3)

Benefits to the subject

7394 21 CFR 50.24(a)(2)

No determination that obtaining IC wasn't feasible

Page 30

BIMO

7396 21 CFR 50.24(a)(3)

Prospect of direct benefit not determined

7398 21 CFR 50.24(a)(6)

No determination that IC procedure/document were approved

7399 21 CFR 50.24(a)(7)

Additional protections of rights and welfare

7410 21 CFR 312.53(a)

Investigator selection

7428 21 CFR 312.53(c)(2)

Investigator CV or other statement of qualifications

7452 21 CFR 312.56(c)

IND safety report

Page 31

BIMO

7453 21 CFR 312.56(b)

Investigator non-compliance

7507 21 CFR 312.52(a)

Transfer of obligations

7519 21 CFR 312.64(c)

Final study report

7534 21 CFR 312.68

FDA access to clinical investigator records

7545 21 CFR 312.120(c)

Foreign clinical trials

7555 21 CFR 312.53(d)

Selecting monitors

7557 21 CFR 312.56(b)

Notification of FDA of termination of investigator

7558 21 CFR 312.57(c)

Record retention requirement

7629 21 CFR 312.56(c)

Annual report

7631 21 CFR 312.53(c)(4)

Financial information - commitment to update

7638 21 CFR 312.20(a)

Failure to submit an IND

Page 32

BIMO

7652 21 CFR 56.113

Reporting

7660 21 CFR 50.24(a)(1)

IRB failed to find/document required conditions

7679 21 CFR 56.106(a)

IRB for CI's in support of research/marketing permits

Page 33

BIMO

LongDesc

Frqncy

An investigation was not conducted in accordance with the [signed statement of investigator] [investigational plan]. Specifically***

123

Failure to prepare or maintain [adequate] [accurate] case histories with respect to [observations and data pertinent to the investigation] [informed consent]. Specifically, *** The IRB [has no] [did not follow its] written procedure for conducting its [initial] [continuing] review of research. Specifically, ***

75

36

Investigational drug disposition records are not adequate with respect to [dates] [quantity] [use by subjects]. Specifically, ***

36

Minutes of IRB meetings have not been [prepared] [maintained] in sufficient detail to show [attendance at the meetings] [actions taken by the IRB] [the vote on actions, including the number of members voting for, against and abstaining] [the basis for requiring changes in or disapproving research] [a written summary of the discussion of controverted issues and their resolution]. Specifically, *** Informed consent was not properly documented in that the written informed consent used in the study [was not approved by the IRB] [was not signed by the subject or the subjects legally authorized representative at the time of consent ] [was not dated by the subject or the subject's legally authorized representative at the time of consent]. Specifically, *** A list of IRB members has not been [prepared] [maintained], identifying members by [name] [earned degrees] [representative capacity] [indications of experience sufficient to describe each member's chief anticipated contribution to IRB deliberations] [any employment or other relationship between each member and the institution]. Specifically, *** Failure to report promptly to the IRB all unanticipated problems involving risk to human subjects or others. Specifically, ***

33

27

20

19

Failure to obtain informed consent in accordance with 21 CFR Part 50 from each human subject prior to [drug administration] [conducting study-related tests] . Specifically***

18

Page 34

BIMO

For other than expedited reviews, the IRB does not always review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. Specifically, *** The IRB uses an expedited review procedure, but [has not adopted] [is not following] a method for keeping members advised of research proposals which have been approved under the procedure. Specifically, *** Failure to [select qualified investigators] [provide investigators with the information needed to conduct the study properly] [ensure proper monitoring of the study] [ensure the study is conducted in accordance with the protocol and/or investigational plan] [ensure that FDA and all investigators are promptly informed of significant new adverse effects or risks]. Specifically, *** Documentation has not been [prepared] [maintained] of written procedures for the IRB, as required by 21 CFR 56.108(a) and (b). Specifically, *** Not all changes in research activity were approved by an Institutional Review Board prior to implementation. Specifically, ***

16

16

15

13

13

Failure to report [promptly] to the sponsor adverse effects that may reasonably be regarded as caused by, or probably caused by, an investigational drug. Specifically, *** Legally effective informed consent was not obtained from a subject or the subject's legally authorized representative, and the situation did not meet the criteria in 21 CFR 50.23 - 50.24 for exception. Specifically, *** The IRB allowed a member to participate in the IRB's [initial] [continuing review] of a project in which the member had a conflicting interest. Specifically, *** The IRB [has no] [did not follow] written procedures for ensuring prompt reporting to [the IRB] [appropriate institutional officials] [the FDA] of any instance of serious or continuing noncompliance with theses regulations or the requirements or determinations of the IRB. Specifically, *** There was no statement in the informed consent document that [described the extent, if any, to which confidentiality of records identifying the subject would be maintained] [noted the possibility that the Food and Drug Administration might inspect the records]. Specifically, ***

12

Page 35

BIMO

The IRB [has no] [did not follow] written procedures for ensuring prompt reporting to [the IRB] [appropriate institutional officials] [the FDA] of any unanticipated problems involving risks to human subjects or others. Specifically, *** The IRB does not conduct continuing review of research at intervals [appropriate to the degree of risk] [of not less than once per year]. Specifically, *** The IRB [has no] [did not follow] written procedures for ensuring prompt reporting to [the IRB] [appropriate institutional officials] [the FDA] of any suspension or termination of IRB approval . Specifically, *** Failure to ensure that an investigation was conducted in accordance with the general investigational plan and protocols as specified in the IND. Specifically, *** The IRB used an expedited review procedure for research which did not appear in an FDA list of categories eligible for expedited review, and which had not previously been approved by the IRB [within one year]. Specifically, *** Failure to obtain [an] [a complete] investigator statement, form FDA-1572, before permitting an investigator to participate in an investigation. Specifically, *** Failure to assure that an IRB [complying with applicable regulatory requirements] was responsible for the initial and continuing review and approval of a clinical study. Specifically, *** The informed consent document lacked an explanation of whom to contact [for answers to pertinent questions about the research and research subjects' rights] [in the event of a research-related injury to the subject]. Specifically, *** The informed consent document did not contain [a description of the procedures to be followed] [identification of any procedures which were experimental]. Specifically, *** The IRB does not include at least one member who is not otherwise affiliated with the institution, and who is not part of the immediate family of a person who is affiliated with the institution. Specifically, *** The IRB [has no] [did not follow its] written procedure for determining which projects [require review more often than annually] [need verification from sources other than the investigator that no material changes have occurred since previous IRB review] . Specifically, ***

Page 36

BIMO

Lack of [adequate] records covering [receipt] [shipment to investigators] [disposition] of an investigational drug. Specifically, ***

The study director failed to assure that all raw data, documentation, protocols, specimens, and final reports were transferred to the archives during or at the close of the study. Specifically, *** Not all nonclinical laboratory studies were conducted in accordance with the protocol. Specifically, ***

The final study report did not include a description of all circumstances that may have affected the quality or integrity of the data. Specifically, ***

Copies have not been maintained of all correspondence between the IRB and the investigators. Specifically, ***

A clinical investigator did not report to the IRB [, within five days of use,] the emergency use of a test article for which the IRB had not reviewed the research proposal. Specifically, *** The IRB did not determine [at the time of initial review] [at the time of continuing review for an ongoing study which was started on/before April 30, 2001] that a study was in compliance with 21 CFR Part 50 Subpart D, "Additional Safeguards for Children in Clinical Investigations." Specifically, *** The IRB [has no] [did not follow its] written procedure for reporting its [findings] [actions] to the [investigator] [institution]. Specifically, ***

The general requirements for informed consent were not met in that the information given was not in language understandable to the subject or the subject's representative. Specifically, *** The study director failed to assure that unforeseen circumstances that might affect the quality and integrity of the nonclinical laboratory study were noted when they occurred and corrective action was taken and documented. Specifically, *** The quality assurance unit failed to maintain a copy of a master schedule sheet that contained all required elements for all nonclinical laboratory studies conducted by the testing facility. Specifically, ***

Page 37

BIMO

The quality assurance unit failed to review the final study report to assure that such report accurately described the methods and standard operating procedures, and that the reported results accurately reflected the raw data of the study. Specifically, *** Procedures have not been established for the handling of the test and control articles to ensure that [there is proper storage] [distribution is made in a manner designed to preclude the possibility of contamination, deterioration, or damage] [proper identification is maintained throughout the distribution process] [the receipt and distribution of each batch is documented including the date and quantity of each batch distributed or returned]. Specifically, ***

Not all changes in, or revisions of, an approved protocol and the reasons therefore were documented, signed by the study director, dated, and maintained with the protocol. Specifically, *** The IRB used an expedited review procedure to review supposedly minor changes to previouslyapproved research, but the changes were not minor in nature. Specifically, *** Records have not been [prepared] [maintained] of all continuing review activities. Specifically, ***

Records required by 21 CFR 56 have not been maintained for three years following completion of the research. Specifically, ***

The IRB [has no] [did not follow its] written procedure for ensuring that changes in approved research, during the periods for which IRB approval had already been given, would not be initiated without IRB review and approval (except where necessary to eliminate apparent immediate hazards to the human subjects). Specifically, *** The IRB [has no] [did not follow its] written procedure for ensuring prompt reporting to the IRB of changes in research activity. Specifically, ***

The informed consent document lacked a description of reasonably foreseeable risks or discomforts to the subject. Specifically, ***

There was [no] [an incomplete] disclosure in the informed consent document of appropriate alternate procedures or courses of treatment, if any, that might be advantageous to the subject. Specifically, ***

Page 38

BIMO

The informed consent document did not contain a statement that [participation was voluntary] [refusal to participate would involve no penalty or loss of benefits to which the subject was otherwise entitled] [the subject might discontinue participation at any time without penalty or loss of benefits to which the subject was otherwise entitled]. Specifically, *** The informed consent document did not include a statement that significant new findings developed during the course of the research, which might relate to the subject's willingness to continue participation, would be provided to the subject. Specifically, *** Testing facility management failed to designate a study director before each study was initiated. Specifically, ***

The study director failed to assure that the protocol, including any change, was approved and was followed. Specifically, ***

The study director failed to assure that all experimental data, including observations of unanticipated responses of the test system, were accurately recorded and verified. Specifically, *** The study director failed to assure that all applicable GLP regulations were followed. Specifically, ***

Not all [equipment used in the generation, measurement, or assessment of data] [equipment used for facility environmental control] is of appropriate design and adequate capacity to function according to the protocol and is suitably located for operation, inspection, cleaning, and maintenance. Specifically, *** Not all equipment used for the generation, measurement, or assessment of data is adequately tested, calibrated and/or standardized. Specifically, *** Not all deviations from standard operating procedures in a study were authorized by the study director and documented in the raw data. Specifically, *** Not all significant changes in established standard operating procedures were properly authorized in writing by management. Specifically, ***

Page 39

BIMO

Standard operating procedures have not been established for [animal room preparation] [animal care] [receipt, identification, storage, handling, mixing, and method of sampling of the test and control articles] [test system observations] [laboratory tests] [handling of animals found moribund or dead during study] [necropsy of animals or postmortem examination of animals] [collection and identification of specimens] [histopathology] [data handling, storage, and retrieval] [maintenance and calibration of equipment] [transfer, proper placement, and identification of animals]. Specifically, ***

A final report was not prepared for each nonclinical laboratory study. Specifically, ***

The IRB is not composed of at least five members [with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution]. Specifically, *** The IRB invited an individual with competence in a special area to assist in the review of complex issues which required expertise beyond or in addition to that available on the IRB; however, the IRB allowed the individual to vote with the IRB. Specifically, *** The IRB does not require that information given to subjects as part of informed consent contain all necessary elements of informed consent. Specifically, ***: Copies have not been [prepared] [maintained] of all [research proposals reviewed] [scientific evaluations, if any, accompanying research proposals] [approved sample consent documents] [progress reports submitted by investigators] [reports of injuries to subjects]. Specifically, *** The IRB approved a clinical investigation in which more than minimal risk to children was presented by 1) an intervention or procedure that held out the prospect of direct benefit for the individual subjects, and/or 2) by a monitoring procedure which was likely to contribute to the individual subjects' well-being. However, the IRB did not [find] [document] that [the risk was justified by the anticipated benefit to the subjects] [the relation of the anticipated benefit to the risk was at least as favorable to the subjects as that presented by available alternative approaches] [adequate provisions had been made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in 21 CFR 50.55]. Specifically, ***

Page 40

BIMO

Permission by parents or guardians for the participation of children as subjects in a clinical investigation was not documented in accordance with and to the extent required by 21 CFR 50.27. Specifically, *** The IRB approved the conduct of research involving children as subjects, but did not determine that the research was in compliance with 21 CFR 50 Subpart D. Specifically, *** The informed consent document did not contain a statement that the test article or procedure might involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) that are currently unforeseeable. Specifically, *** The informed consent document did not contain [a statement that the study involved research] [an explanation of the purposes of the research, and the expected duration of the subject's participation]. Specifically, ***

The IRB does not review all research activities covered by the regulations. Specifically, ***

Failure to monitor the progress of an investigation conducted under your IND. Specifically, ***

Failure to maintain [adequate] written records of the disposition of an investigational drug in accordance with 21 CFR Part 312.57. Specifically, ***

Unused supplies of an investigational drug were not [returned to the sponsor] [disposed of in accordance with sponsor instructions]. Specifically, ***

Investigational records were not retained for a period of two years following [approval of a drug's marketing application] [discontinuance of the investigation and notification of FDA]. Specifically, *** A study drug was [administered to subjects] [provided to persons] not under the investigator's personal supervision or under the supervision of a subinvestigator responsible to the investigator. Specifically, ***

For other than expedited reviews, research approved by the IRB does not always receive the approval of a majority of those IRB members present. Specifically, ***

Page 41

BIMO

The general requirements for informed consent were not met in that [you] [the investigator] did not seek consent under circumstances that [provided the prospective subject or the subject's representative sufficient opportunity to consider whether or not to participate] [minimized the possibility of coercion or undue influence]. Specifically, *** Not all consulting laboratories, contractors, or grantees were notified that the study must be conducted in compliance with FDA GLP regulations. Specifically, *** Not all individuals engaged in the conduct of or responsible for the supervision of a nonclinical laboratory study have education, training, and experience, or combination thereof, to enable that individual to perform assigned functions. Specifically, *** Testing facility management failed to assure that there was a quality assurance unit in conformance with FDA GLP regulations. Specifically, ***

Testing facility management failed to assure that all personnel, resources, facilities, equipment, materials, and methodologies were available as scheduled. Specifically, *** Testing facility management failed to assure that any deviations from FDA GLP regulations reported by the quality assurance unit were communicated to the study director and corrective actions were taken and documented. Specifically, *** The quality assurance unit, for any given study, was not entirely separate from and independent of the personnel engaged in the direction and conduct of that study. Specifically, *** The quality assurance unit failed to determine whether any deviations from approved protocols or standard operating procedures had been made with proper authorization and documentation. Specifically, *** The quality assurance unit failed to prepare and sign a statement to be included with the final study report which specified the dates inspections were made and findings reported to management and to the study director. Specifically, *** The quality assurance unit failed to provide access to the testing facility's written procedures for inspection of nonclinical laboratory studies. Specifically, *** The testing facility does not provide appropriate storage areas for preservation of perishable supplies. Specifically, ***

Page 42

BIMO

The testing facility does not provide storage areas for the test and control article and test and control mixtures [separate from areas housing the test systems] [adequate to preserve the identity, strength, purity, and stability of the articles and mixtures]. Specifically, *** The standard operating procedures for routine inspection, cleaning, maintenance, testing, calibration, and/or standardization of equipment are not adequate. Specifically, *** The testing facility does not have written standard operating procedures setting forth nonclinical laboratory study methods that management is satisfied are adequate to insure the quality and integrity of the data generated in the course of a study. Specifically, *** Not all animal cages, racks and accessory equipment were cleaned and sanitized at appropriate intervals. Specifically, ***

Not all animal feed and water were analyzed periodically to ensure that expected contaminants were not present at levels above those specified in the protocol. Specifically, *** The identity, strength, purity, composition, or other characteristics of each batch of test and control article have not been appropriately defined and documented. Specifically, *** Not all protocols contained the name of the sponsor and the name and address of the testing facility at which the study is being conducted. Specifically, ***

Not all test systems were monitored in conformity with the protocol. Specifically, ***

Data generated without the use of an automated data collection system were not recorded directly, promptly, and legibly in ink. Specifically, ***

Not all changes in entries were made so as not to obscure the original entry, indicated the reason for such change, and were dated and signed or identified at the time of the change. Specifically, *** The final study report did not include the objectives and procedures stated in the approved protocol, including any changes in the original protocol. Specifically, *** The final study report did not include the stability of the test and control articles under the conditions of administration. Specifically, ***

Page 43

BIMO

The final study report did not include a description of the dosage, dosage regimen, route of administration, and duration. Specifically, ***

The final study report did not include the signed and dated reports of each of the individual scientists or other professionals involved in the study. Specifically, *** An individual was not identified as responsible for the archives. Specifically, ***

Not all material retained or referred to in the archives was indexed to permit expedient retrieval. Specifically, ***

Not all required summaries of training and experience and job descriptions were retained for the required period of time. Specifically, ***

Not all required records were retained as original records or as true copies of the original records. Specifically, ***

A clinical investigation requiring prior submission to the FDA was initiated without [IRB review] [IRB approval] [being subject to continuing IRB review]. Specifically, *** The IRB does not include [at least one member whose primary concerns are in the scientific area] [at least one member whose primary concerns are in nonscientific areas]. Specifically, *** The IRB has not [promptly] provided to the sponsor of research involving an exception to informed consent a copy of information that has been publicly disclosed by regulation. Specifically, *** The IRB has not promptly notified in writing [the investigator] [the institution] when the IRB has [approved] [disapproved] [required modifications to secure IRB approval of] proposed research activity. Specifically, *** The IRB approved the conduct of research, but did not determine that the risks to subjects were reasonable in relation to the anticipated benefits (if any) to subjects, and to the importance of the knowledge that might be expected to result. Specifically, *** The IRB approved the conduct of research, but did not determine that informed consent would be appropriately documented. Specifically, ***

Page 44

BIMO

The IRB approved the conduct of research in a situation where some or all of the subjects were likely to be vulnerable to coercion or undue influence, but did not determine that additional safeguards had been included in the study to protect the rights and welfare of those subjects. Specifically, *** Documentation has not been [prepared] [maintained] of all statements of significant new findings provided to subjects, as required by 21 CFR 50.25. Specifically, *** The IRB approved a study in which more than minimal risk to children was presented by [an intervention or procedure that did not hold out the prospect of direct benefit for the subjects] [a monitoring procedure that was not likely to contribute to the well-being of the subjects]. However, the IRB did not [find] [document] that [the risk represented a minor increase over minimal risk] [the intervention or procedure presented experiences to subjects that were reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations] [the intervention or procedure was likely to yield generalizable knowledge about the subjects' disorder or condition that was of vital importance for the understanding or amelioration of the subjects' disorder or condition] [adequate provisions had been made for soliciting the assent of the children and permission of their parents or guardians]. Specifically, ***

The IRB waived the requirement for a written consent form signed by the [subject] [subject's legally authorized representative], without first determining that the requirements in 21 CFR 50.24 for an exception from informed consent for emergency research were met. Specifically, *** A description of any benefits [to the subject] [to others] which might reasonably be expected from the research was not included in the informed consent document. Specifically, *** In approving an investigation without requiring informed consent, the IRB did not [find] [document] that obtaining informed consent was not feasible. Specifically,***

Page 45

BIMO

In approving an investigation without requiring informed consent, the IRB did not [find] [document] that participation in the research held out the prospect of direct benefit to the subjects because [they faced a life-threatening situation requiring intervention] [evidence from preclinical studies supported the potential for intervention to provide a direct benefit to subjects] [associated risks were reasonable under the circumstances]. Specifically,*** In approving an investigation without requiring informed consent, the IRB did not [find] [document] that appropriate informed consent procedures and an informed consent document consistent with 21 CFR 50.25 were in place for use [with subjects or their legally authorized representatives in situations where use of such procedures and documents was feasible] [when providing an opportunity for a family member to object to a subject's participation in the clinical investigation]. Specifically,***

In approving an investigation without requiring informed consent, the IRB did not [find] [document] that additional protections of the rights and welfare of the subjects would be provided, including [consultation with, and public disclosure to, the communities in which the clinical investigation would be conducted, and from which the subjects would be drawn] [establishment of an independent data monitoring committee to exercise oversight of the clinical investigation] [attempting to contact (within the therapeutic window, when obtaining informed consent was not feasible and a legally authorized representative was not reasonably available) the subject's family member who was not a legally authorized representative, and asking whether he or she objected to the subject's participation in the clinical investigation]. Specifically,***

Investigators who were not qualified by training and experience as appropriate experts were selected to investigate a drug. Specifically, ***

Failure to obtain a curriculum vitae or other statement of the qualifications of the investigator, before permitting an investigator to participate in an investigation. Specifically, *** Failure to provide [FDA] [all participating investigators] with [a] [an adequate] written IND safety report. Specifically, ***

Page 46

BIMO

An investigator who did not comply with [the signed agreement] [the general investigational plan] [applicable regulatory requirements] was not [promptly brought into compliance] [terminated]. Specifically, *** Transfer of obligations to a contract research organization [was not described in writing] [did not describe each of the obligations assumed by the contract research organization, where not all obligations were assumed]. Specifically, *** An adequate final report was not provided to the sponsor shortly after completion of the investigator's participation in the investigation. Specifically, ***

Failure to permit an authorized officer or employee of FDA to [have access to] [copy] [verify] records or reports. Specifically, ***

Failure to assure that foreign clinical research was conducted in accordance with [the ethical principles stated in the ``Declaration of Helsinki''] [the laws and regulations of the country in which the research was conducted]. Specifically, ***

Monitors not qualified by experience and training were selected to monitor the progress of a clinical investigation. Specifically, ***

Failure to notify FDA of the ending, for cause, of an investigator's participation in an investigation. Specifically, ***

Records and reports were not retained for two years after [marketing application approval] [discontinuance of the investigation and notification of FDA]. Specifically*** Failure to submit to FDA [within 60 days of the anniversary date that the IND went into effect] an annual report of the investigation. Specifically, ***

Failure to obtain from an investigator a commitment to update financial information, to allow complete and accurate certification or disclosure statements. Specifically, *** The sponsor failed to submit an IND to the FDA prior to conducting a clinical investigation with an investigational new drug. Specifically,***

Page 47

BIMO

The IRB's [suspension] [termination of approval] for research was not reported [promptly] to [the investigator] [appropriate institutional officials] [the Food and Drug Administration]. Specifically, *** In approving an investigation without requiring informed consent, the IRB did not [find] [document] that [the human subjects were in a life-threatening situation] [available treatments were unproven or unsatisfactory] [the collection of valid scientific evidence was necessary to determine the safety and effectiveness of particular interventions]. Specifically, *** An individual authorized to act on behalf of an IRB which reviews clinical investigations that are intended to support applications for research or marketing permits for FDA-regulated products has not submitted registration information. Specifically, ***

Page 48

Devices

Center Name

Cite Id

Ref No

ShortDesc

Devices

630 21 CFR 803.17 3130 21 CFR 820.100(a) 3696 21 CFR 820.100(b) 546 21 CFR 820.75(a)

Lack of Written MDR Procedures Lack of or inadequate procedures Documentation Lack of or inadequate process validation

4189 21 CFR 820.198(a)

General

479 21 CFR 820.50

Purchasing controls, Lack of or inadequate procedures

14713 21 CFR 820.198(a)

Lack of or inadequate complaint procedures

3172 21 CFR 820.198(c)

Investigation of device failures

2327 21 CFR 820.22 3415 21 CFR 820.22 3103 21 CFR 820.30(i) 731 21 CFR 803.50(a)(1)

Quality audits - Lack of or inadequate procedures Quality Audit/Reaudit - conducted Design changes - Lack of or Inadequate Procedures Report of Death or Serious Injury

2371 21 CFR 820.30(a) 732 21 CFR 803.50(a)(2)

Design control - no procedures Report of Malfunction

3118 21 CFR 820.75(a)

Documentation

447 21 CFR 820.40 3125 21 CFR 820.80(d) 3282 21 CFR 820.90(a)

Lack of procedures, or not maintained Lack of or inadequate final acceptance procedures Nonconforming product, Lack of or inadequate procedures Evaluation of suppliers, contractors, etc., requirements

486 21 CFR 820.50(a)

Page 49

Devices

3160 21 CFR 820.184 3666 21 CFR 820.20(c) 3371 21 CFR 820.198(a)(3)

Lack of or inadequate DHR procedures Management review - Lack of or inadequate procedures Processing MDRs {see also 803, 804}

2974 21 CFR 812.110(b)

Investigator non-compliance with agreement/plan/regulations

3233 21 CFR 820.72(a)

Calibration, Inspection, etc. Procedures Lack of or Inadequ DHR content

3159 21 CFR 820.184

3678 21 CFR 820.30(g) 2350 21 CFR 820.25(b) 3669 21 CFR 820.20(c)

Design Validation - Risk analysis not performed/inadequate Training - Lack of or inadequate procedures Management review - defined interval, sufficient frequency Environmental control Lack of or inadequate procedures Training records Design history file

541 21 CFR 820.70(c) 3837 21 CFR 820.25(b) 3104 21 CFR 820.30(j)

2302 21 CFR 820.20(e) 3120 21 CFR 820.80(a) 3121 21 CFR 820.80(b) 2968 21 CFR 812.100

Quality System Procedures Lack of or inadequate procedures - Acceptance activities Lack of or inadequate receiving acceptance procedures Investigator non-compliance with agreement/plan/regulations Procedures

3291 21 CFR 820.100(b)

3369 21 CFR 820.198(a)(1)

Uniform and timely processing

3692 21 CFR 820.100(a)(4)

CAPA verification/validation of corrective/preventive action Investigator's subject records inadequate

14505 21 CFR 812.140(a)(3)

Page 50

Devices

4059 21 CFR 820.22

Quality Audits - defined intervals

3690 21 CFR 820.100(a)(3)

Identification of actions needed

3128 21 CFR 820.90(a) 3680 21 CFR 820.70(a)

Nonconforming product control Process control procedures, Lack of or inadequate procedures Lack of or inadequate organizational structure

419 21 CFR 820.20(b)

3101 21 CFR 820.30(g) 3331 21 CFR 820.181(e) 3331 21 CFR 820.181 4191 21 CFR 806.10(a)(1)

Design validation- Lack of or inadequate procedures DMR - not or inadequately maintained DMR - not or inadequately maintained Report of risk to health

538 21 CFR 820.70(a)

Process control procedures

3127 21 CFR 820.80(e)

Documentation

3201 21 CFR 820.40(a)

Not approved or obsolete document retrieval

537 21 CFR 820.70(a)

Production processes

2650 21 CFR 820.30(f) 3164 21 CFR 820.184(d)

Design verification - Lack of or inadequate procedures Acceptance records

3301 21 CFR 820.100(a)(2)

Investigation procedures

3167 21 CFR 820.198(a) 631 21 CFR 803.17(a)(1)

Complete files maintained Lack of System for Event Evaluations

Page 51

Devices

3299 21 CFR 820.100(a)(1)

Procedure for analysis of data sources

3192 21 CFR 820.30(g) 3263 21 CFR 820.250(b) 3665 21 CFR 820.20(b)(3)

Design validation - user needs and intended uses Sampling plans Management representative

14722 21 CFR 820.40 3687 21 CFR 820.100(a)(1)

Procedures not adequately established or maintained Analysis of data sources

3102 21 CFR 820.30(h) 3108 21 CFR 820.70(e)

Design transfer - Lack of or inadequate procedures Contamination control, Lack of or inadequate procedures

3132 21 CFR 820.120 3119 21 CFR 820.75(b)

Lack of or inadequate procedures for labeling Lack/Inad procedure-Monitoring/Control of Validated Proces DMR device specifications Equipment control activity documentation Calibration documentation

3155 21 CFR 820.181(a) 3235 21 CFR 820.72(a) 3250 21 CFR 820.72(b)(2)

3285 21 CFR 820.90(b)(2) 3206 21 CFR 820.50(b)

Product rework procedures, Lack of or inadequate procedures Approval, inadequate purchasing data

3426 21 CFR 820.50(a)(1) 3286 21 CFR 820.90(b)(1)

Documented evaluation Procedures for product review,disposition lack of/inadequate Management ensuring quality policy is understood Quality policy and objectives

4057 21 CFR 820.20(a)

2269 21 CFR 820.20(a)

2604 21 CFR 820.30(e)

Design review - Lack of or inadequate procedures

Page 52

Devices

539 21 CFR 820.70(b)

Production and Process Change Procedures, lack of or Inad. Document review, approval by designated individual Quality plan Complaints Results of investigation Supplier oversight

454 21 CFR 820.40(a) 2293 21 CFR 820.20(d) 3168 21 CFR 820.198(a) 3380 21 CFR 820.198(e)(6) 3427 21 CFR 820.50(a)(2)

14712 21 CFR 820.184 632 21 CFR 803.17(a)(2)

DHR - not or inadequately maintained Lack of System for Determining MDR Events

2928 21 CFR 812.40

Sponsors' general responsibilities

2328 21 CFR 820.22 3226 21 CFR 820.70(g)(1)

Quality audits - auditor independence Maintenance schedule, Lack of or inadequate schedule Nonconforming product evaluation/investigation Investigator lack of informed consent

3284 21 CFR 820.90(a) 2970 21 CFR 812.100

3688 21 CFR 820.100(a)(1)

Analysis of data/reports from data sources

2351 21 CFR 820.25(b) 3170 21 CFR 820.198(b)

Training Review and evaluation for investigation

3303 21 CFR 820.100(a)(4)

Verify, validate change {see also 820.100(a)}

3433 21 CFR 820.75(c)

Process changes - review, evaluation and revalidation ID label, labeling

3332 21 CFR 820.184(e)

3686 21 CFR 820.90(b)(2)

Product rework documentation, DHR {see also 820.184}

Page 53

Devices

4058 21 CFR 820.20

Management responsibility

6800 21 CFR 807.20 3117 21 CFR 820.70(i)

Establishment not registered Software validation for automated processes

3171 21 CFR 820.198(b) 3268 21 CFR 820.80(b) 3270 21 CFR 820.80(c) 3203 21 CFR 820.40(b) 3288 21 CFR 820.90(b)(1)

Rationale documented for no investigation Incoming inspection, testing, verification Documentation Document change records, maintained. Documentation of disposition, justification, signature

3434 21 CFR 820.75(c)

Documentation - review in response to changes or deviations Personnel

3671 21 CFR 820.25(a)

3676 21 CFR 820.30(f)

Design verification - documentation

3345 21 CFR 820.200(a)

Servicing - Lack of or inadequate procedures

3375 21 CFR 820.198(e) 2985 21 CFR 812.140(a)(3)(ii)

Records of complaint investigation Investigator records of relevant observations inadequate

4212 21 CFR 806.20(b)(4)

Justification for not reporting

502 21 CFR 820.60

Identification procedures, Lack of or inadequate procedures Design input - documentation Design review - documentation

2557 21 CFR 820.30(c) 2630 21 CFR 820.30(e)

3157 21 CFR 820.181(c)

DMR QA procedures and specifications

Page 54

Devices

3231 21 CFR 820.70(i)

Documentation of software validation

3232 21 CFR 820.72(a)

Equipment suitability & capability

3379 21 CFR 820.198(e)(5) 4070 21 CFR 820.30(g)

Nature and details of complaint Design validation - documentation

3425 21 CFR 820.50(a)(1)

Evaluation and Selection, Suppliers, Contractors, etc. Submission Within One Month

812 21 CFR 803.56

3021 21 CFR 812.150(a)(1)

Investigator report of unanticipated adverse effects

3689 21 CFR 820.100(a)(2) 4193 21 CFR 806.10(b)

Investigation Time to report - 10 days

2430 21 CFR 820.30(b)

Design plans - Lack of or inadequate

3262 21 CFR 820.250(a)

Statistical techniques - Lack of or inadequate procedures

3677 21 CFR 820.30(g) 14716 21 CFR 820.30(f) 2984 21 CFR 812.140(a)(3)(i)

Design validation - software validation not performed Design verification - output does not meet input requirement Investigator records of informed consent inadequate Identifying corrective & preventive actions

3302 21 CFR 820.100(a)(3)

7013 21 CFR 812.110(d)

Inadequate financial disclosure by investigator

14507 21 CFR 812.140(a)(3)(ii)

Investigator adverse effect records inadequate

2279 21 CFR 820.20(b)(2)

Resources

Page 55

Devices

3123 21 CFR 820.80(c)

Lack of or inadequate In-process acceptance procedures Lack of or inadequate procedures for handling

3139 21 CFR 820.140

3199 21 CFR 820.40(a)

Document review, approval documentation

3283 21 CFR 820.90(a)

Specific non-conforming product procedures

3432 21 CFR 820.75(b)(2)

Documentation of validated process performance

3328 21 CFR 820.180(b)

Retention period

14720 21 CFR 820.50(a)(3) 3683 21 CFR 820.70(g)

Acceptable supplier records, inadequate records Equipment Installation, Placement, Specified Requirements

2981 21 CFR 812.140(a)(2)(i)

Investigator device accountability inadequate

3309 21 CFR 820.120(b)

Examination for accuracy

4208 21 CFR 806.20(a)

Records not kept

6802 21 CFR 807.21(a)

Annual registration

6803 21 CFR 807.20(a) 2330 21 CFR 820.22 2601 21 CFR 820.30(d) 2648 21 CFR 820.30(f)

Devices not listed Quality audit corrective action, reaudits {see also 820.100} Essential design outputs Design verification procedures

3111 21 CFR 820.70(f)

Buildings

3144 21 CFR 820.160(a)

Control/distribution procedures

Page 56

Devices

3173 21 CFR 820.198(d)

Evaluation, timeliness, identification

3191 21 CFR 820.30(g)

Design validation - production units

3207 21 CFR 820.50(b)

Supplier notification of changes

3149 21 CFR 820.180

Availability

3227 21 CFR 820.70(g)(1)

Activity documentation

3204 21 CFR 820.40(b)

Change records, content

3396 21 CFR 820.80(d)(1)

DMR required activities {see also 820.181}

3414 21 CFR 820.200(d)(6) 3416 21 CFR 820.70(a)(1)

Test and inspection data Process control instructions

3428 21 CFR 820.50(a)(3) 3667 21 CFR 820.20(c)

Acceptable supplier records Management review accomplishment

3333 21 CFR 820.184(f)

Device identification, control numbers

3370 21 CFR 820.198(a)(2)

Oral complaints

633 21 CFR 803.17(a)(3)

Lack of System for Timely Submission of Reports

635 21 CFR 803.17(b)(1)

Info evaluated to determine if event was reportable

778 21 CFR 803.52(f)(1)

Type of Reportable Event

Page 57

Devices

2980 21 CFR 812.140(a)(1)

Investigator correspondence records inadequate

3304 21 CFR 820.100(a)(5)

Changes to correct/prevent quality problems

7012 21 CFR 812.100 2429 21 CFR 820.30(b) 2470 21 CFR 820.30(c)

Investigator lack of control of investigational devices Establish the design and development plan Design input procedures - appropriateness

3141 21 CFR 820.150(a)

Storage procedures to prevent mix-ups

3142 21 CFR 820.150(a)

Storage procedures to avoid release of unsuitable product

3162 21 CFR 820.184(b) 3198 21 CFR 820.40(b)

Quantity manufactured Document changes, review and approval, communication

3224 21 CFR 820.70(g)(2)

Periodic equipment inspection lack of or inadequate procedu Calibration procedures - content

3236 21 CFR 820.72(b)

3269 21 CFR 820.80(b) 3397 21 CFR 820.80(d)(2)

Incoming acceptance records, documentation Review of data and documentation

3841 21 CFR 820.90(b)(2)

Product rework adverse effects {see also 820.184} Design validation - Risk analysis Implementing Personnel Procedures, Health, Cleanliness. Reports and information documentation

14718 21 CFR 820.30(g) 3682 21 CFR 820.70(d)

636 21 CFR 803.17(b)(2)

738 21 CFR 803.52(a)(1)

Patient Name or Other Identifier

2916 21 CFR 812.7(d)

Investigational device represented as safe and /or effective

Page 58

Devices

2973 21 CFR 812.110(a)

Subject participation prior to study approval

2991 21 CFR 812.140(b)(1)

Sponsor correspondence records inadequate

3190 21 CFR 820.30(g) 3300 21 CFR 820.100(a)(1)

Design validation acceptance criteria Statistical methodology

3693 21 CFR 820.100(a)(5)

Implementing changes

4192 21 CFR 806.10(a)(2)

Report of violation of the Act (see 803.52(e)(9))

14508 21 CFR 812.140(a)(4)

Investigator record of protocol deviations inadequate Quality Audit/Reaudit - documentation Sufficient personnel

2339 21 CFR 820.22 2403 21 CFR 820.25(a)

2431 21 CFR 820.30(b) 2649 21 CFR 820.30(f)

Design plans- updated Design verification acceptance criteria

3113 21 CFR 820.70(g)

Equipment design and installation

3156 21 CFR 820.181(b)

DMR production process specifications

3161 21 CFR 820.184(a) 3163 21 CFR 820.184(c) 3218 21 CFR 820.70(c) 3200 21 CFR 820.40(a)

DHR content - manufacturing dates Quantity released Environmental control systemdocumentation/review inspection Document locations, Dissemination, etc.

