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The sections in this general chapter are organized to facilitate the practitioners
understanding of the fundamental quality practices for preparing hazardous drugs
(HDs). The chapter is divided into the following main sections:
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1. Introduction
2. List of HDs
3. Types of Exposure
4. Responsibilities of Personnel Handling HDs
5. Facility Design and Engineering Controls
6. Personal Protective Equipment
7. Hazard Communication Program
8. Training for Compounding Personnel
9. Receiving
10. Transporting
11. Dispensing HD Dosage Forms Not Requiring Alteration
12. Compounding HD Dosage Forms
13. Protection When Administering HDs
14. Cleaning: Deactivation, Decontamination, Cleaning, and Disinfection
15. Spill Control
16. Disposal
17. Environmental Quality and Control
18. Documentation
19. Medical Surveillance
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Appendices
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a.
b.
c.
d.
e.
f.
g.
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1.2 Objective
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The objective of this chapter is to protect personnel and the environment when
handling HDs. This includes but is not limited to receipt, storage, mixing, preparing,
compounding, dispensing, administering, disposing, and otherwise altering, counting,
crushing, or pouring HDs, and includes both sterile and nonsterile products and
preparations. The standards in this chapter apply to all personnel who compound HDs
preparations and all places where HDs are prepared (e.g., pharmacies, hospitals and
other healthcare institutions, patient treatment clinics, physicians practice facilities,
veterinarians offices) and other locations and facilities in which HDs are stored,
transported, and administered. Persons who compound HDs include but are not limited
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1.3 Overview
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(http://www.osha.gov/dsg/hazcom/standards.html)
OSHA Technical Manual (OTM). Section VI: Chapter 2: Controlling Occupational
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All personnel who handle HDs shall be responsible for understanding these
fundamental practices and precautions and for continually evaluating these procedures
and the quality of final HDs to prevent harm to patients or personnel and to prevent
contamination of the environment. Compounding personnel shall be responsible for
safely preparing and handling HDs. Table 1 describes the ISO classified air
environment for handling HDs and Table 2 describes the types of devices for
compounding HDs.
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Particle Count
ISO Class
U.S. FS 209E
ISO (m3)
FS 209E (ft3)
Class 100
3,520
100
Class 10,000
352,000
10,000
Class 100,000
3,520,000
100,000
Limits are in particulates of 0.5 m and larger per cubic meter (current ISO) and cubic feet (former
Federal Standard No. 209E, FS 209E).
b
Adapted from former Federal Standard No. 209E, General Services Administrations, Washington, DC
20407 (September 11, 1992) and ISO 146441:1999, Cleanrooms and associated controlled
environmentsPart I: Classification of air cleanliness. For example, 3,520 particles of 0.5 m/m3 or larger
(ISO Class 5) is equivalent to 100 particles/ft3 (Class 100) (1 m3 = 35.2 ft3).
a
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Type of
Compounding
Type of Device
Containment Ventilated Enclosure (CVE) or Class I Biological Safety
Cabinets (BSC)
Nonsterile
Type of
Compounding
Type of Device
nonsterile compounding, Class II BSCs or CACIs must undergo
thorough cleaning and disinfection before being used for sterile
compounding.]
Sterile
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2. LIST OF HDS
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The National Institute for Occupational Safety and Health (NIOSH) maintains a list of
antineoplastic and other HDs used in healthcare. The entity shall include all items on
the current NIOSH list and may add others not on the NIOSH list. The entitys list shall
be reviewed at least annually and whenever a new agent or dosage form is used. If the
information provided is deemed insufficient to make an informed decision, the drug
should be considered hazardous until more information is available.
Some dosage forms defined as hazardous may not pose a significant risk of direct
occupational exposure because of their dosage formulation (e.g., coated tablets or
capsulessolid, intact medications that are administered to patients without modifying
the formulation). Uncoated tablets may present a risk of exposure from dust by skin
contact and/or inhalation when the tablets are counted. Any solid dosage form may
pose a risk if altered, such as by crushing tablets or making solutions. The entitys
standard operating procedure (SOP) (see Appendix B) shall identify the risk mitigation
strategies for items on the entitys list of HDs.
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3. TYPES OF EXPOSURE
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Routes of unintentional entry of HDs into the body include dermal and mucosal
absorption, inhalation, injection, and ingestion either of contaminated foodstuffs or
mouth contact with contaminated hands. Both clinical and nonclinical personnel may be
exposed to HDs when they create or use aerosols, generate dust, clean up spills, or
touch contaminated surfaces during the receipt, preparation, administration, cleaning, or
disposal of HDs.