3241 21 CFR 820.72(b)(1)

Calibration standard traceability

3290 21 CFR 820.90(b)(2)

Retesting and reevaluation of reworked product

Page 59

Devices

3381 21 CFR 820.198(e)(7) 3264 21 CFR 820.250(b)

Corrective action taken Sampling methods - Lack of or inadequate procedures Verification or validation of changes Management representative implementing the quality system Design changes - validation vs. verification

3681 21 CFR 820.70(b) 4060 21 CFR 820.20(b)(3)(i)

4071 21 CFR 820.30(i)

14711 21 CFR 820.160(a) 14717 21 CFR 820.30(g) 3838 21 CFR 820.40(a)

Lack of or inadequate procedures for distribution Design validation - software validation documentation Document review procedures, designated individual

3312 21 CFR 820.120(d) 642 21 CFR 803.18(b)(1)(i)

Mixups Adverse events--all info not in file

735 21 CFR 803.50(b)(2)

Explanation of Incomplete Information

783 21 CFR 803.52(f)(6)

Evaluation Codes

2910 21 CFR 812.7(a) 2972 21 CFR 812.110(a)

Promotion or test marketing Informed consent obtained prior to study approval Sponsor device disposition records inadequate

2993 21 CFR 812.140(b)(2)

3023 21 CFR 812.150(a)(2)

Investigator report of IRB withdrawal of approval Investigator protocol records inadequate Dissemination of problem information

3064 21 CFR 812.140(a)(4) 3694 21 CFR 820.100(a)(6)

Page 60

Devices

4169 21 CFR 820.100(a)(7)

Identifying relevant info for management review

4213 21 CFR 806.20(b)(5)

Records of communications

6808 21 CFR 807.26

Changes

7006 21 CFR 812.43(c)(5)

No financial disclosure info in investigator agreement

2270 21 CFR 820.20(a) 2481 21 CFR 820.30(c)

Implement quality policy Design input procedures - addressing conflicting requirement

2598 21 CFR 820.30(d)

Design output procedures

2628 21 CFR 820.30(e)

Design review procedures - personnel

3109 21 CFR 820.70(d)

Personnel requirements, Lack of or inadequate requirements Use and removal, Lack of or inadequate procedures Packaging

3115 21 CFR 820.70(h) 3138 21 CFR 820.130

3151 21 CFR 820.180 3175 21 CFR 820.186 3195 21 CFR 820.30(g) 3266 21 CFR 820.86

Legibility QSR Design validation unresolved discrepancies Acceptance status

3377 21 CFR 820.198(e)(3) 3382 21 CFR 820.198(e)(8) 3398 21 CFR 820.80(d)(3)

Device identification and control number Reply to complainant No release signature

Page 61

Devices

3668 21 CFR 820.20(c) 3673 21 CFR 820.30(c)

Management review dates Design input approval documentation

3675 21 CFR 820.30(f) 3325 21 CFR 820.180

Design verification - unresolved discrepancies Storage

3330 21 CFR 820.181(d)

DMR packaging and labeling specifications

3343 21 CFR 820.198(e) 3346 21 CFR 820.200(b) 3349 21 CFR 820.200(d) 3374 21 CFR 820.198(d)(3)

Maintained Analyzing service report No Service reports Determination of relationship of device to event

3376 21 CFR 820.198(e)(2) 3697 21 CFR 820.150(a) 3699 21 CFR 820.160(b) 3702 21 CFR 820.250(a) 14710 21 CFR 820.150 3372 21 CFR 820.198(d) 3372 21 CFR 820.198(d)(1) 3310 21 CFR 820.120(b)

Date complaint received Stock rotation, assessment before release Distribution records Appropriateness Lack of or inadequate procedures for storage. Records of MDR Investigation Records of MDR Investigation DHR documentation of label release {see also 820.184} Files do not contain copies of MDR forms

644 21 CFR 803.18(b)(1)(ii)

650 21 CFR 803.18(e)

Results of evaluation not in mfr's MDR file

658 21 CFR 803.30(a)(2)

Report of Serious Injury Within 10 Days

733 21 CFR 803.50(b)(1)

Reporting Information Reasonably Known

739 21 CFR 803.52(a)(2)

Patient Age or Date of Birth

Page 62

Devices

740 21 CFR 803.52(a)(3)

Patient Gender

741 21 CFR 803.52(a)(4)

Patient Weight

745 21 CFR 803.52(b)(2)

Death

748 21 CFR 803.52(b)(2)(iii)

Injury or Illness Requiring Intervention

749 21 CFR 803.52(b)(3)

Date of Event

751 21 CFR 803.52(b)(5)

Description of the Event or Problem

791 21 CFR 803.52(f)(11)(iii)

Explanation of Required Information Not

796 21 CFR 803.55(a)

Initial Submission of Baseline Report

2913 21 CFR 812.7(b)

Commercialization

2920 21 CFR 812.18(b)

Exporter of investigational device

2935 21 CFR 812.43(b)

Sponsor shipped devices to unqualified person(s) No curriculum vitae in investigator agreement

2937 21 CFR 812.43(c)(1)

2940 21 CFR 812.43(c)(4)(i)

No investigation agreement statement of commitment

2946 21 CFR 812.45

Sponsor provide device information to investigators

Page 63

Devices

2949 21 CFR 812.46(a)

Sponsor securing investigator compliance

2975 21 CFR 812.110(c) 2982 21 CFR 812.140(a)(2)(ii)

Investigator did not supervise use of investigational device Investigator records of persons receiving devices inadequate Investigator records of disposition of devices inadequate

2983 21 CFR 812.140(a)(2)(iii)

2994 21 CFR 812.140(b)(3)

Sponsor records of investigator agreements inadequate Other sponsor records required by FDA inadequate Record retention inadequate

3003 21 CFR 812.140(b)(6)

3007 21 CFR 812.140(d)

3025 21 CFR 812.150(a)(3)

No investigator progress reports

3027 21 CFR 812.150(a)(4)

Investigator non-emergency safety or soundness changes

3032 21 CFR 812.150(a)(5)

Investigator report for lack of informed consent

3034 21 CFR 812.150(a)(6)

Investigator final report

3043 21 CFR 812.150(b)(2)

Sponsor notification of IRB approval withdrawal

3048 21 CFR 812.150(b)(5)

Sponsor progress reports for non-significant risk study Sponsor progress reports for significant risk study Approval of purchasing data {see also 820.40(a)}

3049 21 CFR 812.150(b)(5)

3208 21 CFR 820.50(b)

Page 64

Devices

3305 21 CFR 820.100(a)(6)

Dissemination of problem information procedure

3313 21 CFR 820.120(d)

Records, DHR {see also 820.184(e)}

3402 21 CFR 820.80(e)(3) 3691 21 CFR 820.100(a)(4)

Results Verification vs validation

4216 21 CFR 806.30

Access not permitted

4249 21 CFR 821.25(c)

Not established, maintained

4254 21 CFR 821.30(a) 4430 21 CFR 803.18(d)(1)

Failure to report Distributor responsibilities for records

4436 21 CFR 803.40(a)

Report of death, injury by marketed device

6847 21 CFR 807.30(b) 6849 21 CFR 812.5(a)

Listing not updated or update not timely Label does not contain required information

6850 21 CFR 812.5(b) 6851 21 CFR 812.5(b)

False and misleading label statements Labeling claims of safety and/or effectiveness

9112 21 CFR 809.10(a)(5)

Reagent storage instructions--protect stability

9117 21 CFR 809.10(a)(9)(i)

Lot/Control Numbers - multiple unit product

9147 21 CFR 809.10(b)(11)

Expected Values--range(s)

9176 21 CFR 809.20(b)

Compliance with GMP

Page 65

Devices

14516 21 CFR 812.25(e) 14521 21 CFR 812.36(e)

Sponsor's lack of written monitoring procedures No IRB approval for treatment use

14523 21 CFR 812.43(c) 14525 21 CFR 812.2(c)(7)

No investigator agreement Needs IDE; does not meet definition of a custom device

540 21 CFR 820.70(b)

Production and process changes - failure to follow procedure Responsibility, authority and independence

2276 21 CFR 820.20(b)(1)

2599 21 CFR 820.30(d)

Acceptance criteria and essential outputs

2602 21 CFR 820.30(d) 2627 21 CFR 820.30(e) 2338 21 CFR 820.22

Design output - review and approval Design reviews performed following schedule Quality audit - audit report review

3147 21 CFR 820.170(a)

Lack of or inadequate instructions

3193 21 CFR 820.30(g) 3229 21 CFR 820.70(h) 3230 21 CFR 820.70(i)

Design validation - simulated testing Documentation of removal or reduction Validation of changes to automated process software Remedial action

3237 21 CFR 820.72(b)

3239 21 CFR 820.72(b) 3271 21 CFR 820.80(d)

Remedial action - documentation Quarantine of finished devices

3276 21 CFR 820.80(e) 3386 21 CFR 820.25(b)(2)

Maintained as part of the DHR {see also 820.184} Training on verification/validation defects

Page 66

Devices

3412 21 CFR 820.200(d)(4) 3413 21 CFR 820.200(d)(5) 3417 21 CFR 820.70(a)(2)

Servicing individual Service performed Production monitoring and control

3420 21 CFR 820.70(a)(5)

Criteria for workmanship

3664 21 CFR 820.20(b)(2)

Training

3670 21 CFR 820.20(c)

Management review participants

3674 21 CFR 820.30(d) 3323 21 CFR 820.170(b)

Design output - documentation Installer records

3324 21 CFR 820.170(b)

Installer's documentation of results

3355 21 CFR 820.198(f)

Records accessibility

3684 21 CFR 820.75(a)

Documentation - specific items

3698 21 CFR 820.150(b)

Procedures - receipt and dispatch

3704 21 CFR 820.250(b) 3706 21 CFR 820.250(b) 3839 21 CFR 820.70(a)(4) 3409 21 CFR 820.200(d) 14721 21 CFR 820.70(g)(2)

Reviewed for adequacy Review of sampling methods for adequacy Approval of process equipment Service reports Periodic equipment inspections

Page 67

Devices

LongDesc

Frqncy

Written MDR procedures have not been [developed] [maintained] [implemented]. Specifically, *** Procedures for corrective and preventive action have not been [adequately] established. Specifically, *** Corrective and preventive action activities and/or results have not been [adequately] documented. Specifically, *** A process whose results cannot be fully verified by subsequent inspection and test has not been [adequately] validated according to established procedures. Specifically, *** Complaint handling procedures for [receiving] [reviewing] [evaluating] complaints have not been [established] [defined] [documented] [completed] [implemented]. Specifically, *** Procedures to ensure that all purchased or otherwise received product and services conform to specified requirements have not been [adequately] established. Specifically, *** Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been [adequately] established. Specifically,*** Complaints involving the possible failure of [a device] [labeling] [packaging] to meet any of its specifications were not [reviewed] [evaluated] [investigated] where necessary. Specifically, *** Procedures for quality audits have not been [adequately] established. Specifically, *** Quality [audits][reaudits] have not been performed. Specifically, *** Procedures for design change have not been [adequately] established. Specifically,*** An MDR report was not submitted within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device may have caused or contributed to a death or serious injury. Specifically, *** Procedures for design control have not been established. Specifically,*** An MDR report was not submitted within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur. Specifically, *** Process validation [activities] [results] have not been [documented] [approved] [adequately documented] [adequately approved]. Specifically, *** Document control procedures have not been [established] [maintained]. Specifically,*** Procedures for finished device acceptance have not been [adequately] established. Specifically, *** Procedures have not been [adequately] established to control product that does not conform to specified requirements. Specifically, *** Requirements that must be met by [suppliers] [contractors] [consultants] have not been [adequately] established. Specifically, ***

119 118 114 87

81

70

66

64

60 58 57 53

53 51

46

45 42 41

39

Page 68

Devices

Procedures for device history records have not been [adequately] established. Specifically,*** Procedures for management review have not been [adequately] established. Specifically,*** Complaint handling procedures have not been [established] [defined] [documented] [completed] [implemented] to ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report. Specifically, *** An investigation was not conducted in accordance with [the signed agreement] [the investigational plan] [applicable FDA regulations] [conditions of approval imposed by an IRB] [conditions of approval imposed by FDA]. Specifically, *** Procedures to ensure equipment is routinely [calibrated] [inspected] [checked] [maintained] have not been [adequately] established. Specifically, *** The device history record does not demonstrate that the device was manufactured in accordance with [the device master record] [21 CFR 820].

39 39 39

38

38

37

Risk analysis [was not performed] [is inadequate] [is incomplete]. Specifically, *** Procedures for training and identifying training needs have not been [adequately] established. Specifically, *** Management with executive responsibility has not reviewed the suitability and effectiveness of the quality system [at defined intervals] [with sufficient frequency]. Specifically, *** Procedures to control environmental conditions have not been [adequately] established. Specifically, *** Personnel training is not documented. Specifically, *** The design history file [was not established] [does not demonstrate that the design was developed following the approved design plan] [does not demonstrate that the design was developed following the requirements of 21 CFR 820]. Quality system procedures and instructions have not been established. Specifically,*** Procedures for acceptance activities have not been [adequately] established. Specifically,*** Procedures for acceptance of incoming product have not been [adequately] established. Specifically, *** An investigation was not conducted according to the [signed agreement] [investigational plan] [applicable FDA regulations]. Specifically, *** The procedures addressing documentation of corrective and preventive action activities were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Complaint handling procedures have not been [established] [defined] [documented] [completed] [implemented] to ensure that all complaints are processed in a uniform and timely manner. Specifically, *** Corrective and preventive actions have not been verified or validated to ensure that the action is effective and does not adversely affect the finished device. Specifically, *** Records of each subject's [case history] [exposure to the investigational device] are not all [accurate] [complete] [current]. Specifically, ***

36 35 34

33 33 32

31 29 29 28

28

28

26

26

Page 69

Devices

Quality audits were not performed [at defined intervals] [at sufficient frequency] to determine whether the quality system activities and results comply with quality system procedures. Specifically, *** Not all of the actions needed to correct and prevent the recurrence of nonconforming product and other quality problems have been identified. Specifically, *** Products that do not conform to specifications are not adequately controlled. Specifically, *** Process control procedures that describe any process controls necessary to ensure conformance to specifications have not been [adequately] established. Specifically, *** The organizational structure has not been [adequately] established and maintained to ensure that devices are [designed] [produced] in accordance with 21 CFR 820. Specifically, *** Procedures for design validation have not been [adequately] established. Specifically,*** A device master record has not been [adequately] maintained. Specifically, *** A device master record has not been [adequately] maintained. Specifically, *** A correction or removal, conducted to reduce a risk to health posed by a device, was not reported in writing to FDA. Specifically, *** Process control procedures that describe any process controls necessary to ensure conformance to specifications were not [established] [defined] [documented] [implemented]. Specifically, *** Acceptance activities were not [documented] [maintained as part of the device history record] [adequately documented] [adequately maintained as part of the device history record]. Specifically, *** Documents that were [not approved] [obsolete] were observed at a location where they [could be] [are being] used. Specifically, ***

26

25

25 23

22

22 22 22 20

20

20

20

Production processes were not [developed] [conducted] [controlled] [monitored] to ensure that a device conforms to its specifications. Specifically, *** Procedures for design verification have not been [adequately] established. Specifically,*** The device history record does not include [complete] acceptance records that demonstrate the device is manufactured in accordance with the device master record. Specifically, *** The corrective and preventive action procedures addressing the investigation of the cause of nonconformities relating to product, processes, and the quality system were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Complete complaint files are not maintained. Specifically, *** The written MDR Procedure does not include an internal system which provides for the timely and effective [identification] [communication] [evaluation] of events that may be subject to medical device reporting requirements. Specifically, ***

19

19 19

18

18 17

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Devices

The corrective and preventive procedures addressing the analysis of sources of quality data to identify existing and potential causes of nonconforming product or other quality problems were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Design validation did not ensure the device conforms to defined user needs and intended uses. Specifically, *** Sampling plans are not [written][based on valid statistical rationale]. Specifically, *** No management representative had been appointed to ensure that quality system requirements are met, and to report to management on the performance of the quality system. Specifically, *** Document control procedures have not been adequately [established] [maintained]. Specifically,*** Appropriate sources of quality data are not adequately analyzed to identify existing and potential causes of nonconforming product and other quality problems. Specifically, *** Procedures for design transfer have not been [adequately] established. Specifically,*** Procedures to prevent contamination of equipment or product by substances that may have an adverse effect on product quality have not been [adequately] established. Specifically, *** Procedures to control labeling activities have not been [adequately] established. Specifically, *** Procedures for monitoring and control of process parameters for a validated process have not been [adequately] established. Specifically, *** The device master record does not include or refer to the location of device software specifications. Specifically, *** Equipment [calibrations] [inspections] [checks][maintenance activities] have not been documented. Specifically, *** There is [no] [incomplete] documentation of [the equipment identification] [calibration dates] [the individual performing each calibration] [the next calibration date] for [inspection] [measurement] [test] equipment . Specifically, *** Procedures for rework of nonconforming product have not been [adequately] established. Specifically, *** Purchasing data that clearly describe or reference specified requirements for purchased or otherwise received product and services have not been [approved] [established] [adequately approved] [adequately established]. Specifically, *** The evaluation of potential [suppliers] [contractors] [consultants] was not documented. Specifically, *** Procedures that define the responsibility for review and the authority for the disposition of nonconforming product have not been [adequately] established. Specifically, *** Management with executive responsibility has not ensured that the quality policy is understood, implemented and maintained at all levels of the organization. Specifically, *** The [quality policy] [quality objectives] [was] [were] not established by management with executive responsibility. Specifically, *** Procedures for design review have not been [adequately] established. Specifically,***

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Procedures for changes to a [specification] [method] [process] [procedure] have not been [adequately] established. Specifically, *** Documents were [not reviewed] [not approved] by designated individual(s) prior to issuance . Specifically, *** A quality plan has not been [adequately] established. Specifically, *** Complaint files are not [adequately] maintained. Specifically *** Records of complaint investigations do not include the [dates] [results] of the investigation. Specifically, *** The type and extent of control to be exercised over [the product] [services] [suppliers] [contractors] [consultants] was not clearly defined. Specifically, *** A device history record has not been [adequately] maintained. Specifically, *** The written MDR procedure does not include an internal system which provides for a standardized review process/procedure for determining when an event meets the criteria for reporting. Specifically, *** For an investigational study, [qualified investigators were not selected] [investigators were not provided with the information they need to conduct an investigation properly] [proper monitoring was not ensured] [IRB review and approval were not ensured] [an IDE application was not submitted to FDA for a significant risk study] [reviewing IRBs were not promptly informed of significant new information about an investigation] [FDA was not promptly informed of significant new information about an investigation]. Specifically, *** Individuals who conduct quality audits have direct responsibility for the matters being audited. Specifically, *** Schedules for the adjustment, cleaning, and other maintenance of equipment have not been [adequately] established. Specifically, *** The [evaluation] [investigation] of nonconforming product has not been documented. Specifically, *** Informed consent was not obtained in accordance with the regulations regarding the protection of human subjects. Specifically, *** Not all [data] [reports] from quality data sources are analyzed to identify existing and potential causes of nonconforming product and other quality problems. Specifically, *** Employees have not been adequately trained. Specifically, *** Not all complaints have been [adequately] reviewed and evaluated to determine whether an investigation is necessary. Specifically, *** The procedures addressing verification or validation of corrective and preventive actions were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** A validated process was not [reviewed and evaluated] [revalidated] when changes or process deviations occurred. Specifically, *** The device history record does not include the primary identification label and labeling for each device. Specifically, *** Rework and reevaluation activities have not been [fully] documented in the device history record. Specifically, ***

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Management with executive responsibility has not ensured that an adequate and effective quality system has been fully implemented and maintained at all levels of the organization. Specifically, *** An establishment for which registration is required has not been registered. Specifically, *** Software used as part of [production] [the quality system] has not been [adequately] validated for its intended use according to an established protocol. Specifically, *** Records for complaints where no investigation was made do not include required information. Specifically *** Incoming product was not adequately inspected or tested to verify conformance to specifications. Specifically, *** In-process inspections, tests, or other verification activities and approvals were not documented. Specifically, *** Records of changes to documents were not [adequately] maintained. Specifically, *** There is [no] [incomplete] documentation of the [disposition of nonconforming product] [justification for use of nonconforming product] [the signature of the individual authorizing the use of nonconforming product]. Specifically, *** There is no documentation of the [review and evaluation of a process] [revalidation of a process] performed in response to changes or process deviations. Specifically, *** Personnel do not have the necessary [education] [background] [training] [experience] to perform their jobs. Specifically, *** The design verification results, including [identification of the design] [method(s)] [the date] [the individual(s) performing the verification], were not [adequately] documented in the design history file. Specifically, *** Procedures or instructions for [performing servicing activities] [verifying that servicing meets specified requirements] have not been [adequately] established. Specifically, *** Records of complaint investigations do not include required information. Specifically, *** Records for each subject concerning [previous medical history] [condition upon entering the investigation] [condition during the course of the investigation] [all diagnostic test results] are not all [accurate] [complete] [current]. Specifically, *** A justification for not reporting the correction or removal action to FDA that included [conclusions] [follow-ups] [reviews] by a designated person was not included in the record. Specifically,*** Procedures for identifying product during all stages of receipt, production, distribution, and installation have not been [adequately] established. Specifically, *** Design input requirements were not [adequately] documented. Specifically, *** The design review results, including [identification of the design] [the date] [the individual(s) performing the review], were not documented in the design history file. Specifically, *** The device master record does not include or refer to the location of [all] quality assurance procedures and specifications. Specifically, ***

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Software validation activities and results for computers or automated data processing systems used as part of [production] [the quality system] have not been [adequately] documented. Specifically, *** Certain [inspection] [measuring] [test] equipment is not [suitable for its intended purposes] [capable of producing valid results]. Specifically, *** Records of complaint investigations do not include the nature and details of the complaint. Specifically, *** The results of design validation, including [identification of the design] [method(s)] [the date] [the individual(s) performing validation], were not [adequately] documented in the design history file. Specifically, *** Potential [suppliers] [contractors] [consultants] were not [evaluated] [selected] based on their ability to meet specified requirements. Specifically, *** A supplemental report was not submitted to FDA within one month following receipt of information that was not provided when the initial report was submitted. Specifically, *** A complete and accurate report of an unanticipated adverse device effect was not prepared and submitted [within 10 working days after first learning of the effect] to [the sponsor] [the reviewing IRB]. Specifically, *** Certain indicators of nonconformities are not investigated to determine the cause of the nonconformity. Specifically, *** A report of the required information regarding device correction and removal actions was not sent to FDA within 10 days of initiating the correction or removal. Specifically, *** Design plans that describe or reference the design and development activities and define responsibility for implementation have not been [adequately] established. Specifically, *** Procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics have not been [adequately] established. Specifically,*** Validation of device software [was not performed] [is inadequate] [is incomplete]. Specifically, *** Design verification does not confirm that design output meets design input requirements. Specifically, *** Records documenting that informed consent was obtained for each subject prior to participation in the study are not all [accurate] [complete] [current]. Specifically, *** The procedures addressing identification of corrective and preventive actions were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** The sponsor was not supplied [sufficient financial information to allow submission of complete and accurate certification or disclosure statements] [financial disclosure updates when a relevant change occurred during the course of the study or within one year following study completion]. Specifically, *** Records for each subject concerning [anticipated] [unanticipated] adverse device effects are not all [accurate] [complete] [current]. Specifically, *** Adequate resources have not been provided for performing [management activities] [work] [assessment activities] [audits]. Specifically, ***

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Procedures for the [acceptance] [control] of in-process product have not been [adequately] established. Specifically, *** Procedures for product handling have not been [adequately] established. Specifically,***

The documentation of approval of documents does not include [the document approval date] [the signature of the approving official]. Specifically, *** Procedures for addressing the [identification] [documentation] [evaluation] [segregation] [disposition] [investigation] of nonconforming product were not [defined] [documented] [complete]. Specifically, *** There is [no] [inadequate] documentation of [monitoring and control methods and data] [the date performed] [the individual performing the process] [the major equipment used] for a validated process. Specifically, *** Required records are not retained for [the design and expected life of the device] [at least 2 years from the date of release of the device for commercial distribution]. Specifically, *** Records of acceptable [suppliers] [contractors] [consultants] have not been [adequately] established. The [appropriate design, construction, placement, and installation of manufacturing equipment have not been ensured] [equipment used in the manufacturing process does not meet specified requirements]. Specifically, *** Records of [receipt] [use] [disposal] of a device that relate to the [type and quantity] [dates of receipt] [batch number or code mark] of the device are not all [accurate] [complete] [current]. Specifically, *** Labeling was not sufficiently examined by a designated individual for accuracy including [the correct expiration date] [control numbers] [storage instructions] [handling instructions] [certain additional processing instructions] before release. Specifically, *** There is no record maintained of a correction or removal action that was not required to be reported to FDA. Specifically,*** Your annual registration [is not current] [was not updated within 30 days of receipt of form FDA 2891a from FDA]. Specifically, *** Devices for which listing is required have not been listed. Specifically, *** Quality reaudits [are not adequately performed] [do not cover corrective actions for the problem areas]. Specifically, *** Design outputs that are essential for the proper functioning of the device were not [completely] identified. Specifically, *** Procedures for verifying that design output meets design input were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Buildings [are not of suitable design] [do not contain sufficient space] to [perform necessary operations] [prevent mix-ups] [assure orderly handling of product]. Specifically, *** Procedures for the control and distribution of finished devices have not been [established] [defined] [documented] [complete] [implemented] to ensure that only devices approved for release are distributed. Specifically, ***

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Complaints representing events that are MDR reportable were not [promptly reviewed, evaluated, and investigated by a designated individual] [maintained in a separate portion of the complaint files] [clearly identified]. Specifically, *** The design was not validated [under defined operating conditions] [using initial production units, lots or batches or their equivalents]. Specifically, *** There is no agreement with [suppliers] [contractors] [consultants] to notify you of changes in the product or service. Specifically, *** Required records [are not maintained at a location that is reasonably accessible to responsible officials of the manufacturer and to employees of the FDA] [were not made readily available for review and copying by the FDA] [are not legible] [are not stored to minimize deterioration and prevent loss] [are not backed up when stored in automated data processing systems]. Specifically, *** Maintenance activities, including the [date] [individuals performing those activities], have not been documented. Specifically, *** Records of changes did not include [a description of the change] [identification of the affected documents] [the signature of the approving official(s)] [the approval date] [when the change became effective]. Specifically, ***

Finished devices were released for distribution prior to completion of activities required in the Device Master Record. Specifically, *** Service reports do not include applicable test and/or inspection data. Specifically, *** Process controls are not conducted in accordance with documented instructions and standard operating procedures. Specifically, *** Records of acceptable [suppliers] [contractors] [consultants] were not maintained. Specifically, *** Management reviews do not ensure that the quality system satisfies [the requirements of part 820] [your quality policy and objectives]. Specifically, *** The device history record does not include [certain] [any] device identifications and control numbers used. Specifically, *** Complaint handling procedures have not been [established] [defined] [documented] [completed] [implemented] to ensure that all oral complaints are documented upon receipt. Specifically, *** The written MDR procedure does not include an internal system which provides for timely transmission of complete medical device reports to [FDA] [manufacturers]. Specifically, *** The written MDR procedure does not include documentation and recordkeeping requirements for all information that was evaluated to determine if an event was reportable. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not indicate in Block H the type of reportable event. Specifically, ***

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Records relating to correspondence with [another investigator] [an IRB] [the sponsor] [a monitor] [FDA], including required reports, are not all [accurate] [complete] [current]. Specifically, *** Changes in methods and procedures needed to correct and prevent identified quality problems are not [implemented] [recorded] [effective]. Specifically, *** Devices under investigation were not properly controlled. Specifically, *** A design and development plan has not been [established] [defined] [documented] [implemented]. Specifically, *** Procedures to ensure that a device's design input requirements are appropriate and address its intended use, including user/patient needs, were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Procedures for controlling the storage of product in storage areas and stock rooms were not [established] [defined] [documented] [complete] [implemented] to prevent mix-ups, damage, other adverse effects. Specifically, *** Procedures for controlling the storage of product in storage areas and stock rooms are not adequate to ensure that no obsolete, rejected, or deteriorated product is distributed. Specifically, *** The device history record does not include the quantity of devices manufactured. Specifically, *** Changes to documents were not [reviewed and approved by an individual(s) in the same function or organization that performed the original review and approval] [communicated to appropriate personnel in a timely manner]. Specifically, *** Procedures for conducting periodic inspections to ensure adherence to equipment maintenance schedules have not been [adequately] established. Specifically, *** Calibration procedures do not include [specific directions and limits for accuracy and precision] [provisions for remedial action]. Specifically, *** Acceptance or rejection of incoming product was not documented. Specifically, *** Finished devices were released for distribution before the associated data and documentation was reviewed. Specifically, *** Documentation of rework and reevaluation activities does not include a determination of whether there has been any adverse effect from rework upon the product. Specifically, *** Results of the design risk analysis were not [adequately] documented. Specifically, *** Requirements addressing the [health] [cleanliness] [personal practices] [clothing] of employees have not been implemented. Specifically, *** The written MDR procedure does not include documentation and recordkeeping requirements for all Medical Device Reports and information submitted to [FDA] [device manufacturers]. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block A the patient name or other identifier. Specifically, *** An investigational device was represented as being [safe] [effective] for the purposes for which it [is] [was] being investigated. Specifically, ***

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Subjects were allowed to participate in an investigation prior to obtaining [IRB] [FDA] approval to conduct the investigation. Specifically, *** Records relating to correspondence with [another sponsor] [a monitor] [an investigator] [an IRB] [FDA], including required reports are not all [accurate] [complete] [current]. Specifically, *** Acceptance criteria were not established prior to the performance of validation activities. Specifically, *** Corrective and preventive action procedures addressing the use of appropriate statistical methodology to identify existing and potential causes of nonconforming product or other quality problems were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Corrective and preventive action procedures addressing implementation and recording of changes in methods and procedures to correct and prevent identified quality problems were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** A violation of the FD&C Act involving a device which might present a risk to health was not reported to FDA. Specifically, *** Records showing [dates] [reasons for] each deviation from the protocol are not all [accurate] [complete] [current]. Specifically,*** The dates of quality [audits][reaudits] have not been documented. Specifically, *** Insufficient personnel to assure that all procedures are appropriately carried out as required by the quality system. Specifically, *** Design plans were not [reviewed] [updated] [approved] as design and development evolves. Specifically, *** Acceptance criteria were not [established] [defined] [documented] [complete] [implemented] prior to the performance of verification activities. Specifically, *** Equipment used in the manufacturing process has not been appropriately [designed] [constructed] [placed] [installed] to facilitate maintenance, adjustment, cleaning, and use. Specifically, *** The device master record does not include or refer to the location of [all] production and process specifications. Specifically, *** The device history record does not include manufacturing dates. Specifically, *** The device history record does not include the quantity of devices released for distribution. Specifically, *** Inspections of environmental control system were not [documented] [reviewed]. Specifically, *** Documents were not available at all locations for which they are designated, used, or otherwise necessary. Specifically, *** A calibration standard used for [inspection] [measurement] [test] equipment is not traceable to national or international standards nor is it an independent reproducible standard. Specifically, *** Rework of nonconforming product did not include [complete] retesting and reevaluation to ensure that the reworked product met current approved specifications. Specifically, ***

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Records of complaint investigations do not include any corrective action taken. Specifically, *** Procedures to ensure sampling methods are adequate for their intended use have not been [adequately] established. Specifically,*** Changes to a [specification] [method] [process] [procedure] were not verified or validated. Specifically, *** The management representative has not ensured that the quality system requirements are effectively established and maintained. Specifically, *** Procedures were not [established] [defined] [documented] [completed] to address when verification of design changes is sufficient in lieu of validation prior to their implementation. Specifically, *** Procedures for control and distribution of finished devices have not been [adequately] established. Specifically,*** Results of the validation of the device software were not [adequately] documented. Specifically, *** The document control procedures do not designate an individual to review documents for adequacy and approve them prior to issuance. Specifically, ***

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Labeling and packaging operations were not controlled to prevent labeling mix-ups. Specifically, *** MDR event files do not contain or reference all adverse event information in the possession of the reporting entity, including documentation of the deliberations and decision making process used to determine if an event was or was not reportable. Specifically, *** An MDR report with incomplete information was submitted to FDA without a statement explaining why such information was incomplete and the steps taken to obtain the information. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not include in Block H the evaluation codes (including event codes, method of evaluation, result and conclusion codes). Specifically, *** An investigational device was [promoted] [test marketed] prior to FDA approval/clearance. Specifically, *** Written informed consent of potential subjects to participate in an investigation was obtained prior to obtaining [IRB] [FDA] approval to conduct the investigation. Specifically, *** Records of disposition of a device which describe the batch number or code marks of any devices [returned to the sponsor] [repaired] [disposed of by the investigator or another person] and the reasons for and method of disposition reports are not all [accurate] [complete] [current]. Specifically, *** A report of the withdrawal of approval by the reviewing IRB was not prepared and submitted to the sponsor [within five working days]. Specifically, *** Copies maintained of the study protocol are not all [accurate] [complete] [current]. Specifically, *** Information related to quality problems or nonconforming product is not disseminated to those directly responsible for assuring the [quality of the product] [prevention of the quality problem]. Specifically, ***

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Procedures addressing identification of relevant information to be submitted for management review were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** A copy of all communications regarding the correction or removal action was not contained in the record. Specifically,*** FDA was not notified within 30 days of changes in [individual ownership] [corporate structure] [partnership structure] [location] of your registered establishment. Specifically, *** A signed agreement was not obtained from each participating investigator that includes [sufficient accurate financial disclosure information to allow the sponsor to submit a complete and accurate certification or disclosure statement] [a commitment to promptly update financial disclosure information if any relevant changes occur during the investigation and for one year following completion of the study]. Specifically, *** Not all employees [know there is] [understand] [fully implement] the quality policy. Specifically, *** Procedures for addressing incomplete, ambiguous, or conflicting design input requirements were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Procedures for defining and documenting design output in terms that allow an adequate evaluation of conformance to design input requirements were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Procedures were not [established] [defined] [documented] [complete] [implemented] for ensuring that participants at each design review include [representatives of all functions concerned with the design stage being reviewed] [an individual who does not have direct responsibility for the design stage being reviewed] [any specialists needed]. Specifically, *** Requirements have not been [adequately] established to address personnel [health] [cleanliness] [personal practices] [clothing]. Specifically, *** Procedures for the use and removal of manufacturing material have not been [adequately] established. Specifically, *** Device packaging and/or shipping containers are not designed and constructed to protect the device from alteration or damage during processing, storage, handling, and distribution. Specifically, *** Required records are not legible. Specifically, *** The quality system record has not been [adequately] maintained Specifically *** Unresolved discrepancies were noted at the completion of the design validation. Specifically, *** The acceptance status of product was not [identified to indicate conformance or nonconformance with acceptance criteria] [maintained]. Specifically, *** Records of complaint investigations do not include device identifications and control numbers used. Specifically, *** Records of complaint investigations do not include any reply to the complainant. Specifically, *** Finished devices were released for distribution without signature of the individual designated to authorize such release. Specifically, ***

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The results and/or dates of management reviews are not documented. Specifically, *** The approval of design input requirements [(including the date and signature of the individual approving the requirements)] was not documented. Specifically, *** Unresolved discrepancies were noted at the completion of the design verification. Specifically, *** Required records [are not stored so as to minimize deterioration and prevent loss] [that are stored in automated data processing systems are not backed up]. Specifically, *** The device master record does not include or refer to the location of [packaging] [labeling] procedures and specifications. Specifically, *** Records of complaint investigations are not maintained by the formally designated unit. Specifically, *** Service reports were not analyzed following appropriate statistical methods. Specifically, *** Service reports were not documented. Specifically, *** Investigation of MDR reportable complaints did not include a determination of the relationship of the device to the reported incident or adverse event. Specifically, *** Records of complaint investigations do not include the date the complaint was received. Specifically, *** Product was not stored to facilitate proper stock rotation and to assess its condition as appropriate. Specifically, *** Distribution records [were not maintained] [do not include or refer to the location of required information]. Specifically, *** There is no information to support the appropriateness of the statistical techniques used. Specifically, *** Procedures for the control of storage areas and stock rooms have not been [adequately] established. Specifically,*** Investigation records of MDR reportable complaints do not include required information. Specifically *** Investigation records of MDR reportable complaints do not include required information. Specifically *** The DHR does not include [complete] records of examination and release of device labeling, including date and signature of the examiner. Specifically, *** MDR event files do not contain copies of all MDR forms and other information related to the event that was submitted to [FDA] [the manufacturer] [the importer] [the distributor] [other entities]. Specifically, *** The results of the evaluation of each event are not documented and maintained in the manufacturer's MDR event file. Specifically, *** The user facility did not submit FDA Form 3500A or electronic equivalent to the [known device manufacturer] [FDA, because the device manufacturer was unknown,] within 10 working days of becoming aware of information that reasonably suggests that a device has or may have caused or contributed to a serious injury to a patient of the facility. Specifically, *** An MDR report submitted to FDA did not include all information that was reasonably known to the manufacturer. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block A the patient's age or date of birth. Specifically, ***

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An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block A the patient's gender. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block A the patient's weight. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not indicate in Block B that the outcome attributed to the adverse event was death. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not indicate in Block B the outcome attributed to the adverse event was a serious injury or illness requiring intervention to prevent permanent impairment of a body structure or function. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block B the date of the event. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not contain in Block B a description of the event or problem to include [a discussion of how the device was involved] [the nature of the problem] [the patient follow-up or required treatment] [any environmental conditions that may have influenced the event]. Specifically, *** An individual medical device manufacturer report submitted per FDA Form 3500A did not include in Block H an explanation of why any required information was not provided and the steps taken to obtain such information. Specifically, *** A baseline report on FDA Form 3417 or approved electronic equivalent was not submitted following the first MDR report on a device model. Specifically, *** An investigational device was commercialized by charging the [subjects] [investigators] a price larger than that necessary to recover costs of manufacture, research, development, and handling. Specifically, *** An investigational device was exported without obtaining FDA's approval prior to exportation and without complying with the export requirements of Section 802 of the Food, Drug, and Cosmetic Act. Specifically, *** Investigational devices were shipped to individuals who were not qualified investigators participating in the investigation. Specifically, *** The signed investigator agreements obtained from each participating investigator do not all include the investigator's curriculum vitae. Specifically, *** A signed agreement that includes a statement of the investigator's commitment to conduct an investigation in accordance with the [agreement] [investigational plan] [applicable FDA regulations] [conditions of approval imposed by the reviewing IRB] [conditions of approval imposed by the FDA] was not obtained from each participating investigator. Specifically, *** Not all investigators participating in the investigation were supplied with copies of the [investigational plan] [report of prior investigations of the investigational device]. Specifically, ***

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An investigator was not complying with the [signed agreement] [investigational plan] [requirements of the regulations] [conditions of approval imposed by the IRB or FDA] and [compliance of the investigator was not promptly secured] [shipments of the investigational device to the investigator were not discontinued] [the investigator's participation in the investigation was not terminated]. Specifically, *** An investigational device was used for subjects not under the supervision of an authorized investigator. Specifically, *** Records of persons who [received] [used] [disposed] of each device are not all [accurate] [complete] [current]. Specifically, *** Records that relate to the [reason why devices] [quantity of devices that] were [returned to the sponsor] [repaired] [disposed of] are not all [accurate] [complete] [current]. Specifically, *** Signed investigator agreements that include the required financial disclosure information are not all [accurate] [complete] [current]. Specifically, *** Records that FDA requires to be maintained for [a category of investigation] [a particular investigation] are not all [accurate] [complete] [current]. Specifically, *** Required records were not all maintained [during the investigation] [for a period of two years after the date on which an investigation was terminated or completed] [for a period of two years after the date that the records were no longer required for purposes of supporting a premarket approval application or a notice of completion of a product development protocol]. Specifically, *** Progress reports on the investigation were not submitted [at the required intervals] [at least yearly] to the [sponsor] [monitor] [reviewing IRB]. Specifically, *** In a non-emergency situation, [changes to] [deviations from] the investigational plan that could have affected [the scientific soundness of the plan] [the rights, safety, or welfare of human subjects] were initiated without prior approval of the changes from [the sponsor] [FDA] [the IRB] . Specifically, *** A report to the [sponsor] [reviewing IRB] regarding the use of an investigational device without obtaining informed consent was not submitted [within five working days after the use occurred]. Specifically, *** A final report to the [sponsor] [reviewing IRB] was not submitted [within three months] after [termination] [completion] of the investigation. Specifically, *** Notification of withdrawal of approval of an investigation by a reviewing IRB was not sent [within five working days of withdrawal] to [FDA] [all reviewing IRBs] [all participating investigators]. Specifically, *** For an investigation subject to the abbreviated requirements, progress reports were not [always] submitted to all reviewing IRBs [at required intervals] [at least annually]. Specifically, *** Progress reports for a significant risk device study were not submitted [at required intervals] [at least yearly] to [FDA] [all reviewing IRBs]. Specifically, *** The purchasing data were not approved. Specifically, ***

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The corrective and preventive action procedures addressing dissemination of information on quality problems and nonconforming product to responsible individuals were not [established] [defined] [documented] [complete] [implemented]. Specifically, *** Labels and labeling used for each finished product, lot, or batch, were not sufficiently documented in the DHR. Specifically, *** Acceptance records did not include the results of certain acceptance activities. Specifically, *** There is no corrective and preventive action procedure to determine when verification can be conducted in lieu of validation. Specifically, *** FDA personnel were not permitted access to required records and reports for devices subject to correction and removal actions. Specifically,*** Written procedures for the collection, maintenance, and auditing of device tracking information were not [established] [implemented] [complete] [provided to the FDA]. Specifically,*** A distributor of a tracked device failed to provide required tracking information promptly. Specifically,*** Device complaint records are not [established] [maintained] by the device distributor, including any relevant [incident information] [information regarding the evaluation of the allegations]. Specifically, *** The importer failed to submit a report to FDA on FDA form 3500A, with a copy to the manufacturer, within 30 days after receiving information that one of its marketed devices may have caused or contributed to a [death] [serious injury]. Specifically, *** Device listing information was not updated [in a timely manner]. Specifically, *** The label for an investigational device does not include [the name and place of business of manufacturer, packer, or distributor] [the quantity of contents] [the statement "CAUTION -- Investigational device. Limited by Federal (or United States) law to investigational use."]. Specifically, *** The labeling for an investigational device bears a statement that is [false] [misleading]. Specifically, *** The labeling for an investigational device misrepresents that the device is [safe] [effective] for the purposes for which it is being investigated. Specifically, *** A reagent [product label] [outside container] [wrapper] does not include [adequate] storage instructions [which are based on reliable, meaningful, and specific test methods] [which protect the stability of the product] . Specifically, *** Lot or control numbers on a multiple unit in vitro diagnostic [product label] [outside container] [wrapper] do not permit tracing of the identity of the individual units. Specifically, *** The product labeling accompanying an in vitro diagnostic product does not include [a statement of the appropriate range of expected values as obtained with the product from studies of various populations] [a description as to how the range was established] [identification of the population on which the range was established]. Specifically, *** In vitro diagnostic products are not being manufactured in accordance with the good manufacturing practices set forth in the Quality System Regulation. Specifically, ***

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Page 84

Devices

There are no written procedures for monitoring an investigational device study. Specifically,*** A treatment use study of an investigational device did not [comply with the regulations governing informed consent] [have IRB approval]. Specifically, *** A signed investigator agreement was not obtained from each participating investigator . Specifically,*** A clinical investigation requires an IDE, as the device does not meet the definition of a custom device in that it is [generally available in finished form for purchase or dispensing upon prescription] [generally available to, or generally used by, other physicians or dentists] [not a modification of a cleared/approved device made to comply with the order of an individual physician or dentist] [offered for commercial distribution through labeling or advertisement]. Specifically, *** Established procedures were not followed [completely] in making changes to [specifications] [methods] [processes] [procedures]. Specifically, *** Employees who manage, perform, and assess work affecting quality have not been [assigned the appropriate responsibility and authority] [provided the independence and authority] to accomplish their work. Specifically, **** Design output procedures do not [contain or reference acceptance criteria] [ensure that essential design outputs are identified] [allow for an adequate evaluation of conformance to design input requirements]. Specifically, *** Design output was not [reviewed] [approved] before release. Specifically, *** Design reviews were not performed at appropriate times, following the review schedule. Specifically, *** Reports of results of quality [audits] [reaudits] are not reviewed by management having responsibility for the matters audited. Specifically, *** [Installation instructions] [inspection instructions] [test procedures] have not been [adequately] established. Specifically,*** The design was not validated under actual or simulated use conditions. Specifically, *** The removal or reduction of manufacturing material has not been documented. Specifically, *** Changes to software used as part of [production] [the quality system] were not [adequately] validated before approval and issuance. Specifically, *** When test/measurement equipment was found to not meet accuracy and precision limits, [no] [inadequate] action was taken to [bring the equipment into calibration] [evaluate whether there was any adverse effect on the device's quality]. Specifically, *** Evaluations of out-of-calibration equipment and remedial actions taken were not documented. Specifically, *** Finished devices were not adequately controlled until acceptance tests were completed, results approved, and devices released. Specifically, *** Acceptance records were not maintained as part of the device history record. Specifically, *** Employees who perform verification and validation activities have not been made aware of defects and errors they may encounter in performing their jobs. Specifically, ***

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Page 85

Devices

Service reports do not include the name of service person. Specifically, *** Service reports do not include what service was performed. Specifically, *** During production, [process parameters] [component and device characteristics] are not [fully] monitored and controlled. Specifically, *** Criteria for workmanship have not been expressed in documented standards or by means of identified and approved representative samples. Specifically, *** Personnel are not adequately trained to perform [management activities] [work] [assessment activities] [audits]. Specifically, *** Documentation does not show that management with executive responsibility participated in management reviews. Specifically, *** Design output was not [adequately] documented before release. Specifically, *** The person installing the device did not [adequately] document the inspection and test results to demonstrate proper installation. The person installing the device did not document complete inspection and test results to demonstrate proper installation. Specifically, *** Investigated complaints and records of investigation were not accessible to the manufacturing establishment. Specifically, *** Documentation of process validation activities and results does not include [the date and signature of the individuals approving the validation] [the major equipment validated]. Specifically, *** Procedures were not established for authorizing receipt from and dispatch to storage areas and stock rooms. Specifically, *** Sampling methods have not been reviewed for adequacy for their intended use. Specifically, *** The review of sampling methods for adequacy for their intended use was not documented. Specifically, *** Process equipment has not been approved. Specifically, *** Service reports [are not documented] [do not include the required information]. Specifically, *** Periodic inspections of equipment [were not] conducted to ensure adherence to applicable maintenance schedules [were not documented]. Specifically, ***

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Page 86

Drugs

Center Name

Cite Id

Ref No

ShortDesc

Drugs

1105 21 CFR 211.22(d)

Procedures not in writing, fully followed

1358 21 CFR 211.100(b)

SOPs not followed / documented

2027 21 CFR 211.192

Investigations of discrepancies, failures

3603 21 CFR 211.160(b)

Scientifically sound laboratory controls

3585 21 CFR 211.110(a)

Control procedures to monitor and validate performance

1361 21 CFR 211.100(a)

Absence of Written Procedures

1215 21 CFR 211.67(b)

Written procedures not established/followed

1112 21 CFR 211.25(a)

Training--operations, GMPs, written procedures

1213 21 CFR 211.67(a)

Cleaning / Sanitizing / Maintenance

1274 21 CFR 211.68(a)

Calibration/Inspection/Checking not done

Page 87

Drugs

1883 21 CFR 211.165(a)

Testing and release for distribution

2009 21 CFR 211.188

Prepared for each batch, include complete information

1177 21 CFR 211.63

Equipment Design, Size and Location

2419 21 CFR 211.198(a)

Complaint Handling Procedure

1890 21 CFR 211.165(e)

Test methods

9001 21 CFR 211.22(a)

Lack of quality control unit

4314 21 CFR 211.84(d)(2)

Reports of Analysis (Components)

1111 21 CFR 211.25(a)

Training , Education , Experience overall

4352 21 CFR 211.160(b)(4)

Calibration - at intervals, written program, remedial action

1133 21 CFR 211.25(a)

GMP Training Frequency

2026 21 CFR 211.192

Quality control unit review of records

Page 88

Drugs

4391 21 CFR 211.180(e)(2)

Items to cover on annual reviews

1914 21 CFR 211.166(a)

Lack of written stability program

4402 21 CFR 211.192

Written record of investigation incomplete

1787 21 CFR 211.80(a)

Procedures To Be in Writing

1809 21 CFR 211.160(a)

Following/documenting laboratory controls

1912 21 CFR 211.166(a)

Written program not followed

3570 21 CFR 211.100(a)

Approval and review of procedures

4303 21 CFR 211.67 b)

Written procedures fail to include

1227 21 CFR 211.67(c)

Cleaning/maintenance records not kept

1767 21 CFR 211.137(a)

Expiration date lacking

1540 21 CFR 211.125(a)

Strict control not exercised over labeling issued

Page 89

Drugs

4413 21 CFR 211.194(a)(8)

Second person sign off

2028 21 CFR 211.192

Extent of discrepancy, failure investigations

1451 21 CFR 211.113(b)

Procedures for sterile drug products

4576 21 CFR 211.192

No written record of investigation

2031 21 CFR 211.194(a)

Complete test data included in records

3565 21 CFR 211.58

Buildings not maintained in good state of repair

4389 21 CFR 211.198(a)

Procedures to be written and followed

4340 21 CFR 211.142

Written warehousing procedures established/followed

1194 21 CFR 211.42(c)

Defined areas of adequate size for operations

3632 21 CFR 211.170(b)

Annual visual exams of drug products

1975 21 CFR 211.182

Written records kept in individual logs

1452 21 CFR 211.113(b)

Validation lacking for sterile drug products

Page 90

Drugs

1943 21 CFR 211.180(e)(1)

Review of representative number of batches

4372 21 CFR 211.188(b)(8)

Labeling control records including specimens or copies

1550 21 CFR 211.125(f)

Procedures Written and Followed

2007 21 CFR 211.186(a)

Signature and checking of records -2 persons

2205 21 CFR 211.186(b)(9)

Manufacturing Instructions and Specifications

3571 21 CFR 211.100(a)

Changes to Procedures Not Reviewed, Approved

3572 21 CFR 211.100(b)

Procedure Deviations Recorded and Justified

1098 21 CFR 211.22(c)

Approve or reject procedures or specs

1261 21 CFR 211.68(a)

Written calibration / inspection records not kept

1810 21 CFR 211.160(a)

Lab controls established, including changes

1942 21 CFR 211.180(e)

Records reviewed annually

4306 21 CFR 211.80(a)

Written Procedures Not Followed

Page 91

Drugs

3602 21 CFR 211.160(a)

Deviations from laboratory control requirements

1434 21 CFR 211.42(c)(10)(iv) Environmental Monitoring System

2619 21 CFR 211.198(b)(2)

Complaint Investigation/Follow-Up Findings

3547 21 CFR 211.46(b)

Equipment for Environmental Control

4336 21 CFR 211.150

Written distribution procedure

1411 21 CFR 211.105(b)

Distinctive ID or code not recorded in batch record

1450 21 CFR 211.113(a)

Procedures for non-sterile drug products

1626 21 CFR 211.130

Procedures are written, and followed

1790 21 CFR 211.80(b)

Handling and Storage to Prevent Contamination

1801 21 CFR 211.84(a)

Components withheld from use pending release

1891 21 CFR 211.165(f)

Failing drug products not rejected

3583 21 CFR 211.110(a)

Written in-process control procedures

Page 92

Drugs

4307 21 CFR 211.80(d)

Status of Each Lot Identified

4342 21 CFR 211.142(b)

Storage under appropriate conditions

4369 21 CFR 211.188(b)(11)

Identification of persons involved, each significant step

1885 21 CFR 211.165(b)

Microbiological testing

1926 21 CFR 211.166(b)

Adequate number of batches on stability

2034 21 CFR 211.194(d)

Laboratory equipment calibration records

3561 21 CFR 211.56(b)

Written sanitation procedures lacking

1833 21 CFR 211.84(d)(1)

Identity Testing of Each Component

1844 21 CFR 211.84(d)(2)

Establish reliability of supplier's C of A

4401 21 CFR 211.186(b)(9)

Complete instructions, procedures, specifications et. al.

1263 21 CFR 211.68(b)

Computer control of master formula records

1448 21 CFR 211.111

Establishment of time limitations

Page 93

Drugs

1978 21 CFR 211.182

Personnel dating/signing equipment log

3559 21 CFR 211.56(a)

Sanitation--buildings not clean, free of infestation

3613 21 CFR 211.160(b)(4)

Establishment of calibration procedures

8911 21 CFR 314.81(b)(1)(ii)

Failure to meet specifications

1134 21 CFR 211.25(b)

Supervisor Training/Education/Experience

1270 21 CFR 211.68(b)

input/output verification

4368 21 CFR 211.188(b)(12)

Investigations made into any unexplained discrepancy

1920 21 CFR 211.166a)(3)

Valid stability test methods

2033 21 CFR 211.194(c)

Testing and standardization of standards et. al.

3616 21 CFR 211.165(d)

Acceptance criteria for sampling & testing

6732 21 CFR 314.80(c)(1)(i)

Late submission of 15-day report

Page 94

Drugs

1169 21 CFR 211.42(a)

Buildings of Suitable Size, Construction, Location

1136 21 CFR 211.25(c)

Inadequate number of personnel

1505 21 CFR 211.122(d)

Label storage access limited to authorized personnel

1886 21 CFR 211.165(c)

Sampling and testing plans not described

4338 21 CFR 211.150(b)

Recall facilitation

4341 21 CFR 211.142(a)

Quarantine - written procedures

4357 21 CFR 211.166(a)

Results not used for expiration dates, storage cond.

4377 21 CFR 211.188(b(3)

Identification of each component or in-process material

4400 21 CFR 211.186(b)(8)

Description of containers, labels, et. al.

1033 21 CFR 211.22(a)

Authority lacking to review records, investigate errors

1802 21 CFR 211.84(b)

Representative Samples

3582 21 CFR 211.105(a)

Identification of containers, lines, equipment

Page 95

Drugs

4353 21 CFR 211.160(b)(4)

Instruments, apparatus, et. al. not meeting specs

4373 21 CFR 211.188(b)(7)

Actual yield, % of theoretical yield

4406 21 CFR 211.194(a)(2)

Suitability of testing methods verified

1049 21 CFR 211.22(a)

Approve or reject components, products

1395 21 CFR 211.103

Actual vs. theoretical yields not determined

1454 21 CFR 211.115(a)

Reprocessing procedures not written or followed

1632 21 CFR 211.130(c)

Lot or control number assigned

2008 21 CFR 211.186(a)

Written procedures followed

3614 21 CFR 211.160(b)(4)

Written calibration procedures

4315 21 CFR 211.84(d)(2)

Testing Each Component for Conformity with Specs

4366 21 CFR 211.188(a)

Accurate reproduction included

8907 21 CFR 314.81(b)(1)(ii)

Contamination, chemical or physical change, deterioration

Page 96

Drugs

1086 21 CFR 211.22(b)

Adequate lab facilities not available

1495 21 CFR 211.122(a)

Written procedures describing in detail

1774 21 CFR 211.142(a)

Quarantine - actual practice

1777 21 CFR 211.150(b)

Distribution Recall System

1798 21 CFR 211.82(b)

Quarantine Storage of Components

2003 21 CFR 211.184(c)

Individual inventory record

2035 21 CFR 211.194(e)

Stability testing records not included

2567 21 CFR 211.198(a)

Adverse Drug Experience

3557 21 CFR 211.52

Washing and toilet facilities are deficient

1851 21 CFR 211.84(e)

Rejecting When Specifications Not Met

4378 21 CFR 211.188(b)(2)

Identity of major equipment and lines used

1079 21 CFR 211.22(a)

Contract drug products--lack of responsibility

Page 97

Drugs

1456 21 CFR 211.115(b)

Reprocessing/quality control unit

1498 21 CFR 211.122(b)

Labeling and packaging improperly approved/released

1879 21 CFR 211.180(c)

Records not made readily available to FDA

3550 21 CFR 211.46(c)

Exhaust systems inadequate to control air contamination

3553 21 CFR 211.48(a)

Plumbing System Defects

3629 21 CFR 211.170(b)

Reserve samples identified, representative, stored

4320 21 CFR 211.84(d)(6)

Microbiological Contamination Exam

4351 21 CFR 211.160(b)(3)

Drug products - samples representative, identified properly

4404 21 CFR 211.194(a)(1)

Sample identification and other information

6730 21 CFR 314.80(b)

Failure to develop written procedures

1159 21 CFR 211.28(a)

Clothing appropriate for duties performed

1162 21 CFR 211.28(a)

Protective Apparel Not Worn

Page 98

Drugs

4399 21 CFR 211.186(b)(7)

Theoretical yield statement including percentages

1388 21 CFR 211.101(d)

Component addition checked by 2nd person

1435 21 CFR 211.42(c)(10)(v) Cleaning System

1728 21 CFR 211.87

Retest of approved components/containers/closures

1797 21 CFR 211.82(a)

Examination on receipt, before acceptance

1917 21 CFR 211.166(a)(1)

Sample size - test intervals

1976 21 CFR 211.182

Specific information required in individual logs

2020 21 CFR 211.188(b)(8)

Labeling Control Records and Label Copies

3562 21 CFR 211.56(c)

Written procedures lacking for use of pesticides etc.

4304 21 CFR 211.68(b)

Written record not kept of program and validation data

4309 21 CFR 211.84(c)(2)

Containers sampled so as to prevent contamination

4313 21 CFR 211.84(c)(6)

Containers Marked to Show Samples Taken

Page 99

Drugs

4323 21 CFR 211.115(a)

Reprocessing procedures lack steps to be taken

4325 21 CFR 211.110(a)

Control procedures fail to include the following

4328 21 CFR 211.122(a)

Written procedures not followed

4355 21 CFR 211.165(c)

Sampling and testing plans not followed

4370 21 CFR 211.188(b)(10)

Records of any sampling performed

4410 21 CFR 211.194(a)(5)

Calculations performed are in the records

8935 FDCA 760(b)(1)

Failure of responsible person to report AE (non-RX Drug)

1163 21 CFR 211.28(b)

Habits of good sanitation & health

1168 21 CFR 211.34

Consultant Records

1843 21 CFR 211.84(d)(2)

Component written specification

4375 21 CFR 211.188(b)(5)

In-process and laboratory control results

4380 21 CFR 211.198(b)(3)

Determination not to conduct investigation of complaint

Page 100

Drugs

4388 21 CFR 211.198(a)

Complaints reviewed by Quality Control Unit

1222 21 CFR 211.67(b)(4)

Cleaning SOPs/equipment identification

1256 21 CFR 211.68(b)

Backup file not maintained

1266 21 CFR 211.42(d)

Penicillin processing area not kept separate

1436 21 CFR 211.42(c)(10)(vi) Equipment to control conditions

1449 21 CFR 211.111

Deviations of production time limits

1496 21 CFR 211.122(a)

Sampling/testing of labeling/packaging materials

1630 21 CFR 211.130(b)

Unlabeled filled containers controls

1633 21 CFR 211.130(d)

Examination of packaging and labeling

1636 21 CFR 211.130(e)

Packaging line inspection before use

1637 21 CFR 211.130(e)

Packaging line inspection after use

1725 21 CFR 211.134(c)

Examinations documented

Page 101

Drugs

1869 21 CFR 211.94(c)

Containers & Closures Clean, Sterilized, Pyrogen-free

1876 21 CFR 211.180(a), (b)

Record maintenance 1 year (except exempt OTC)

1918 21 CFR 211.166(a)(2)

Stability sample storage conditions described

1957 21 CFR 211.180(e)(2)

Review of problem drugs

1977 21 CFR 211.182

Dedicated equipment: records part of batch record

2012 21 CFR 211.188(b)

Batch production and Batch Control Record Requirements

2017 21 CFR 211.188(b)(5)

In-Process and Laboratory Control Results

2021 21 CFR 211.188(b)(9)

Container/Closure Description

2203 21 CFR 211.186(b)(7)

Theoretical Yield and Percentages

2402 21 CFR 211.194(a)(5)

Testing Calculations

2621 21 CFR 211.198(b)(3)

Reason for Not Conducting Complaint Investigation

3592 21 CFR 211.110(c)

In-process materials characteristics testing

Page 102

Drugs

3594 21 CFR 211.110(d)

Rejected in-process materials not quarantined

3611 21 CFR 211.160(b)(3)

Acceptance of drug products

3623 21 CFR 211.170(a)

Active ingredient retained sample kept

3639 21 CFR 211.204

Returned drug procedures in writing and followed

3641 21 CFR 211.204

Record information inclusions

4302 21 CFR 211.56(b)

Written sanitation procedures not followed

4316 21 CFR 211.84(d)(3)

Testing Containers & Closures Conformity with Specs

4317 21 CFR 211.84(d)(3)

Certificates of Testing (Containers, Closures)

4322 21 CFR 211.101(d)

Component release checked by 2nd person

4349 21 CFR 211.160(b)(2)

In-process samples representative, identified properly

4403 21 CFR 211.194(b)

Test method modification records do not include

4412 21 CFR 211.194(a)(7)

Signatures and dates--person who performs test

Page 103

Drugs

6736 21 CFR 314.80(c)(1)(ii)

Submission of report follow-up

6833 21 CFR 314.80(c)(2)(ii)

Incomplete periodic safety report

1207 21 CFR 211.65(b)

Substances That Come in Contact

1842 21 CFR 211.84(d)(1)

Component identity verification

1852 21 CFR 211.94(a)

Reactive/Additive/Absorptive Containers/Closures

4376 21 CFR 211.188(b)(4)

Weights and measures of components used

4382 21 CFR 211.198(b)(2)

Written record of complaint to include findings, follow-up

4383 21 CFR 211.198(b)(1)

Written complaint record must include

4385 21 CFR 211.198(b)

Records maintained for 1 year (except certain OTC drugs)

4387 21 CFR 211.198(a)

Reporting of adverse drug experience to FDA

Page 104

Drugs

4396 21 CFR 211.186(b)(4)

Variations in component amounts not justified

1220 21 CFR 211.67(b)(3)

Cleaning SOPs/instructions

1224 21 CFR 211.67(b)(6)

Cleaning SOP/inspection

1393 21 CFR 211.103

Yield calculations not verified by 2nd person

1396 21 CFR 211.42(c)(2)

Rejected Material Area

1421 21 CFR 211.42(c)(10)

Aseptic Processing Area

1430 21 CFR 211.42(c)(10)(i)

Floors, walls, ceiling surfaces

1433 21 CFR 211.42(c)(10)(iii) Air Supply

1541 21 CFR 211.125(b)

Examination of issued labels

1546 21 CFR 211.125(d)

Destruction of excess labels with lot numbers

1629 21 CFR 211.130(a)

Prevention of cross contamination, mix-ups

1722 21 CFR 211.134(a)

Correct labels during finishing operations

Page 105

Drugs

1770 21 CFR 211.137(d)

Expiration date location on labeling

1794 21 CFR 211.80(d)

Disposition recorded by lot identification

1922 21 CFR 211.166(a)(4)

Testing in same container - closure system

1927 21 CFR 211.166(b)

Accelerated stability studies

2004 21 CFR 211.184(d)

Labeling: documentation of exam and review

2019 21 CFR 211.188(b)(7)

Documentation of Actual Yield and Theoretical Yield

2200 21 CFR 211.186(b)(4)

Variation in the Amount of Components Used

2399 21 CFR 211.194(a)(2)

Laboratory Test Method Verification

2618 21 CFR 211.198(b)(1)

Complaint Record required information

3445 21 CFR 211.65(a)

Equipment construction - reactive surfaces

3545 21 CFR 211.44

Adequate lighting not provided

3548 21 CFR 211.46(c)

Air filtration system lacking in production area

Page 106

Drugs

3551 21 CFR 211.46(d)

Penicillin air handling systems not kept separate

3567 21 CFR 211.84(d)(2)

Component identification test

3569 21 CFR 211.89

Quarantine of Rejected Components et. al.

3591 21 CFR 211.110(b)

In-process materials specifications

3615 21 CFR 211.160(b)(4)

Test devices not meeting specifications

4324 21 CFR 211.110(b)

In-process materials specifications testing

4344 21 CFR 211.160(b)(1)

Sampling and testing procedures described

4345 21 CFR 211.160(b)(1)

Samples (various types) representative, identified properly

4350 21 CFR 211.160(b)(3)

Drug products-sampling procedures/specifications

4359 21 CFR 211.170(a)(1), (b)(1) Retention time of reserve samples, in general

4364 21 CFR 211.176

Failing to test for penicillin crosscontamination

4407 21 CFR 211.194(a)(2)

Reference and method not stated

Page 107

Drugs

4409 21 CFR 211.194(a)(4)

Data secured in course of each test

4411 21 CFR 211.194(a)(6)

Test results, comparison with standards not included

4415 21 CFR 211.204

Returned drug products with doubt cast as to safety et. al.

8912 21 CFR 314.81(b)(2)

Timely submission

6832 21 CFR 314.80(c)(2)

Late submission of annual safety reports

1167 21 CFR 211.34

Qualifications lacking

1174 21 CFR 211.42(b)

Product flow through building is inadequate

1846 21 CFR 211.84(d)(3)

Establish reliability of supplier's C of A

1849 21 CFR 211.84(d)(6)

Objectionable microbiological contamination

4386 21 CFR 211.198(b)

Written complaint record to be maintained at facility

4392 21 CFR 211.186(b)(1)

Name, strength, dosage form

Page 108

Drugs

4394 21 CFR 211.186(b)(3)

Components complete listing

4395 21 CFR 211.186(b)(4)

Weight or measure of each component

1223 21 CFR 211.67(b)(5)

Cleaning SOPs/equipment protection

1371 21 CFR 211.101(a)

Batches Formulated to less than 100%

1409 21 CFR 211.42(c)(4)

In-Process Material Area

1413 21 CFR 211.42(c)(5)

Mfg / Processing Operations Area

1418 21 CFR 211.42(c)(7)

Quarantined Drug Products Area

1431 21 CFR 211.42(c)(10)(ii) Temperature / Humidity Controls

1503 21 CFR 211.122(c)

Records not kept for each shipment

1506 21 CFR 211.122(e)

Destruction of obsolete labeling

1509 21 CFR 211.122(h)

Printing devices

1545 21 CFR 211.125(c)

Label reconciliation discrepancies evaluation/investigation

Page 109

Drugs

1724 21 CFR 211.134(b)

Representative samples after completion

1726 21 CFR 211.86

Rotation of components/containers/closures

1791 21 CFR 211.80(c)

Storage off Floor, Spaced Suitably

1932 21 CFR 211.167(a)

Sterility/pyrogen-free testing

1939 21 CFR 211.167(c)

Controlled release test methods written, followed

1958 21 CFR 211.180(f)

Responsible firm officials notified in writing

1979 21 CFR 211.182

Chronological Order of Equipment Log Entries

2001 21 CFR 211.184(b)

Component Test Records

2005 21 CFR 211.184(e)

Records of disposition of rejected material

2011 21 CFR 211.188(a)

Accurate reproduction

2014 21 CFR 211.188(b)(2)

Identification of Equipment and Lines

2015 21 CFR 211.188(b)(3)

Identification of Components and InProcess Materials

Page 110

Drugs

2016 21 CFR 211.188(b)(4)

Weights and Measures of Components Used

2022 21 CFR 211.188(b)(10)

Documentation of Sampling Performed

2023 21 CFR 211.188(b)(11)

Identification of Persons Performing Significant Steps

2024 21 CFR 211.188(b)(12)

Documentation of Batch Investigations

2032 21 CFR 211.194(b)

Test method modification records not maintained

2397 21 CFR 211.194(a)(1)

Description and Identification of Samples

2401 21 CFR 211.194(a)(4)

Complete Test Data

2420 21 CFR 211.198(a)

Quality Control Review

3554 21 CFR 211.48(a)

Potable water standards not met

3555 21 CFR 211.48(b)

Drains--Size, Back-siphonage Prevention

3556 21 CFR 211.50

Sewage and refuse disposal in safe manner

3558 21 CFR 211.52

Washing and toilet facilities not provided and accessible

Page 111

Drugs

3573 21 CFR 211.101(b)

Measured components for manufacturing

3581 21 CFR 211.101(d)

Verification of component addition

3588 21 CFR 211.110(a)(3)

Mixing adequacy

3605 21 CFR 211.160(b)(1)

Specification description of sample/testing

3606 21 CFR 211.160(b)(1)

Retesting

3609 21 CFR 211.160(b)(2)

In-process sample representation/identification

3610 21 CFR 211.160(b)(3)

Drug product sample

3630 21 CFR 211.170(b)

Drug product reserve containers

3631 21 CFR 211.170(b)

Investigation of reserve sample deterioration

3633 21 CFR 211.170(b)(1)

Reserve sample retention time

3640 21 CFR 211.204

Returned drug products identified and held

4305 21 CFR 211.68(b)

Backup data not assured as exact and complete

Page 112

Drugs

4308 21 CFR 211.94(d)

Written Procedures to Remove Pyrogens Not Followed

4318 21 CFR 211.84(d)(4)

Microscopic Exam of Components

4319 21 CFR 211.84(d)(5)

Exam for Filth, Insects, Extraneous Adulterants

4321 21 CFR 211.101(b)

Identification of new containers

4327 21 CFR 211.122(c)

Records fail to include

4343 21 CFR 211.160(b)(1)

Incoming lots - conformance to written specs-

4348 21 CFR 211.160(b)(2)

In-process materials - sampling, testing procedures

4354 21 CFR 211.165(d)

Acceptance/Rejection Levels

4356 21 CFR 211.166(b)

Tentative expiration date

4360 21 CFR 211.170(b)

Reserve drug product sample quantity - all tests

4362 21 CFR 211.170(a)(3), (b)(3) Retention time for exempt OTC drug products

Page 113

Drugs

4374 21 CFR 211.188(b)(6)

Inspection of packaging and labeling area

4405 21 CFR 211.194(a)(2)

Statement of methods and data

4416 21 CFR 211.204

Reprocessed returned drug products

4417 21 CFR 211.204

Associated batches implicated, investigated

8906 21 CFR 314.81(b)(1)(i)

Mix-up

8908 21 CFR 314.81(b)(2)(i)

Summary

8910 21 CFR 314.81(b)(2)(iii)

Labeling information

8913 21 CFR 314.81(b)(2)(iv)(a)Reports re: chemical, physical, or other properties

8917 21 CFR 314.81(b)(2)(vi)(b)Completed, unpublished clinical trials

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Drugs

6704 21 CFR 310.305(c)

Submission of report to incorrect office

6728 21 CFR 314.80(b)

Failure to review ADE information

6823 21 CFR 314.80(c)

Failure by applicant to report ADE

6825 21 CFR 314.80(c)(1)(iii)

Non-applicant reports to applicant

6829 21 CFR 314.80(c)(2)

Failure to report non-alert ADEs

6830 21 CFR 314.80(c)(2)

Interval

6831 21 CFR 314.80(c)(2)

Late submission of quarterly safety reports

6840 21 CFR 314.80(f)(1)

Wrong form - domestic ADE

6841 21 CFR 314.80(f)(1)

Wrong form - foreign ADE

8922 21 CFR 314.81(b)(2)(viii) Post marketing study status report for other studies

10022 21 CFR 310.305(a)

Failure to develop written procedures

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LongDesc

Frqncy

The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed]. Specifically, ***

149

Written production and process control procedures are not [followed in the execution of production and process control functions] [documented at the time of performance]. Specifically, *** There is a failure to thoroughly review [any unexplained discrepancy] [the failure of a batch or any of its components to meet any of its specifications] whether or not the batch has been already distributed. Specifically, *** Laboratory controls do not include the establishment of scientifically sound and appropriate [specifications] [standards] [sampling plans] [test procedures] designed to assure that [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity. Specifically, *** Control procedures are not established which [monitor the output] [validate the performance] of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. Specifically, *** There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Specifically, *** Written procedures are not [established] [followed] for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. Specifically, *** Employees are not given training in [the particular operations they perform as part of their function] [current good manufacturing practices] [written procedures required by current good manufacturing practice regulations]. Specifically, *** Equipment and utensils are not [cleaned] [maintained] [sanitized] at appropriate intervals to prevent [malfunctions] [contamination] that would alter the safety, identity, strength, quality or purity of the drug product. Specifically, *** Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance. Specifically, ***

104

98

83

82

81

71

66

61

60

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Drugs

Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the [final specifications] [identity and strength of each active ingredient] prior to release. Specifically, *** Batch production and control records [are not prepared for each batch of drug product produced] [do not include complete information relating to the production and control of each batch]. Specifically, *** Equipment used in the manufacture, processing, packing or holding of drug products is not [of appropriate design] [of adequate size] [suitably located] to facilitate operations for its [intended use] [cleaning and maintenance]. Specifically, *** Procedures describing the handling of written and oral complaints related to drug products are [not written or followed] [deficiently written or followed]. Specifically, ***

57

56

51

47

The [accuracy] [sensitivity] [specificity] [reproducibility] of test methods have not been [established] [documented]. Specifically, ***

43

There is no quality control unit. Specifically, ***

43

Reports of analysis from component suppliers are accepted in lieu of testing each component for conformity with all appropriate written specifications, without [performing at least one specific identity test on each component] [establishing the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals]. Specifically, *** Employees engaged in the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] required to perform their assigned functions. Specifically, *** The calibration of [instruments] [apparatus] [gauges] [recording devices] is not done at suitable intervals [in accordance with an established written program] [with provisions for remedial action in the event accuracy and/or precision limits are not met]. Specifically, *** GMP training is not conducted [on a continuing basis] [with sufficient frequency] to assure that employees remain familiar with CGMP requirements applicable to them. Specifically, ***

42

41

41

39

Drug product production and control records, are not [reviewed] [approved] by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Specifically, ***

39

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Drugs

Written procedures are not [established] [followed] for evaluations done at least annually and including provisions for a review of [complaints] [recalls] [returned or salvaged drug products] [investigations conducted for each drug product]. Specifically, *** There is no written testing program designed to assess the stability characteristics of drug products. Specifically, ***

38

37

Written records of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications] do not [always] include the conclusions and follow-up. Specifically, *** Written procedures are lacking which describe in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures]. Specifically, *** Established [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] are not [followed] [documented at the time of performance]. Specifically, ***

37

34

34

The written stability testing program is not followed. Specifically, ***

34

Written procedures are not [drafted, reviewed and approved by the appropriate organizational units] [reviewed and approved by the quality control unit]. Specifically, ***

31

Written procedures for cleaning and maintenance fail to include [assignment of responsibility] [maintenance and cleaning schedules] [description in sufficient detail of methods, equipment and materials used] [description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance] [instructions for removal or obliteration of previous batch identification] [instructions for protection of clean equipment from contamination prior to use] [parameters relevant to the operation]. Specifically, ***

31

Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment. Specifically, ***

29

Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use. Specifically, *** Strict control is not exercised over labeling issued for use in drug product labeling operations. Specifically, ***

29

28

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Drugs

Laboratory records do not include the initials or signature of a second person showing that the original records have been reviewed for [accuracy] [completeness] [compliance with established standards]. Specifically, *** Investigations of [an unexplained discrepancy] [a failure of a batch or any of its components to meet any of its specifications] did not extend to [other batches of the same drug product] [other drug products that may have been associated with the specific failure or discrepancy]. Specifically, *** Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed]. Specifically, ***

28

27

26

Written records are not [always] made of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications]. Specifically, ***

26

Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards. Specifically, , *** Buildings used in the [manufacturing] [processing] [packing] [holding] of a drug product are not maintained in a good state of repair. Specifically, ***

24

24

Procedures describing the handling of all written and oral complaints regarding a drug product are not [established] [written] [followed]. Specifically, ***

23

Procedures describing the warehousing of drug products are not [established] [followed]. Specifically, ***

23

The [separate or defined areas][control systems] necessary to prevent contamination or mix-ups are deficient. Specifically, ***

22

Reserve samples from representative sample lots or batches of drug products selected by acceptable statistical procedures are not examined visually at least once a year for evidence of deterioration. Specifically, *** Written records of major equipment [cleaning] [maintenance] [use] are not included in individual equipment logs. Specifically, ***

22

21

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include [adequate] validation of the sterilization process. Specifically, ***

19

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Drugs

Written procedures are not [established] [followed] for evaluations conducted at least annually to review records associated with a representative number of batches, whether approved or rejected. Specifically, *** Batch production and control records do not include complete labeling control records, including specimens or copies of all labeling used for each batch of drug product produced. Specifically, *** Procedures describing in sufficient detail the controls employed for the issuance of labeling are not [written] [followed]. Specifically, ***

19

19

18

The master production and control records for each batch size of drug product are not [prepared, dated, and signed by one person with a full handwritten signature] [independently checked, dated, and signed by a second person]. Specifically, *** The master production and control records are deficient in that they do not include complete [manufacturing] [control] [instructions] [sampling] [testing] [procedures] [specifications] [special notations] [precautions]. Specifically, *** Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit]. Specifically, ***

18

18

18

Deviations from written production and process control procedures are not [recorded] [justified]. Specifically, ***

18

The quality control unit lacks responsibility to [approve] [reject] all procedures or specifications impacting on the [identity] [strength] [quality] [purity] of drug products. Specifically, ***

17

Records of the [calibration checks] [inspections] of automatic, mechanical or electronic equipment, including computers or related systems are not maintained. Specifically, ***

17

The establishment of [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] including any changes thereto, are not [drafted by the appropriate organizational unit] [reviewed and approved by the quality control unit]. Specifically, *** Records are not maintained so that data therein can be reviewed at least annually to evaluate the quality standards of each drug product to determine the need for changes in specifications or manufacturing or control procedures. Specifically, *** Written procedures are not followed for the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures]. Specifically, ***

17

17

17

Page 120

Drugs

Deviations from written [specifications] [standards] [sampling plans] [test procedures] [laboratory mechanisms] are not [recorded] [justified]. Specifically, ***

16

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specifically, ***

15

Complaint records are deficient in that they do not include the findings of the [investigation] [follow-up]. Specifically, ***

15

Equipment for adequate control over [air pressure] [microorganisms] [dust] [humidity] [temperature] is not provided when appropriate for the manufacture, processing, packing or holding of a drug product. Specifically, *** Written distribution procedures are not [established] [followed]. Specifically, ***

15

15

The batch records do not record the distinctive [identification number] [code] [name of equipment] to identify major equipment to show the specific equipment used in the manufacture of a batch of a drug product. Specifically, *** Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not [established] [written] [followed]. Specifically, ***

14

14

Procedures designed to assure that correct [labels] [labeling] [packaging materials] are used for drug products are not [written] [followed]. Specifically, ***

14

There was a failure to handle and store [components] [drug product containers] [closures] at all times in a manner to prevent contamination. Specifically, ***

14

Each lot of [components] [drug product containers] [closures] is not withheld from use until the lot has been sampled, tested, examined, and released by the quality control unit. Specifically, *** Drug products failing to meet established [standards] [specifications] [quality control criteria] are not rejected. Specifically, ***

14

14

Written procedures are not [established] [followed] that describe the [in-process controls] [tests] [examinations] to be conducted on appropriate samples of in-process materials of each batch. Specifically, ***

14

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Drugs

Each lot of [components] [drug product containers] [closures] was not appropriately identified as to its status in terms of being quarantined, approved or rejected. Specifically, ***

14

Drug products are not stored under appropriate conditions of [temperature] [humidity] [light] so that their identity, strength, quality, and purity are not affected. Specifically, ***

14

Batch production and control records do not include the identification of the persons [performing] [directly supervising] [checking] each significant step in the operation, for each batch of drug product produced. Specifically, *** Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing. Specifically, ***

14

13

An adequate number of batches of each drug product are not tested [nor are records of such data maintained] to determine an appropriate expiration date. Specifically, ***

13

Laboratory records do not include complete records of the periodic calibration of laboratory [instruments] [apparatus] [gauges] [recording devices]. Specifically, ***

13

There is a lack of written procedures [assigning responsibility] [providing cleaning schedules] [describing in sufficient detail the methods, equipment and materials to be used] for sanitation. Specifically, *** The identity of each component of a drug product is not verified by conducting at least one test to verify the identity, using specific identity tests if they exist. Specifically, ***

13

12

Establishment of the reliability of the component supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals. Specifically, ***

12

Master production and control records lack [complete manufacturing and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed]. Specifically, *** Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Specifically, *** Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product. Specifically, ***

12

12

12

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Drugs

The persons [performing] [double-checking] the cleaning and maintenance are not [dating] [signing or initialing] the equipment cleaning and use log. Specifically, ***

12

Buildings used in the manufacture, processing, packing or holding of drug products are not [maintained in a clean and sanitary condition] [free of infestation by rodents, birds insects, and other vermin]. Specifically, *** Procedures describing the calibration of instruments, apparatus, gauges and recording devices are [not written or followed] [deficiently written or followed]. Specifically, ***

12

12

An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning a failure of one or more distributed batches of a drug to meet the specifications established for it in the application. Specifically, *** Individuals responsible for supervising the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] to perform their assigned functions in such a manner as to assure the drug product has the safety, identity, strength, quality and purity that it purports or is represented to possess. Specifically, *** Input to and output from [the computer] [related systems of formulas] [records or data] are not checked for accuracy. Specifically, ***

12

11

11

Batch production and control records do not include the results of any investigation made into any unexplained discrepancy, whether or not the batch of drug product had already been distributed. Specifically, *** The written stability program for drug products does not include [reliable] [meaningful] [specific] test methods. Specifically, ***

11

10

Laboratory records do not include complete records of any testing and standardization of laboratory [reference standards] [reagents] [standard solutions]. Specifically, ***

10

Acceptance criteria for the sampling and testing conducted by the quality control unit is not adequate to assure that batches of drug products meet [each appropriate specification] [appropriate statistical quality control criteria] as a condition for their approval and release. Specifically, *** Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information. Specifically, ***

10

10

Page 123

Drugs

Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable [size] [construction] [location] to facilitate cleaning, maintenance, and proper operations. Specifically, *** The number of qualified personnel is inadequate to [perform] [supervise] the [manufacture] [processing] [packing] [holding] of each drug product. Specifically, ***

Access to the storage area for labels and labeling materials is not limited to authorized personnel. Specifically, ***

Sampling and testing plans for drug products are not described in written procedures which include the [method of sampling] [number of units per batch to be tested]. Specifically, ***

A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary, has not been established. Specifically, ***

Written procedures for the warehousing of drug products do not include quarantine of drug products before release by the quality control unit. Specifically, ***

Results of stability testing are not used in determining [appropriate storage conditions] [expiration dates]. Specifically, ***

Batch production and control records do not include the specific identification of each batch of [component] [in-process material] used for each batch of drug product produced. Specifically, ***

Master production and control records lack [a description of the drug product containers, closures and packaging materials] [a specimen or copy of each label and all other labeling] [the signatures and dates entered by the person or persons responsible for the approval of labeling]. Specifically, *** The quality control unit lacks authority to [review production records to assure that no errors have occurred] [fully investigate errors that have occurred]. Specifically, ***

Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination. Specifically, ***

All [compounding and storage containers] [processing lines] [major equipment] used during the production of a batch of drug product is not properly identified at all times to indicate [contents] [the phase of processing of the batch]. Specifically, ***

Page 124

Drugs

The use of [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications was observed. Specifically, ***

The batch production and control records do not include a statement of the [actual yield] [percentage of theoretical yield] at appropriate stages of processing for each batch of drug product produced. Specifically, *** The suitability of all testing methods is not verified under actual conditions of use. Specifically, ***

The quality control unit lacks the responsibility and authority to [approve] [reject] all [components] [drug product containers] [closures] [in process materials] [packaging material] [labeling] [drug products]. Specifically, *** Actual yield and percentages of theoretical yield are not determined at the conclusion of each appropriate phase of [manufacturing] [processing] [packaging] [holding] of the drug product. Specifically, *** Procedures prescribing a system for reprocessing batches to insure that the reprocessed batches will conform with all established standards, specifications, and characteristics are not [written] [followed]. Specifically, *** The drug product is not identified with a lot or control number that permits the determination of the history of the manufacture and control of the batch. Specifically, ***

Procedures for the preparation of master production and control records are not [described in a written procedure] [followed]. Specifically, ***

Written calibration procedures for instruments, apparatus, gauges, and recording devices are deficient in that they do not include specific [directions] [schedules] [limits for accuracy and precision] [provisions for remedial action if limits are not met]. Specifically, *** Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality. Specifically, ***

Batch production and control records for each batch of drug product produced do not include an accurate reproduction of the appropriate master production or control record which was checked for accuracy, dated and signed. Specifically, ***

An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning [bacteriological contamination] [significant chemical, physical, or other change or deterioration] in a distributed drug product. Specifically, ***

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Drugs

Adequate lab facilities for testing and approval or rejection of [components] [drug product containers] [closures] [packaging materials] [in-process materials] [drug products] are not available to the quality control unit. Specifically, *** There is a lack of written procedures describing in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of labeling and packaging materials. Specifically, *** Drug products are not quarantined before being released by the quality control unit. Specifically, ***

The distribution system is deficient in that each lot of drug product cannot be readily determined to facilitate its recall if necessary. Specifically, ***

Incoming [components] [drug product containers] [closures] are not stored under quarantine until they have been tested or examined, as appropriate, and released. Specifically, ***

Records fail to include an individual inventory record of each [component] [reconciliation of the use of each component] [drug product container] [drug product closure] with sufficient information to allow determination of any associated batch or lot of drug product. Specifically, *** Laboratory records do not include complete records of all stability testing performed. Specifically, ***

Complaint procedures are deficient in that they do not include provisions that allow for the review to determine if the complaints represent [serious] [unexpected adverse drug experiences] which are required to be reported to FDA. Specifically, *** Washing and toilet facilities lack [hot and cold water] [soap or detergent] [air driers or single-service towels] [cleanliness]. Specifically, ***

Failure to reject any lot of [components] [drug product containers] [closures] that did not meet the appropriate written specifications for identity, strength, quality, and purity. Specifically, *** Batch production and control records do not include the identity of individual major [equipment] [lines] used for each batch of drug product produced. Specifically, ***

The quality control unit lacks responsibility for approving or rejecting drug products [manufactured] [processed] [packed] [held] under contract by another company. Specifically, ***

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Drugs

Reprocessing was performed without the [review] [approval] of the quality control unit. Specifically, ***

Labeling and packaging materials not meeting the appropriate written specifications were [approved] [released for use]. Specifically, ***

Records associated with drug product [components] [containers] [closures] [labeling] [production] [control] [distribution] and within the retention period for such records, were not made readily available for authorized inspection. Specifically, *** Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production. Specifically, ***

The plumbing system contains defects that could contribute to the contamination of drug products. Specifically, ***

Reserve drug product samples are not [appropriately identified] [representative of each lot or batch of drug product] [retained and stored under conditions consistent with product labeling]. Specifically, *** Each lot of a [component] [drug product container] [closure] that is liable to microbiological contamination that is objectionable in view of its intended use is not subjected to microbiological tests before use. Specifically, *** Samples taken of drug products for determination of conformance to written specifications are not [representative] [properly identified]. Specifically, ***

Laboratory records do not include [a description of the sample received for testing] [the source or location from where the sample was obtained] [the quantity of the sample] [the lot number or other distinctive code of the sample] [the date the sample was taken] [the date the sample was received for testing]. Specifically, *** Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of post marketing adverse drug experiences. Specifically, ***

Clothing of personnel engaged in the [manufacturing] [processing] [packing] [holding] of drug products is not appropriate for the duties they perform. Specifically, ***

Protective apparel is not worn as necessary to protect drug products from contamination. Specifically, ***

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Drugs

Master production and control records lack a statement of theoretical yield [including the maximum and minimum percentages of theoretical yield beyond which investigation is required]. Specifically, *** Each component is not added to a batch by one person and verified by a second person. Specifically, ***

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the [room] [equipment] to produce aseptic conditions. Specifically, ***

Approved [components] [drug product containers] [closures] are not retested or reexamined as appropriate for identity, strength, quality and purity after [storage for long periods] [exposure to conditions that might have an adverse effect] with subsequent approval or rejection by the quality control unit. Specifically, *** Each container or grouping of containers of [components] [drug product containers] [closures] is not examined visually upon receipt and before acceptance for [appropriate labeling as to contents] [container damage] [broken seals] [contamination]. Specifically, *** The written stability program for drug products does not include [sample size] [test intervals] based on statistical criteria for each attribute examined to assure valid estimates of stability. Specifically, *** Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed]. Specifically, ***

The batch production and control records are deficient in that they do not include [complete labeling control records] [specimen] [copy] of labeling. Specifically, ***

Written procedures are lacking for the use of [rodenticides] [insecticides] [fungicides] [fumigating agents] [cleaning and sanitizing agents] designed to prevent the contamination of [equipment] [components] [drug product containers] [closures] [packaging, labeling materials] [drug products]. Specifically, *** A written record of the program along with appropriate validation data has not been maintained in situations where backup data is eliminated by computerization or other automated processes. Specifically, *** Containers are not [opened] [sampled] [resealed] in a manner designed to prevent contamination of [their contents] [other components] [other drug product containers or closures]. Specifically, *** Containers from which samples have been taken are not marked to show that samples have been taken from them. Specifically, ***

Page 128

Drugs

Reprocessing procedures lack the steps to be taken to insure that reprocessed batches will conform with all established standards, specifications, and characteristics. Specifically, ***

Control procedures fail to include [tablet or capsule weight variation] [disintegration time] [adequacy of mixing to assure uniformity and homogeneity] [dissolution time and rate] [clarity, completeness or pH of solutions]. Specifically,*** Written procedures for the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of packaging and labeling materials are not followed. Specifically, ***

Written procedures for sampling and testing plans are not followed for each drug product. Specifically, ***

Batch production and control records do not include a record of any sampling performed, for each batch of drug product produced. Specifically, ***

Laboratory records do not include a record of all calculations performed in connection with the test. Specifically, ***

Serious adverse event(s) for a non-prescription drug used in the United States has not been reported to the Secretary. Specifically, ***

Production personnel were not practicing good sanitation and health habits. Specifically, ***

Records are not maintained stating the consultant's [name] [address] [qualifications] [type of service provided]. Specifically, ***

Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality. Specifically, ***

Batch production and control records do not include [inprocess] [laboratory control] results for each batch of drug product produced. Specifically, ***

The written record did not include the [reason an investigation was found not to be necessary] [name of the responsible person making the determination not to conduct an investigation] when an investigation into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications] was not conducted. Specifically, ***