The following list of activities may result in exposures through skin contact, inhalation,
ingestion, or injection:
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floors, and final drug preparations (e.g., bottles, bags, cassettes, and syringes)
Contacting or inhaling HD residue or aerosolization from another patients
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Each entity shall have a compounding supervisor who is the designated individual
responsible for developing and implementing appropriate procedures; overseeing facility
compliance with this chapter and other applicable laws, regulations, and standards;
ensuring competency of personnel; and assuring environmental control of the
compounding areas. The compounding supervisor shall also be responsible for the
continuous monitoring of the facility and compounded sterile preparations (CSPs),
including reports of all testing from all contractors and laboratories on facilities, CSPs,
and/or their components.
All personnel involved with mixing, compounding, and otherwise handling HDs shall be
responsible for compounding HDs of acceptable strength, quality, and purity and in
accordance with a prescription or medication order from a licensed prescriber.
Compounding personnel shall be responsible for dispensing the finished preparation
with appropriate packaging and labeling in compliance with the requirements and
recommendations established by the applicable federal, state, and local agencies,
including state boards of pharmacy, Occupational Safety and Health Administration
(OSHA), NIOSH, Environmental Protection Agency (EPA), and other organizations
(e.g., accrediting organizations, where appropriate). Individuals who are engaged in HD
compounding shall be competent in HD compounding and should continually expand
their compounding knowledge by participating in seminars, training programs, and/or
studying appropriate literature. They shall be knowledgeable in the contents of chapters
795 , 797 , and 1163 , other applicable USP chapters and General Notices and
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Requirements, and applicable federal and state laws, regulations, and guidelines.
Personnel who transport, compound, or administer HDs shall document training
according to OSHA standards (see OSHA Standard 1910.120 Hazardous Waste
Operations and Emergency Response) and other applicable laws and regulations.
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Facilities as described in this chapter for both nonsterile and sterile HD compounding
are in addition to the requirements to chapters 795 and 797 .
HDs shall be handled under conditions that promote patient safety, worker safety,
environmental protection, and infection prevention. Manipulation of HDs requires
appropriate administrative controls, PPE, engineering and environmental controls, and
work practices.
Access to areas where HDs are stored and prepared shall be restricted to authorized
staff to protect persons not involved in HD handling. The location of the HD
compounding area shall be located away from break rooms and refreshment areas for
staff, patients, or visitors to reduce risk of exposure. Signs designating the hazard shall
be prominently displayed before entry into the HD area.
Separate designated areas shall be available for (see Appendix D):
Unpacking HDs
Nonsterile HD compounding (if performed by the entity)
Sterile HD compounding (if performed by the entity)
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All HD storage areas and containers, regardless of the formulation, shall be labeled as
such to prevent improper handling.
Unless the HDs already exist in their final unit dose or unit-of-use packaging, HDs shall
be stored separately from other inventory in a manner to prevent contamination and
personnel exposure, which includes storage in a negative pressure room with at least
12 air changes per hour (ACPH). Depending upon pharmacy design, HD storage within
the HD buffer area can fulfill this storage criterion.
Refrigerated HDs shall be stored in a dedicated refrigerator in the HD storage room,
buffer room, or containment segregated compounding area (C-SCA). In a containment
secondary engineering control (C-SEC) used for sterile preparations, an exhaust
located adjacent to the refrigerators compressor and behind the refrigerator should be
considered.
HDs shall be stored at or below eye level, in containers that minimize the risk of
breakage and leakage, and shall not be stored on the floor. Areas prone to specific
types of natural disasters (e.g., earthquakes) shall ensure that storage meets applicable
safety precautions, such as secure shelves with raised front lips. Storage of sterile and
nonsterile HDs may be intermingled. HD storage in a sterile compounding buffer area
shall be limited to those used for sterile compounding (see chapter 797 ).
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5.3.1 BACKGROUND
HDs shall be prepared only under conditions that protect the healthcare workers and
other personnel in the preparation and storage areas. Within this chapter, engineering
controls are divided into three categories representing primary, secondary, and
supplementary levels of control (see Appendix A and Appendix C for more details). CPECs provide the environment at the point of use and are integrated into the C-SEC
(i.e., room). The C-SEC supports the C-PEC. Supplemental engineering controls are
adjunct controls [e.g., closed-system drug-transfer device (CSTD)] used in conjunction
with primary and secondary control strategies.
HDs that require alteration shall be manipulated (mixed, diluted, compounded, and
others) in a C-PEC in an area that is physically separated from other preparation areas,
that is under negative pressure, and has at least 12 ACPH. Additional criteria are listed
below.
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skin; it shall not be within an ISO Class 7 buffer area. An eyewash station or other
emergency or safety precautions that meet applicable laws and regulations shall be
readily available; however, care must be taken to locate them in areas where their
presence will not interfere with required ISO classifications.