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Drugs

Written procedures describing the handling of complaints do not include provisions for [review by the quality control unit of any complaint involving the possible failure of a drug product to meet any of its specifications] [a determination as to the need for an investigation of any unexplained discrepancy] [explaining the reasons for the failure of the batch or any of its components to meet specifications]. Specifically, *** Procedures for the cleaning and maintenance of equipment are deficient regarding the removal or obliteration of the previous batch identification. Specifically, ***

Failure to maintain a backup file of data entered into the computer or related system. Specifically, ***

The operations relating to the [manufacture] [processing] [packing] of penicillin are not performed in facilities separate from those used for other drug products for human use. Specifically, *** Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions. Specifically, ***

Deviations from production time limits [are not justified] [are not documented] [compromise the quality of the drug product]. Specifically, ***

Labeling and packaging materials are not [representatively sampled] [examined] [tested] upon receipt and before use in packaging and labeling of a drug product. Specifically, ***

Filled drug product containers which are set aside and held in an unlabeled condition are not [identified] [handled] to preclude mislabeling of individual containers, lots or portions of lots. Specifically, *** Examination of packaging and labeling materials for suitability and correctness before packaging operations is [not performed] [not documented in the batch production records]. Specifically, *** Inspection of the [packaging] [labeling] facilities immediately before use is not done to assure that all drug products have been removed from previous operations. Specifically, ***

Inspection of the [packaging] [labeling] facilities is not done after use to assure that materials not suitable for subsequent operations have been removed. Specifically, ***

The results of the examination of the packaged and labeled products were not documented in the batch production or control records. Specifically, ***

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Drugs

Drug product [containers] [closures] were not [clean] [sterilized and processed to remove pyrogenic properties] to assure that they are suitable for their intended use. Specifically, ***

All records of [production] [control] [distribution] [components] [drug product containers] [closures] [labeling] associated with a batch of drug product are not maintained at least one (1) year after the expiration date. Specifically, *** The written stability program for drug products does not describe the storage conditions for samples retained for testing. Specifically, ***

The procedures for the annual quality standards record evaluation are deficient in that they do not address a review of [complaint] [recall] [returned drug product] [salvaged drug product] [investigation] records for each drug product. Specifically, *** The records of [cleaning] [maintenance] [use] for dedicated equipment are not part of the batch record. Specifically, ***

The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in [manufacturing] [processing] [packing] [holding]. Specifically, *** The batch production and control records are deficient in that they do not include [in-process] [laboratory] control results. Specifically, ***

The batch production and control records are deficient in that they do not include a description of drug product containers and closures. Specifically, ***

The master production and control records are deficient in that they do not include a statement of theoretical yield and [minimum] [maximum] [yield percentages]. Specifically, ***

Laboratory records are deficient in that they do not include all calculations performed during testing. Specifically, ***

Complaint records are deficient in that they do not document the reason and the individual making the decision not to conduct a complaint investigation. Specifically, ***

In-process materials are not tested for [identity] [strength] [quality] [purity] and approved or rejected by the quality control unit [during the production process] [after storage for long periods]. Specifically, ***

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Drugs

Rejected in-process materials are not [identified] [controlled under a quarantine system] to prevent their use in manufacturing or processing operations for which they are unsuitable. Specifically, *** Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for drug products. Specifically, ***

A sample which is representative of each lot in each shipment of each active ingredient is not [appropriately identified] [retained]. Specifically, ***

Procedures describing the [holding] [testing] [reprocessing] of returned drug products are not [in writing] [followed]. Specifically, ***

Records of returned drug products do not include the [name] [labeled potency] [lot, control or batch number] [reason for return] [quantity] [date of disposition] [ultimate disposition]. Specifically, *** Written procedures for sanitation are not followed. Specifically, ***

Containers and closures are not tested for conformance with all appropriate written procedures. Specifically, ***

Certificates of testing of [containers] [closures] are accepted in lieu of testing without [a visual identification] [establishing the reliability of the supplier's test results through appropriate validation of the test results at appropriate intervals]. Specifically, *** Each container of component dispensed to manufacturing is not examined by a second person to assure that [the component was released by the quality control unit] [the weight or measure is correct as stated in the batch records] [the containers are properly identified]. Specifically, *** Samples taken of in-process materials for determination of conformance to specifications are not [representative] [properly identified]. Specifically, ***

Records maintained of any modification of an established method employed in testing do not include [the reason for the modification] [the data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method]. Specifically, *** Laboratory records do not include [the initials or signature of the person who performs each test] [the date(s) the tests were performed]. Specifically, ***

Page 132

Drugs

Follow-up reports were not submitted [within 15 calendar days of receipt of new information] [as requested by FDA] concerning post marketing 15-day reports. Specifically, ***

Not all periodic reports contained [a narrative summary and analysis of the information in the report] [an analysis of the post marketing 15-day Alert reports submitted during the reporting interval] [an FDA Form 3500A for each adverse drug experience not reported as a post marketing 15-day Alert report] [an index containing a line listing of your patient identification number and adverse reaction term(s)] [a history of actions taken since the last report because of adverse drug experiences]. Specifically, *** Substances required for equipment operations such as lubricants and coolants come in contact with [components] [drug product containers] [closures] [in-process materials] [drug product] so as to alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements. Specifically, *** Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed. Specifically,***

Drug product containers or closures are [reactive] [additive] [absorptive] so as to alter the safety, identity, strength, quality, and purity of the drug beyond the official or established requirements. Specifically, *** Batch production and control records do not include the weights and measures of components used in the course of processing each batch of drug product produced. Specifically, ***

Written records of investigation of a drug complaint do not include [the findings of the investigation] [the follow-up]. Specifically, ***

Written complaint records do not include, where known, [the name and strength of the drug product] [lot number] [name of complainant] [nature of complaint] [reply to complainant]. Specifically, *** Written complaint file records involving a drug product are not maintained until at least 1 year after the expiration date of the drug product, or 1 year after the date the complaint was received, whichever is longer. Specifically, *** Written procedures describing the handling of all written and oral complaints do not include provisions for review to determine whether the complaint represents a serious and unexpected adverse drug experience which is required to be reported to the Food and Drug Administration. Specifically, ***

Page 133

Drugs

The master production and control records indicate unjustified variations in the amount of components necessary for preparation of the dosage form. Specifically, ***

Procedures for the cleaning and maintenance of equipment are deficient regarding sufficient detail of the methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance. Specifically, ***

Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use. Specifically, ***

Yield calculations are not performed by one person and independently verified by a second person. Specifically, ***

Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the holding of rejected [components] [drug product containers] [closures] [labeling] before disposition. Specifically,*** Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products. Specifically,***

Aseptic processing areas are deficient in that [floors] [walls] [ceilings] are not smooth and/or hard surfaces that are easily cleanable. Specifically,***

Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure. Specifically, ***

Labeling materials issued for a batch were not carefully examined for identity and conformity to the labeling specified in the master or batch production records. Specifically, ***

Excess labeling bearing lot or control numbers is not destroyed. Specifically, ***

There is insufficient physical or spatial separation from operations and other drug products to prevent mix-ups and cross-contamination. Specifically, ***

Packaged and labeled products are not examined during finishing operations to provide assurance that containers and packages in the lot have the correct label. Specifically, ***

Page 134

Drugs

Drug product expiration dates do not appear on the labeling in the manner prescribed by regulations.. Specifically, ***

The distinctive code for each lot of [components] [drug product containers] [closures] is not used in recording the disposition of each lot. Specifically, ***

The written stability program does not assure testing of the drug product in the same container-closure system as that in which the drug product is marketed. Specifically, ***

Accelerated stability studies, combined with basic stability information, used to support tentative expiration dates are not supported with ongoing full shelf life studies. Specifically, ***

There is no documentation of the examination and review of labels and labeling for conformity with [established specifications] [the assigning of a lot or control number]. Specifically, *** The batch production and control records are deficient in that they do not include a statement of the [actual yield] [percentage of theoretical yield]. Specifically, ***

The master production and control records are deficient in that they lack a justification for the variation in the amount of components used in the preparation of a dosage form. Specifically, *** Verification of the suitability of the testing methods is deficient in that they are not [performed under actual conditions of use] [documented on the laboratory records]. Specifically, ***

Complaint records are deficient in that they do not include the known [name and strength of the drug product] [lot number] [name of complainant] [nature of complaint] [reply to complainant]. Specifically, *** Equipment surfaces that contact [components] [in-process materials] [drug products] are reactive, additive or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. Specifically, *** Adequate lighting is not provided in all areas. Specifically, ***

The production area air supply lacks an appropriate air filtration system. Specifically, ***

Page 135

Drugs

Air-handling systems for the [manufacture] [processing] [packing] of penicillin are not completely separate from those for other drug products for human use. Specifically, ***

Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis. Specifically, ***

Rejected [components] [drug product containers] [closures] are not controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable. Specifically, *** In-process specifications are not [consistent with drug product final specifications] [derived from previous acceptable process average and process variability estimates where possible] [determined by the application of suitable statistical procedures where appropriate]. Specifically, *** Test devices are deficient in that [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications are used. Specifically, ***

Examination and testing of samples is not done to assure that in-process materials conform to specifications. Specifically, ***

Written specifications for laboratory controls do not include a description of the [sampling] [testing] procedures used. Specifically, ***

Samples taken to determine conformance to appropriate written specifications for the acceptance of each lot within each shipment of [components] [drug product containers] [closures] [labeling] are not [representative] [adequately identified]. Specifically, *** Laboratory controls do not include a determination of conformance to [written descriptions of sampling procedures] [appropriate specifications] for drug products. Specifically, ***

Reserve samples for [active ingredients] [drug products] are not retained for one year after the expiration date of the drug product.

Non-penicillin drug products were not tested for the presence of penicillin, when a reasonable possibility existed that a nonpenicillin drug product has been exposed to a crosscontamination with penicillin. Specifically, *** Laboratory records of methods of testing used do not [indicate the method] [provide the reference] when employing methods in [recognized standard references] [an approved new drug application and the referenced method is not modified]. Specifically, ***

Page 136

Drugs

Laboratory records do not include a complete record of all data secured in the course of each test, including all [graphs] [charts] [spectra] from laboratory instrumentation, properly identified to show the [specific component] [drug product container] [closure] [in-process material] [lot tested] [drug product tested]. Specifically, *** Laboratory records do not include a statement of the results of tests and how the results compare with established standards of identity, strength, quality, and purity for the [component] [drug product container] [closure] [in-process material] [drug product] tested. Specifically, *** Returned drug products held, stored or shipped before or during their return under conditions which cast doubt on their safety, identity, strength, quality or purity are not [destroyed] [subjected to examination, testing or other investigation to prove the drug products do meet all the necessary parameters]. Specifically, *** An annual report was not submitted [each year] [within 60 days of the anniversary date of U.S. approval of the application] to the FDA division responsible for reviewing the application. Specifically, *** Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application. Specifically, ***

Consultants lack sufficient education, training and experience to advise on the subject for which they are retained. Specifically, ***

The flow of [components] [drug product containers] [closures] [labeling] [in-process materials ] [drug products] though the building is not designed to prevent contamination. Specifically, *** Establishment of the reliability of the [container] [closure] supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals. Specifically, *** Each lot of a [component] [drug product containers] [closures] liable to objectionable microbiological contamination is deficiently subjected to microbiological tests before use. Specifically, *** A written record of each complaint is not maintained in a file designated for drug product complaints [at the facility where the drug product was manufactured, processed or packed] [at a facility other than the facility in which the drug product was manufactured, processed or packed provided the written records are readily available for inspection at that other facility]. Specifically, *** The master production and control records do not include [the name and strength of the product] [a description of the dosage form]. Specifically, ***

Page 137

Drugs

The master production and control records do not include a complete list of components [designated by names or codes sufficiently specific to indicate any special quality characteristics]. Specifically, *** The master production and control records lack an accurate statement of the [weight] [measure] of each component [using the same weight system for each component]. Specifically, ***

Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use. Specifically, ***

Written production and control procedures include batches formulated with the intent to provide less than 100 percent of the labeled or established amount of active ingredient. Specifically, *** Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of inprocess materials. Specifically, ***

Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations. Specifically, ***

Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the quarantine storage of drug products prior to release. Specifically, ***

Aseptic processing areas are deficient regarding [temperature] [humidity] controls. Specifically, ***

Records are not maintained for each shipment received of each different labeling and packaging material. Specifically, ***

Obsolete or outdated labels, labeling and packaging materials are not destroyed. Specifically, ***

Printing devices used to imprint labeling upon the drug product [unit label] [case] are not monitored to assure that all imprinting conforms to the print specified in the batch production record. Specifically, *** Discrepancies found outside preset limits when reconciling the quantities of labeling issued, used and returned, were not [evaluated] [investigated]. Specifically, ***

Page 138

Drugs

Samples of representative units were not [collected] [visually examined] for correct labeling at the completion of finishing operations. Specifically, ***

There is a lack of rotation so that the oldest approved stock of [components] [drug product containers] [closures] is used first. Specifically, ***

Bagged or boxed components of drug product [containers] [closures] are not [stored off the floor] [suitably spaced to allow cleaning and inspection]. Specifically, ***

Each batch of drug product purporting to be [sterile] [pyrogenfree] is not laboratory tested to determine conformance to such requirements. Specifically, ***

Test procedures describing the testing of controlled release dosage form drug product are not [written] [followed]. Specifically, ***

Procedures are not established which are designed to assure that the responsible officials of the firm, if they are not personally involved in or immediately aware of such actions, are notified in writing of [investigations conducted] [recalls] [reports of inspectional observations issued by FDA] [any regulatory actions brought by FDA relating to good manufacturing practices]. Specifically, *** The entries in the equipment cleaning and use logs are not in chronological order. Specifically, ***

The [component] [drug product container] [closure] [labeling] records do not include the [results of tests or examinations performed] [the conclusions derived from tests or examinations performed]. Specifically, *** Records do not include the disposition of rejected [components] [drug product containers] [closures] [labeling]. Specifically, ***

The batch production and control records are deficient in that they are not [an accurate reproduction of the appropriate master production or control record] [checked for accuracy, dated, and signed]. Specifically, *** The batch production and control records are deficient in that they do not include the identity of major [equipment] [lines] used. Specifically, ***

The batch production and control records are deficient in that they do not include specific identification of each [batch of component] [in-process material] used. Specifically, ***

Page 139

Drugs

The batch production and control records are deficient in that they do not include [weights] [measures] of components used in the process. Specifically, ***

The batch production and control records are deficient in that they do not include documentation of sampling performed. Specifically, ***

The batch production and control records are deficient in that they do not include identification of persons [performing] [supervising] [checking] each significant step in the operation. Specifically, *** The batch production and control records are deficient in that they do not include documentation of batch investigations performed. Specifically, ***

Complete records are not maintained of any modification of an established method employed in testing. Specifically, ***

Laboratory records are deficient in that they do not include a [description and identification of the sample received] [quantity] [lot number] [date sample taken] [date sample received for testing]. Specifically, *** Laboratory records are deficient in that they do not include a complete record of all data obtained during testing. Specifically, ***

Complaint procedures are deficient in that they do not include provisions that allow for the review and determination of an investigation by the quality control unit. Specifically, ***

The potable water being permitted for use in the potable water system fails to meet standards prescribed by the Environmental Protection Agency. Specifically, ***

Drains are not [of adequate size] [provided with an air break or other mechanical device to prevent back-siphonage where connected directly with a sewer]. Specifically, ***

Disposal of [sewage] [trash] [refuse] from the [building] [immediate premises] is not done in a safe and sanitary manner. Specifically, ***

Washing and toilet facilities are not [provided] [easily accessible to working areas]. Specifically, ***

Page 140

Drugs

Components for drug product manufacturing are not [weighed] [measured] [subdivided as appropriate]. Specifically, ***

Each component is not added to the batch by one person and verified by a second person.. Specifically, ***

The in process control procedures were deficient in that they did not include an examination of the adequacy of mixing to assure uniformity and homogeneity. Specifically, ***

The specifications for components, drug product containers or closures and labeling are deficient in that they do not include a description of the [sampling plan] [testing procedures]. Specifically, *** The specifications for [components] [drug product containers] [closure] are deficient in that they do not include appropriate retesting requirements. Specifically, ***

In-process samples are not [representative] [properly identified]. Specifically, ***

Drug product samples are not [representative of the entire batch] [properly identified]. Specifically, ***

Drug product reserve samples are not stored in [the same immediate container-closure system as the marketed product] [an immediate container-closure system that has essentially the same characteristics as the marketed product]. Specifically, *** Evidence of reserve drug product sample deterioration was not [investigated] [recorded and maintained with other stability data]. Specifically, ***

The retention period for drug product reserve samples (except those described in 211.170(b)(2) and (3)) is deficient in that they are not retained for one year after the expiration date of the drug product. Specifically, *** Returned drug products are not [identified as such] [held]. Specifically, ***

Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems. Specifically, ***

Page 141

Drugs

Written [standards or specifications] [methods of testing] [methods of cleaning] [methods of sterilizing] [methods of processing] to remove pyrogenic properties of drug product containers and closures are not followed. Specifically, *** Components are not microscopically examined when appropriate. Specifically, ***

Each lot of [components] [drug product containers] [closures] that is liable to contamination with filth, insect infestation or other extraneous adulterants is not examined against established specifications for such contamination. Specifically, *** For components removed from the original containers, the new container fails to be identified with [component name or item code] [receiving or control number] [weight or measure] [batch for which component was dispensed including product name, strength and lot number]. Specifically, *** Records kept for each different labeling and packaging material shipment fail to include [the receipt] [results of examination or testing] [a statement of whether the shipment was accepted or rejected]. Specifically, *** Laboratory controls do not include determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] used in the manufacture, processing, packing, or holding of drug products. Specifically, *** Laboratory controls do not include a description of [sampling] [testing] procedures for in-process materials. Specifically, ***

The statistical quality control criteria fail to include appropriate [acceptance levels] [rejection levels]. Specifically, ***

Where data from accelerated studies was used to project a tentative expiration date beyond a date supported by actual shelf life studies, there were no [stability studies] [drug product testing at appropriate intervals] conducted until the tentative expiration date was verified or the appropriate expiration date determined. Specifically, *** The reserve sample of drug product does not consist of at least twice the quantity necessary to perform all the required tests of drug product. Specifically, ***

Reserve samples for [active ingredients in OTC drug products] [OTC drug products] which are exempt from bearing an expiration date are not retained for 3 years after the lot or batch of drug product is distributed. Specifically, ***

Page 142

Drugs

Batch production and control records do not include results of the inspection of the packaging and labeling area [before] [after] use for each batch of drug product produced. Specifically, ***

Laboratory records do not include a statement of [each method used in the testing of a sample] [the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested]. Specifically, *** Returned drug products were reprocessed without assuring that the subsequent drug product met the appropriate standards of safety, identity, strength, quality and purity. Specifically, ***

No appropriate investigation was conducted when a returned drug product appeared to implicate associated batches of drug products. Specifically, ***

An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning an incident that caused a drug product or its labeling to be [mistaken for] [applied to] another article. Specifically, *** An annual report did not include [a brief summary of significant new information from the previous year that might affect the safety, effectiveness, or labeling of the drug product] [a brief description of actions the applicant has taken or intends to take as a result of this new information] [a brief description of actions the applicant has taken or intends to take as a result of new information from the previous year that might affect the safety, effectiveness, or labeling of the drug product] [a brief statement whether labeling supplements for pediatric use have been submitted and whether new studies in the pediatric population have been initiated]. Specifically, ***

An annual report did not include [currently used professional labeling] [patient brochures or package inserts] [a representative sample of the package labels] [a summary of any changes in labeling that have been made since the last report, listed by date in the order in which they were implemented, or if no changes, a statement of that fact]. Specifically, *** An annual report did not include reports of [experiences] [investigations] [studies] [tests] involving [chemical or physical properties] [properties of the drug] which, as new information, might affect FDA's previous conclusions about the safety or effectiveness of the drug. Specifically, *** An annual report did not include [summaries] [prepublication manuscripts] of completed, unpublished clinical trials conducted by, or otherwise obtained by, the applicant. Specifically, ***

Page 143

Drugs

Postmarketing 15-day Alert reports have been submitted to FDA, but not to FDA's Division of Pharmacovigilance and Epidemiology. Specifically, ***

Adverse drug experience information obtained or otherwise received from any source was not [promptly] reviewed, including information from [commercial marketing experience] [post marketing clinical investigations] [post marketing epidemiological/surveillance activities] [reports in the scientific literature] [unpublished scientific papers]. Specifically, ***

Adverse drug experience information has not been reported to FDA. Specifically, ***

You, as a non-applicant, elected to submit to the applicant (rather than to FDA) all reports of adverse drug experiences that were both serious and unexpected. However, you did not submit each report to the applicant [within five calendar days of your receipt of the information]. Specifically, *** Individual ADEs which were not reported to FDA in a post marketing 15-day alert have not been included in a periodic safety report. Specifically, ***

Periodic reports of non-alert adverse drug experiences have not been submitted [quarterly for an application which was approved less than three years ago] [yearly for an application which was approved three or more years ago]. Specifically, *** Not all quarterly periodic adverse drug experience reports have been submitted within 30 days of the close of the quarter. Specifically, ***

An FDA Form 3500A has not been completed for each report of a domestic adverse drug experience. Specifically, ***

An FDA Form 3500A or CIOMS I form has not been completed for each report of a foreign adverse drug experience. Specifically, ***

An annual report did not include a status report for all post marketing studies being performed by, or on behalf of, the applicant and not covered by the requirements of 21 CFR 314.81(b)(2)(vii). Specifically, *** Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of postmarketing adverse drug experiences. Specifically, ***

Page 144

Foods

Center Name

Cite Id

Ref No

'ShortDesc

Foods

1560 21 CFR 110.35(c)

Lack of effective pest exclusion

1524 21 CFR 123.11(b)

Sanitation monitoring

905 21 CFR 123.6(b)

HACCP plan implementation

1306 21 CFR 110.20(b)(7)

Screening

1422 21 CFR 110.20(b)(4)

Floors, walls and ceilings

1552 21 CFR 110.35(a)

Buildings/sanitary

1287 21 CFR 110.20(a)(1)

Harborage areas

1553 21 CFR 110.35(a)

Buildings/good repair

1525 21 CFR 123.11(c)

Sanitation Records

1554 21 CFR 110.35(a)

Cleaning and sanitizing operations

Page 145

Foods

990 21 CFR 110.10(b)(3)

Not washed/sanitized when appropriate

1695 21 CFR 110.80(b)(2)

Manufacturing conditions

6004 21 CFR 123.6(c)(4)

Monitoring - adequacy

904 21 CFR 123.6(b)

No HACCP plan

1701 21 CFR 110.80(b)(7)

Equipment, containers, utensils

1405 21 CFR 110.10(b)(6)

Failure to wear

1427 21 CFR 110.20(b)(5)

Safety lighting and glass

2386 21 CFR 110.80(a)(1)

Storage

960 21 CFR 123.6(c)(2)

Critical control points

1007 21 CFR 110.10(b)(9)

Precautions against contamination-micro, foreign substances

959 21 CFR 123.6(c)(1)

Food safety hazards

963 21 CFR 123.6(c)(5)

Corrective action plan

908 21 CFR 123.6(d)

Signed and dated

Page 146

Foods

961 21 CFR 123.6(c)(3)

Critical limits

1689 21 CFR 110.80

Reasonable precautions

1562 21 CFR 110.35(d)

Failure to clean - general

1556 21 CFR 110.35(b)(2)

Storage requirements

1424 21 CFR 110.20(b)(4)

Drip and condensate

6008 21 CFR 123.8(a)(3)

Verification - record review - frequency

1292 21 CFR 110.20(b)(1)

Sufficient space

2392 21 CFR 110.80(b)(1)

Maintenance of equip., utensils, and finished food packaging

1597 21 CFR 110.37(b)(3)

As source of contamination

1615 21 CFR 110.93

Storage/transportation of finished goods (contamination)

1581 21 CFR 110.37(e)

Running water at suitable temperature

6001 21 CFR 123.11(b)

Sanitation monitoring documentation

945 21 CFR 123.12(a)(2)

Importer verification

Page 147

Foods

1005 21 CFR 110.10(b)(7)

Storage of personal items

1125 21 CFR 110.40(a)

Materials and workmanship

1006 21 CFR 110.10(b)(8)

Personal food/drink/tobacco

1066 21 CFR 110.40(b)

Seams on food contact surfaces

3659 21 CFR 110.37(e)(3)

Hand drying

6020 21 CFR 123.9(a)

Records - content

3661 21 CFR 110.37(e)(5)

Signs

985 21 CFR 110.10(b)(1)

Suitable outer garments

1126 21 CFR 110.40(a)

Precluding contaminants

1565 21 CFR 110.35(d)(3)

Non-food-contact surfaces (S)

3658 21 CFR 110.37(e)(2)

Hand cleaning and sanitizing preparations

933 21 CFR 123.8(a)(2)(ii)

Calibration - adequacy

1402 21 CFR 110.10(b)(4)

Unsecured jewelry

Page 148

Foods

3652 21 CFR 110.37(e)(1)

Suitable locations

6021 21 CFR 123.10

HACCP training or qualification

12720 21 CFR 1.225

Not registered

1429 21 CFR 110.20(b)(6)

Fans/air blowing equipment

1698 21 CFR 110.80(b)(5)

Work-in-progress

1172 21 CFR 110.40(e)

Lack of thermometer

1173 21 CFR 110.40(f)

Q.C. instrument accuracy, maintenance

6005 21 CFR 123.6(c)(6)

Verification procedures - adequacy

1571 21 CFR 110.35(d)(5)

Shown to be effective

1578 21 CFR 110.37(f)

Odor, attractant for pests, harborage

901 21 CFR 123.6(a)

Hazard analysis

1406 21 CFR 110.10(b)(6)

Effective use of hair restraint

1598 21 CFR 110.37(b)(4)

Drainage

Page 149

Foods

1599 21 CFR 110.37(b)(5)

Backflow prevention

906 21 CFR 123.6(b)

HACCP plan location

1067 21 CFR 110.40(c)

Non food-contact equipment in processing area

1426 21 CFR 110.20(b)(5)

Adequate lighting

3643 21 CFR 110.10(b)(5)

Glove condition

6018 21 CFR 123.7(a)

Corrective action per predetermined plan

1702 21 CFR 110.80(b)(8)

Metal / extraneous materials

9931 21 CFR 120.6(b)

Sanitation monitoring

1696 21 CFR 110.80(b)(3)

Holding foods - refrigerate/freeze/heat

4470 21 CFR 108.25(c)(2)

Process filing

3656 21 CFR 110.37(d)(3)

Self-closing doors

Page 150

Foods

6007 21 CFR 123.9(a)

Records entries - timing

1293 21 CFR 110.20(b)(2)

Contamination with microorganisms, chemicals, filth, etc.

1709 21 CFR 110.80(b)(13)

Filling, assembling, packing controls

1596 21 CFR 110.37(b)(2)

Convey sewage

1570 21 CFR 110.35(d)(5)

Safe and adequate for use

913 21 CFR 123.8(a)(1)

Reassessment of HACCP plan

6015 21 CFR 123.6(c)(6)

Verification procedures none/frequency

1602 21 CFR 110.37(a)

Suitable temp. and pressure

2388 21 CFR 110.80(a)(5)

Holding in bulk or suitable containers

3654 21 CFR 110.37(d)(1)

Maintained

931 21 CFR 123.8(d)

Verification - recordkeeping

1763 21 CFR 110.35(b)(1)

Safe and adequate for use

6006 21 CFR 123.6(c)(7)

Records values/observations

Page 151

Foods

918 21 CFR 123.8(a)

Verification - reviewers qualifications

1128 21 CFR 110.40(a)

Installation and maintenance of equipment (S)

3080 21 CFR 114.83

Scheduled process establishment

6010 21 CFR 123.8(a)(3)(i)

Monitoring record review adequacy

1289 21 CFR 110.20(a)(3)

Drainage

6019 21 CFR 123.8(a)(2)

Ongoing verification - complaints, calibration records

3086 21 CFR 114.100(b)

Maintenance of processing and production records

2393 21 CFR 110.80(b)(1)

Teardown equipment/thorough cleaning

1132 21 CFR 110.40(a)

Food-contact - unlawful indirect additives

3647 21 CFR 110.10(c)

Training of handlers and supervisors

9930 21 CFR 120.6(c)

SSOP records

1403 21 CFR 110.10(b)(4)

Hand jewelry - remove/cover

1130 21 CFR 110.40(a)

Food-contact - withstand food & cleaning cmpds.

Page 152

Foods

1425 21 CFR 110.20(b)(4)

Spacing of equipment

3073 21 CFR 114.80(a)(2)

pH testing

1090 21 CFR 110.40(d)

Holding, conveying, mfg systems design & construction

2361 21 CFR 110.80

Testing

2384 21 CFR 110.80(a)(7)

Receipt/storage - liquid and dry raw materials

3655 21 CFR 110.37(d)(2)

Good repair

6009 21 CFR 123.8(a)(3)(iii)

Verification - record review calibration

1184 21 CFR 110.35(e)

Storage of cleaned portable equipment (S)

932 21 CFR 123.7(d)

Corrective action documentation

1129 21 CFR 110.40(a)

Food-contact - corrosion resistant

3071 21 CFR 114.80(a)(1)

Scheduled process

3078 21 CFR 114.80(b)

Code - required elements

3712 21 CFR 110.93

Storage/transportation of finished goods (deterioration)

Page 153

Foods

12742 21 CFR 120.8(a)

HACCP plan not implemented

2385 21 CFR 110.80(a)(1)

Inspection, segregation, handling of raw materials

2396 21 CFR 110.80(b)(6)

Conveyor transportation

3657 21 CFR 110.37(d)(4)

Doors opening into processing areas

9941 21 CFR 120.8(a)

No HACCP plan

1561 21 CFR 110.35(c)

Insecticides/rodenticides

4479 21 CFR 108.25(e)

Recall procedures

6016 21 CFR 123.6(c)(7)

Records system

9947 21 CFR 120.11(b)

HACCP plan - not validated

986 21 CFR 110.10(b)(2)

Personal cleanliness

3660 21 CFR 110.37(e)(4)

Devices and fixtures

9954 21 CFR 120.11(a)(1)(iv)

Verification - CCP, CA record review

2394 21 CFR 110.80(b)(6)

Contamination by raw materials, refuse, other ingredients

Page 154

Foods

3085 21 CFR 114.100(a)

Raw materials, packaging, finished product

1642 21 CFR 113.100(b)

Review not signed/dated

1766 21 CFR 110.35(b)(1)

Unacceptable toxic compounds

3662 21 CFR 110.37(e)(6)

Refuse receptacles

4181 21 CFR 113.89

Process deviation identification

4421 21 CFR 110.20(a)

Maintenance of grounds

6022 21 CFR 123.12(c)

Lack of records

9935 21 CFR 120.7(a)

No hazard analysis

9939 21 CFR 120.7(c)

All hazards not considered

1577 21 CFR 110.37(f)

Contamination of food, contact surfaces, water supplies, etc

1708 21 CFR 110.80(b)(12)

Batters, breading, gravies, sauces, etc.

3075 21 CFR 114.80(a)(4)

Container testing

Page 155

Foods

6014 21 CFR 123.6(c)(2)

Monitoring - none

6017 21 CFR 123.7(c)

Corrective action per regulation

9955 21 CFR 120.11(a)(1)

Verification activities - minimum

12745 21 CFR 120.8(b)(1)

HACCP plan - food hazards not listed

12747 21 CFR 120.8(b)(3)

HACCP plan - critical limits not listed or not adequate

12721 21 CFR 1.234

Registration not updated

3645 21 CFR 110.10(d)

Supervision

15858 21 CFR 111.75(a)(1)(i)

Component - verify identity, dietary ingredient

15927 21 CFR 111.103

Written procedures - quality control operations

1288 21 CFR 110.20(a)(2)

Roads/yards/parking lots

1566 21 CFR 110.35(d)(4)

Single-service articles

3082 21 CFR 114.89

Process deviation

Page 156

Foods

4515 21 CFR 108.35(c)(2)

Process filing

9958 21 CFR 120.12(c)

Records - signed/dated

12734 21 CFR 120.12(a)

Records required - not maintained

12744 21 CFR 120.8(b)(4)

HACCP plan - monitoring procedures none listed

12746 21 CFR 120.8(b)(2)

HACCP plan - critical control points not listed

12755 21 CFR 120.11(a)(1)(iv)

Records - not signed and dated by qualified individual

12755 21 CFR 120.11(a)(1)(iv)

Records - not signed and dated by qualified individual

15797 21 CFR 111.553

Written procedures - product complaint

1196 21 CFR 110.10(a)

Employees with illness, lesions, contamination source

1060 21 CFR 123.11(a)

SSOP(S)

3067 21 CFR 114.80(a)

Quality control procedures

Page 157

Foods

4296 21 CFR 110.80(a)(5)

Temperature and humidity

9919 21 CFR 120.10(a)

Corrective action - predetermined plan inadequate

9928 21 CFR 120.12(b)

Records - general - include name, date, time

9932 21 CFR 120.6(a)

Sanitation SSOP - none or not implemented

1176 21 CFR 110.40(f)

Insufficient number of Q.C. instruments

1316 21 CFR 113.87(c)

Initial temperature

1568 21 CFR 110.35(d)(2)

Before use and after interruption

1601 21 CFR 110.37(a)

Safe and adequate sanitary quality

1641 21 CFR 113.100(b)

Review not done/timely

1697 21 CFR 110.80(b)(4)

Preventive control measures

1711 21 CFR 110.80(b)(15)

Proper pH controls

2389 21 CFR 110.80(a)(5)

Identify rework

Page 158

Foods

3062 21 CFR 114.10

Personnel

3088 21 CFR 114.100(b)

Processing and production - required information

3663 21 CFR 110.40(e)

Lack of automatic control / alarm (S)

3877 21 CFR 113.60(c)

Coding - required elements

4464 21 CFR 108.25(c)(1)

Registration

4475 21 CFR 108.25(c)(3)(i)

Process adherence

6002 21 CFR 123.11(b)

Sanitation corrections

6012 21 CFR 123.8(a)(3)(iii)

Calibration record review adequacy

15532 21 CFR 111.255(b)

Batch record - complete

950 21 CFR 123.12(d)

Determination of compliance

975 21 CFR 123.9(b)(1)

Record retention

1669 21 CFR 110.80(a)(3)

Aflatoxin and other natural toxins

4179 21 CFR 113.83

Records of process establishment

Page 159

Foods

15762 21 CFR 111.205(a)

Master manufacturing record - each batch

15410 21 CFR 111.14(b)(2)

Personnel - records - training

899 21 CFR 123.16

Process controls

938 21 CFR 123.9(c)

Official review

1329 21 CFR 113.100(a)

Processing entries not done/not timely

1330 21 CFR 113.100(a)

Processing entry missing information

1487 21 CFR 113.87(b)

Visual indicators not used

1529 21 CFR 113.89

Process deviation log/file

3857 21 CFR 113.60(a)

Record of visual closure examination

4295 21 CFR 110.40(a)

Food contact - non-toxic materials

9943 21 CFR 120.8(a)

HACCP plan - location and type of juice

12733 21 CFR 120.11(a)(1)(iv)(C)

Calibration, testing - record review timeliness

12743 21 CFR 120.8(b)(4)

HACCP plan - monitoring procedures not adequate

Page 160

Foods

12749 21 CFR 120.8(b)(6)

HACCP plan - verify procedures / frequency - none listed

15494 21 CFR 111.25(c)

Procedures - equipment - cleaning, sanitizing

15498 21 CFR 111.27(d)

Equipment - maintain, clean, sanitize

15642 21 CFR 111.455(a)

Hold - temperature, humidity, light

15763 21 CFR 111.205(a)

Master manufacturing record - unique formulation

15862 21 CFR 111.75(a)(2)

Appropriate tests, examinations; certificate of analysis

15869 21 CFR 111.75(c)

Specifications met - verify; finished batch

15401 21 CFR 111.12(b)

Personnel - quality control operations

17004 FDCA 402(a)

Food Field Exam

972 21 CFR 123.8(a)(1)

Modification HACCP plan

1040 21 CFR 113.10

Operators

1290 21 CFR 110.20(a)(4)

Waste disposal

1428 21 CFR 110.20(b)(6)

Adequate ventilation

Page 161

Foods

1471 21 CFR 113.83

Scheduled processes not established

1639 21 CFR 113.100(b)

Entries not timely

1665 21 CFR 110.80(a)(2)

Pasteurization or other adequate treatment

1688 21 CFR 110.80

Supervisory competence

2301 21 CFR 129.80(f)

Bacteriological contamination of containers and closures (S)

2387 21 CFR 110.80(a)(1)

Washing and cleaning

2391 21 CFR 110.80(a)(6)

Thawed appropriately

3089 21 CFR 114.100(c)

Process deviations- identification and records

3090 21 CFR 114.100(d)

Product distribution

3651 21 CFR 110.37(b)(5)

Cross contamination

3881 21 CFR 113.60(d)

Post process handling - automatic equipment design (S)

4519 21 CFR 108.35(c)(3)(i)

Process adherence

4524 21 CFR 108.35(g)

Approved school

Page 162

Foods

9961 21 CFR 120.24(a)

Process controls - HACCP plan - 5 log reduction

9986 21 CFR 120.24(c)

Process controls - not exempt, single facility

15302 21 CFR 120.11(a)(2)

Calibration, testing - no records

15434 21 CFR 111.15(d)(2)

Pest control measures

15723 21 CFR 111.365(i)

Metal, foreign material

15641 21 CFR 111.453

Written procedures - holding

15839 21 CFR 111.70(e)

Specifications - identity, purity, strength, composition

2427 21 CFR 110.80(b)(9)

Proper disposal of adulterated product

929 21 CFR 123.8(b)

Verification - corrective action

1045 21 CFR 113.10

Supervisors

1255 21 CFR 129.20(a)

Bottling room separation

1473 21 CFR 113.83

Scientific methods not performed

1660 21 CFR 113.40(a)(1)

MIG thermometer not used as reference

Page 163

Foods

1706 21 CFR 110.80(b)(10)

Mechanical manufacturing control

1945 21 CFR 129.80(d)

Records of sanitizing times and intensities (S)

2887 21 CFR 113.40(j)

Conform to requirements

3077 21 CFR 114.80(b)

Visible code

3644 21 CFR 110.10(b)(5)

Impermeable (S)

3823 21 CFR 113.40(b)(1)

Records of calibration (S)

3870 21 CFR 113.60(a)(2)

Glass containers, capper efficiency check

3872 21 CFR 113.60(a)(3)

Closures other than double seams and glass

3876 21 CFR 113.60(c)

Coding - failure to mark

4420 21 CFR 110.110(c)

Defects not reduced to lowest level

4511 21 CFR 108.25(f)

Approved school

4523 21 CFR 108.35(f)

Recall procedures

9917 21 CFR 120.10(c)

Corrective action documentation

Page 164

Foods

12748 21 CFR 120.8(b)(5)

HACCP plan - corrective action plan not included

15425 21 CFR 111.15(i)

Hand-washing facilities

15443 21 CFR 111.15(b)(2)

Physical plant - repair

15550 21 CFR 111.260(j)

Batch record - manufacture

15586 21 CFR 111.155(e)

Components - contamination, deterioration, mixups

15659 21 CFR 111.475(b)(1)

Written procedures - holding; distributing

15665 21 CFR 111.303

Written procedures - tests, examinations; specifications met

15698 21 CFR 111.320(a)

Examination, testing; appropriate

15736 21 CFR 111.353

Manufacturing operations - written procedures

15744 21 CFR 111.210(h)(2)

Master manufacturing record sampling, tests, examinations

15748 21 CFR 111.210(f)

Master manufacturing record theoretical yield,expected yield

15732 21 CFR 111.365(a)

Conditions, controls -protect; microorganisms, contamination

15761 21 CFR 111.205(b)(1)

Master manufacturing record specifications; quality

Page 165

Foods

15790 21 CFR 111.403

Written procedures - labeling operations

15853 21 CFR 111.73

Specifications met - identity, purity, strength, composition

15861 21 CFR 111.75(a)(2)(ii)(A)

Component - qualify supplier

15897 21 CFR 111.83(a)

Reserve sample - collect, hold

16013 21 CFR 111.140(b)(1)

Records - quality control operations; responsibilities

16042 21 CFR 111.503

Written procedures - returned dietary supplement

15819 21 CFR 111.55

Production, process controls implement

15928 21 CFR 111.103

Written procedure quality control operations material review

15382 21 CFR 111.8

Written procedures - personnel qualifications

15402 21 CFR 111.12

Personnel - quality control personnel qualified

976 21 CFR 123.9(b)(2)

Process adequacy records

1303 21 CFR 113.81(f)

Critical Factors

1379 21 CFR 129.35(a)(4)(iv)

Compliance with standards

Page 166

Foods

1500 21 CFR 113.89

Evaluation by process authority

1534 21 CFR 113.100(b)

Entries not done

1600 21 CFR 110.37(a)

General inadequacy

1643 21 CFR 113.100(c)

Incomplete information

1645 21 CFR 113.100(c)

Records review infrequent / not done

1651 21 CFR 113.40(a)(1)

Thermometer calibration

1670 21 CFR 110.80(a)(4)

Safety assurance - pests/extraneous materials

1734 21 CFR 113.40(a)(2)

Corresponding with MIG

1751 21 CFR 113.40(a)(8)

Size, fully open

1761 21 CFR 129.80(a)

Record keeping requirements

1812 21 CFR 129.80(c)

Testing of cleaning/sanitizing solutions

3072 21 CFR 114.80(a)(1)

Thermal processing

3650 21 CFR 110.35(d)(1)

Wet cleaning

Page 167

Foods

3862 21 CFR 113.60(a)(1)

Failure to perform teardown examinations

3875 21 CFR 113.60(b)

Cooling water - residual sanitizer (S)

4465 21 CFR 114.100(c)

Process deviations - action to rectify

4476 21 CFR 108.25(c)(3)(ii)

Process information availability

9926 21 CFR 120.14(a)

Importer - written procedures

9936 21 CFR 120.7(a)

Hazard analysis - written - elements

9981 21 CFR 120.12(b)(4)

Records - actual values

12751 21 CFR 120.8(b)(7)

HACCP plan - recordkeeping system

15492 21 CFR 111.25(a)

Procedures - calibrating instruments

15496 21 CFR 111.27(b)

Instruments - calibration

15531 21 CFR 111.255(a)

Batch record - every batch

15442 21 CFR 111.15(b)(1)

Physical plant - clean and sanitary

Page 168

Foods

15454 21 CFR 111.16

Written procedures - pest control

15567 21 CFR 111.260(l)(4)

Batch record - approved, released, rejected

15737 21 CFR 111.210(h)(5)

Corrective action plans

15747 21 CFR 111.210(g)

Packaging description, representative label

16057 21 CFR 111.535(b)(1)

Records - returned dietary supplement: written procedures

15759 21 CFR 111.205(b)(2)

Master manufacturing record controls, procedures

15778 21 CFR 111.415(b)

Dietary supplement - protect, contamination

15801 21 CFR 111.560(b)

Quality control, review, approve; investigate, followup

16071 21 CFR 111.35(b)(3)

Documentation - instruments, controls; calibrations

15935 21 CFR 111.105(d)

Quality control - basis; tests, examinations

15944 21 CFR 111.105(i)

QC - required operations master manufacturing/batch records

15951 21 CFR 111.110(c)

Quality control operations - tests, examinations; results

15893 21 CFR 111.80(c)

Specifications - representative samples; finished batch

Page 169

Foods

16083 21 CFR 111.35(b)(6)

Documentation - equipment functions; intended use

15825 21 CFR 111.65

Quality control - quality, dietary supplement

15829 21 CFR 111.70(b)(1)

Specifications - component identity

15830 21 CFR 111.70(b)(2)

Specifications-component purity, strength, composition

15832 21 CFR 111.70(c)(1)

In-process identity, purity, strength, composition

15391 21 CFR 111.10(b)(3)

Hand washing

15404 21 CFR 111.12(c)

Personnel - education, training, experience

1197 21 CFR 110.10(a)

Lack of instruction/reporting of health conditions

949 21 CFR 123.12(c)

Records, English

977 21 CFR 123.9(b)(3)

Records stored at another location

1093 21 CFR 110.40(g)

Compressed air/gases

1277 21 CFR 129.20(d)

Enclosed room for container washing and sanitizing

1331 21 CFR 113.100(a)(1)

Still retorts

Page 170

Foods

1351 21 CFR 129.35(a)(3)(i)

Sampling of product & ops water

1353 21 CFR 129.35(a)(3)(i)

Sampling for micro contaminants

1394 21 CFR 129.37(a)

Sanitization practices

1423 21 CFR 129.37(d)

Containers kept sanitary

1483 21 CFR 113.87(a)

Operating processes not posted

1533 21 CFR 113.100(b)

RTC identification

1559 21 CFR 110.35(c)

Guard/guide dogs

1648 21 CFR 113.40(a)(1)

No MIG thermometer

1735 21 CFR 113.40(a)(2)

Unauthorized adjustment

1757 21 CFR 113.40(a)(8)

Observable

1806 21 CFR 129.80(b)(1)

Records of mechanical washers

1944 21 CFR 129.80(d)

Sanitizing operations inadequate

2115 21 CFR 113.40(b)(8)

Drain valve

Page 171

Foods

2142 21 CFR 113.40(b)(1)

No MIG thermometer

2154 21 CFR 113.40(b)(2)

Unauthorized adjustment

2271 21 CFR 129.80(e)

Package identification

2272 21 CFR 129.80(e)

Plant records

2273 21 CFR 129.80(g)

Representative samples

2274 21 CFR 129.80(g)(1)

Bacteriological

2362 21 CFR 110.80

Reject and rework

2367 21 CFR 129.80(a)

Effective treatment

2837 21 CFR 113.40(g)(4)

Critical factors

2848 21 CFR 113.40(g)(1)(i)(b)

Corresponding with MIG

2870 21 CFR 113.40(g)(1)(ii)(e)

Readings with sufficient frequency

3068 21 CFR 114.80(a)(1)

pH control

Page 172

Foods

3083 21 CFR 114.89

Process deviation evaluation

3091 21 CFR 114.100(e)

Retention

3093 21 CFR 114.89

Process deviation evaluation - record

3648 21 CFR 110.20(a)(4)

Neighboring grounds

3653 21 CFR 110.37(d)

Readily accessible

3709 21 CFR 110.80(a)(1)

Inspection of containers and carriers upon receipt

3859 21 CFR 113.60(a)

Frequency of visual closure examinations (S)

3865 21 CFR 113.60(a)(1)

Corrective actions following teardown examinations

3874 21 CFR 113.60(b)

Cooling water - failure to chlorinate, etc.

4530 21 CFR 114.100(c)

Process deviations - product disposition

15338 21 CFR 80.38(a)

Label with certified lot number

Page 173

Foods

9921 21 CFR 120.10(b)

Corrective action - no predetermined plan

9929 21 CFR 120.12(b)(4)

Records - information not entered when observed

9946 21 CFR 120.11(b)

Validation - reviewer's qualifications

9953 21 CFR 120.11(a)(1)(iv)(A)

CCP record review adequacy

9964 21 CFR 120.25

Finished product not analyzed for E.coli

12703 21 CFR 129.80(a)

Product samples

12717 21 CFR 129.80(h)

Certificates

12732 21 CFR 120.10(a)

Corrective action - predetermined plan

15305 21 CFR 120.14(a)(2)

Importer - implementation of affirmative steps

15480 21 CFR 111.20(h)

Physical plant - screening against pests

15481 21 CFR 111.23(b)

Records - cleaning, pest control

Page 174

Foods

15491 21 CFR 111.25

Equipment - procedures

15534 21 CFR 111.255(c)

Batch record - each step

15546 21 CFR 111.260(f)

Batch record - yield

15547 21 CFR 111.260(g)

Batch record - results; monitoring

15429 21 CFR 111.15(k)

Sanitation supervisors - assigned

15453 21 CFR 111.16

Written procedures - cleaning

15458 21 CFR 111.20(d)(1)(i)

Floors, walls, ceilings

15552 21 CFR 111.260(j)(2)

Batch record - initials; each step

15562 21 CFR 111.260(l)(1)

Batch record - quality control review; production

15570 21 CFR 111.153

Written procedures - components

15572 21 CFR 111.153

Written procedures - labels

15582 21 CFR 111.155(e)

Components - contamination, deterioration, mixups

15604 21 CFR 111.165(b)

Product received - visually examine invoice, guarantee, cert

Page 175

Foods

15619 21 CFR 111.180(b)(1)

Written procedures - packaging, labeling received

15648 21 CFR 111.465(a)(2)

Hold - reserve sample; closure system

15652 21 CFR 111.465(b)

Retain reserve samples - 1 year, 2 years

15675 21 CFR 111.315(b)

Sampling plans; establish, follow

15733 21 CFR 111.365

Manufacturing operations - prevent contamination

15702 21 CFR 111.320(b)

Examination, testing; scientifically valid

15712 21 CFR 111.325(b)(2)(ii)

Records - document; results

15645 21 CFR 111.455(c)

Hold - mixup, contamination, deterioration

16051 21 CFR 111.525(b)

Returned dietary supplement - release

16058 21 CFR 111.535(b)(2)

Records - ret'nd dietary supplement: material review, dispos

15768 21 CFR 111.420(c)

Repackaged, relabeled - quality control: approve, rejects

15771 21 CFR 111.415(h)

Obsolete labels, packaging - dispose

15775 21 CFR 111.415(e)

Dietary supplement containers mixups

Page 176

Foods

15776 21 CFR 111.415(d)

Packaging, labeling - physical separation

15780 21 CFR 111.415

Fill, assemble, package, label master record

15786 21 CFR 111.410(b)

Labels - issuance, use

15791 21 CFR 111.403

Written procedures -packaging operations

15796 21 CFR 111.430(b)

Records - packaging, labeling operations

15799 21 CFR 111.560(a)(1)

Product complaint - quality control review

15809 21 CFR 111.570(b)(1)

Written procedures - product complaint; review, investigate

15811 21 CFR 111.570(b)(2)(i)

Record - person document; time of performance

15989 21 CFR 111.127

Quality control operations - packaging, labeling

16072 21 CFR 111.35(b)(3)

Instruments, controls; calibrate date, reference std, method

15967 21 CFR 111.117(b)

Quality control operations - calibration records

15972 21 CFR 111.120(b)

QC operations -specifications; components, packaging, labels

Page 177

Foods

15984 21 CFR 111.123(a)(8)

Quality control - finished batch, distribution

15870 21 CFR 111.75(c)(1)

Specifications met - verify; production, process control

15871 21 CFR 111.75(c)(2)

Specifications met - test, examinations; compliance

15872 21 CFR 111.75(c)(3)

Specifications met identity,purity, strength, comp,; basis

15882 21 CFR 111.75(h)(2)

Tests, examinations - scientifically valid

15883 21 CFR 111.75(i)

Corrective action plan

15817 21 CFR 111.570(b)(2)(ii)(F)

Record - product complaint; findings

15828 21 CFR 111.70(a)

Specifications - manufacturing process

15831 21 CFR 111.70(b)(3)

Specifications - contamination limits

15840 21 CFR 111.70(e)

Specifications - contamination limits

15841 21 CFR 111.70(f)

Specifications - product received for packaging, labeling

15932 21 CFR 111.105(a)

Processes, specifications, written procedures

Page 178

Foods

15388 21 CFR 111.10(b)

Personnel - hygienic practices

15393 21 CFR 111.10(b)(4)

Hand jewelry - remove

15395 21 CFR 111.10(b)(5)

Gloves

15396 21 CFR 111.10(b)(6)

Hair restraints

15409 21 CFR 111.14(b)(1)

Personnel - records - written procedures

15358 FDCA 761(c)(1)

Timing of AE report submission (dietary supplement)

15351 FDCA 761(b)(1)

No AE report made (dietary supplement)

2428 21 CFR 110.80(b)(9)

Proper reconditioning

3892 21 CFR 113.60(a)

Regular observations for gross closure defects

939 21 CFR 123.9(f)

Computerized records

1258 21 CFR 113.60(c)

Coding - visible

1273 21 CFR 129.20(b)

Non-sealed system

1276 21 CFR 129.20(c)

Adequate ventilation

Page 179

Foods

1294 21 CFR 110.20(b)(3)

Outdoor fermentation

1300 21 CFR 113.81(c)

Fill

1301 21 CFR 113.81(d)

Exhausting

1302 21 CFR 113.81(e)

pH

1317 21 CFR 113.87(d)

Timing devices

1320 21 CFR 113.87(g)

Bleeder mufflers

1324 21 CFR 113.100(d)

Distribution record

1359 21 CFR 129.35(a)(3)(i)

Maintaining sample & analysis records

1417 21 CFR 129.37(c)

Exam, handling of single service containers et. al.

1453 21 CFR 129.40(a)(1)

Suitability - equipment and utensils

1467 21 CFR 129.40(a)(2)

Suitability - contact surfaces

1472 21 CFR 113.83

Critical factors not stated

1474 21 CFR 113.83

Calculations not performed

Page 180

Foods

1475 21 CFR 113.83

Incubation tests - number of commercial runs (S)

1485 21 CFR 113.87(a)

Scheduled processes not available

1486 21 CFR 113.87(b)

System not established

1501 21 CFR 113.89

Evaluation records

1502 21 CFR 113.89

Failure to reprocess or destroy product found underprocessed

1532 21 CFR 113.100(a)(7)

Other systems

1563 21 CFR 110.35(d)(1)

Low-moisture food requirements

1569 21 CFR 110.35(d)(2)

Continuous operations

1595 21 CFR 110.37(b)(1)

Sufficient quantities of water

1649 21 CFR 113.40(a)(1)

Scale and range

1691 21 CFR 113.40(a)(4)

Steam controller

1732 21 CFR 113.40(a)(2)

Range

1740 21 CFR 113.40(a)(2)

Well bleeder

Page 181

Foods

2056 21 CFR 123.28(a)

HACCP plan

2101 21 CFR 113.40(a)(13)

Measured, recorded

2103 21 CFR 113.40(a)(13)(ii)

Closing vacuum

2143 21 CFR 113.40(b)(1)

Scale and range

2144 21 CFR 113.40(b)(1)

Thermometer calibration

2149 21 CFR 113.40(b)(1)

Not used as reference

2151 21 CFR 113.40(b)(2)

Range

2167 21 CFR 113.40(b)(9)

No indicator

2169 21 CFR 113.40(b)(9)

Operator check and recording

2221 21 CFR 113.40(b)(10)(i)

Check valve

2275 21 CFR 129.80(g)(2)

Chemical, physical, radiological

2285 21 CFR 129.80(f)

Reject / reprocess

2309 21 CFR 113.40(c)(1)

Unreadable thermometer

Page 182

Foods

2321 21 CFR 113.40(c)(2)

Unauthorized adjustment

2336 21 CFR 113.40(c)(5)

Condensate bleeder

2390 21 CFR 110.80(a)(6)

Kept frozen prior to use

2513 21 CFR 113.40(e)(7)

Measured and recorded

2526 21 CFR 113.40(f)(1)

No MIG thermometer

2843 21 CFR 113.40(g)(1)(i)(a)

Not used as reference

2849 21 CFR 113.40(g)(1)(i)(b)

Unauthorized adjustment

2864 21 CFR 113.40(g)(1)(ii)(b)

Process deviations per 113.89

2886 21 CFR 113.40(i)

Inadequate instruments

2888 21 CFR 113.40(j)

Critical factors

2889 21 CFR 113.40(g)(2)(i)(a)

Instrumentation

2890 21 CFR 113.40(g)(2)(i)(a)

Automatic recording devices

2899 21 CFR 113.40(g)(2)(ii)(c)

Required information

Page 183

Foods

2901 21 CFR 113.40(i)

Critical factors

3649 21 CFR 110.35(d)(1)

Dry and sanitary

3708 21 CFR 110.80(a)(1)

Water quality -- wash, rinse, convey food

3771 21 CFR 113.40(a)(7)

Location of steam spreader perforations (S)

3801 21 CFR 113.40(b)(1)

Date last tested for accuracy (S)

3804 21 CFR 113.40(a)(2)

Air filtration for temperature controllers (S)

3856 21 CFR 113.60(a)

Visual

3860 21 CFR 113.60(a)

Pertinent observations

3863 21 CFR 113.60(a)(1)

Frequency of teardown examinations (S)

3864 21 CFR 113.60(a)(1)

Recording of teardown examinations

4067 21 CFR 113.40(a)(12)(iii)

Venting, other installations

4178 21 CFR 113.83

Commercial production variations

4514 21 CFR 108.35(c)(1)

Registration

Page 184

Foods

4517 21 CFR 108.35(c)(2)(ii)

Process change substantiation

4526 21 CFR 108.35(h)

Record inspection and copying

4528 21 CFR 108.35(c)(2)(ii)

Process change recording

4529 21 CFR 108.35(c)(2)(ii)

Process change reporting to CFSAN

15322 21 CFR 74 subpart C

Color additives intended for use in cosmetics

15310 21 CFR 70.25

Color additive labeling

9792 21 CFR 106.30(b)(3)

Stability analysis

9799 21 CFR 106.100(d)

Premix supplier

9832 21 CFR 107.20(c)

"Use by" date

9938 21 CFR 120.7(d)

Hazard analysis - evaluation of effect on safety (S)

9949 21 CFR 120.11(b)

HACCP plan not modified

9962 21 CFR 120.24(b)

Process controls - direct treatment not exempt

Page 185

Foods

9963 21 CFR 120.24(c)

Process controls - exempt process, single facility

12701 21 CFR 129.35(a)(4)(iii)

Testing for disinfectants & DBPs

12704 21 CFR 129.80(a)

Analytical frequency

12707 21 CFR 129.80(g)(3)

Records of analyses

12709 21 CFR 129.80(c)

Records of cleaning/sanitizing solutions

12750 21 CFR 120.8(b)(6)

HACCP plan - valid procedures / frequency - none listed

15001 21 CFR 113.60(a)

Corrective actions

15301 21 CFR 120.24(b)

Process controls - citrus

15411 21 CFR 111.14(b)(2)

Personnel - records - training date, type, persons

15473 21 CFR 111.20(c)(7)

Physical plant - separate areas holding

15482 21 CFR 111.23(c)

Records - water

15499 21 CFR 111.27(a)

Equipment - design - suitable

15507 21 CFR 111.27(a)(5)(i)

Refrigerator, freezer - temperature recording device

Page 186

Foods

15509 21 CFR 111.27(a)(6)

Instruments, controls - accurate, precise, maintained

15511 21 CFR 111.27(d)

Equipment - maintain - general

15518 21 CFR 111.27(d)(4)

Contact surfaces - not in direct contact - cleaning

15526 21 CFR 111.30(c)

Equipment - automated - calibrate, inspect

15527 21 CFR 111.30(c)

Equipment - automated - QC check

15529 21 CFR 111.30(e)

Equipment - controls, intended use

15533 21 CFR 111.255(c)

Batch record - follow master

15536 21 CFR 111.255(d)

Batch record - originals, copies, electronic

15542 21 CFR 111.260(b)

Batch record - date, time; maintenance

15543 21 CFR 111.260(c)

Batch record - date, time; maintenance

15544 21 CFR 111.260(d)

Batch record - component; unique identifier

15431 21 CFR 111.15(e)(1)

Water supply - not component suitability

15444 21 CFR 111.15(c)(1)

Cleaning compounds

Page 187

Foods

15447 21 CFR 111.15(c)(3)

Cleaning compounds and toxic materials - holding

15452 21 CFR 111.15(f)(5)

Plumbing - backflow, cross connection

15456 21 CFR 111.20(b)

Physical plant - space; equipment, materials

15461 21 CFR 111.20(d)(1)(iii)

Physical plant - ventilation, environmental control

15468 21 CFR 111.20(c)(2)

Physical plant - material review and disposition

15554 21 CFR 111.260(j)(2)(ii)

Batch record - initials; verifying weight

15557 21 CFR 111.260(k)

Batch record - packaging, labeling

15559 21 CFR 111.260(k)(1)

Batch record - identifier; labels

15561 21 CFR 111.260(k)(3)

Batch record - tests, examinations; results

15565 21 CFR 111.260(l)(2)

Batch record - reprocessing, repackaging

15566 21 CFR 111.260(l)(3)

Batch record - approved, released, rejected; batch

15579 21 CFR 111.155(c)(1)

Components - representative samples

Page 188

Foods

15580 21 CFR 111.155(c)(2)

Quality control - components; tests, examination results

15583 21 CFR 111.155(d)(1)

Components - identify lot received

15584 21 CFR 111.155(d)(1)

Components - identify lot produced

15589 21 CFR 111.160(c)

Packaging, labels - quarantine

15592 21 CFR 111.160(c)(1)

Packaging - visual identification; containers, closures

15597 21 CFR 111.160(c)(3)

Labels - quality control; approve, release

15602 21 CFR 111.160(e)

Packaging, labels - mixups

15605 21 CFR 111.165?

Product received - quarantine

15607 21 CFR 111.165(c)(2)

Product received - quality control; documentation; specs

15608 21 CFR 111.165(c)(3)

Product received - quality control; approve

15614 21 CFR 111.170

Quarantine component, package, labels, rejected product

15618 21 CFR 111.180(b)(1)

Written procedures - components

Page 189

Foods

15646 21 CFR 111.460(a)

Hold, identify - in-process material

15660 21 CFR 111.475(b)(2)

Records - product distribution

15662 21 CFR 111.303

Written procedures - laboratory operations

15671 21 CFR 111.315

Laboratory control processes requirements

15672 21 CFR 111.315

Laboratory control processes reviewed, approved

15679 21 CFR 111.315(b)(1)

Laboratory control processes sampling plans; packaging

15683 21 CFR 111.315(c)

Examination, testing methods; criteria for selecting

15689 21 CFR 111.315(b)(3)

Sampling plans; finished batches

15693 21 CFR 111.315(b)(1)

Laboratory control processes sampling plans; labeling

15734 21 CFR 111.360

Manufacturing operations - sanitation

15735 21 CFR 111.355

Manufacturing operations - design

15743 21 CFR 111.210(h)(3)

Master manufacturing record - specific actions; quality

15746 21 CFR 111.210(h)(1)

Instructions; specifications; quality

Page 190

Foods

15749 21 CFR 111.210(e)

Master manufacturing record intentional overage

15752 21 CFR 111.210(c)

Master manufacturing record components; weight, measure

15754 21 CFR 111.210(a)

Master manufacturing record - dietary ingredients

15755 21 CFR 111.205(c)

Master manufacturing record: readily available

15756 21 CFR 111.205(c)

Master manufacturing record: electronic

15708 21 CFR 111.325(a)

Written procedures, laboratory operations

15709 21 CFR 111.325(b)(2)

Laboratory methodology followed

15624 21 CFR 111.180(b)(3)

Documentation - components

15630 21 CFR 111.180(b)(3)(i)

Document - required operation

16037 21 CFR 111.605

Records - keep: 1 year, 2 years

16040 21 CFR 111.610(a)

Records - available; FDA

16046 21 CFR 111.503

Written procedures returned dietary supplement investigation

16053 21 CFR 111.535(a)

Records - returned dietary supplement: 1 year, 2 years

Page 191

Foods

16060 21 CFR 111.535(b)(4)

Returned dietary supplement: reevaluation, determination

15774 21 CFR 111.415(f)(1)

Batch-lot,control number packaged, labeled dietary supplemen

15784 21 CFR 111.410(c)

Packaging, labels - master manufacturing record

15785 21 CFR 111.410(b)

Label, packaging - discrepancies

15787 21 CFR 111.410(b)

Packaging - issuance, use

15800 21 CFR 111.560(a)(2)

Product complaint - quality control investigate

15802 21 CFR 111.560(c)

Product complaint - review, investigation

15806 21 CFR 111.570(a)

Records - product complaints: originals, copies, electroni

15813 21 CFR 111.570(b)(2)(ii)(B)

Record - product complaint; batch, lot, control number

15922 21 CFR 111.95(b)(3)

Documentation - ensure specifications met

15995 21 CFR 111.127(d)

QC operations - packaged, labeled; specifications

15954 21 CFR 111.113(a)(2)

QC master manufacturing record; material review, disposition

Page 192

Foods

15955 21 CFR 111.113(a)(3)

Quality control - adulteration; material review, disposition

15963 21 CFR 111.113(b)(2)

Quality control - reject; specification not met

16066 21 CFR 111.35(b)(1)(i)

Written procedures - instruments, controls; calibrating

16068 21 CFR 111.35(b)(1)(iii)

Equipment, utensils; maintaining, cleaning, sanitizing

16070 21 CFR 111.35(b)(2)

Document-equipment date of use, maintain, clean, sanitize

16074 21 CFR 111.35(b)(4)

Records - equipment; calibrations, inspections, checks

16089 FDCA 417(d)(1)(A)

Reportable food report - submission

15966 21 CFR 111.117(a)

Quality control operations - calibrating processes

15973 21 CFR 111.120(c)

QC operations - material review, disposition decision

15975 21 CFR 111.120(e)

Quality control operations - quarantine

15933 21 CFR 111.105(b)

Quality control - supplier qualification

15934 21 CFR 111.105(c)

Basis; in-process, component, specifications

15939 21 CFR 111.105(g)

Quality control - reserve samples

Page 193

Foods

15949 21 CFR 111.110(a)

QC-Laboratory control processes; production, process control

15950 21 CFR 111.110(b)

Quality control operations - tests, examinations

15977 21 CFR 111.123(a)(1)

QC operations - master manufacturing record, modifications

15983 21 CFR 111.123(a)(7)

Quality control operations - finished batch, specifications

15868 21 CFR 111.75(b)(2)

Specifications met - deviation, unanticipated occurrence

15875 21 CFR 111.75(d)(1)

Documentation specifications met; exempted, periodic testing

15885 21 CFR 111.77(a)

Specifications not met - reject, quality control

15894 21 CFR 111.80(d)

Specifications - representative samples; unique lot

15899 21 CFR 111.83(b)(1)

Reserve sample container-closure contamination,deterioration

15901 21 CFR 111.83(b)(3)

Reserve sample - retained

15908 21 CFR 111.90(b)(1)

Reprocessed, dietary supplement - no material review

15920 21 CFR 111.95(b)(1)

Records - established specifications

15999 21 CFR 111.127(h)

QC operations - packaging, labeling; approving, rejecting

Page 194

Foods

16007 21 CFR 111.135

Quality control operations - product complaints

16008 21 CFR 111.135

Quality control operations - product complaints; investigate

16022 21 CFR 111.140(b)(3)(iv)

Material review, disposition, follow-up; identification

16025 21 CFR 111.140(b)(3)(vii)

material review, disposition, follow-up; signature

15820 21 CFR 111.55

Production, process controls packaged, labeled

15821 21 CFR 111.60(a)

Production, in- process control system - design, quality

15823 21 CFR 111.60(b)

Production, in-process control system review, approved

15826 21 CFR 111.65

Quality control - packaged, labeled

15838 21 CFR 111.70(d)

Specifications - labels, packaging

15842 21 CFR 111.70(f)

Specifications - product received for packaging, labeling

15845 21 CFR 111.73

Specifications met - quality

15848 21 CFR 111.73

Specifications met - component purity, strength, composition

15850 21 CFR 111.73

Specifications met in-process purity, strength, composition

Page 195

Foods

'LongDesc

Frqncy

Effective measures are not being taken to [exclude pests from the processing areas] [protect against the contamination of food on the premises by pests]. Specifically, *** You are not monitoring the sanitation conditions and practices with sufficient frequency to assure conformance with Current Good Manufacturing Practices including [safety of water that comes into contact with food or food contact surfaces, including water used to manufacture ice] [condition and cleanliness of food contact surfaces] [prevention of cross-contamination from insanitary objects] [maintenance of hand washing, hand sanitizing, and toilet facilities] [protection of food, food packaging material, and food contact surfaces from adulteration] [proper labeling, storage and use of toxic chemicals] [control of employee health conditions] [exclusion of pests]. Specifically, ***

443

353

You did not implement the [monitoring] [recordkeeping] [verification] procedures listed in your HACCP plan. Specifically, ***

281

Failure to provide adequate screening or other protection against pests. Specifically, ***

263

The plant is not constructed in such a manner as to allow [floors] [walls] [ceilings] to be [adequately cleaned and kept clean] [kept in good repair]. Specifically, *** Failure to maintain buildings, fixtures, or other physical facilities in a sanitary condition. Specifically, ***

245

243

Failure to [properly store equipment] [remove litter and waste] [cut weeds or grass] that may constitute an attractant, breeding place, or harborage area for pests, within the immediate vicinity of the plant buildings or structures. Specifically, *** Failure to maintain [buildings] [fixtures] [physical facilities] in repair sufficient to prevent food from becoming adulterated. Specifically, ***

215

215

You are not maintaining sanitation control records that document [monitoring] [corrections of sanitation deficiencies] for [safety of water that comes into contact with food or food contact surfaces, including water used to manufacture ice] [condition and cleanliness of food contact surfaces] [prevention of cross-contamination from insanitary Failure to conduct cleaning and sanitizing operations for utensils and equipment in a manner that protects against contamination of [food] [food-contact surfaces] [food-packaging materials]. Specifically, ***

171

169

Page 196

Foods

Employees did not [wash] [sanitize] hands thoroughly in an adequate hand-washing facility [before starting work] [after each absence from the work station] [at any time their hands may have become soiled or contaminated]. Specifically, *** Failure to [manufacture] [package] [store] foods under conditions and controls necessary to minimize [the potential for growth of microorganisms] [contamination]. Specifically, *** Your HACCP plan lists monitoring [procedures] [frequencies] that do not ensure compliance with the critical limit. Specifically***

166

163

162

You do not have a written HACCP plan that outlines controls for a food safety hazard that is reasonably likely to occur. Specifically, ***

156

Failure to [construct] [handle] [maintain] equipment, containers and utensils used to [convey] [hold] [store] food in a manner that protects against contamination. Specifically, *** Failure to wear [hair nets] [head bands] [caps] [beard covers] [hair restraints] where appropriate. Specifically, ***

156

149

Failure to provide safety-type [light bulbs] [lighting fixtures] [skylights] [glass] suspended over exposed food. Specifically, ***

147

Failure to store raw materials in a manner that [protects against contamination] [minimizes deterioration]. Specifically, ***

147

Your HACCP plan does not list one or more critical control points that are necessary for each of the identified food safety hazards. Specifically, *** Failure to take necessary precautions to protect against contamination of [food] [food contact surfaces] [food packaging systems] with [microorganisms] [foreign substances]. Specifically, *** Your HACCP plan does not list the food safety hazards that are reasonably likely to occur. Specifically, ***

142

142

141

Your HACCP plan includes a corrective action plan that is not in accordance with 21 CFR 123.7(b) to ensure [affected product is not entered into commerce] [the cause of the deviation was corrected]. Specifically*** Your HACCP plan was not signed and dated [upon initial acceptance] [upon modification] [at least annually]. Specifically, ***

139

134

Page 197

Foods

Your HACCP plan [does not list a critical limit that ensures control of one or more hazards] [lists a critical limit that does not ensure control of one or more hazards]. Specifically, All reasonable precautions are not taken to ensure that production procedures do not contribute contamination from any source. Specifically, *** Failure to clean [food-contact surfaces] [utensils] as frequently as necessary to protect against contamination of food. Specifically, ***

130

129

128

Failure to properly [identify] [hold] [store] toxic [cleaning compounds] [sanitizing agents] [pesticide chemicals] in a manner that protects against contamination of [food] [food-contact surfaces] [food-packaging materials]. Specifically, *** The plant is not constructed in such a manner as to prevent [drip] [condensate] from contaminating [food] [food-contact surfaces] [foodpackaging materials]. Specifically, *** You did not review [some of] your [critical control point monitoring] [corrective action] records within one week of the day that the records are made. Specifically, *** Failure to provide sufficient space for [placement of equipment] [storage of materials] as necessary for the maintenance of sanitary operations and the production of safe food. Specifically, *** Failure to maintain [equipment] [utensils] [finished food containers] in an acceptable condition through appropriate cleaning and sanitizing. Specifically, *** Plumbing constitutes a source of contamination to [food] [water supplies] [equipment] [utensils]. Specifically, ***

127

126

117

112

112

105

Failure to [store] [transport] finished food under conditions that would protect against [physical] [chemical] [microbial] contamination. Specifically, *** Hand-washing facilities lack running water of a suitable temperature. Specifically, ***

102

99

Your sanitation control records do not accurately document the conditions or practices observed at your firm. Specifically***

96

You do not have or have not implemented [written verification procedures] [product specifications] [an affirmative step] for ensuring that [fish] [fishery products] you import are processed in compliance with the Seafood HACCP regulation. Specifically, ***

88

Page 198

Foods

Personal [clothing] [belongings] were stored in an area where [food is exposed] [equipment or utensils are washed]. Specifically, ***

87

The [design] [materials] [workmanship] of [equipment] [utensils] does not allow proper [cleaning] [maintenance]. Specifically, ***

87

Employees were observed to be [eating food] [chewing gum] [drinking beverages] [using tobacco] in areas where [food is exposed] [equipment or utensils are washed]. Specifically, *** Failure to have smoothly bonded or well maintained seams on food contact surfaces, to minimize accumulation of [food particles] [dirt] [organic matter] and the opportunity for growth of microorganisms. Specifically, *** Lack of a sanitary towel service or suitable hand drying devices. Specifically, ***

84

82

81

Your records do not include the [name and location of the processor or importer] [date and time of the activity the record reflects] [signature or initials of the person performing the operation] [identity of the product and the production code, if any]. Specifically, *** Lack of posted, readily understandable signs directing employees to wash and sanitize hands as appropriate. Specifically, ***

80

78

Suitable outer garments are not worn that protect against contamination of [food] [food contact surfaces] [food packaging materials]. Specifically, *** The [design] [construction] [use] of equipment and utensils fails to preclude the adulteration of food with [lubricants] [fuel] [metal fragments] [contaminated water] [contaminants]. Specifically, *** Failure to clean non-food-contact surfaces of equipment as frequently as necessary to protect against contamination. Specifically, ***

77

73

73

Lack of effective hand [cleaning] [sanitizing] preparations. Specifically, ***

73

Your process monitoring equipment is not calibrated to ensure that it reads accurately. Specifically, ***

72

Employees failed to remove unsecured jewelry or other objects which might fall into [food] [equipment] [containers]. Specifically, ***

71

Page 199

Foods

Failure to provide [hand washing] [hand sanitizing] facilities at each location in the plant where needed. Specifically, ***

69

No one associated with your firm has completed the required HACCP training or is HACCP qualified through job experience. Specifically, ***

66

Your food facility is not registered as required. Specifically, ***

64

Failure to [locate] [operate] fans and other air-blowing equipment in a manner that minimizes the potential for contaminating [food] [foodcontact surfaces] [food-packaging materials]. Specifically, *** Failure to handle work-in-progress in a manner that protects against contamination. Specifically, ***

64

62

Lack of an accurate indicating thermometer, temperature measuring device, or temperature recording device in each freezer and cold storage compartment used to store food capable of supporting the growth of microorganisms. Specifically, *** Instruments used for [measuring] [regulating] [recording] conditions that control or prevent the growth of undesirable microorganisms are not [accurate] [adequately maintained]. Specifically,*** Your HACCP plan lists verification [procedures] [frequencies] that have not been developed in accordance with 21 CFR 123.8(a) to ensure that your HACCP plan is adequate to control food safety hazards, and is being effectively implemented. Specifically, *** The [facility] [procedure] [machine] used for [cleaning] [sanitizing] of [equipment] [utensils] has not been shown to provide adequate [cleaning] [sanitizing treatment]. Specifically, *** The [conveyance] [storage] [disposal] of [rubbish] [offal] does not minimize the [development of odor] [potential for waste becoming an attractant and harborage or breeding place for pests]. Specifically, *** You did not conduct, or have conducted for you, a hazard analysis to determine whether there are food safety hazards that are reasonably likely to occur for each kind of fish and fishery product you process. Specifically, *** Failure to wear [hair nets] [head bands] [caps] [beard covers] [appropriate hair restraints] in an effective manner. Specifically, ***

61

58

57

53

53

50

50

Plumbing is not [of adequate size and design] [adequately installed and maintained] to provide adequate floor drainage. Specifically, ***

50

Page 200

Foods

Lack of backflow protection from piping systems that discharge [waste water] [sewage]. Specifically, ***

50

Your HACCP plan is not specific to [the location where the fish are processed] [the kind of fish or fishery product processed]. Specifically, *** Non food-contact equipment in [manufacturing] [food handling] areas is not constructed so that it can be kept in a clean condition. Specifically, *** Failure to provide adequate lighting in [hand-washing areas] [dressing and locker rooms] [toilet rooms] [areas where food is examined, stored, or processed] [areas where equipment and utensils are cleaned]. Specifically, *** Gloves used in food handling are not maintained in an intact, clean, and sanitary condition. Specifically, ***

49

49

48

48

You did not take corrective action that ensured [affected product was not entered into commerce] [the cause of the deviation was corrected]. Specifically,*** Failure to take effective measures to protect against the inclusion of [metal] [extraneous material] in food. Specifically, ***

48

47

You are not monitoring the sanitation conditions and practices with sufficient frequency to assure conformance with current good manufacturing practice including [safety of water that comes into contact with food or food contact surfaces, including water used to manufacture ice] [condition and cleanliness of food contact surfaces] [prevention of cross-contamination from insanitary objects] [maintenance of hand washing, hand sanitizing, and toilet facilities] [protection of food, food packaging material, and food contact surfaces from adulteration] [proper labeling, storage and use of toxic chemicals] [control of employee health conditions] [exclusion of pests]. Specifically, ***

47

Failure to hold foods which can support the rapid growth of undesirable microorganisms at a temperature that prevents the food from becoming adulterated. Specifically, *** Failure to provide the FDA, before packing any new product, information on the scheduled processes for each acidified food in each container size. Specifically, *** Toilet facilities lack self-closing doors. Specifically, ***

42

42

40

Page 201

Foods

Processing or other information was not [always] entered on your records at the time it was observed. Specifically, ***

40

Proper precautions to protect [food] [food-contact surfaces] [foodpackaging materials] from contamination with [microorganisms] [chemicals] [filth] [extraneous material] cannot be taken because of deficiencies in plant [size] [construction] [design]. Specifically, *** Failure to perform [filling] [assembling] [packaging] in a manner that protects food from becoming contaminated. Specifically, ***

39

39

Plumbing is not [of adequate size and design] [adequately installed and maintained] to properly convey sewage and liquid disposable waste from the plant. Specifically, *** Sanitizing agents are [inadequate] [unsafe] under conditions of use. Specifically, ***

38

36

Your verification procedures do not include, at a minimum, reassessment of the HACCP plan [at least annually] [whenever modifications to the process are made]. Specifically, *** Your HACCP plan does not list verification [procedures] [frequencies] that have been developed to ensure that the HACCP plan is adequate to control food safety hazards, and is being effectively implemented. Specifically, *** Failure to provide running water [at a suitable temperature] [under suitable pressure] for [processing of food] [cleaning of equipment, utensils and food-packaging materials] [employee sanitary facilities]. Specifically, *** Failure to hold [raw materials] [rework materials] [ingredients] in bulk or in suitable containers so as to protect against contamination. Specifically, *** Failure to maintain toilet facilities in a sanitary condition. Specifically, ***

35

35

34

34

34

You do not maintain records of [calibration of process-monitoring instruments] [periodic end-product or in-process testing]. Specifically, *** Use of cleaning compounds and sanitizing agents which are not [free from undesirable microorganisms] [safe and adequate under the conditions of use]. Specifically, *** Your monitoring records do not contain the actual values and observations obtained during monitoring. Specifically, ***

32

31

31

Page 202

Foods

The [reassessment of your HACCP plan] [monitoring, corrective action, or verification record review] was not done by an individual who had successfully completed training in the application of HACCP principles to fish and fishery product processing, or was otherwise qualified through job experience to perform these functions. Specifically, *** Failure to [install] [maintain] equipment so as to facilitate cleaning of [the equipment] [all adjacent spaces]. Specifically, ***

30

29

A scheduled process was not established by a qualified person who has expert knowledge acquired through appropriate training and experience in acidification and processing of acidified foods. Specifically, *** Your review of critical control point monitoring records does not [ensure that the records are complete] [verify that they document values that are within critical limits]. Specifically, *** Lack of adequate drainage of areas which may contribute to contamination of food by [seepage] [foot-borne filth] [providing a breeding place for pests]. Specifically, *** Your verification procedures do not include, at a minimum, ongoing verification activities including [review of consumer complaints] [calibration of process monitoring instruments] [review of monitoring, corrective action, and calibration records]. Specifically, *** Failure to maintain [processing] [production] records showing adherence to the scheduled processes, including records of [pH measurement] [critical factors] intended to ensure a safe product. Specifically, *** Failure to take apart equipment as necessary to ensure thorough cleaning. Specifically, ***

29

29

28

28

27

26

Failure to maintain food contact surfaces to protect food from contamination by any source, including unlawful indirect food additives. Specifically, *** Appropriate training in food handling techniques and food protection principles has not been provided to [food handlers] [supervisors]. Specifically, *** You do not [always] maintain sanitation standard operating procedure records that document [the monitoring of conditions and practices during processing] [corrections to conditions and practices that were not met]. Specifically, *** Failure to [remove] [adequately cover] hand jewelry which cannot be adequately sanitized during periods where food is being manipulated by hand. Specifically, *** Food contact surfaces are not designed to [withstand the environment of their intended use] [withstand the action of food] [withstand cleaning compounds and sanitizing agents]. Specifically, ***

25

25

25

23

22

Page 203

Foods

Aisles or working spaces between equipment and walls are [obstructed] [of inadequate width]. Specifically, ***

22

Failure to exercise sufficient control including [frequent testing] [recording of results] so that the finished equilibrium pH values are not higher than 4.6. Specifically, *** Lack of appropriate [design] [construction] to enable [holding] [conveying] [manufacturing] systems to be maintained in an appropriate sanitary condition. Specifically, *** Failure to perform [chemical] [microbial] [extraneous material] testing where necessary to identify [sanitation failures] [possible food contamination]. Specifically, *** Failure to receive and store [liquid] [dry] raw materials in bulk form in a manner which protects against contamination. Specifically, ***

21

20

20

20

Failure to keep toilet facilities in good repair. Specifically, ***

20

You did not review [some of] your calibration records within a reasonable time after the records were made. Specifically, ***

20

Failure to store cleaned and sanitized portable equipment in a [location] [manner] which protects food-contact surfaces from contamination. Specifically, *** You do not have records that document corrective actions that were taken. Specifically, ***

19

18

Lack of corrosion-resistant food contact surfaces. Specifically, ***

18

Acidified food is not manufactured in accordance with the scheduled process. Specifically, ***

18

Each container is not marked with an identifying code specifying the [establishment where the product was packed] [product contained therein] [year] [date] [packing period]. Specifically, *** Failure to [store] [transport] finished food under conditions that would protect against deterioration of the food and its container. Specifically, ***

18

18

Page 204

Foods

You did not [fully] implement the [monitoring] [validation] [verification] [recordkeeping] procedures listed in your HACCP plan. Specifically, *** Failure to [inspect] [segregate] [handle] raw materials to ascertain that they are clean and suitable for processing into food. Specifically, ***

18

17

Failure to take effective measures to protect food transported by conveyor from contamination. Specifically, ***

17

Toilet doors open into areas where food is exposed to airborne contamination, and there are no alternative means taken to prevent such contamination. Specifically, *** You do not have a written HACCP plan that outlines controls for one or more food safety hazards that are reasonably likely to occur. Specifically, *** Use of [insecticides] [rodenticides] without observing necessary precautions and restrictions to protect against contamination of [food] [food-contact surfaces] [food-packaging materials]. Specifically, *** Failure to prepare and maintain in files current procedures for [recalling products that may be injurious to health] [identifying, collecting, warehousing and controlling products] [determining the effectiveness of recalls] [notifying FDA] [implementing recall programs]. Specifically, *** Your HACCP plan does not provide for a recordkeeping system that documents the monitoring of the critical control points. Specifically, ***

17

17

16

16

16

You did not validate that your HACCP plan is adequate to control food hazards [at least once within 12 months after implementation] [at least annually] [when a change in the process occurred that could have affected the hazard analysis or altered the HACCP plan in any way]. Specifically, *** Employees in contact with [food] [food-contact surfaces] [foodpackaging materials] were not maintaining adequate personal cleanliness. Specifically, *** Devices and fixtures are not designed and constructed to protect against recontamination of clean, sanitized hands. Specifically, ***

16

15

15

You did not review [all of] your [critical control point monitoring] [corrective action] records within one week (7 days) of the day the records are made. Specifically, *** Failure to take effective measures to protect finished food from contamination by [raw materials] [refuse] [other ingredients] . Specifically, ***

15

14

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Records are not maintained of the examination of [raw materials] [packaging materials] [finished products] [supplier's guarantees or certificates] to verify compliance with FDA regulations and guidelines or action levels. Specifically, *** Failure of the reviewer to [sign or initial] [date] the [processing records] [production records] [recording temperature chart(s)] after the completion of the processing of a low-acid food product. Specifically, *** Storage or use of toxic materials which are not required to maintain clean and sanitary conditions, are unnecessary for use in laboratory testing procedures, are unnecessary for plant and equipment maintenance, and are unnecessary for use in plant operations. Specifically, *** Refuse receptacles for hand washing facilities are not [constructed] [maintained] to protect against contamination of food. Specifically, ***