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5.4Nonsterile HD Compounding
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Minimum of 12 ACPH
Maintained at a negative pressure of at least 0.01 inches of water column relative
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C-PEC
C-SEC
Airflow
Maximum BUD
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Function
Compounding sterile HD in
a cleanroom
CPEC
Airflow
Maximum
BUD
BSC
30 ACPH
or
ISO 7
(HEPA
CACI Cleanroom supply)
As listed in
797
12 ACPH
(exhaust)
As listed in
797
C-SEC
Compounding sterile HD in
a CACI that meets the
requirements listed in 797
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CACI C-SCA
Compounding low- or
medium-risk sterile HDs in a
BSC. [NOTEThis
configuration is not
acceptable for high-risk
12 ACPH
3
sterile HD compounding.]
BSC C-SCA
(exhaust)
See Appendix D for best practices for compounding sterile HDs.
12 hours
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water column relative to all adjacent spaces (rooms, above ceiling, and
corridors). [
NOTEAlthough negative pressure within the HD buffer area is important, the
negative pressure should not be so strong that it induces environmental
contamination migration into the buffer area from unclassified adjacent spaces.]
Incorporate the remaining relevant design criteria specified in chapter 797
Rooms through which entry into the negative-pressure buffer room occurs (anteroom
or non-HD buffer room) shall be positive-pressure ISO Class 7 or better so that inward
air migration is of equal cleanliness classification to that in the negative-pressure buffer
area. A pressure indicator shall be installed that can be readily monitored for correct
room pressurization.
Because the anteroom leading into the HD buffer room plays an important function in
terms of total contamination control within the buffer room, the anteroom must be
constructed using principles similar to those used in non-HD sterile compounding.
These include:
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Although not a recommended facility design, if the negative pressure HD buffer room
is entered though the positive-pressure, non-HD buffer room, additional facility criteria
are required:
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certification to ensure that particles are not compromising the air quality of the
negative-pressure buffer room. Other methods of containment (such as sealed
containers) may be used if the entity can demonstrate HD containment and
appropriate environmental control.
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HD CSPs prepared in this cleanroom configuration may use the BUDs listed in chapter
797 , based on risk levels and storage temperature.
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Minimum of 12 ACPH
Maintained at a negative pressure of at least 0.01 inches of water column relative
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HD CSPs compounded in this CACI/C-SCA configuration may use the BUDs listed in
chapter 797 based on risk levels and storage temperature.
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Minimum of 12 ACPH
Maintained at a negative pressure of at least 0.01 inches of water column relative
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Some CSTDs have been shown to limit the potential for generating aerosols during
compounding; however, there is no certainty that all CSTDs will perform adequately.
There does not yet exist a universal performance protocol by which all CSTDs are
evaluated for containment. Until such a protocol is developed and adopted, users
should carefully evaluate the performance claims associated with available CSTDs.
When a widely-accepted protocol for CSTD performance evaluation is developed, users
are encouraged to focus upon CSTD manufacturers that subject their CSTD devices to
independent evaluation under this protocol. CSTDs used as a supplemental control for
compounding shall be used inside a C-PEC. CSTDs should be used when
compounding HDs when the dosage form allows. CSTDs shall be used when
administering HDs when the dosage form allows.
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The garbing and gloving requirements listed here shall be used for compounding any
HD (nonsterile and sterile) in any setting and when using any and all C-PECs.
The SOP manual (see Appendix B) of the compounding facility shall specifically
describe the appropriate PPE to be worn based on a written safety and health program.
PPE, in addition to those listed below, may be used to reduce exposure or to protect
workers from contamination.
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6.1 Gloves
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Use powder-free gloves, because the powder can contaminate the work area
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or weak spots.
Wear two pairs of ASTM-tested chemotherapy gloves when compounding,
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Hand hygiene shall be performed in accordance with the CDC Guidelines for
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6.2 Gowns
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Disposable gowns that protect the worker from spills and splashes of HDs and waste
materials and that have been tested to resist permeability by HDs shall be worn when
handling HDs. Selection of gowns shall be based on the HDs used.
Disposable gowns made of polyethylene-coated polypropylene or other laminate
materials offer better protection than those of noncoated materials. Gowns shall close in
the back (no open front), have long sleeves, and have closed cuffs that are elastic or
knit. Gowns shall not have seams or closures that could allow drugs to pass through.
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Cloth laboratory coats, surgical scrubs, isolation gowns, or other absorbent materials
are not appropriate outer wear when handling HDs, because they permit the permeation
of HDs and can hold spilled drugs against the skin and increase exposure.
The following work practices shall be followed:
Wear gowns whenever there is a possibility of HD contact with skin or clothing
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Head and hair (including beard and moustache, if applicable) and shoe covers shall be
worn to reduce the possibility of particulate or microbial contamination in HD
compounding areas. Hair, head, and shoe covers provide additional protection from
contact with HD residue on surfaces and floors.