14

13

13

13

Failure to identify, from processor check or otherwise, deviations from the scheduled process or critical factors which are out of control. Specifically, *** Maintenance of the grounds is inadequate to protect against contamination of food. Specifically, ***

13

13

You do not have records to document the performance and results of the affirmative steps taken to demonstrate that [fish] [fishery products] imported into the United States were processed in accordance with the seafood HACCP regulation. Specifically, *** You did not develop, or have developed for you, a written hazard analysis to determine whether there are food hazards that are reasonably likely to occur for [each type of] juice you produce. Specifically, *** . Specifically, *** In evaluating what food hazards are reasonably likely to occur, [you] [the person who performed the evaluation for you] did not consider [microbiological contamination] [parasites] [chemical contamination] [unlawful pesticide residues] [decomposition] [natural toxins] [use of unapproved color or food additives] [presence of undeclared ingredients that may be allergens] [physical hazards]. Specifically, *** The [conveyance] [storage] [disposal] of [rubbish] [offal] does not protect against contamination of [food] [food-contact surfaces] [water supplies] [ground surfaces]. Specifically, *** Failure to treat and maintain [batters] [breading] [sauces] [gravies] [dressings and similar preparations] in a manner that protects against [contamination] [growth of microorganisms]. Specifically, *** Failure to [test] [examine] containers often enough to ensure that containers suitably protect the food from leakage and contamination. Specifically, ***

13

13

13

12

12

12

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Your HACCP plan does not list the [procedures for monitoring] [frequency of monitoring] at each critical control point to ensure compliance with the critical limit. Specifically, You did not take corrective action that ensured [the affected product was segregated] [a review of the affected product was done to determine its acceptability] [affected product was not entered into commerce] [the cause of the deviation was corrected] [the HACCP plan was reassessed in a timely manner to determine if modifications were needed to reduce the risk of reoccurrence of the deviation and modified as necessary]. Specifically, *** Your verification activities do not include, at a minimum, [review of consumer complaints to determine whether they relate to the performance of the HACCP plan] [calibration of process monitoring instruments] [end-product or in-product testing] [review of critical control point monitoring, corrective action, and calibration records] to ensure that your HACCP system is being properly implemented. Specifically, *** Your HACCP plan does not list all food hazards that are reasonably likely to occur. Specifically, ***

12

12

12

12

Your HACCP plan [does not list one or more of the critical limits that must be met at each critical control point] [lists a critical limit that does not prevent, eliminate, or reduce to an acceptable level the occurrence of an identified food hazard]. Specifically, *** You did not submit an update to your facility's registration within 60 calendar days of [a change] [changes] to the registration information previously submitted. Specifically, *** Responsibility for assuring compliance with current good manufacturing practices relating to personnel has not been assigned to competent supervisory personnel. Specifically, *** You did not conduct at least one appropriate test or examination to verify the identity of a dietary ingredient, prior to its use. Specifically, *** You did not [establish] [follow] written procedures for quality control operations. Specifically, ***

12

11

11

11

11

Failure to properly maintain [roads] [yards] [parking lots] so that they do not constitute a source of contamination in areas where food is exposed. Specifically, *** Failure to [store] [handle] [dispense] [use] [dispose of] single-service articles in a manner that protects against the contamination of food and food-contact surfaces. Specifically, *** Failure to fully reprocess, thermally process as a low-acid food under 21 CFR 113, or set aside for further evaluation as to any potential public health significance, a portion of food which [deviated from a scheduled process] [had an equilibrium pH of the finished product higher than 4.6]. Specifically, ***

10

10

10

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Failure to provide FDA, before packing any new product, information as to the scheduled process for each low-acid canned food in each container. Specifically, *** Your [written hazard analysis] [written HACCP plan], required by the juice HACCP regulation, [was] [were] not signed and dated [upon initial acceptance] [upon modification] [upon verification] [upon validation] [by the most responsible individual onsite at the processing facility or by a higher level official]. Specifically, *** You do not maintain [complete] records documenting [the implementation of your sanitation standard operating procedure] [your written HACCP plan] [your written hazard analysis] [monitoring of critical control points and their critical limits] [corrective actions taken in response to a deviation] [the verification of your HACCP system] [the validation of your HACCP plan] [the validation of your hazard analysis]. Specifically, *** Your HACCP plan does not list the [procedures for monitoring] [frequency of monitoring] at each critical control point to ensure compliance with the critical limits. Specifically, *** Your HACCP plan does not list the critical control points for each of the identified food hazards. Specifically, ***

10

10

10

10

10

Your review of [critical control point monitoring records] [corrective action records] [calibration records] [periodic end-product or in-process testing records] are not [performed] [signed] [dated] by an individual who is trained in the application of HACCP principles to juice processing or otherwise qualified through job experience. Specifically, *** Your review of [critical control point monitoring records] [corrective action records] [calibration records] [periodic end-product or in-process testing records] are not [performed] [signed] [dated] by an individual who is trained in the application of HACCP principles to juice processing or otherwise qualified through job experience. Specifically, *** You did not [establish] [follow] written procedures for the requirements to review and investigate a product complaint. Specifically, ***

10

10

10

Employees who appear to have an [illness] [open lesion] [abnormal source of microbial contamination] are not excluded from operations where there is a reasonable possibility of [food] [food contact surfaces] [food packaging materials] becoming contaminated. Specifically, *** You [do not have] [have not implemented] a written standard sanitation operating procedure (SSOP). Specifically, ***

Appropriate quality control procedures are not employed to ensure that finished foods do not present a health hazard. Specifically, "***

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Failure to hold [raw materials] [rework materials] [ingredients] at proper temperature and humidity to prevent the food from becoming adulterated. Specifically, *** Your HACCP plan includes a corrective action plan that does not ensure that [no product injurious to health or otherwise adulterated will enter commerce] [the cause of the deviation will be corrected] when a deviation from a critical limit occurs. Specifically, *** Your required records do not [always] include [the name of the processor] [the name of the importer] [the location of the processor] [the location of the importer] [the date and time of the activity] [the signature or initials of the person performing the operation or creating the record] [the identity of the product] [the production code]. Specifically, *** You do not [always] have or have not implemented a sanitation standard operating procedure that addresses sanitation conditions and practices before, during and after processing. Specifically, *** An inadequate number of instruments used for [measuring] [regulating] [recording] conditions that control or prevent the growth of undesirable microorganisms. Specifically,*** The initial temperature of the contents of a container to be processed was [not determined] [not recorded] with sufficient frequency to ensure the temperature was not lower than the minimum initial temperature stated in the scheduled process. Specifically, *** Failure to clean and sanitize food-contact surfaces in wet-processing [before use] [after any interruption during which they may have been contaminated], to preclude contamination with microorganisms. Specifically, *** Failure to use water which is [safe] [of adequate sanitary quality] in food and on food-contact surfaces. Specifically, ***

A review of processing and production records by a qualified representative of plant management was not done [within one working day after the completion of the process] [before shipment or release for distribution] to determine [completeness of the records] [whether product was processed as specified by the scheduled process]. Specifically, *** Failure to use adequate [sterilization] [irradiation] [pasteurization] [freezing] [refrigeration] [pH control] [water activity control] to destroy or prevent the growth of undesirable microorganisms in food. Specifically, *** Failure to adequately [monitor pH] [maintain a pH of 4.6 or below] for foods that rely principally on the control of pH to prevent the growth of undesirable microorganisms. Specifically, *** Failure to identify material scheduled for rework as such. Specifically, ***

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Operators of processing and packaging systems are not under the operating supervision of a person who has attended and satisfactorily completed a school approved by the Commissioner. Specifically, *** The [processing] [production] records do not contain sufficient additional information such as [product code] [date] [container size] [product] to permit a public health hazard evaluation of the processes applied to each [lot] [batch] [portion] of production. Specifically, *** Lack of [an automatic control for regulating temperature] [an automatic temperature alarm system] for each freezer and cold storage compartment used to store food capable of supporting the growth of microorganisms. Specifically, *** The required container identification fails to include the [establishment where packed] [product] [year packed] [day packed] [period during which packed]. Specifically, *** Failure to register with the FDA information including the name, principal place of business and the location of the processing establishment within 10 days after engaging in the manufacture, processing and packaging of acidified foods. Specifically, *** Failure to process each food in conformity with at least the scheduled process filed with FDA. Specifically, ***

You did not correct sanitation deficiencies in a timely manner. Specifically,***

Your review of calibration records does not ensure [that the records are complete] [that the activities occurred in accordance with your written procedures]. Specifically, *** Your batch production record did not include complete information relating to the production and control of each batch. Specifically, ***

You have not provided evidence that the [fish] [fishery products] you import have been processed under conditions that comply with the Seafood HACCP regulation. Specifically, *** Your [monitoring] [corrective action] [verification] records are not maintained at your facility for at least the required time period. Specifically, *** There is no assurance that [raw materials] [ingredients] which are susceptible to contamination with aflatoxin or other natural toxins comply with current FDA standards before being incorporated into food. Specifically, *** Failure to maintain complete records covering all aspects of the establishment of the [process] [associated incubation tests] by the person or organization making the determination. Specifically, ***

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You did not [prepare] [follow] a written master manufacturing record for each batch size of a dietary supplement that you manufactured. Specifically, *** You did not make and keep documentation of training. Specifically, ***

Your HACCP Plan for [smoked] [smoke flavored] fishery product does not include controls for Clostridium botulinum. Specifically, ***

You did not make available for official review and copying at reasonable times [all records] [all plans and procedures] required by the regulations. Specifically, *** Required information was not entered on designated forms at the time the observation was made by the retort or processing system operator or designated person. Specifically, *** Forms used to record processing or production information lack the [product] [code number] [date] [retort or processing system number] [container size] [approximate number of containers per coding interval] [initial temperature] [actual processing time] [mercury-in-glass thermometer readings] [recording thermometer readings] [appropriate processing data]. Specifically, *** Heat-sensitive indicators or other means are not used to visually show that a thermal process has been applied to containers in a retort basket, truck, car, or crate used to hold containers in a retort. Specifically, *** Process deviations were not recorded in a separate file or log that details both the deviations and the actions taken. Specifically, ***

Failure to record observations of visual closure examinations performed by a qualified person during production. Specifically, ***

Food-contact surfaces are not made of non-toxic materials. Specifically, ***

Your HACCP plan is not specific to [each location where juice is processed] [each type of juice processed]. Specifically, ***

You did not review [all of] your [calibration] [periodic end-product testing] [in-process testing] records within a reasonable time after the records were made. Specifically, *** Your HACCP plan lists monitoring [procedures] [frequencies of performing procedures] that do not ensure compliance with the critical limits. Specifically, ***

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Your HACCP plan does not list the verification [procedures] [frequencies] that have been developed to ensure that the HACCP plan is being implemented. Specifically, *** You did not [establish] [follow] written procedures for maintaining, cleaning, and sanitizing, equipment, utensils, and any other contact surfaces that are used to manufacture, package, label, or hold components or dietary supplements. Specifically, *** You did not [maintain] [clean] [sanitize] equipment and utensils used to manufacture, package, label, or hold components or dietary supplements. Specifically, *** You did not hold [components] [dietary supplements] under appropriate conditions of temperature, humidity, or light so that their identity, purity, strength, and composition are not affected. Specifically, *** You did not [prepare] [follow] a written master manufacturing record for each unique formulation of a dietary supplement that you manufactured. Specifically, *** You did not conduct appropriate tests or examinations or rely on a certificate of analysis to determine whether components met established specifications. Specifically, *** You did not verify that your finished batch of dietary supplement meets product specifications for [identity] [purity] [strength] [composition] [limits on contamination that may adulterate or that may lead to adulteration of the dietary supplement]. Specifically, *** You have not identified personnel to be responsible for your quality control operations. Specifically, ***

During a field examination of food products at your facility the following [was] [were] observed:

You did not immediately modify your HACCP plan after a reassessment revealed the plan to no longer be adequate. Specifically, *** Operators of [processing systems] [retorts] [aseptic processing systems] [product formulating systems] are not under the operating supervision of a person that has attended and satisfactorily completed, a school approved by the Commissioner. Specifically, *** Failure to properly maintain operating systems for waste treatment and disposal so that they do not constitute a source of contamination in areas where food is exposed. Specifically, *** Failure to provide [adequate ventilation] [control equipment] to minimize odors and vapors in areas where they may contaminate food. Specifically, ***

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Scheduled processes for low-acid foods have not been established by qualified persons having expert knowledge of thermal processing. Specifically, *** Entries on [processing records] [production records] were not made at the time the specific retort or processing system condition or operation occurred. Specifically, *** [Raw materials] [Ingredients] which contain levels of microorganisms that may produce food poisoning or other disease are not pasteurized or otherwise adequately treated. Specifically, *** The function of supervising overall sanitation of the plant has not been designated to the supervision of one or more competent individuals assigned responsibility for this function. Specifically, *** You do not take a bacteriological swab and/or rinse count at least every three months from at least four containers and closures selected just prior to filling and sealing. Specifically, *** Failure to adequately [wash] [clean] raw materials as necessary to remove soil or other contamination. Specifically, ***

Failure to thaw frozen raw materials in a manner that prevents them and other ingredients from becoming adulterated. Specifically, ***

Departures from a scheduled process having a possible bearing on public health or the safety of a food are not [noted] [identified] [recorded] [made the subject of a separate file (or log identifying the appropriate data) delineating them]. Specifically, *** Records identifying initial distribution of finished product are not maintained. Specifically, ***

Systems that discharge waste water or sewage are cross-connected to systems that carry water for food or food manufacturing. Specifically, *** Automatic equipment used to handle filled containers is not designed or operated so as to preserve the can seam or other container closure integrity. Specifically, *** Failure to process each low-acid canned food in conformity with at least the scheduled process. Specifically, ***

Failure to have personnel involved in [retorts] [thermal processing systems] [aseptic processing and packaging systems] [thermal processing systems] [container closure inspections] under the operating supervision of a person who has attended and satisfactorily completed a school approved by the Commissioner. Specifically, ***

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Your HACCP plan does not include control measures that will consistently produce a 5 log reduction in the most resistant microorganism of public health significance that is likely to occur in the juice, for a period at least as long as the shelf life of the product. Specifically, *** You do not conduct the 5-log reduction process and perform final packaging of your juice within a single production facility operating under current good manufacturing practices. Specifically, *** You do not maintain records of [calibration of process-monitoring instruments] [periodic end-product or in-process testing]. Specifically, *** You did not take effective measures [to exclude pests from the physical plant] [to protect against contamination of components, dietary supplements, and contact surfaces on the premises by pests]. Specifically, *** You did not use effective measures to protect against the inclusion of metal or other foreign material in [components] [dietary supplements]. Specifically, *** You did not [establish] [follow written] procedures for holding and distributing operations. Specifically, ***

You did not establish product specifications for the [identity] [purity] [strength] [composition] of the finished dietary supplement. Specifically, *** Failure to dispose of adulterated [food] [raw materials] in a manner which protects against the contamination of other food. Specifically, *** You did not take immediate corrective action to ensure that [no affected product entered into commerce] [the cause of the deviation was corrected] [the HACCP plan was reassessed] when your verification procedure revealed the need to take a corrective action. Specifically, *** Supervisors have not satisfactorily completed training in a school approved by the Commissioner for areas under their responsibility. Specifically, *** The bottling room is not [adequately] separated from other plant operations or storage areas, so as to protect against contamination. Specifically, *** No acceptable scientific methods of establishing heat sterilization processes or procedures recognized by competent processing authorities were used in the determination of the scheduled process. Specifically, *** The mercury-in-glass thermometer was not the reference thermometer for indicating processing temperatures. Specifically, ***

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Failure to perform mechanical manufacturing steps so as to protect food against contamination. Specifically, ***

You do not maintain [adequate] records regarding [the intensity of the sanitizing agent] [the time duration that the sanitizing agent was in contact with the surface being sanitized]. Specifically, *** The system, equipment, and procedures used for thermal processing of foods in hermetically sealed containers [did not conform to the applicable requirements of 21 CFR 113.40] [did not conform to methods and controls specified in the scheduled process] [were not operated and administered in a manner that ensures commercial sterility is achieved]. Specifically, *** Each container is not marked with an identifying code permanently visible to the naked eye. Specifically, ***

Gloves used for food handling are not impermeable. Specifically, ***

Failure to maintain records of accuracy checks of temperatureindicating devices specifying [date] [standard used] [method used] [person performing the test]. Specifically, *** Failure to measure the cold water vacuum of the glass container capper before actual filling operations. Specifically, ***

Failure to [have a qualified person] perform appropriate detailed inspections and tests [at intervals of sufficient frequency] to ensure proper closing machine performance and consistently reliable hermetic seal production. Specifically, *** Failure to mark each hermetically sealed container of low-acid processed food with an identifying code that is permanently visible to the naked eye. Specifically, *** Quality control operations were not used at all times to reduce natural or unavoidable defects to the lowest level currently feasible

Failure to have personnel involved in [acidification] [pH control] [heat treatment] [critical factors] under the operating supervision of a person who has attended and satisfactorily completed a school approved by the Commissioner. Specifically, *** Failure to prepare and maintain in files current procedures for [recalling products which may be injurious to health] [identifying, collecting, warehousing and controlling products] [determining effectiveness of recalls] [notifying FDA] [implementing recall programs]. Specifically, *** You do not have records that [fully] document corrective actions that were taken. Specifically, ***

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Your HACCP plan does not include corrective action plans that have been developed. Specifically, ***

Your hand-washing facilities [are not adequate] [are not convenient] [do not furnish running water at a suitable temperature]. Specifically, *** You did not maintain your physical plant in repair sufficient to prevent components, dietary supplements, or contact surfaces from becoming contaminated. Specifically, *** Your batch production records did not include documentation, at the time of performance, of the manufacture of the batch. Specifically, ***

You did not hold components under conditions that will [protect against contamination] [protect against deterioration] [avoid mixups]. Specifically, *** You did not make and keep written procedures for holding and distributing operations. Specifically, ***

You did not [establish] [follow] written procedures for the tests and examinations conducted to determine whether specifications are met. Specifically, *** You did not verify that the laboratory examination and testing methodologies are appropriate for their intended use. Specifically, ***

You did not [establish] [follow] written procedures for manufacturing operations. Specifically, ***

The written instructions in your master manufacturing record did not include [procedures for sampling] [a cross-reference to procedures for tests or examinations]. Specifically, *** Your master manufacturing record did not include a statement of [the theoretical yield for each point, step, or stage of the manufacturing process to ensure quality control] [the expected yield of the finished dietary supplement.] Specifically, *** You did not perform manufacturing operations under conditions and controls that protect against [the potential for growth of microorganisms] [the potential for contamination]. Specifically, *** Your master manufacturing record did not identify specifications for the points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement. Specifically, ***

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You did not [establish] [follow] written procedures for labeling operations. Specifically, ***

You did not determine whether you met established product specifications for [identity] [purity] [strength] [composition of the finished batch of the dietary supplement]. Specifically, *** You did not qualify a supplier of a component by establishing the reliability of the supplier's certificate of analysis through confirmation of the results of their tests or examinations. Specifically, *** You did not collect and hold reserve samples of packaged and labeled dietary supplements that you distributed. Specifically, ***

You did not make and keep written procedures for the responsibilities of the quality control operations. Specifically, ***

You did not [establish] [follow] written procedures for when a returned dietary supplement is received. Specifically, ***

You did not implement a system of production and process controls that covers all stages of manufacturing, packaging, labeling, and holding of dietary supplements to ensure the quality of the dietary supplement. Specifically, *** You did not [establish] [follow] written procedures for quality control operations for conducting a material review and making a disposition decision. Specifically, *** You did not [establish] [follow] written procedures for determining personnel qualification requirements. Specifically, ***

The personnel you identified to perform quality control operations [are not qualified to do so] [do not have the education, training or experience to perform the assigned functions]. Specifically, *** The records that relate to the general adequacy of your [processes] [equipment] were not maintained for at least two years after their applicability to the product you produced. Specifically, *** The critical factors identified in the schedule process for the prevention of the growth of microorganisms not destroyed by the thermal process are not controlled in a manner to ensure the limits established are not exceeded. Specifically, *** Finished bottled water does not comply with bottled water quality standards. Specifically, ***

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Failure to have a deviation from the scheduled process evaluated for public health significance by a competent processing authority. Specifically, *** Required entries on [processing records] [production records] were not made by the retort or processing system operator or other designated person for specific retort operations or conditions specified in the scheduled process. Specifically, *** Failure to use a water supply that is [sufficient for the operations] [derived from an adequate source]. Specifically, ***

Written records of all container closure examinations did not specify [product code] [date of container closure inspection] [time of container closure inspection] [measurements obtained] [corrective actions taken]. Specifically, *** Written records of all container closure examinations are [not reviewed by management] [not reviewed by management with sufficient frequency] to ensure that the containers are hermetically sealed. Specifically, *** Mercury-in-glass thermometers were not tested against a known accurate standard thermometer [upon installation] [yearly] to ensure accuracy. Specifically, *** There is no assurance that [raw materials] [ingredients] [rework materials] which are susceptible to contamination with [pests] [undesirable microorganisms] [extraneous materials] comply with current FDA standards and defect action levels. Specifically, *** Failure to properly adjust the temperature-recording device. The temperature recorded on the temperature-recording device chart [was higher than] [did not agree with] the mercury-in-glass thermometer during processing. Specifically, *** Bleeders were [smaller than 1/8-inch] [not wide open during the entire process] [not open during come-up-time]. Specifically, ***

You do not maintain records at the plant pertaining to physical inspection of equipment used for treatment of product water, including the [type and date] [conditions found] [performance and effectiveness of equipment]. Specifically, *** You do not [sample] [test] cleaning and sanitizing solutions [as often as necessary] to assure adequate performance. Specifically, ***

Acidified foods are not thermally processed to an extent that is sufficient to destroy the vegetative cells of microorganisms of public health significance and those of nonhealth significance capable of growing in the food. Specifically, *** Failure to sanitize and thoroughly dry, prior to use, food-contact surfaces which have been wet cleaned. Specifically, ***

Page 218

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Failure to [have a qualified individual] perform teardown examinations of double seam cans . Specifically, ***

No measurable residual of the cooling water sanitizer at the water discharge point of the container cooler. Specifically, ***

Failure to record the action taken to rectify a departure from a scheduled process. Specifically, ***

Failure to provide the FDA, after written request, any process and procedure information deemed necessary to determine the adequacy of the process. Specifically, *** You do not have written procedures that describe [product specifications] [affirmative steps] to ensure that juice you receive for import into the United States was processed in accordance with the juice HACCP regulation. Specifically, *** Your written hazard analysis does not consist of [an identification of food hazards] [an evaluation of each food hazard identified to determine if it must be addressed in the HACCP plan] [an identification of the control measures that can be applied] [a review of your current process to determine whether modifications are necessary] [an identification of critical control points]. Specifically, *** Your records do not [always] contain the actual values and observations obtained during monitoring. Specifically, ***

Your HACCP plan does not provide for a recordkeeping system that documents the monitoring of critical control points. Specifically, ***

You did not [establish] [follow] written procedures for calibrating instruments and controls that you use in manufacturing or testing a component or dietary supplement. Specifically, *** You did not calibrate instruments or controls used in manufacturing or testing a component or dietary supplement [before the first use] [at the frequency specified in writing by the manufacturer or at routine intervals or as necessary] to ensure the accuracy and precision of the instruments or controls. Specifically, *** You did not prepare a batch production record every time you manufactured a batch of dietary supplement. Specifically, ***

You did not maintain your physical plant in a clean and sanitary condition. Specifically, ***

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You did not [establish] [follow] written procedures for pest control. Specifically, ***

Your batch production records did not include documentation that quality control personnel approved and released, or rejected, the packaged and labeled dietary supplement. Specifically, *** The written instructions in your master manufacturing did not include instructions for corrective action plans to use when specifications are not met. Specifically, *** Your master manufacturing record did not include a [description of the packaging] [a representative label, or a cross-reference to the physical location of the actual or representative label]. Specifically, You did not make and keep records of written procedures for fulfilling requirements for returned dietary supplements. Specifically, ***

Your master manufacturing record did not establish [controls] [procedures] to ensure that each batch met specifications. Specifically, *** You did not protect manufactured dietary supplements from contamination during [filling] [assembling] [packaging] [labeling] operations. Specifically, *** Your quality control personnel did not [review and approve decisions about whether to investigate a product complaint] [review and approve the findings and followup action of an investigation]. Specifically, *** You did not make and keep documentation of calibrations for instruments or controls that you use in manufacturing or testing a component or dietary supplement. Specifically, *** Your quality control personnel did not review and approve the documentation setting forth the basis for why the results of appropriate tests or examinations for each product specification will ensure that the finished batch of the dietary supplement meets product specifications. Specifically, *** Your quality control personnel did not perform required operations for the [master manufacturing record] [batch record] [manufacturing operations]. Specifically, *** Your quality control operations did not include reviewing and approving the results of required [tests] [examinations]. Specifically, ***

You did not collect representative samples [of a subset] of finished batches of dietary supplements that you manufacture [before releasing for distribution] to verify that the finished batch of dietary supplement meets established product specifications. Specifically, ***

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You did not make and keep documentation of the controls you use to ensure that equipment functions according to its intended use. Specifically, *** You did not implement quality control operations to ensure the quality of the dietary supplement. Specifically, ***

You did not establish an identity specification for each component. Specifically, ***

You did not establish component specifications for [purity] [strength] [composition]. Specifically, ***

You did not establish in-process specifications for a point, step, or stage in the master manufacturing record where control is necessary to help ensure that specifications are met for [identity] [purity] [strength] [composition]. Specifically, *** Your personnel did not thoroughly [wash] [wash and sanitize] their hands in an adequate hand-washing facility [before starting work] [at any time when the hands may have become soiled or contaminated]. Specifically, *** Personnel engaged in [manufacturing] [packaging] [labeling] [holding] dietary supplements do not have the education, training, or experience to perform the person's assigned functions. Specifically, *** Personnel with adverse health conditions are not instructed to report to their supervisors. Specifically, ***

The records that document the performance and results of the affirmative step you chose are not in English. Specifically, ***

You did not immediately return your records for official review upon demand. Specifically, ***

Failure to ensure that compressed air or other gases [mechanically introduced into food] [used to clean food-contact surfaces or equipment] have been treated in such a way that foods are not contaminated with unlawful indirect food additives. Specifically, *** You do not [wash] [sanitize] containers for bottled drinking water in an enclosed room. Specifically, ***

Forms used in recording specific processing and production information for still retorts lack [the time that steam was turned on] [the time that the retort reached processing temperature] [the time that steam was shut off] [venting time] [venting temperature]. Specifically, ***

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You do not take and analyze samples of [product] [operations] source water [as often as necessary] [at least once every year for chemical contamination] [at least once every four years for radiological contaminants]. Specifically, *** The [product] [operations] source water that is obtained from other than a public water system is not sampled and analyzed for microbiological contaminants at least once each week. Specifically, *** You do not adequately [clean] [sanitize] the product water-contact surfaces of all [multiservice containers] [utensils] [pipes] [equipment] used in the [transportation] [processing] [handling] [storage] of product water. Specifically, *** You do not [fill] [cap] [close] [seal] [package] containers in a sanitary manner so as to preclude contamination of the bottled drinking water. Specifically, *** Operating processes for each product and container size were not [posted in a conspicuous place near the processing equipment] [readily available to the retort or processing system operator] [readily available to FDA investigators]. Specifically, *** Recording thermometer charts were not identified by [date] [retort number] [data to correlate with written records of lots processed]. Specifically *** The [guard dog] [guard dogs] [guide dog] [guide dogs] in the plant are likely to result in the contamination of [food] [food-contact surfaces] [food-packaging materials]. Specifically, *** Failure to install a mercury-in glass thermometer on each retort. Specifically, ***

There was no means to prevent unauthorized changes in adjustment to the temperature-recording device. Specifically, ***

Failure to install bleeders so that the operator can observe that they are functioning properly. Specifically, ***

You do not keep records of [inspection and conditions found] [physical maintenance] [performance] for mechanical washers. Specifically, ***

Sanitizing operations are not adequate to effect sanitation of the intended product water-contact surfaces and critical areas. They do not meet the minimum times and intensities required by the regulations. Specifically, *** Failure to install a [nonclogging] [water tight] drain valve [with screened openings]. Specifically, ***

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Failure to install a mercury-in glass thermometer on each retort. Specifically, ***

There was no means to prevent unauthorized changes in adjustment to the temperature-recording device. Specifically, ***

You do not identify each unit package from a [batch] [segment of a continuous production run] of bottled drinking water with a production code which identifies [the particular batch] [the segment of production run] [the day produced]. Specifically, *** You do not record and maintain information as to the [kind of product] [volume produced] [date produced] [lot code used] [distribution of finished product to wholesale and retail outlets]. Specifically, *** Samples for [bacteriological] [chemical] [physical] [radiological] analysis are not primary containers or unit packages from a batch or segment of a continuous run for each type of bottled drinking water. Specifically, *** You do not take and analyze samples of bottled drinking water for bacteriological testing at least once a week [for each type of bottled drinking water produced during a day's production run]. Specifically, *** Food which has become contaminated to the extent of being adulterated within the meaning of the Act is not rejected or if permissible, treated or processed to eliminate the contamination.. Specifically, *** Your treatment of product water is not done in such a manner as to be effective in accomplishing the intended purpose. Specifically, ***

Critical factors were not [measured] [recorded on the processing record] at intervals of sufficient frequency to ensure that the factors are within the limits specified in the scheduled process. Specifically, *** Failure to properly adjust the temperature-recording device. The temperature recorded on the temperature-recording device chart [was higher than] [did not agree with] a known accurate mercury-in-glass thermometer. Specifically, *** Measurements or observations of the [temperature-indicating device in the holding tube outlet] [temperature recorder in the holding tube outlet] [temperature recorder-controller at the final heater outlet] [differential pressure recorder-controller] [product flow rate] [sterile air pressure] [proper performance of seam seals or similar devices] were not [performed] [recorded] at intervals of sufficient frequency to ensure the values were as specified in the scheduled process for aseptic packaging operations. Specifically *** Acidified foods are not manufactured, processed and packaged to [achieve within the time designated in the scheduled process] [maintain] a pH value of 4.6 or lower in all finished foods. Specifically, ***

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Process deviations are not evaluated by a competent processing authority in accordance with procedures recognized by competent processing authorities as being adequate to detect any potential hazard to public health. Specifically, *** Required records are not maintained at the processing plant or other reasonably accessible location for a period of three years from the date of manufacture. Specifically, *** Failure to record the [procedures used in the evaluation of process deviations] [results of process deviation evaluations]. Specifically, ***

Failure to take adequate care to exclude contamination of food from adverse conditions on bordering grounds not under your control. Specifically, *** Failure to provide employees with [readily accessible] [adequate] toilet facilities. Specifically, ***

Failure to inspect [containers] [carriers] of raw materials upon receipt to ensure that their condition does not contribute to the contamination or deterioration of food. Specifically, *** Failure to record visual container closure observations [at intervals of thirty (30) minutes or less] [following a jam in a closing machine] [after closing machine adjustment] [after startup following a prolonged shutdown]. Specifically, *** Failure to note corrective actions taken following teardown examination of double seam cans. Specifically, ***

Failure to chlorinate or otherwise sanitize container cooling water as necessary for cooling canals and recirculated water supplies. Specifically, *** Failure to record the disposition of product involved in a departure from a scheduled process. Specifically, ***

Immediately after notification that a batch of color additive has been certified, the person requesting certification did not label the batch with the certified lot number. Specifically, ***

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Your HACCP plan does not include a corrective action plan. There was a deviation from a critical limit and you did not take corrective action that ensured [affected product was segregated and held] [a review of the affected product by someone who is adequately trained or experienced was done to determine its acceptability] [product that was injurious to health or otherwise adulterated was not entered into commerce] [the cause of the deviation was corrected] [the HACCP plan was verified by someone meeting the training requirements of the regulation to determine if modifications were needed to reduce the risk of recurrence of the deviation and to modify the HACCP plan as necessary]. Specifically, ***

Processing and other information is not [always] entered on your records at the time it is observed. Specifically, ***

Your [validation of the HACCP plan] [validation of the hazard analysis] was not done by an individual who had successfully completed training in the application of HACCP principles to juice processing or otherwise qualified through job experience to perform these function. Specifically, *** Your review of critical control point monitoring records does not [ensure that the records are complete] [verify that they document values that are within critical limits]. Specifically, *** You do not [always] analyze your finished juice product for biotype I Escherichia coli. Specifically, ***

You do not take product water samples after processing and prior to bottling. Specifically, ***

You did not retain at the plant current certificates or notifications of approval issued by the government agency or agencies approving the source and supply of product water and operations water. Specifically, *** Your HACCP plan includes a corrective action plan. There was a deviation from a critical limit and you did not take corrective action that ensured [product that was injurious to health or otherwise adulterated did not enter commerce] [the cause of the deviation was corrected]. Specifically, *** You have not implemented affirmative steps to ensure juice you receive for import into the United States was processed in accordance with the juice HACCP regulation. Specifically, *** Your physical plant did not use adequate screening or other protection against pests. Specifically, ***

You did not make and keep records of the written procedures for [cleaning the physical plant] [pest control]. Specifically, ***

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You did not [establish] [follow] written procedures for fulfilling the requirements for equipment and utensils. Specifically, ***

You did not perform each step in the production of a batch, according to the master production record. Specifically, ***

Your batch production records did not include [a statement of the actual yield] [a statement of the percentage of theoretical yield] at appropriate phases of processing. Specifically, *** Your batch production records did not include the actual results obtained during a monitoring operation. Specifically, ***

You did not assign one or more employees to supervise overall sanitation. Specifically, ***

You did not [establish] [follow] written procedures for cleaning the physical plant. Specifically, ***

Your [floors] [walls] [ceilings] were not designed and constructed so they can be adequately cleaned and kept clean and in good repair. Specifically, *** Your batch production records did not include initials of the persons performing each step. Specifically, ***

Your batch production records did not include documentation that quality control personnel reviewed the batch production record. Specifically, *** You did not [establish] [follow] written procedures for the requirements for components of dietary supplements. Specifically, ***

You did not [establish] [follow] written procedures for the requirements for labels received. Specifically, ***

You did not hold components under conditions that will [protect against contamination] [protect against deterioration] [avoid mixups]. Specifically, *** You did not visually examine the supplier's invoice, guarantee, or certification in a shipment of received product to ensure that the received product was consistent with your purchase order. Specifically, ***

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You did not make and keep written procedures for fulfilling the requirements that apply to packaging and labeling received. Specifically, *** Your reserve sample of a dietary supplement was not held using the same container-closure system in which the packaged and labeled dietary supplement was distributed. Specifically, *** You did not retain reserve samples for the required time. Specifically, ***

You did not [establish] [follow] sampling plans for obtaining representative samples. Specifically, ***

You did not take necessary precautions during the manufacture of a dietary supplement to prevent contamination of [components] [dietary supplements]. Specifically, *** You did not identify and use an appropriate scientifically valid method for each established specification for which testing or examination is required to determine whether the specification was met. Specifically, *** The documentation for laboratory tests and examinations did not include the results of the testing and examination. Specifically, ***

You held [components] [dietary supplements] [packaging] [labels] under conditions that lead to mix-up, contamination, or deterioration. Specifically, *** Your quality control personnel did not approve or reject the release for distribution of a returned dietary supplement that was reprocessed. Specifically, *** You did not make and keep records of a material review and disposition decision on a returned dietary supplement. Specifically, ***

Your quality control personnel did not approve or reject each batch of [repackaged] [relabeled] dietary supplement prior to its release for distribution. Specifically, *** You did not suitably dispose of labels and packaging for dietary supplements that are obsolete or incorrect to ensure that they are not used in any future packaging and label operations. Specifically, *** You did not [identify] [identify by effective means] filled dietary supplement containers that are set aside and held in unlabeled condition for future label operations, to prevent mixups. Specifically, ***

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You did not establish physical or spatial separation of [packaging] [label] operations from operations on other components and dietary supplements to prevent mixups. Specifically, *** You did not [fill] [assemble] [package] [label] [perform operations related to packaging and labeling] in a way that ensured that the dietary supplement is packaged and labeled as specified in the master manufacturing record. Specifically, *** You did not control the [issuance] [use] of labels, Specifically, ***

You did not [establish] [follow] written procedures for packaging operations. Specifically, ***

You did not make and keep records of the written procedures for [packaging] [labeling] operations. Specifically, ***

A qualified person did not review a product complaint to determine whether the product complaint involves a possible failure of a dietary supplement to meet specifications or any other requirements. Specifically, *** You did not make and keep written procedures to fulfill the requirements that apply to the review and investigation of a product complaint. Specifically, *** The person who performed a requirement relating to product complaints did not document, at the time of performance, that the requirement was performed. Specifically, *** You do not have quality control operations for [packaging] [labeling]. Specifically, ***

Your calibration documentation did not [identify the instrument or control calibrated] [provide the date of calibration] [identify the reference standard used] [include the certification of accuracy of the known reference standard] [include a history of recertification of accuracy of a known reference standard] [identify the calibration method used] [include appropriate limits for accuracy and precision] [provide the calibration reading or readings found] [identify the recalibration method used] [identify the reading or readings of recalibration found if the accuracy or precision limits were not met] [include the initials of the person who performed the calibration or recalibration]. Specifically, *** Your quality control operations did not include periodically reviewing all records for calibration of instruments and controls. Specifically, ***

Your quality control operations did not include determining whether [components] [packaging] [labels] conform to established specifications. Specifically, ***

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Your quality control operations did not include approving and releasing, or rejecting, each finished batch for distribution. Specifically, ***

You did not select one or more established specifications for [identity] [purity] [strength] [composition] [limits on contamination that may adulterate or that may lead to adulteration of the dietary supplement] that, if tested or examined on the finished batches of the dietary supplement, would verify that the production and process control system is producing a dietary supplement that meets all product specifications. Specifically, *** You did not conduct appropriate tests or examinations to determine compliance with the specifications established for [identity] [purity] [strength] [composition] [limits on contamination that may adulterate or that may lead to adulteration of the dietary supplement]. Specifically, *** You did not provide adequate documentation of your basis for determining that compliance with the specification[s] you selected for identity, purity, strength, and composition will ensure that the finished batch of dietary supplement meets the specification[s]. Specifically, *** You did not ensure that the tests or examinations that you used to determine whether the specifications are met are appropriate, scientifically valid methods. Specifically, *** You did not establish a corrective action plan to use when an established specification is not met. Specifically, ***

The written record of a product complaint did not include the [findings of the investigation] [followup action taken]. Specifically, ***

You did not establish a specification for a point, step, or stage in the manufacturing process where control is necessary to ensure [the quality of the dietary supplement] [that the dietary supplement is packaged and labeled as specified in the master manufacturing record]. Specifically, *** You did not establish limits for contamination that may adulterate or may lead to adulteration of the finished dietary supplement. Specifically, *** You did not establish product specifications for limits on contamination that may adulterate, or that may lead to adulteration of, the finished dietary supplement. Specifically, *** You did not establish specifications to [sufficiently] assure that the product you received for packaging or labeling as a dietary supplement is adequately identified and is consistent with your purchase order. Specifically, Your quality control personnel did not approve or reject [processes] [specifications] [written procedures] [controls] [tests] [examinations] [deviations or modifications] that may affect the identity, purity, strength, or composition of a dietary supplement. Specifically, ***

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Your personnel did not use hygienic practices to the extent necessary to protect against contamination of components, dietary supplements, or contact surfaces. Specifically, *** Your personnel did not remove hand jewelry that cannot be adequately sanitized during periods in which components or dietary supplements are manipulated by hand. Specifically, *** Your personnel used gloves that were not [intact] [clean] [in a sanitary condition] [made of impermeable material]. Specifically, ***

Your personnel did not wear [effective] hair restraints [in an effective manner]. Specifically, ***

You did not make and keep written procedures for [preventing microbial contamination from sick or infected personnel] [hygienic practices] [determining personnel qualification requirements]. Specifically, *** An adverse event report for a dietary supplement was not submitted to the Secretary of HHS within 15 business days of receipt of the report,. Specifically, *** No report was made of a serious adverse event associated with a dietary supplement marketed in the United States. Specifically, ***

Failure to use a proven effective method of reconditioning adulterated food. Specifically, ***

Failure to make regular observations for gross closure defects during production runs. Specifically ***

Your computerized records do not provide that appropriate controls are implemented to ensure the integrity of the electronic data and signatures. Specifically, *** Hermetically sealed containers do not have an identifying code permanently visible to the naked eye. Specifically ***

You do not conduct processing operations in a sealed system under pressure, and you do not provide [adequate] protection against contamination of the water and the system. Specifically, *** The ventilation in the [processing room] [bottling room] [container washing and sanitizing area] is not adequate to minimize condensation. Specifically, ***

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Proper precautions to protect food in outdoor bulk fermentation vessels cannot be taken because of deficiencies in plant [construction] [design]. Specifically, *** The filling of containers is not controlled to ensure that the filling requirements specified in the scheduled process are met. Specifically, *** The exhausting of containers for removal of air is not controlled to meet the conditions for which the process was designed. Specifically, *** The equilibrium pH of the finished product is not controlled so as to meet the pH requirements in the scheduled process. Specifically, ***

Failure to provide accurate timing devices to ensure that the processing and venting times specified in the scheduled process are achieved. Specifically, *** Failure to keep on file evidence that mufflers on [bleeders] [the vent system] are operating in a manner that does not impede the removal of air . Specifically, *** Distribution records are not maintained to identify the initial distribution of the finished product. Specifically, ***

You do not maintain records on file at the plant pertaining to [approval of the source water by government agencies] [sampling and analyses for which you are responsible]. Specifically, *** Single service [containers] [caps] [seals] are not [examined] [washed, rinsed and sanitized when necessary] [handled in a sanitary manner] prior to use. Specifically, *** Not all plant equipment and utensils are suitable for their intended use. Specifically, ***

Not all material used for product water contact surfaces [is nontoxic and nonabsorbent] [can be adequately cleaned and sanitized] [is in compliance with section 409 of the Federal Food, Drug and Cosmetic Act]. Specifically, *** Critical factors that may affect the scheduled process are not specified in the scheduled process. Specifically, ***

Calculations used to determine heat sterilization processes were not performed according to procedures recognized by competent processing authorities. Specifically, ***

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Incubation tests for confirmation of the scheduled process did not include containers from each of four or more actual commercial production runs. Specifically, *** Scheduled processes were not readily available to the [retort or processing system supervisor] [FDA Investigator]. Specifically, ***

A system of traffic control to prevent unretorted product from bypassing the retort system has not been established. Specifically, ***

No records were made of the [procedures] [results] of the evaluation done by a process authority following a deviation from the scheduled process. Specifically, *** Failure to fully reprocess or destroy product determined by a competent processing authority not to have received a thermal process sufficient to render it free of microorganisms of potential public health significance. Specifically, *** Forms used in recording specific processing and production information for other systems lack critical factors specified in the formulation of the product or in the scheduled process. Specifically, *** Food contact surfaces used for [manufacturing] [holding] low-moisture food were [wet] [insanitary] at time of use. Specifically, ***

Failure to clean and sanitize utensils and food-contact surfaces of equipment in continuous wet-processing operations as necessary. Specifically, *** Plumbing is not [of adequate size and design] [adequately installed and maintained] to carry sufficient quantities of water to required locations throughout the plant. Specifically, *** The mercury-in-glass thermometer [had divisions not readable to 1 degree F] [had a temperature range that exceeded 17 degrees per inch of graduated scale]. Specifically, *** Failure to equip retorts with automatic steam controllers to maintain retort temperatures. Specifically, ***

Graduations on the temperature-recording device exceeded 2 degrees F within a range of 10 degrees F of the processing temperature. Specifically, *** Failure to have a 1/16-inch or larger bleeder. Specifically, ***

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Your HACCP plan for raw molluscan shellfish does not include controls to ensure the molluscan shellfish are harvested from an approved source. Specifically, *** Critical factors are not [measured] [recorded] on the processing record at intervals of sufficient frequency to ensure that the factors are within limits specified in the scheduled process. Specifically, *** Closing machine vacuum is not [observed] [recorded] at intervals of sufficient frequency to ensure that the vacuum is as specified in the scheduled process. Specifically, *** A mercury-in-glass thermometer [lacked divisions readable to 1 degree F] [had a temperature range that exceeded 17 degrees per inch of graduated scale]. Specifically, *** Mercury-in-glass thermometers were not tested against a known accurate standard thermometer [upon installation] [at least once a year] [as frequently as necessary]. Specifically, *** A mercury-in-glass thermometer was not the reference instrument used for indicating processing temperatures. Specifically, ***

Graduations on the temperature-recording device exceeded 2 degrees F within a range of 10 degrees F of the processing temperature. Specifically, *** There is no means to determine the water level in a retort during operations. Specifically, ***

The operator failed to [check] [record] the water level at intervals sufficient to ensure adequacy of the water level. Specifically, ***

There is no check valve provided in the air supply line to prevent water from entering the air supply line. Specifically, ***

You do not take and analyze samples of bottled drinking water for [chemical] [physical] [radiological] testing at least annually [for each type of bottled drinking water produced during a day's production run]. Specifically, *** You did not reject or reprocess containers that were not [sound] [properly capped or sealed] [properly coded and labeled]. Specifically, *** Mercury-in-glass thermometers were not installed where they can be accurately and easily read. Specifically, ***

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There was no means of preventing unauthorized changes in adjustment to the temperature-recording device. Specifically, ***

The condensate bleeder was not checked with sufficient frequency to ensure removal of condensate or equipped with an automatic alarm system for the continuous monitoring of condensate bleeder functioning. Specifically, *** Failure to keep frozen raw materials frozen prior to use. Specifically, ***

Critical factors were not [measured] [recorded] at intervals of sufficient frequency to ensure that the factors are within limits specified in the scheduled process. Specifically, *** Each retort did not have a mercury-in glass thermometer (MIG). Specifically ***

The temperature-indicating device was not used as the reference instrument for indicating processing temperatures. Specifically, ***

There is no means of preventing unauthorized changes in adjustment to the temperature-recording device. Specifically, ***

Process deviations are not handled in accordance with 21 CFR 113.89. Specifically, ***

The time and temperature of processing and other critical factors specified in the scheduled process were not measured with instruments having adequate accuracy or dependability. Specifically, *** Critical factors are not [measured] [recorded] at intervals of sufficient frequency to ensure that the factors are within limits specified in the scheduled process. Specifically, *** The [container and closure sterilization system] [product filling and closing system] was not instrumented to demonstrate that required sterilization is being accomplished continuously. Specifically, *** Automatic recording devices were not used to record [sterilization media flow rates] [temperature] [concentration] [factors specified in the scheduled process] for container sterilizing, filling, and closing operations. Specifically, *** Observations and measurements of operating conditions did not include [sterilization media flow rates] [temperatures] [container and closure rates through the sterilizing system] [batch container sterilization conditions]. Specifically, ***

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Critical factors are not [measured] [recorded] at intervals of sufficient frequency to ensure that the factors are within limits specified in the scheduled process. Specifically, *** Failure to keep food-contact surfaces used in the [manufacture] [holding] of low-moisture food in a dry, sanitary condition at the time of use. Specifically, *** Water [used] [re-used] to [wash] [rinse] [convey] food is not [safe] [of adequate sanitary quality]. Specifically, ***

Perforations in the steam spreader along the bottom of the retort are not located along the top 90 degrees of the steam spreader. Specifically, *** Failure to provide a tag, seal, or other means of identity, including the date of last calibration of the mercury-in-glass thermometer. Specifically, *** Failure to have adequate filter systems to ensure a supply of clean, dry air to air-operated temperature controllers. Specifically, ***

Failure of the operator, closure supervisor, or other qualified person to visually examine [the top seam of a can randomly selected from each seaming head] [the closure of a typical container]. Specifically *** Failure to record all pertinent visual closure observations. Specifically, ***

Teardown examinations of double seam cans (and recording of the results) were performed at intervals exceeding four hours. Specifically, *** Failure to record teardown examinations of double seam cans [at intervals of sufficient frequency] [on enough containers from each seaming station] to ensure maintenance of seam integrity. Specifically, *** Failure to have heat distribution data on file which demonstrates that adequate venting of air is accomplished, for retort installations which deviate from the diagrams in [113.40(a)(12)(i)(a)] [113.40(a)(12)(i)(b)] [113.40(a)(12)(i)(c)] [113.40(a)(12)(i)(d)] [113.40(a)(12)(ii)(a)] [113.40(a)(12)(ii)(b)]. Specifically, *** Failure to provide for the type, range, and combination of variations encountered in commercial production in establishing the scheduled process. Specifically, *** Failure to register with the FDA information including the name, principal place of business and the location of the processing establishment within 10 days after engaging in the manufacture, processing and packaging of low-acid canned foods. Specifically, ***

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Failure to obtain substantiation by a qualified scientific authority as to the adequacy of any intentional change in a previously filed scheduled process, where the change is basic to the adequacy of that scheduled process. Specifically, *** Failure to permit [inspection] [copying] of records [of processing] [of deviations in processing] [of container closure inspections] [specified in 21 CFR 113], upon written demand by FDA, to verify the adequacy of processing, the integrity of container closure and the coding of the product. Specifically, *** For an intentional change in a previously filed scheduled process, substantiation was not [promptly recorded] [verified in writing by the authority] [placed in your files for review by FDA]. Specifically, *** For an intentional change in a previously filed scheduled process, failure to submit to CFSAN, within 30 days after first use, [a complete description of the modifications made and utilized] [a copy of the file record showing prior substantiation by a qualified scientific authority as to the safety of the changed process]. Specifically, *** A color additive subject to certification intended for use in the manufacture of a cosmetic is not from a certified batch. Specifically, ***

Color additive was not labeled with [the name of the straight color] [the name of each ingredient comprising the color additive] [a statement indicating general limitations for use] [the amount of each straight color in terms of weight per unit/volume or percent by weight] [an expiration date]. Specifically, *** Failure to conduct stability analysis on representative samples of finished product batches. Specifically, ***

Failure to maintain records of the results of all testing conducted to provide certificates and guarantees concerning nutrient premixes for infant formulas. Specifically, *** Failure to provide a "Use by ____" date on an infant formula label. Specifically, ***

You did not evaluate [product ingredients] [processing procedures] [packaging] [storage] [intended use] [facility and equipment function and design] [plant sanitation, including employee hygiene] to determine the potential effect on the safety of the finished food for the intended consumer. Specifically, *** You did not immediately modify your HACCP plan after a validation revealed that the plan was no longer adequate. Specifically, ***

Your treatments intended to achieve a 5-log reduction in the most resistant microorganism of public health significance are not applied directly to the juice, and the exemption for surface treatment of fruit does not apply. Specifically, ***

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You do not process and perform final product packaging in a single facility operating under current good manufacturing practices. Specifically, *** Your [product] [operations] source water from a non-public source has been treated with a chlorine-based disinfectant or ozone, but has not been tested for residual disinfectants and disinfection by-products that are likely to result from such treatment. Specifically, *** You do not analyze product water samples as often as necessary to assure uniformity and effectiveness of the treatment processes performed by the plant. Specifically, *** For analyses of bottled water, you do not maintain records of [date of sampling] [type of product] [production code] [results]. Specifically, ***

You do not maintain records of [sampling] [testing] of cleaning and sanitizing solutions. Specifically, ***

Your HACCP plan does not list the validation [procedures] [frequencies] that have been developed to ensure that the HACCP plan is adequate to control food hazards that are reasonably likely to occur. Specifically, *** When a teardown examination revealed gross closure defects, [adequate] corrective action was not taken. Specifically, ***

The surface treatments on your citrus fruit do not ensure a 5 log reduction in the most resistant microorganism of public health significance because [the process begins before culling and cleaning] [the fruit is not tree picked] [the 5 log pathogen reduction is not performed in a single facility]. Specifically, *** Your training documentation did not include the [date of the training] [type of training] [persons trained]. Specifically, ***

You [did not have] [did not use] separate or defined areas of adequate size or other control systems prevent contamination or mixups of components or dietary supplements during holding operations. Specifically, *** You did not make and keep records that show that the water you use [complies with applicable Federal, State, and local requirements] [does not contaminate the dietary supplement]. Specifically, *** You did not use equipment or utensils of appropriate design, construction, and workmanship to enable them to be [suitable for its intended use] [adequately cleaned] [properly maintained]. Specifically, *** Your freezer, refrigerator, or other cold storage compartment that you use to hold components or dietary supplements does not have an indicating thermometer, temperature-measuring device, or temperaturerecording device that indicates and records, or allows for recording by hand, the accurate temperature within the compartment. Specifically, ***

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You used instruments or controls that were not [accurate and precise] [adequately maintained] [adequate in number for their designated uses]. Specifically, *** You did not [maintain] [clean] [sanitize] equipment, utensils, and contact surfaces used to manufacture, package, label, or hold components or dietary supplements. Specifically, *** You did not clean surfaces that do not come into direct contact with components or dietary supplements as frequently as necessary to protect against contaminating components or dietary supplements. Specifically, *** You did not routinely [calibrate] [inspect] [check] the automated, mechanical, or electronic equipment to ensure proper performance. Specifically, *** Your quality control personnel did not periodically review routine [calibrations] [inspections] [checks] of your automated, mechanical, or electronic equipment. Specifically, *** You did not [establish] [use] appropriate controls to ensure that your automated, mechanical, or electronic equipment functions in accordance with its intended use. Specifically, *** Your batch production record did not accurately follow the appropriate master manufacturing record. Specifically, ***

You did not keep batch production records as original records, true copies, or as electronic records. Specifically, ***

Your batch production records did not include the identity of equipment and processing lines used in producing the batch. Specifically, ***

Your batch production records did not include the date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross-reference to records, such as individual equipment logs, where this information is retained. Specifically, *** Your batch production records did not include the unique identifier that you assigned to [a component] [a product that you received from a supplier for packaging or labeling as a dietary supplement] [the packaging used] [the label used]. Specifically, *** Water that does not become a component of the dietary supplement was not [safe and sanitary] [at suitable temperature] [under appropriate pressure] for all uses. Specifically, *** You did not use cleaning compounds that [are free from microorganisms of public health significance] [are safe and adequate under the conditions of use]. Specifically, ***

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You did not [identify] [hold] cleaning compounds, sanitizing agents, pesticides, pesticide chemicals, or other toxic materials in a manner that protects against contamination of components, dietary supplements, or contact surfaces. Specifically, *** The plumbing in your physical plant allows [backflow from] [cross connection between] piping systems that discharge waste water or sewage and piping systems that carry water used for manufacturing dietary supplements, for cleaning contact surfaces, or for use in bathrooms or hand-washing facilities. Specifically, *** Your physical plant did not have adequate space for the orderly placement of equipment and holding of materials as necessary [for maintenance, cleaning, and sanitizing operations] [to prevent contamination and mixups of components and dietary supplements]. Specifically, *** Your physical plant did not have [adequate ventilation] [environmental control equipment] to minimize odors and vapors in areas where they may contaminate components, dietary supplements, or contact surfaces. Specifically, *** You [did not have] [did not use] separate or defined areas of adequate size or other control systems to prevent contamination or mixups of components or dietary supplements by separating components, dietary supplements, packaging, and labels that are to be used in manufacturing from those that are awaiting material review and disposition decision, reprocessing, or disposal. Specifically, *** Your batch production records did not include the initials of the person responsible for verifying the weight or measure of each component used in the batch. Specifically, *** Your batch production records did not include documentation, at the time of performance, of [packaging] [labeling] operations. Specifically, *** Your batch production records did not include [the unique identifier assigned to labels used] [the quantity of the labels used] [reconciliation of discrepancies between issuance and use of labels]. Specifically, *** Your batch production records did not include the results of any tests or examinations conducted on packaged and labeled dietary supplements or a cross-reference to the physical location of such results. Specifically, *** Your batch production records did not include documentation that quality control personnel approved or rejected [reprocessing] [repackaging]. Specifically, *** Your batch production records did not include documentation that quality control personnel approved and released, or rejected, a batch for distribution. Specifically, *** You did not collect representative samples of components while the components were quarantined. Specifically, ***

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Foods

Your quality control personnel did not review and approve the results of [tests] [examinations] conducted on components while the components were quarantined. Specifically, *** You did not identify each unique lot within each unique shipment of components that you received in a manner that allows you to trace the lot to [the supplier] [the date received] [the name of the component] [the status of the component] [the dietary supplement that you manufactured and distributed]. Specifically, *** You did not identify each lot of components that you produced in a manner that allows you to trace the lot to [the supplier] [the date received] [the name of the component] [the status of the component] [the dietary supplement that you manufactured and distributed]. Specifically, *** You did not quarantine [packaging] [labels] before you used them in the manufacture of a dietary supplement. Specifically, ***

You did not conduct a visual identification of the immediate containers and closures of packaging while the packaging was quarantined. Specifically, *** Your quality control personnel did not approve labels for use in the manufacture of a dietary supplement and release them from quarantine. Specifically, *** You did not hold [packaging] [labels] under conditions that will avoid mixups. Specifically, ***

You did not quarantine received product. Specifically, ***

Your quality control personnel did not review and approve documentation to determine whether quarantined received product meets established specifications. Specifically, *** Your quality control personnel did not approve quarantined received product for [packaging] [labeling] as a dietary supplement. Specifically, *** You did not clearly identify, hold, and control under a quarantine system for appropriate disposition [a component] [packaging] [labels] [product] that you received for packaging or labeling as a dietary supplement that was rejected and unsuitable for use in manufacturing, packaging, or labeling operations. Specifically, *** You did not make and keep written procedures for fulfilling the requirements that apply to components of dietary supplements. Specifically, ***

Page 240

Foods

You did not identify and hold in-process material under conditions that protect against mixup, contamination, or deterioration. Specifically, ***

You did not make and keep records of product distribution. Specifically, ***

You did not [establish] [follow] written procedures for laboratory operations. Specifically, ***

You did not [establish] [follow] laboratory control processes. Specifically, ***

The laboratory control processes that you established and followed were not reviewed and approved by quality control personnel. Specifically, *** You did not [establish] [follow] sampling plans for obtaining representative samples of packaging. Specifically, ***

You did not [establish] [follow] laboratory control processes for use of criteria for selecting appropriate examination and testing methods. Specifically, *** You did not [establish] [follow] sampling plans for obtaining representative samples of finished batches of dietary supplements. Specifically, *** You did not [establish] [follow] sampling plans for obtaining representative samples of labels. Specifically, ***

You did not conduct manufacturing operations in accordance with adequate sanitation principles. Specifically, ***

You did not design or select manufacturing processes that ensure that product specifications are consistently met. Specifically, ***

The written instructions in your master manufacturing record did not include specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement. Specifically, *** The written instructions in your master manufacturing record did not include specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement. Specifically, ***

Page 241

Foods

Your master manufacturing record did not include a statement of intentional overage amount of a dietary ingredient. Specifically, ***

Your master manufacturing record did not include an accurate weight or measure of each component to be used. Specifically, ***

Your master manufacturing record did not include the [name] [strength] [concentration] [weight] [measure] of each dietary ingredient for each batch size. Specifically, *** You did not have records or copies of records required for your master manufacturing records readily available during the required retention period for inspection and copying by FDA when requested. Specifically, *** Your electronic master manufacturing records do not comply with the electronic records requirements. Specifically, ***

You did not make and keep written procedures for laboratory operations. Specifically, ***

You did not make and keep documentation that established laboratory methodology was followed. Specifically, ***

You did not make and keep documentation that the requirements that apply to production and process control for components of dietary supplements were met. Specifically, *** The person who performed a required operation did not document, at the time of performance, that the required operation was performed. Specifically, *** You did not keep required written records for 1 year past the shelf life date or for 2 years beyond the date of distribution of the last batch of dietary supplements associated with the records. Specifically, *** You did not have required records, or copies of such records, readily available during the retention period for inspection and copying by FDA when requested. Specifically, *** You did not [establish] [follow] written procedures for conducting an investigation of your manufacturing processes and other batches for a returned dietary supplement. Specifically, *** You did not keep the records required for returned dietary supplements for the required time period. Specifically, ***

Page 242

Foods

You did not make and keep records [of documentation of the reevaluation by quality control personnel of a dietary supplement that was reprocessed] [of the determination by quality control personnel of whether the reprocessed dietary supplement met established product specifications]. Specifically, *** You did not assign a batch, lot, or control number to each lot of packaged and labeled dietary supplement from a finished batch of dietary supplement. Specifically, *** You did not examine, before [packaging] [labeling] operations, [packaging] [labels] for each batch of dietary supplement to determine whether the [packaging] [labels] conformed to the master manufacturing record. Specifically, *** You did not control the reconciliation of any issue and use [label discrepancies] [packaging discrepancies]. Specifically, ***

You did not control the [issuance] [use] of packaging. Specifically, ***

A qualified person did not investigate a product complaint that involved a possible failure of a dietary supplement to meet a specification, or other requirement. Specifically, *** Your review and investigation of a product complaint did not extend to all relevant batches and records. Specifically, ***

You did not keep the records required for product complaints as original records, true copies, or as electronic records. Specifically, ***

The written record of a product complaint did not include the batch, lot, or control number of the dietary supplement. Specifically, ***

You did not make and keep documentation for why meeting in-process specifications, in combination with meeting component specifications, helps ensure that the dietary supplement meets the specifications for [identity][ purity][ strength][ composition][ limits on contamination that may adulterate or may lead to adulteration of the finished batch of the dietary supplement]. Specifically, *** Your quality control operations did not include determining whether the finished [packaged] [labeled] dietary supplement conforms to established specifications. Specifically, *** Your quality control personnel did not conduct a material review and make a disposition decision when a batch deviated from the master manufacturing record. Specifically, ***

Page 243

Foods

Your quality control personnel did not conduct a material review and make a disposition decision for an unanticipated occurrence during the manufacturing operations that adulterated or may lead to adulteration of the [component] [dietary supplement] [packaging]. Specifically, *** Your quality control personnel did not reject a [component] [dietary supplement] [package] [label] when an established specification was not met. Specifically, *** You did not make and keep written procedures for calibrating instruments or controls that you use in [manufacturing] [testing] a component or dietary supplement. Specifically, *** You did not make and keep written procedures for [maintaining] [cleaning] [sanitizing] equipment and utensils that are used to manufacture, package, label, or hold components or dietary supplements. Specifically, *** You did not make and keep documentation of [the date of the use] [maintenance] [cleaning] [sanitizing] of the equipment. Specifically, ***

You did not make and keep written records of calibrations, inspections, or checks of automated, mechanical, or electronic equipment. Specifically, *** You did not submit a reportable food report to FDA within 24 hours after you determined that a food was a reportable food. Specifically, *** Your quality control operations did not include reviewing and approving all processes for calibrating instruments and controls. Specifically, ***

Your quality control operations did not include conducting a required material review and making a required disposition decision for [components] [packaging] [labels] prior to [their] use. Specifically, *** Your quality control operations did not include approving, and releasing from quarantine, all [components] [packaging] [labels] before they were used. Specifically, *** Your quality control personnel did not review and approve the documentation setting forth the basis for qualification of suppliers. Specifically, *** Your quality control personnel did not review and approve the documentation setting forth the basis for why meeting in-process specifications, in combination with meeting component specifications, will help ensure that the identity, purity, strength, and composition of the dietary supplement are met. Specifically, *** Your quality control personnel did not ensure that required reserve samples were collected and held. Specifically, ***

Page 244

Foods

Your quality control operations did not include reviewing and approving laboratory control processes associated with the production and process control system. Specifically, *** Your quality control operations did not include ensuring that [tests] [examinations] required for your laboratory operations were conducted. Specifically, *** Your quality control operations did not include reviewing and approving [master manufacturing records] [modifications to the master manufacturing records]. Specifically, *** Your quality control operations did not include determining whether each finished batch conforms to established product specifications. Specifically, *** You did not monitor the in-process points, steps, or stages to detect any deviation or unanticipated occurrence that may result in a failure to meet specifications. Specifically, *** You did not document why an exempted product specification is met without verification by periodically testing the finished batch. Specifically, *** Your quality control personnel did not reject a [component] [dietary supplement] [package] [label] for which a specification was not met. Specifically, *** You did not collect representative samples of [each unique shipment] [each unique lot within each unique shipment] product that you received for packaging or labeling as a dietary supplement to determine whether the received product meets established specifications. Specifically, *** Your reserve sample of a dietary supplement that was distributed to be packaged and labeled was not held using a container-closure system that provides essentially the same characteristics to protect against contamination or deterioration as the one in which it was distributed for packaging and labeling elsewhere. Specifically, *** You did not retain reserve samples for the required time. Specifically, ***

You reprocessed a dietary supplement for which quality control personnel did not [conduct a material review] [make a disposition decision to approve the reprocessing]. Specifically, *** You did not make and keep records of established specifications. Specifically, ***

Your quality control operations for packaging and labeling did not include approving for release, or rejecting, any packaged and labeled dietary supplement. Specifically, ***

Page 245

Foods

You do not have quality control operations for product complaints. Specifically, ***

Your quality control operations for product complaints did not include [reviewing and approving decisions about whether to investigate a product complaint] [reviewing and approving the findings and followup action of any investigation performed]. Specifically, *** Your documentation of your material review and disposition decision and followup did not include identification of the action taken to correct, and prevent a recurrence of, the deviation or the unanticipated occurrence. Specifically, *** Your documentation of your material review and disposition decision and followup did not include the signature [of the individual designated to perform the quality control operation] [of each qualified individual who provides information relevant to that material review and disposition decision]. Specifically, *** You did not implement a system of production and process controls that covers all stages of manufacturing, packaging, labeling, and holding of dietary supplements to ensure that the dietary supplement is [packaged] [labeled] as specified in the master manufacturing record. Specifically, *** Your production and in-process control system is not designed to ensure that the dietary supplement is manufactured, packaged, labeled, and held in a manner that will ensure the quality of the dietary supplement. Specifically, *** Your production and in-process control system was not reviewed and approved by quality control personnel. Specifically, ***

You did not implement quality control operations to ensure that the dietary supplement is [packaged] [labeled] as specified in the master manufacturing record. Specifically, *** You did not establish [label] [packaging] specifications. Specifically, ***

You did not establish specifications to [sufficiently] assure that the product you received for packaging or labeling as a dietary supplement is adequately identified and is consistent with your purchase order. Specifically, *** You did not determine whether you met specifications established to ensure the quality of the dietary supplement. Specifically, ***

You did not determine whether you met established component specifications established to ensure the [purity] [strength] [composition] of dietary supplements manufactured using the components. Specifically, *** You did not determine whether you met in-process specifications to ensure the [purity] [strength] [composition] of the dietary supplements. Specifically, ***

Page 246

Human Tissue

Center Name

Cite Id

Ref No

ShortDesc

Human tissue for transplantation

12221 21 CFR 1271.47(a)

Procedures for all steps

12336 21 CFR 1271.180(a)

Procedures to meet core CTGP

12416 21 CFR 1271.260(e)

Storage temperatures recorded, maintained

12310 21 CFR 1271.160(a)

All core requirements covered in program

12230 21 CFR 1271.50(a)

Responsible person to determine, document

12213 21 CFR 1271.47(a)

Donor eligibility procedures

12326 21 CFR 1271.160(c)

Quality audits performed periodically

12247 21 CFR 1271.55(d)(2)

Accurate, indelible, legible

12277 21 CFR 1271.75(a)(1)

Risk factors, clinical evidence

12334 21 CFR 1271.170(c)

Trained or re-trained as necessary

12431 21 CFR 1271.265(e)

Procedures and release criteria

12457 21 CFR 1271.320(a)

Procedures re complaints

Page 247

Human Tissue

12309 21 CFR 1271.160(a)

Program is appropriate for the HCT/Ps

12369 21 CFR 1271.200(b)

Procedures inadequate

12223 21 CFR 1271.47(b)

Review and approval of procedures

12229 21 CFR 1271.50(a)

Determination based on screening and testing

12237 21 CFR 1271.55(a)(3)

Summary--records used to make determination

12283 21 CFR 1271.75(e)

Abbreviated procedure

12332 21 CFR 1271.170(b)

Qualifications lacking

12433 21 CFR 1271.265(f)

Return to inventory--procedures

12231 21 CFR 1271.50(b)(1)

Donor screening standards

12286 21 CFR 1271.80(b)

Specimen collections not timely

12301 21 CFR 1271.150(c)(1)(iii)

Ensurane of compliance

12311 21 CFR 1271.160(b)(1)

Ensuring appropriate core requirements followed

12312 21 CFR 1271.160(b)(2)

Procedures for complaints and other information

Page 248

Human Tissue

12338 21 CFR 1271.180(b)

Review and approval-responsible person

12414 21 CFR 1271.260(d)

Corrective actions

12417 21 CFR 1271.260(e)

Periodic review of temperatures

12421 21 CFR 1271.265(a)

Acceptance criteria designed to prevent CD

12429 21 CFR 1271.265(d)

Shipping conditions appropriate

12435 21 CFR 1271.270(a)

Records maintained concurrently

12492 21 CFR 1271.85(a)

Infection with communicable disease agents

12493 21 CFR 1271.90(b)

Eligibility not required--warning labels

12496 21 CFR 1271.85(b)(2)

SOP for release; reactive for CMV

15020 21 CFR 1271.200(e)

Documentation of maintenance and cleaning

12225 21 CFR 1271.47(d)

Departures: recording and justifying

12239 21 CFR 1271.55(b)(2)

Listing and interpretation of CD tests performed

12246 21 CFR 1271.55(d)(1)(iii)

Documentation--determination, by whom, date

Page 249

Human Tissue

12314 21 CFR 217.160(b)(2)(iii)

Risk assessment, quarantine, recall, FDA

12322 21 CFR 1271.160(b)(4)

Training of personnel

12323 21 CFR 1271.160(b)(5)

Monitoring systems

12324 21 CFR 1271.160(b)(6)

Deviations--Investigation, documenting, trending

12325 21 CFR 1271.160(b)(6)

Deviations--evaluation, cause, corrective action

12339 21 CFR 1271.180(c)

Availability of procedures

12365 21 CFR 1271.195(d)

Documentation not maintained

12372 21 CFR 1271.200(c)

Calibrated per established schedules

12375 21 CFR 1271.210(a)

Use prior to verification

12399 21 CFR 1271.230(a)

Process validation procedures

12411 21 CFR 1271.260(a)

Contamination, mix ups, improper release

12444 21 CFR 1271.270(e)

Contract firms--identities and responsibilities

12453 21 CFR 1271.290(e)

Documenting disposition of each HCT/P

Page 250

Human Tissue

3744 21 CFR 1270.33(a)

Accurate, indelible, legible

12222 21 CFR 1271.47(a)

Design of procedures to ensure compliance

12236 21 CFR 1271.55(a)(2)

Eligibility statement--basis of determination

12238 21 CFR 1271.55(b)(1)

Statement re: certified testing lab

12240 21 CFR 1271.55(b)(3)

Name and address on summary

12242 21 CFR 1271.55(c)

Name and personal info on accompanying records

12279 21 CFR 1271.75(b)

Risk factors, leukocyte-rich cells or tissues

12282 21 CFR 1271.75(d)

Donors with risks not determined ineligible

12287 21 CFR 1271.80(c)

Kits not FDA approved, specifically labeled

12288 21 CFR 1271.80(c)

Manufacturer instructions not followed

12319 21 CFR 1271.160(b)(3)

Actions taken and documented

12328 21 CFR 1271.160(d)

Validation for intended use

12337 21 CFR 1271.180(a)

Design adequate to bar spread of CD's

Page 251

Human Tissue

12359 21 CFR 1271.195(a)(3)

Aseptic processing---cleaning, disinfecting

12364 21 CFR 1271.195(c)

Monitoring-microorganisms where appropriate

12368 21 CFR 1271.200(a)

Capable of valid results

12370 21 CFR 1271,200(c)

Calibration procedures and schedules (general)

12395 21 CFR 1271.225

Verification/validation

12398 21 CFR 1271.230(a)

Validation & approval--established procedures

12437 21 CFR 1271.270(a)

Records incomplete

15024 21 CFR 1271.320(b)

Available for review and copying by FDA

3745 21 CFR 1270.33(a)

Person involved, dates, details

3758 21 CFR 1270.35(c)

Receipt and/or distribution

12232 21 CFR 1271.50(b)(2)

Donor testing not negative for CD agents

12234 21 CFR 1271.55(a)(1)

Identification code affixed to container

12235 21 CFR 1271.55(a)(1)

Personal information included in I.D. code

Page 252

Human Tissue

12243 21 CFR 1271.55(d)(1)

Documentation maintained (general)

12252 21 CFR 1271.60(a)

Completion of eligibility determination

12257 21 CFR 1271.60(c)(2)

Records stating determination not completed

12258 21 CFR 1271.60(c)(3)

Statement of restrictions

12270 21 CFR 1271.65(a)

Improper release prevention--storage, I.D.

12272 21 CFR 1271.65(b)(2)

Labeled re: biohazard, risks, test results

12290 21 CFR 1271.80(d)(1)

Reactive tests--not determined ineligible

12291 21 CFR 1271.80(d)(2)

Plasma diluted test specimens

12315 21 CFR 1271.160(b)(2)

Sharing of information (general)

12320 21 CFR 1271.160(b)(3)

Actions verified, short and long term solutions

12343 21 CFR 1271.190(a)

State of repair

12344 21 CFR 1271.190(a)

Lighting, ventilation, plumbing

12351 21 CFR 1271.190(d)(1)

Procedures for cleaning, sanitation

Page 253

Human Tissue

12356 21 CFR 1271.195(a)

Adequate control, proper conditions

12362 21 CFR 1271.195(b)

Corrective actions

12371 21 CFR 1271.200(a)

Cleaned, sanitized per established schedules

12373 21 CFR 1271.200(d)

Inspected routinely

12387 21 CFR 1271.220(a)

Causing contamination, increasing risks

12396 21 CFR 1271.225

Approval and timely communication

12405 21 CFR 1271.250(a)

Controlling the labeling of HCT/Ps

12408 21 CFR 1271.250(c)

All labeling requirements met

12409 21 CFR 1271.250(c)

Documentation of donor eligibility

12412 21 CFR 1271.260(b)

Storage temperatures appropriate

12415 21 CFR 1271.260(e)

Temperature limits

12423 21 CFR 1271.265(b)

Shipment in quarantine of HCT/Ps

12424 21 CFR 1271.265(c)(1)

Release criteria verified, documented

Page 254

Human Tissue

12427 21 CFR 1271.265(c)(3)

HCT/Ps made under departure from process

12432 21 CFR 1271.265(e)

Documentation elements for activities

12436 21 CFR 1271.270(a)

Accurate, indelible, legible

12440 21 CFR 1271.270(b)

Prompt retrieval from multiple locations

12443 21 CFR 1271.270(d)

Retention time (10 year rules)

12447 21 CFR 1271.290(b)

Establishing a system

12458 21 CFR 1271.320(b)

Designated complaint file

12460 21 CFR 1271.320(c)

Review and evaluation, report to FDA

12470 21 CFR 1271.350(a)(2)

15 day reporting timeframe

12472 21 CFR 1271.350(b)(1)

Deviations not investigated

12473 21 CFR 1271.350(b)(2)

Deviations not reported to FDA

12490 21 CFR 1271.85(b)(1)

Cell-associated CD

15019 21 CFR 1271.160(d)

Computer software verification

Page 255

Human Tissue

LongDesc

Frqncy

Procedures for all steps performed in the [testing] [screening] [determining] of donor eligibility of HCT/Ps were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Procedures appropriate to meet core CGTP requirements for all steps that you perform in the manufacture of HCT/Ps were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Storage temperatures of HCT/Ps were not [recorded] [maintained]. Specifically, ***

29

22

13

A quality program which addresses all of the core CGTP requirements, appropriate for the HCT/Ps manufactured and the manufacturing steps performed, has not been [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** The eligibility of an HCT/P donor was not [determined] [documented] by a responsible person, based on results of donor screening and donor testing. Specifically, ***

11

10

Procedures for all steps performed in the [testing] [screening] [determining] of donor eligibility of HCT/Ps were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Periodic quality audits of activities related to core CGTP requirements have not been performed. Specifically, ***

Donor eligibility records are not [accurate] [indelible] [legible]. Specifically, ***

Donors were not screened by a review of relevant medical records for [risk factors] [clinical evidence] of communicable disease agents and diseases. Specifically, ***

Personnel have not been [trained] [re-trained as necessary] to adequately perform their assigned responsibilities. Specifically, ***

Procedures including release criteria for activities relating to the [receipt] [shipment] [distribution] of HCT/Ps were not [established] [maintained] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Procedures for the [review] [evaluation] [documentation] [investigation] of complaints relating to core CGTP requirements were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, ***

Page 256

Human Tissue

A quality program appropriate for the HCT/Ps manufactured and manufacturing steps performed has not been [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Procedures for the [cleaning] [sanitizing] [maintenance] of equipment were not [established] [maintained] [defined] [documented] [implemented] [followed] [revised]. Specifically, *** Donor eligibility procedures were not [reviewed] [approved] by a responsible person before implementation. Specifically, ***

HCT/P donors were not determined to be eligible based on the results of donor screening and testing. Specifically, ***

After completion of the donor-eligibility determination, HCT/Ps were not accompanied with the summary of the records used to make the donor-eligibility determination. Specifically, *** The abbreviated donor screening procedure [was used for donors who had no complete donor screening procedure in the previous six months] [did not determine and document changes in the donor's medical history that would make the donor ineligible]. Specifically, *** Personnel do not have the necessary [education] [experience] [training] to ensure competent performance of their assigned functions. Specifically, ***

Procedures for determining if HCT/Ps that were returned to the establishment are suitable to be returned to inventory were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Donor screening of HCT/P donors considered eligible indicated that the donor was not free of [risk factors for infection due to communicable disease agents] [clinical evidence of infection due to communicable disease agents] [risk factors associated with xenotransplantation]. Specifically, *** Donor specimens used for testing of communicable disease agents were not collected at the appropriate time. Specifically, ***

You did not ensure that establishment(s) that by contract, agreement or arrangement, perform manufacturing steps for you were in compliance with [applicable CGTP requirements prior to the initiation of the contract, agreement of arrangement] [applicable CGTP requirements after information became available that suggested the establishment was no longer in compliance]. Specifically, *** The quality program has not ensured that appropriate procedures related to core CGTP requirements were [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [approved] [revised]. Specifically, *** The quality program has not ensured that procedures exist for [receiving] [investigating] [evaluating] [documenting] information relating to core CGTP requirements, including complaints.

Page 257

Human Tissue

Procedures for core CGTP requirements were not [reviewed] [approved] by a responsible person before implementation. Specifically, ***

Corrective actions were not [performed] [documented] when proper storage conditions were not met. Specifically, ***

Recorded storage temperatures were not periodically reviewed to ensure that temperatures have been within acceptable limits. Specifically, ***

Incoming HCT/Ps were not [accepted] [rejected] [placed in quarantine] based on preestablished criteria designed to prevent communicable disease transmission. Specifically, *** Appropriate shipping conditions were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised] for each type of HCT/P. Specifically, *** Records were not maintained concurrently with the performance of each step. Specifically, ***

Donors were not tested for evidence of infection with communicable disease agents. Specifically, ***

HCT/Ps for which the donor eligibility determination was not performed were not prominently labeled with the appropriate warning statements. Specifically, ***

A standard operating procedure for the release of HCT/Ps from donors that test reactive for cytomegalovirus (CMV) was not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically. *** Documentation of equipment maintenance, cleaning, sanitization, and calibration was not maintained. Specifically, ***

Departures from donor eligibility procedures relevant to preventing risks of communicable disease transmission were not [recorded] [justified]. Specifically, ***

The summary of records for HCT/Ps did not contain [a listing] [an interpretation of results] of all communicable disease tests performed. Specifically, ***

Documentation of [the donor-eligibility determination] [the responsible person who made the donor-eligibility determination] [the date of the donor-eligibility determination] was not maintained. Specifically, ***

Page 258

Human Tissue

The quality program has not ensured that procedures include provisions for [assessing the risk of] [quarantine of] [recall of] [reporting to FDA on] HCT/Ps that have been made available for distribution and for which there is information related to the possible contamination or communicable disease transmission. Specifically, *** The quality program has not ensured the proper training and education of personnel involved in core GTP activities. Specifically, ***

The quality program has not established and maintained appropriate monitoring systems. Specifically, ***

The quality program does not include [the investigation] [the documentation] [the trending] [the reporting] of HCT/P deviations relating to core CTGP requirements. Specifically, *** Investigation of deviations related to core CGTP requirements did not include [a review and evaluation of the deviation] [efforts to determine the cause of the deviation] [corrective action(s) to address the deviation and prevent recurrence]. Specifically, *** Procedures for core CTGP requirements were not available to personnel in the area where operations are performed, or in a nearby area when such availability is impractical. Specifically, *** Documentation of environmental control and monitoring activities was not maintained. Specifically, ***

Equipment used for [inspection] [measuring] [testing] was not calibrated according to established schedules. Specifically, ***

Supplies and reagents were used before they were verified to meet specifications designed to prevent the introduction, transmission, or spread of communicable disease. Specifically, *** Procedures to validate and approve processes that cannot be fully verified by inspection and tests were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Storage areas and stock rooms were not controlled [to prevent mix-ups, contamination and cross contamination of HCT/Ps, supplies and reagents] [to prevent HCT/Ps from improperly being made available for distribution]. Specifically, *** The [name and address] [list of responsibilities] of establishment(s) that perform manufacturing steps for you [was not maintained] [was not made available to FDA during an inspection]. Specifically, *** A method has not been [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised] in the tracking system [to document the disposition of each HCT/P] [to permit the prompt identification of the consignee of the HCT/P, if any]. Specifically, ***

Page 259

Human Tissue

Failure to maintain records which are [accurate] [indelible] [legible]. Specifically, ***

Procedures were not designed to ensure compliance with the donor eligibility requirements. Specifically, ***

After the completion of the donor-eligibility determination, HCT/Ps were not accompanied with a statement whether the donor has been determined to be eligible or ineligible, based on the results of screening and testing. Specifically, *** The summary of records for HCT/Ps did not contain a statement that the communicable disease testing was performed by a laboratory certified to perform such testing on human specimens under the Clinical Laboratory Improvement Act of 1988 or has met equivalent requirements determined by the Centers for Medicare and Medicaid Services. Specifically, *** The summary of records for HCT/Ps did not contain the [name] [address] of the establishment that made the donor-eligibility determination. Specifically, ***

The accompanying records for HCT/Ps included [the donor's name] [personal information that might identify the donor]. Specifically, ***

Donors of leukocyte-rich cells or tissues were not screened by a review of relevant medical records for [risk factors] [clinical evidence] of cell-associated communicable disease agents and diseases. Specifically, *** Donors were not determined to be ineligible that had [risk factors or clinical evidence of communicable disease agents] [communicable disease risks associated with xenotransplantation]. Specifically, *** Communicable disease agent tests [were not FDA-licensed, approved or cleared donor screening tests] [were not specifically labeled for cadaveric specimens when such a test was available and cadaveric specimens were used]. Specifically, *** Testing for communicable disease agents was not performed in accordance with the manufacturer's instructions. Specifically, ***

The quality program has not ensured that appropriate corrective actions relating to core CGTP requirements are [taken] [documented]. Specifically, ***

The performance of [custom computer software] [commercial computer software that has been customized or programmed], including changes to computer software, has not been validated for the intended use, when such software is relied upon to comply with core GTP requirements. Specifically, *** Procedures were not designed to prevent circumstances that increase the risk of communicable disease introduction, transmission and spread through the use of HCT/Ps. Specifically, ***

Page 260

Human Tissue

Environmental controls do not provide for adequate [cleaning] [disinfecting] of [rooms] [equipment] to ensure aseptic processing. Specifically, ***

Environmental conditions were not monitored for microorganisms. Specifically, ***

Equipment used for [inspection] [measuring] [testing] was not capable of producing valid results. Specifically, ***

The [procedures] [schedules] for the calibration of equipment used for [inspection] [measuring] [testing] were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, *** Process changes were not [validated] [verified] to ensure the change does not cause an adverse impact elsewhere in operations. Specifically, ***

Processes with results which could not be fully verified by inspection and tests, were not validated and approved according to established procedures. Specifically, ***

Records [did not identify the person performing the work] [did not show the dates of entries] [were not detailed as necessary to provide a complete history of work performed] [did not relate to the HCT/P involved]. Specifically, *** The complaint file was not made available for review and copying upon request from FDA. Specifically, ***

Records fail to [identify the person performing the work] [include the dates of the various entries] [be as detailed as necessary to provide a complete history of the work performed and to relate the records to the particular tissue involved]. Specifically, *** Records fail to include documentation of receipt and/or distribution of human tissue. Specifically, ***

Donor testing of HCT/P donors considered eligible was not negative or nonreactive for relevant communicable disease agents. Specifically, ***

After the completion of the donor-eligibility determination, HCT/Ps were not accompanied with a distinct identification code affixed to the HCT/P container. Specifically, *** The distinct identification code affixed to the HCT/P container included an individual's [name] [social security number] [medical record number]. Specifically, ***

Page 261

Human Tissue

Documentation was not maintained after the donor-eligibility determination was complete. Specifically, ***

HCT/Ps were not kept in quarantine until completion of the donor-eligibility determination. Specifically, ***

HCT/Ps shipped in quarantine prior to the completion of the donor-eligibility determination were not accompanied by records that stated the donor-eligibility determination had not been completed. Specifically, *** HCT/Ps shipped in quarantine prior to the completion of the donor-eligibility determination were not accompanied by records that stated the product must not be implanted, transplanted, infused or transferred until completion of the donor-eligibility determination. Specifically, *** HCT/Ps from ineligible donors are not [stored] [identified] in a manner to prevent improper release. Specifically, ***

HCT/Ps from ineligible donors which were made available for limited use were not prominently labeled with [the Biohazard legend] [a statement warning of communicable disease risks] [a statement warning of the reactive test results]. Specifically, *** Donors whose specimens test reactive on screening tests for communicable disease agents were not determined to be ineligible. Specifically, ***

Donors were not determined to be ineligible whose communicable disease test specimens were plasma diluted, and [the donor was not tested using a specimen which was taken before transfusion or infusion and within seven days before recovery of the cells or tissue] [an appropriate algorithm was not used to determine that the plasma dilution did not affect the test results]. Specifically, *** The quality program has not ensured that procedures exist for sharing of information pertaining to the possible contamination or communicable disease transmission of HCT/Ps. Specifically, *** Corrective actions relating to core CGTP requirements [have not been verified to ensure effectiveness and compliance with CGTP] [did not include both short term corrective actions to address the immediate deficiency and long term corrective actions to prevent recurrence]. Specifically, *** Facilities were not maintained in a good state of repair. Specifically, ***

Facilities did not provide adequate [lighting] [ventilation] [plumbing] [drainage] [access to sinks and toilets] to prevent the introduction, transmission or spread of communicable disease. Specifically, *** Procedures for facility cleaning and sanitation were not [established] [maintained] [defined] [documented] [implemented] [followed] [revised]. Specifically, ***

Page 262

Human Tissue

Environmental conditions existed in which [contamination or cross contamination of HCT/Ps or equipment] [the accidental exposure of HCT/Ps to communicable disease agents] could occur, and [environmental conditions were not adequately controlled] [proper conditions for operations were not provided]. Specifically, *** Appropriate corrective actions were not taken related to the inspections of environmental control systems. Specifically, ***

Equipment used for manufacturing HCT/Ps was not [cleaned] [sanitized] [maintained] according to established schedules. Specifically, ***

Equipment was not routinely inspected for [cleanliness] [sanitation] [calibration] [adherence to maintenance schedules]. Specifically, ***

HCT/Ps were not processed in a way [that does not cause contamination or cross contamination during processing] [that does not increase the risk of introduction, transmission, or spread of communicable disease]. Specifically, *** Process changes were [not approved by a responsible person with appropriate knowledge and background prior to implementation] [not communicated to personnel in a timely manner]. Specifically, *** Procedures to control the labeling of HCT/Ps were not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, ***

Labeling procedures did not ensure that HCT/Ps are labeled in accordance with all labeling requirements. Specifically, ***

Labeling procedures did not ensure that HCT/Ps made available for distribution are accompanied by documentation of the donor eligibility determination. Specifically, ***

HCT/Ps were not stored at appropriate temperatures. Specifically, ***

Acceptable temperature limits were not established for the storage of HCT/Ps at each step of the manufacturing process to inhibit the growth of infectious agents. Specifically, *** HCT/Ps shipped as pre-distribution shipments [within your establishment] [between establishments] which do not meet the criteria for being available for distribution were not shipped in quarantine. Specifically, *** Release criteria were not [verified] [documented] to have been met through a review of manufacturing and tracking records before HCT/Ps were made available for distribution. Specifically, ***

Page 263

Human Tissue

A responsible person did not determine that HCT/Ps manufactured under a departure from procedures do not increase the risk of communicable disease prior to making the HCT/Ps available for distribution. Specifically, *** Documentation for activities related to the [receipt] [shipment] [distribution] of HCT/Ps did not include [identification of the HCT/P and the establishment that supplied the HCT/P] [activities performed and the results of each activity] [date(s) of activity] [quantity of HCT/P subject to the activity] [disposition of the HCT/P (identity of consignee)]. Specifically, *** Records were not [accurate] [indelible] [legible]. Specifically, ***

The records management system was not designed to ensure that records stored in more than one location can be promptly identified and retrieved. Specifically, ***

Records were not retained for the appropriate length of time, [10 years after their creation] [at least 10 years after the date of administration of a particular HCT/P] [at least 10 years after the date of a particular HCT/Ps distribution, disposition, or expiration, whichever is latest, when the date of administration is not known] [10 years after the appropriate disposition of archived specimens of dura mater]. Specifically, *** A tracking system that enables the tracking of HCT/Ps back and forth from the donor to the consignee or final disposition was not [established] [maintained] [defined] [documented] [implemented] [followed] [reviewed] [revised]. Specifically, **** Complaints received were not maintained in a file designated for complaints. Specifically, ***

Complaints were not reviewed and evaluated to determine [if the complaint is related to an HCT/P deviation or adverse reaction] [whether a report to FDA is required]. Specifically, *** Adverse reactions were not reported to FDA using form FDA 3500A within 15 calendar days of initial receipt of information. Specifically, ***

HCT/P deviations related to distributed HCT/Ps for which the establishment performed a manufacturing step were not investigated. Specifically, ***

HCT/P deviations relating to core CGTP requirements that occurred [in your establishment] [at an establishment under contract, agreement, or arrangement with your establishment] were not reported to FDA. Specifically, *** Donors of leukocyte-rich cells or tissues were not tested for cell-associated communicable diseases. Specifically, ***

The performance of computer software has not been verified. Specifically, ***

Page 264

Parts 1240 & 1250

Center Name

Cite Id

Ref No

ShortDesc

Parts 1240 and 1250

7036 21 CFR 1250.67

Prevention of contamination

6560 21 CFR 1250.32(a)

Contamination

7032 21 CFR 1250.63

Prevention of the spread of communicable diseases

6552 21 CFR 1250.28

Handling to avoid contamination

6558 21 CFR 1250.30(d)

Plumbing design, installation, maintenance

6570 21 CFR 1250.33(c)

Storage and handling after bactericidal treatment

6569 21 CFR 1250.33(b)

Equipment kept clean

7053 21 CFR 1250.75(b)

Sanitary sewers or alternative methods

6555 21 CFR 1250.30(a)

Clean and free from flies, rodents, and other vermin

6564 21 CFR 1250.33(a)

Maintained in good repair

Page 265

Parts 1240 & 1250

6581 21 CFR 1250.38(b)

Soap, sanitary towels, water

6572 21 CFR 1250.34

Thermometers

6591 21 CFR 1250.42(a)

Backflow protection

6593 21 CFR 1250.42(b)

Connections easily cleanable, located and protected

7090 21 CFR 1250.82(e)

Backflow prevention - general

6580 21 CFR 1250.38(b)

Signs

7051 21 CFR 1250.75(a)

Contamination of passenger stations

7055 21 CFR 1250.75(b)

Equipment for cleaning and flushing

6549 21 CFR 1250.27

Storage of perishables

6567 21 CFR 1250.33(b)

Cleaning of multiuse eating and drinking utensils

6584 21 CFR 1250.39

Containers - watertight, readily cleanable, non-absorbent

Page 266

Parts 1240 & 1250

6585 21 CFR 1250.39

Containers - close-fitting covers

7041 21 CFR 1250.70(a)

Adequate and readily accessible

6561 21 CFR 1250.32(b)

Clean hands

6565 21 CFR 1250.33(a)

Adequate facilities for cleaning, bactericidal treatment

6579 21 CFR 1250.38(a)

Suitable design and construction

6609 21 CFR 1250.49

Clean and free of flies and mosquitoes

7038 21 CFR 1250.67

Signs for non-potable water

7042 21 CFR 1250.70(a)

Clean and sanitary

7089 21 CFR 1250.82(d)

Identification marks on tanks and piping

6612 21 CFR 1250.50

Designed to permit ready cleaning

7054 21 CFR 1250.75(b)

Soil cans and removable containers

Page 267

Parts 1240 & 1250

7092 21 CFR 1250.82(f)

Cleaning, disinfecting, flushing

7111 21 CFR 1250.87

Cross connections

6531 21 CFR 1250.22

Clean, wholesome, free from spoilage

6554 21 CFR 1250.30(a)

Ventilation and lighting

6568 21 CFR 1250.33(b)

Cleaning of all other utensils

6582 21 CFR 1250.38(c)

Maintained in clean condition

6588 21 CFR 1250.41

Submittal of construction plans

Page 268

Parts 1240 & 1250

LongDesc

Frqncy

Failure to [design] [construct] [maintain] [operate] servicing area [piping systems] [hydrants] [taps] [faucets] [hoses] [buckets] [equipment] in such a manner as to prevent contamination of [drinking] [culinary] water. Specifically, ***

73

Not all food-handling operations are accomplished so as to minimize the possibility of contaminating [food] [drink] [utensils]. Specifically, ***

36

Servicing area are not [provided with all necessary sanitary facilities] [operated] [maintained] as to prevent the spread of communicable diseases. Specifically, ***

36

Ice coming into contact with [food] [drink] is not [handled] [stored] in such a manner as to avoid contamination. Specifically, ***

21

Plumbing is not [designed] [installed] [maintained] so as to prevent contamination of [the water supply] [food] [food utensils]. Specifically, ***

18

Failure to [store] [handle] utensils, after bactericidal treatment, in such a manner as to prevent contamination before reuse. Specifically, ***

14

Failure to keep all equipment clean. Specifically, ***

11

Failure to dispose of toilet wastes through [sanitary sewers] [methods assuring sanitary disposal]. Specifically, ***

10

Not all [kitchens] [galleys] [pantries] [places] where food is prepared, served, or stored are [clean] [free from flies, rodents, and other vermin]. Specifically, ***

Not all [utensils] [working surfaces] used in connection with [preparation] [storage] [serving] of [food] [beverages] are maintained in good repair. Specifically, ***

Page 269

Parts 1240 & 1250

Hand washing facilities for use by food-handling employees lack [soap] [sanitary towels] [hot and cold running water]. Specifically, ***

Failure to equip each refrigerator with a thermometer located in the warmest region thereof. Specifically, ***

A water system not protected against backflow. Specifically, ***

Filling connections not [easily cleanable] [located and protected] so as to minimize the hazard of contamination of the water supply. Specifically, ***

Lack of backflow prevention in the installation of [pipes] [fittings] conveying potable water to [fixtures] [apparatus] [equipment]. Specifically, ***

Signs directing food-handling employees to wash their hands after each use of toilet facilities are not [posted] [readily observable by such employees]. Specifically, ***

Failure to dispose of human wastes in such a manner as to avoid contamination of passenger [areas] [stations]. Specifically, ***

Equipment for [cleaning soil cans and removable containers] [flushing nonremovable containers and waste carts] is [not designed so as to prevent backflow into the water line] [used for a purpose connected with the handling of food, water, or ice]. Specifically, *** Failure to keep perishable [food] [drink] at or below 50 degrees Fahrenheit except when being prepared or kept hot for serving. Specifically, ***

Failure to [thoroughly clean in warm water] [subject to an effective bactericidal treatment] multiuse eating and drinking utensils after each use. Specifically, ***

Garbage containers are not [watertight] [readily cleanable] [non-absorbent]. Specifically, ***

Page 270

Parts 1240 & 1250

Garbage containers lack close-fitting covers. Specifically, ***

Adequate [toilet] [washroom] [locker] [essential sanitary] facilities for use of employees are not readily accessible adjacent to [places] [areas] where [land] [air] conveyances are [serviced] [maintained] [cleaned]. Specifically, ***

Persons with unclean hands were engaged in handling [food] [drink] [utensils] [equipment]. Specifically, ***

Adequate facilities are not provided for the [cleaning] [bactericidal treatment] of [multiuse eating and drinking utensils] [equipment used in the preparation of food and beverages]. Specifically, ***

Failure to provide [toilet] [lavatory] facilities of suitable design and construction for use by food-handling employees. Specifically, ***

Not all conveyances were kept [clean] [free of flies and mosquitoes] while in transit. Specifically, ***

Outlets for non-potable water are not posted with [permanent] signs warning that the water is unfit for drinking. Specifically, ***

Failure to maintain [toilet] [washroom] [locker] [essential sanitary] facilities for use of employees in a clean and sanitary condition. Specifically, ***

Not all [tanks] [piping] bear clear marks of identification. Specifically, ***

Lack of design of [toilet] [lavatory] facilities so as to permit ready cleaning. Specifically, ***

Failure to [thoroughly] clean [soil cans] [removable containers] prior to return to use. Specifically, ***

Page 271

Parts 1240 & 1250

Failure to [clean] [disinfect] [flush] a potable water system when required by FDA to prevent the introduction, transmission, or spread of communicable diseases. Specifically, ***

Systems for wash water do not meet the requirements of a potable water system, and the distribution system is crossconnected to a system carrying water of lower sanitary quality. Specifically, ***

Not all [food] [drink] served onboard is [clean] [wholesome] [free from spoilage]. Specifically, ***

Not all [kitchens] [galleys] [pantries] [places] where food is prepared, served, or stored are adequately [lighted] [ventilated]. Specifically, ***

Failure to [thoroughly clean in warm water] [subject to an effective bactericidal treatment] utensils (other than multiuse utensils) following the day's operation. Specifically, ***

Failure to maintain toilet rooms in a clean condition. Specifically, ***

Failure to submit plans for the [construction] [major reconstruction] of [sanitary equipment] [facilities] to FDA for review. Specifically, ***

Page 272

Rad Health

Center Name

Cite Id

Ref No

ShortDesc

Radiological health

5007 21 CFR 1002.13

Failure to submit

5194 21 CFR 1040.10(g)(9)

Label locations

5700 21 CFR 1002.10

Failure to submit, distinct marking

5144 21 CFR 1040.10(f)(2)(i)

Safety interlock not provided

5443 21 CFR 1020.30(g)

Providing adequate assembly information

5005 21 CFR 1002.11

Failure to submit

5006 21 CFR 1002.12

Not submitted prior to introduction

5032 21 CFR 1010.2(b)

Certification label or tag

5034 21 CFR 1010.2(c)

Certification not based on adequate test/testing program ID label lacks name and address

5043 21 CFR 1010.3(a)(1)

Page 273

Rad Health

5044 21 CFR 1010.3(a)(2)

ID label lacks place, month & year of manufacture Variances - Improper certification

5048 21 CFR 1010.4(d)

5141 21 CFR 1040.10(e)(1)

Certification tests inadequate

5147 21 CFR 1040.10(f)(2)(iii)(b) No multiple safety interlocks for Class II emission limits

5150 21 CFR 1040.10(f)(3)

Remote interlock connector

5152 21 CFR 1040.10(f)(5)(i)

Emission indicator - Class II & IIIa

5155 21 CFR 1040.10(f)(5)(iii)

Emission indicator pre 8/20/86

5171 21 CFR 1040.10(g)(3)

Class IV "Danger" label

Page 274

Rad Health

5173 21 CFR 1040.10(g)(5)(i)

Aperture label - laser radiation

5185 21 CFR 1040.10(g)(7)(i)

DIPH label wording Class II

5195 21 CFR 1040.10(g)(10)

Labels legible, visible, permanent

5200 21 CFR 1040.10(h)(1)(iv)

User info - list controls, etc.

5203 21 CFR 1040.10(h)(2)(i)

Reproduction of affixed information

5213 21 CFR 1040.11(c)

Demonstration laser products

5479 21 CFR 1020.30(n)

Compliance measurement

5690 21 CFR 1002.10(g)

Methods and procedures in testing radiation safety

5769 21 CFR 1020.33(c)(2)(i)(a) CTDI along the axis of rotation of the phantom

Page 275

Rad Health

5784 21 CFR 1010.2(b)

Certification other than by tag or label

5802 21 CFR 1002.13

Lack of required elements

5811 21 CFR 1002.30(a)(1)

Quality control procedures

Page 276

Rad Health

LongDesc

Frqncy

You did not submit an annual report [by the September 1 deadline] for products requiring one. Specifically, ***

All labels affixed to a laser product were not affixed so as to make unnecessary during reading, human exposure to laser radiation in excess of the accessible emission limits of Class I radiation or the limits of collateral radiation established in table VI of 21 CFR 1040.10(d). Specifically, *** You did not submit a required product report [distinctly marked "Radiation Safety Product Report of (your name)"] prior to the introduction of the product into commerce. Specifically, *** Each laser product was not provided with at least one safety interlock for each portion of the protective housing which is designed to be removed or displaced during operation or maintenance, when such removal or displacement permitted human access to laser or collateral radiation in excess of the accessible emission limits of Class I and table VI. Specifically, *** Instructions for [assembly] [installation] [adjustment] [testing] of components adequate to assure that the product will comply with the regulations, when [assembled] [installed] [adjusted] [tested] as directed, was not provided to [assemblers] [persons other than assemblers, upon request, at a cost not to exceed the cost of publication and distribution] Specifically, ***

You did not submit a required supplemental report, prior to the introduction of the product into commerce, for a new or modified model within a model or chassis family. Specifically, *** You did not submit an abbreviated report, required by 21 CFR 1002.1, prior to introduction of the product. Specifically, *** A certification label or tag is not [in the English language] [permanently affixed or inscribed] [legible] [readily accessible to view when the product is fully assembled for use]. Specifically, *** Certification was not based upon [a test, in accordance with the standard] [a testing program in accordance with good manufacturing practices]. Specifically, *** An identification label failed to provide the name and address of the [manufacturer] [individual or company under whose name the product was sold]. Specifically, ***

Page 277

Rad Health

An identification label fails to provide the [place] [month] [year] of manufacture. Specifically, ***

Failure to modify the [tag] [label] [certification] of a product for which a variance has been granted to state [that the product conforms to the applicable standard, except with respect to those characteristics covered by the variance] [that the product conforms with the provisions of the variance] [the assigned number and effective date of the variance]. Specifically *** The tests on which certification is based failed to account for [all errors and statistical uncertainties in the measurement process] [increases in emission and degradation in radiation safety with age]. Specifically, *** A laser product was not provided with either multiple safety interlocks or a means to preclude removal or displacement of the interlocked portion of the protective housing, when failure of a single interlock allowed laser radiation in excess of the accessible emission limits of Class II to be emitted directly through the opening created in the protective housing. Specifically, *** Each laser system classified as a Class IIIb or Class IV laser product [was not incorporated with a readily available remote interlock connector having an electrical potential difference of no greater than 130 root-meansquare volts between terminals.] [had no means to prevent, when the terminals of the connector are not electrically joined, human access to all laser and collateral radiation from the laser product in excess of the accessible emission limits of Class I and table VI.] Specifically, ***

An emission indicator was not incorporated in each laser system classified as a Class II or Class IIIa laser product that provides a visible or audible signal during emission of accessible laser radiation in excess of the accessible emission limits of Class I. Specifically, *** Both laser and laser energy source fail to incorporate an emission indicator, when the laser and laser energy source are housed separately and can be operated at a separation distance of greater than 2 meters (laser systems manufactured on or before August 20, 1986). Specifically, *** Each Class IV laser product does not have affixed a label [bearing the DANGER logotype specified in the regulation] [bearing the wording "LASER RADIATION-AVOID EYE OR SKIN EXPOSURE TO DIRECT OR SCATTERED RADIATION" in the position specified in the regulation] [bearing the wording "CLASS IV LASER PRODUCT" in the position specified in the regulation]. Specifically, ***

Page 278

Rad Health

The warning statement "AVOID EXPOSURE---Laser radiation is emitted from this aperture" was not affixed in close proximity to each aperture through which is emitted accessible laser or collateral radiation in excess of the accessible emission limits of Class I and table VI of Section 1040.10(d). Specifically, *** Labels regarding Class II accessible laser radiation which [are visible on the product prior to and during interlock defeat] [are in close proximity to the opening created by the removal or displacement of such portion of the protective housing] [include the wording: "CAUTION --- Laser radiation when open and interlock defeated. DO NOT STARE INTO BEAM."] were not provided for defeatably interlocked protective housings. Specifically, *** Labels which are legible and clearly visible during operation, maintenance, or service are not permanently affixed to or inscribed on laser products. Specifically, *** The manufacturer did not provide or cause to be provided a listing of [all controls] [all adjustments] [all procedures for operation and maintenance] [the warning: "Caution --- use of controls or adjustments or performance of procedures other than those specified The manufacturer did not provide or cause to be provided in all [catalogs] [specification sheets] [descriptive brochures] pertaining to each laser product, a legible reproduction of [the class designation] [the warning] [the information required for positions 1, 2, and 3 of the applicable logotype] required b to be affixed to the product. Specifically, *** Each demonstration laser product [does not comply with all of the applicable requirements for a Class I, IIa, II, or IIIa laser product] [prevent human access to laser radiation in excess of the accessible emission limits of Class I, IIa, II or IIIa]. Specifically, *** Compliance with the aluminum equivalence limits was not determined by x-ray measurements made [at a potential of 100 kilovolts peak] [with an x-ray beam that has a half-value layer of 2.7 millimeters of aluminum]. Specifically, *** A product report did not describe the methods and procedures employed in testing and measuring each model with respect to electronic product radiation safety, including [the control of unnecessary, secondary, or leakage electronic product radiation] [the applicable quality control procedures used for each model] [the basis for selecting testing and quality control procedures]. Specifically, *** The computed tomography dose index (CTDI) is not provided to users for locations along the axis of rotation of the dosimetry phantom. Specifically, ***

Page 279

Rad Health

Certification of a product is not in conformance with [the manner prescribed in an applicable standard] [the alternate means approved by FDA]. Specifically, *** An annual report which you submitted did not [summarize the contents of the records required by 21 CFR 1002.30(a)] [provide the volume of products produced, sold, or installed] [cover the 12-month period ending on June 30 preceding the due date of the report]. Specifically, *** You have not [established] [maintained] records containing a description of quality control procedures with respect to electronic product radiation safety. Specifically, ***

Page 280

Veterinary Medicine

Center Name Veterinary medicine

Cite Id

Ref No 4185 FDCA 402(a)(4)

ShortDesc Record keeping

7001 FDCA 402(a)(4)

Drug inventory

4093 21 CFR 530.11(d)

Tissue residue

4182 FDCA 501(a)(5)

Extra label use w/o veterinary client-patient relationship

1360 FDCA 501(a)(5)

Expired drugs

4097 21 CFR 530.20(a)(2)(iv)

Tissue residue

13509 FDCA 402(a)(4)

Identity of animals

4298 21 CFR 530.11(a)

Rx not followed

4186 FDCA 402(a)(4)

System for administration of drugs

13521 21 CFR 530.41(a)

Drugs prohibited for extralabel use in food producing animal

1442 FDCA 402(a)(4)

Records review prior to slaughter

1389 21 CFR 530.11(a)

Withdrawal period

4184 FDCA 501(a)(5)

Conditions of use

13508 FDCA 402(a)(4)

Medication status of animals

Page 281

Veterinary Medicine

1362 21 CFR 530.11(a)

Species or class

1446 FDCA 402(a)(4)

Hospital pen

4545 21 CFR 225.120

Vermin and pest infestation

1366 21 CFR 530.11(a)

Dosage level

1457 FDCA 402(a)(4)

Feeding colostrum

4560 21 CFR 225.165

Establishment and use of adequate procedures

1373 21 CFR 530.11(a)

Route of administration

1469 21 CFR 225.20(b)(3)

Pest access minimized

1811 21 CFR 225.58(b)(1)

Three assays per year

4099 21 CFR 530.20(a)(2)(ii)

Extended withdrawal period

4098 21 CFR 530.20(a)(2)(i)

Diagnosis and evaluation of conditions

1491 21 CFR 225.30(b)(2)

Maintenance reasonably clean & orderly

4111 21 CFR 530.12(c)

Directions for use

4113 21 CFR 530.12(e)

Withdrawal, withholding, or discard time

4552 21 CFR 225.142

Adequate procedures for Type A and Type B articles

13534 21 CFR 511.1(b)(7)(ii)

Records: Maintenance

Page 282

Veterinary Medicine

1262 21 CFR 225.10(b)(2)

Evaluation and supervision of employees

1466 21 CFR 225.20(b)(2)

Maintained in clean and orderly condition

1493 21 CFR 225.30(b)(4)

Calibration of scales and metering devices

1850 21 CFR 225.58(d)

Assay results out of specification

2075 21 CFR 225.102(b)(1)

Preparation of MRF

4131 21 CFR 589.2000(c)(1)(i)

Renderers

4132 21 CFR 589.2000(d)(1)

Protein blenders, feed manufacturers, distributors

4137 21 CFR 589.2000(d)(1)

Maintaining records

4183 FDCA 501(a)(5)

Frequency of administration

4553 21 CFR 225.142

Packaged Type A and Type B designated areas

1638 21 CFR 225.42(b)(5)

Elements of receipt record

1744 21 CFR 225.42(b)(6)

Daily inventory record kept

1760 21 CFR 225.42(b)(6)

Lot number or shipment I.D. number

1765 21 CFR 225.42(b)(6)(i) - (v) Information required

1782 21 CFR 225.42(b)(7)

Daily comparison, actual vs theoretical

Page 283

Veterinary Medicine

1821 21 CFR 225.58(b)(1)

First batch assay

1923 21 CFR 225.65(b)

Reasonable and effective procedures followed

1952 21 CFR 225.80(b)(2)

Proofreading labels, labeling, placards

4094 21 CFR 530.11(b)

Use in animal feed

4108 21 CFR 530.12(a)

Name and address - drug dispensed by veterinarian

4112 21 CFR 530.12(d)

Cautionary statements

4541 21 CFR 225.42(b)

Adequate procedures established

4547 21 CFR 225.130

Cleanliness, inspection, cleanout

4567 21 CFR 225.202

Facilitation of recall

13541 FDCA 501(a)(5)

Use of veterinary prescription drugs without a prescription

13541 FDCA 501(a)(5)

Use of veterinary prescription drugs without a prescription

1376 21 CFR 530.11(a)

Frequency and duration

1465 21 CFR 225.20(b)(1)

Building grounds maintenance

1482 21 CFR 225.30(b)(1)

Capability to produce a medicated feed

1535 21 CFR 225.42(b)(2)

Storage of packaged drugs

1539 21 CFR 225.42(b)(3)

Identification and storage of bulk drugs

Page 284

Veterinary Medicine

1575 21 CFR 225.42(b)(4)

Integrity and identity

1880 21 CFR 225.58(e)

Distribution discontinued

1882 21 CFR 225.58(e)

Subsequent production

1925 21 CFR 225.65(b)(2)

Flush material handling

1955 21 CFR 225.80(a)

Appropriate labeling for medicated feed

2074 21 CFR 225.102(a)

Lack of MRF

2076 21 CFR 225.102(b)(1)

Elements of the MRF

2093 21 CFR 225.102(b)(2)(i)-(iv)Elements of production record(s)

2097 21 CFR 225.102(b)(4)

Daily review of production records

2232 21 CFR 225.115(b)(1)

Maintaining records of complaints

2233 21 CFR 225.115(b)(1)

Records of oral or written complaints

2352 21 CFR 226.58(a)

Specifications, test procedures components

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2359 21 CFR 226.58(e)

Test method reliability

4100 21 CFR 530.20(a)(2)(iii)

Identity of treated animals

4101 21 CFR 530.20(a)(1)

Approved drug available

4115 21 CFR 530.13(a)

From bulk drugs

4118 21 CFR 530.13(b)(3)

Outside of scope of professional practice

4119 21 CFR 530.13(b)(4)

Inadequate procedures and processes

4146 21 CFR 589.2000(e)(1)

Written clean-out procedures

4147 21 CFR 589.2000(e)(1)

Written product separation procedures

4453 21 CFR 225.10(b)(1)

Employees lack understanding

4544 21 CFR 225.120

Buildings--space and access

4554 21 CFR 225.142

Bulk Type A and Type B storage

4555 21 CFR 225.142

Use in accord with directions

4564 21 CFR 225.180

Bagged or bulk deliveries

4569 21 CFR 225.202

Records kept one year

13524 21 CFR 511.1(b)(8)(iv)

Medical claims

13526 21 CFR 511.1(b)(8)(ii)

Sponsor/CRO: Reporting of hazards

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13528 21 CFR 511.1(b)(8)(ii)

Sponsor: Monitoring

13531 21 CFR 511.1(b)(7)(iii)

Reports: Adequate and Timely

13532 21 CFR 511.1(b)(7)(ii)

Records: Test article accountability

13535 21 CFR 511.1(b)(7)(i)

Sponsor/CRO: education, training, experience

13539 21 CFR 511.1(b)(4)

No NCIE submitted

13567 21 CFR 589.2001(c)(2)(iv) Label "Do not feed to animals"

13568 21 CFR 589.2001(c)(2)(v) Marking with readily detected agent

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LongDesc Treatment records were not [maintained] [complete]. Specifically,***

Frqncy 127

You lack an adequate inventory system for determining the quantities of drugs used to medicate your [cows] [calves] [livestock]. Specifically, ***

81

Causing a residue of an approved human or animal drug above an established safe level, safe concentration, or tolerance, through use of the drug contrary to its labeling. Specifically, *** Use of [a human] [an animal] drug in a manner contrary to label directions without benefit of a valid veterinary client-patient relationship. Specifically, ***

78

40

Expired drug(s) were observed in the drug storage area. Specifically, ***

27

Causing an illegal residue in a food-producing animal of an approved human or animal drug through [prescribing the use of] [using] the drug contrary to its labeling, and failing to take appropriate measures to assure that [assigned timeframes for withdrawal were met] [no illegal residue would occur]. Specifically, *** Failure to [identify] [maintain records regarding the identity of] [record the existing identification of] the animal(s) that you [purchased] [transported] and delivered for [sale] [consignment] at [an auction yard] [a slaughter plant]. Specifically, *** Failure to follow your veterinarian's prescription for [dosage] [frequency and duration of treatment] [route of administration] [species or class of animal] [pre-slaughter withdrawal time] [special cautionary directions]. Specifically, *** Failure to have a system to control administration of drug treatments to your animals. Specifically, ***

27

26

21

20

A prohibited [drug] [substance] was administered in an extralabel manner to [a] foodproducing animal(s). Specifically, ***

19

Failure to systematically review treatment records prior to offering an animal for slaughter for human food, to assure that drugs have been used only as directed and that appropriate withdrawal times have been observed. Specifically, *** Administration of an approved animal drug contrary to the labeling, without benefit of a valid veterinarian-client-patient relationship, in that pre-slaughter withdrawal time was not observed. Specifically, *** Administration of a drug for conditions not [specified in its labeling] [prescribed]. Specifically, ***

16

13

13

Failure to inquire about the medication status of the animal(s) that you [transported] [purchased] and delivered for [sale] [consignment] at [an auction yard] [a slaughter plant]. Specifically, ***

11

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Administration of an approved human or animal drug to a [species of animal] [class of animal] for which the drug was not labeled, without benefit of a valid veterinarian-clientpatient relationship. Specifically, *** Failure to [identify] [segregate] [quarantine] treated animals. Specifically, ***

Buildings and grounds are not constructed and maintained in a manner to minimize vermin and pest infestation. Specifically, ***

Administration of an approved animal drug in excess of the indicated dosage, without benefit of a valid veterinarian-client-patient relationship. Specifically, ***

Feeding colostrum or milk from treated cows to calves intended for slaughter. Specifically, ***

Adequate procedures are not [established] [used] for all equipment used in the production and distribution of medicated feeds to avoid unsafe contamination of medicated [and nonmedicated] feeds. Specifically, *** Administration of an approved animal drug via a route, [oral] [intramuscular] [intravenous] [subcutaneous] [topical] [intramammary] [intrauterine], which was not indicated in the labeling, without benefit of a valid veterinarian-client-patient relationship. Specifically, *** The building is not constructed to minimize access by [rodents] [birds] [insects] [pests]. Specifically, ***

Periodic assays are not performed during the calendar year on at least three representative samples of medicated feeds requiring a medicated feed mill license, for each drug or drug combination used. Specifically, *** A substantially extended withdrawal period, supported by appropriate scientific information, was not established for the use of an approved drug in a food-producing animal, in an extralabel manner. Specifically, *** Failure to make a careful diagnosis and evaluation of the conditions for which an approved human or animal drug was to be used in a food-producing animal, contrary to the drug's labeling. Specifically, *** Equipment is not maintained in a reasonably clean and orderly manner. Specifically, ***

Failure to provide labeling containing directions for use as specified by the veterinarian for a human or animal drug prescribed for use in an animal contrary to the drug's labeling. Specifically, *** Failure to provide labeling containing [withdrawal] [withholding] [discard] time as specified by the veterinarian for a human or animal drug prescribed for use in an animal contrary to the drug's labeling. Specifically, *** Adequate procedures are not [established] [maintained] for the [identification] [storage] [inventory control (receipt and use)] of all Type A medicated articles and Type B medicated feeds intended for use in the manufacture of medicated feeds. Specifically, *** Complete records of the investigation were not maintained. Specifically, ***

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Failure to provide an on-going program of evaluation and supervision of employees in the manufacture of medicated feeds. Specifically, ***

Buildings are not maintained in a reasonably clean and orderly manner. Specifically, ***

Failure to calibrate scales and metering devices [upon installation] [at least once a year after installation] [as frequently as necessary] to insure their accuracy. Specifically, ***

Failure to [investigate] [implement corrective action] [maintain a record on the premises of corrective action] when assay results show medicated feeds [not in accord with label specifications] [not within permissible assay limits]. Specifically,*** A Master Record File providing the complete procedure for manufacturing a specific product is not [prepared] [checked] [dated] [signed or initialed] by a qualified person. Specifically, *** Products that contain or may contain prohibited material fail to bear a label containing the caution statement, "Do not feed to cattle or other ruminants." Specifically, ***

Products that contain or may contain prohibited material fail to bear the caution statement, "Do not feed to cattle or other ruminants." Specifically, ***

Receipt of materials that contain or may contain protein derived from mammalian tissues, and failure to maintain records sufficient to track the materials throughout their receipt, processing, and distribution. Specifically, *** Administration of a drug [over a longer time period] [more frequently] than [specified in its labeling] [prescribed]. Specifically, ***

The [packaged Type A medicated articles] [packaged Type B medicated feed] are not [stored in designated areas] [stored in their original closed containers]. Specifically, ***

Drug receipt records do not accurately indicate the [identity] [quantity] [name of the supplier] [supplier's lot number or other identifying number] [date of receipt] [condition of the drug when received] [return of any damaged drugs] for each lot of drug received. Specifically, *** Failure to maintain a daily inventory record for each drug used in the manufacture of medicated feeds. Specifically, ***

The daily inventory records for drugs do not include [the manufacturer's lot number] [the feed manufacturer's shipment identification number]. Specifically, ***

Daily inventory records for each drug used do not include [the quantity of drug on hand at the beginning and end of the work day] [the amount of each drug used, sold, or otherwise disposed of] [the batches or production runs of medicated feed in which each drug was used] [information concerning any semiprocessed intermediate mix to be used in a medicated feed] [the action taken to reconcile any discrepancies in the inventory record]. Specifically, *** A daily comparison is not made between the actual amount of drug used and the theoretical amount of drug to be used in terms of the [semiprocessed] [intermediate] [finished] medicated feeds manufactured. Specifically, ***

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No assay was performed on the first batch for the calendar year of medicated feed requiring a medicated feed mill license. Specifically, ***

All equipment that comes in contact with [active drug components] [feeds in process] [finished medicated feed] is not subject to all reasonable and effective procedures to prevent unsafe contamination of manufactured feed. Specifically, *** Incoming [labels] [labeling] [placards] are not proofread upon receipt from the printer against the Master Record Files to verify suitability and accuracy. Specifically, ***

An approved drug was used in or on an animal feed in a manner not in accordance with the approved labeling. Specifically, ***

Failure to provide labeling showing the name and address of the prescribing veterinarian for a human or animal drug prescribed for use in an animal contrary to the drug's labeling. Specifically, *** Failure to provide labeling containing cautionary statements as specified by the veterinarian for a human or animal drug prescribed for use in an animal contrary to the drug's labeling. Specifically, *** Adequate procedures are not established for the [receipt] [storage] [inventory control] of all drugs to aid in assuring their identity, strength, quality and purity when incorporated into products. Specifically, *** Equipment for producing medicated feeds of intended potency and purity is not [maintained in a reasonably clean and orderly manner] [designed, constructed, installed and maintained so as to facilitate inspection and use of cleanout procedures]. Specifically, *** The [formula] [production] [distribution] records are not adequate to facilitate the recall of specific batches of medicated feed that have been distributed. Specifically, ***

Administration of veterinary prescription drugs was performed without the lawful written or oral order of a licensed veterinarian. Specifically, ***

Administration of veterinary prescription drugs was performed without the lawful written or oral order of a licensed veterinarian. Specifically, ***

Administration of an approved animal drug [more frequently] [for a longer time period] than specified in the labeling, without benefit of a valid veterinarian-client-patient relationship. Specifically, *** The building grounds are not routinely maintained so that they are reasonably free from [litter, waste, and refuse] [uncut weeds and grass] [improperly stored equipment]. Specifically, *** Equipment does not possess the capability to produce a medicated feed of intended [potency] [safety] [purity]. Specifically, ***

Packaged drugs are not stored in their original closed containers. Specifically, ***

Bulk drugs are not [identified] [stored] in a manner such that their identity, strength, quality, and purity will be maintained. Specifically, ***

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Failure to properly [identify] [store] [handle] [control] drugs in the mixing areas to maintain their integrity and identity. Specifically, ***

Distribution of a medicated feed which failed to meet its labeled drug potency was not discontinued. Specifically, ***

Following distribution of a medicated feed which failed to meet its labeled drug potency, subsequent production of that feed was resumed prior to the establishment of proper control procedures. Specifically, *** Material used for cleanout by flushing is not properly [identified] [stored] [used in a manner] to prevent unsafe contamination of other feeds. Specifically, ***

Medicated feed is not identified by appropriate labeling which provides the user with directions for use which if adhered to, will assure the article is safe and effective for its intended purpose. Specifically, *** Failure to have a Master Record File for manufacturing a specific product, which provides the complete procedure for manufacturing a specific product. Specifically, ***

The Master Record File does not contain [the name of the medicated feed] [the name and weight percentage or measure of each drug or drug combination and each nondrug ingredient to be used in manufacturing a stated weight of medicated feed] [a copy or description of the label that will accompany the medicated feed] [manufacturing instructions or reference thereto that have been determined to yield a properly mixed medicated feed of the specified formula for each medicated feed produced] [appropriate control directions including the collection of samples for specified laboratory assays] [the basis for estimating quantity produced, where actual yield cannot be accurately determined when finished feed is stored in bulk]. Specifically, *** Production record(s) fail to include [the product identification] [the date of production] [a written endorsement in the form of a signature or initials by a responsible individual] [the quantity and name of drug components used] [the theoretical quantity of medicated feed to be produced] [the actual quantity of the medicated feed produced] [an estimate of the quantity to be produced and stored in bulk, based on the basis for the estimate in the MRF]. Specifically, *** The batch production records are not checked by a responsible individual at the end of the working day to determine whether all required production steps have been performed. Specifically, *** The original or copy of a record of each oral or written complaint received relating to the safety and effectiveness of the product produced is not maintained on the premises. Specifically, *** The record of each oral or written complaint relating to the safety and effectiveness of a medicated feed fails to include the [date of the complaint] [complainant's name] [complainant's address] [name and lot or control number or date of manufacture] [specific details of the complaint] [correspondence from the complainant and/or memoranda of conversations] [description of all investigations made by the manufacturer] [method of disposition of the complaint]. Specifically, *** Laboratory controls do not include adequate specifications and test procedures to assure that drug components used in the manufacture of Type A medicated articles conform to appropriate specifications. Specifically, ***

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Laboratory controls do not include adequate provisions to check the [reliability] [accuracy] [precision] of laboratory test procedures. Specifically, ***

Failure to assure that the identity of a food-producing animal was maintained, where you had prescribed or dispensed an approved human or animal drug contrary to the drug's labeling. Specifically, *** Failure to determine that an approved animal drug was clinically ineffective for its intended use in a food-producing animal, prior to prescribing or dispensing an approved human or animal drug contrary to the drug's labeling. Specifically, *** Compounding an animal drug from a bulk drug. Specifically, ***

Compounding of an approved drug for use in an extralabel manner was not performed by a licensed [pharmacist] [veterinarian] within the scope of a professional practice. Specifically, *** Failure to follow adequate procedures and processes to ensure the safety and effectiveness of a compounded animal drug. Specifically, ***

Failure to maintain written clean-out procedures to prevent carryover of protein derived from mammalian tissues to animal protein or feeds that may be used for ruminants. Specifically, *** Failure to maintain procedures for separating products which may contain protein derived from mammalian tissues from all other protein products, from the time of receipt until the time of shipment. Specifically, *** All employees involved in the manufacture of medicated feeds do not have an understanding of the [manufacturing or control operations they perform] [location and proper use of equipment]. Specifically, *** Buildings for the production of medicated feed lack adequate space for [equipment] [processing] [orderly receipt and storage of medicated feed] [access to equipment for routine maintenance and cleaning]. Specifically, *** Bulk [Type A medicated articles] [Type B medicated feeds] are not identified and stored in a manner such that their identity, strength, quality and purity will be maintained. Specifically, *** All [Type A medicated articles] [Type B medicated feeds] are not used in accordance with their labeled mixing directions. Specifically, ***

All deliveries of medicated feeds, whether bagged or in bulk, are not adequately labeled to assure that the feed can be properly used. Specifically, ***

Records identifying the formulation, date of mixing, and date of shipment (if not for own use) are not retained on the premises for one year following the date of last distribution. Specifically, *** Representations were made that the new animal drug under investigation is [safe][effective]. Specifically, ***

The [sponsor][CRO] failed to promptly investigate and report to the FDA and investigators any findings associated with use of the new animal drug that may suggest significant hazards pertinent to the safety of the drug. Specifically, ***

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The [sponsor][CRO] did not provide for current monitoring of the investigation by a qualified person. Specifically, ***

The investigator did not furnish adequate and timely reports of the investigation to the sponsor. Specifically, ***

Complete records of the receipt and disposition of each shipment or delivery of the test article were not maintained by the investigator. Specifically, ***

The [sponsor][CRO] did not assure that the new animal drug was shipped only to investigators who have the scientific training and/or experience to evaluate the safety and/or effectiveness of the drug. Specifically, *** A Notice of Claimed Investigational Exemption for a New Animal Drug (NCIE) was not submitted prior to the shipment of that drug for clinical testing. Specifically, ***

Failure to conspicuously label [cattle materials prohibited in animal feed] [products that contain or may contain cattle materials prohibited in animal feed] with the statement "Do not feed to animals". Specifically,*** Failure to mark [cattle materials prohibited in animal feed] [products that contain or may contain cattle materials prohibited in animal feed] with an agent that can be readily detected on visual inspection. Specifically,***

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