The following work practices shall be followed:
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Do not wear shoe covers outside the HD compounding areas to avoid spreading
provide additional protection for the areas of the arms that may come in contact
with HDs within BSCs. Use disposable sleeve covers to protect the wrist area,
and remove the covers carefully after the task is complete. Discard sleeve
covers after one use, and contain and dispose of them as trace contaminated or
trace chemotherapy waste.
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Appropriate eye and face protection shall be worn when handling HDs outside an
engineering control. A full-facepiece respirator also provides eye and face protection.
Goggles shall be used when eye protection is needed; eye glasses alone or safety
glasses with side shields do not provide adequate protection to the eyes from splashes.
Many HDs are irritating to eyes and mucous membranes. Follow these work practices
when using eye and face protection:
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Use eye and face protection when manipulating an HD outside of a C-PEC (e.g.,
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Use face shields in combination with goggles to provide a full range of protection
against splashes to the face and eyes. Face shields alone do not provide full
eye and face protection.
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Consider all PPE worn when handling HDs as being contaminated with, at a minimum,
trace quantity of HDs. Unless local regulations prohibit, these items shall be incinerated
at a regulated medical waste incinerator. They should not be placed into red bag or red
sharps containers.
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familiar with this chapter. They shall be knowledgeable with the contents of
chapters 795 , 797 , and 1163 ; specific publications of NIOSH Alert:
Preventing Occupational Exposures to Antineoplastic and Other Hazardous
Drugs in Health Care Settings, Medical Surveillance for Healthcare Workers
Exposed to Hazardous Drugs, OSHA Technical Manual, and Controlling
Occupational Exposure to Hazardous Drugs; and other relevant publications,
including how to read and interpret SDSs.
All compounders shall read and become familiar with each of the entitys SOPs
(see Appendix B) related to hazardous compounding, including those involving
the facility, equipment, PPE, compounding processes, hazardous waste
disposal, evaluation, packaging, storage, spill containment, decontamination,
and dispensing or delivery.
The compounding supervisor or designee shall demonstrate the procedures for
the compounder and shall observe and guide the employee throughout the
training process. The compounder shall then repeat the procedure without any
assistance from, but under the direct supervision of, the compounding
supervisor or designee.
The compounding supervisor shall routinely monitor the work of the compounder
and ensure that the compounder is following appropriate HD precautions and
that the compounders calculations and work are accurate and adequately
performed. The monitoring shall be documented as part of the entitys
competency assessment program.
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9. RECEIVING
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The compounding supervisor shall ensure that the products and components received
are consistent with principles of Good Distribution Practices. HDs should be received
from the supplier sealed in impervious plastic to segregate them from other drugs, to
allow for safety in the receiving and internal transfer process, and should be
immediately delivered to the C-SEC. HDs shall only be stored in areas with the
ventilation controls described in this chapter.
Receiving personnel shall be trained per the entitys SOP (see Appendix B). Training
shall be documented.
PPE, including ASTM-tested, powder-free chemotherapy gloves, shall be worn when
handling HDs (see Appendix F for PPE requirements). A spill kit shall be accessible in
the receiving area.
The entity shall enforce policies that include a tiered approach, including:
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- Clean the Class I device (see 14. Cleaning section), and discard
the mat and cleaning disposables as hazardous waste.
Damaged packages or shipping cartons shall be considered spills that shall be
reported to the compounding supervisor and conform to other entity-defined reporting
processes. Clean-up shall comply with established SOPs (see Appendix B).
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10. TRANSPORTING
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Personnel transporting HDs shall be trained and their competency documented. HDs
require safeguards to maintain the integrity of the HD and to minimize the potential for
breakage or spill exposure of these products to the environment and to personnel who
may come in contact with them.
Drugs that have been identified as requiring HD handling precautions shall be clearly
labeled at all times during their transport and use. HDs shall be transported in closed
containers that minimize the risk of breakage or leakage.
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The entity shall establish SOPs (see Appendix B) pertaining to packaging, transport,
and handling of HDs. The SOPs shall address prevention of accidental exposures or
spills, personnel training to respond to exposure, and use of a spill kit. Examples of
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When HDs are distributed to locations outside the premises in which they are
compounded, compounding personnel shall select packing containers and materials
that are expected to maintain physical integrity, stability, and sterility (if needed) of HDs
during transit. Packing shall be selected that simultaneously protects HDs from damage,
leakage, contamination, and degradation and protects personnel who transport packed
HDs. The entitys approved SOPs (see Appendix B) shall specifically describe
appropriate packing containers and insulating and packing materials, based on
information from product specifications, vendors, and the experience of the
compounding personnel. Written instructions that clearly explain how to safely open
containers of packed HDs shall be provided to patients and other recipients. Transport
of HDs shall be labeled, stored, and handled in accordance with applicable federal,
state, and local regulations.
Compounding personnel shall ascertain that temperatures of HDs during transit by the
selected mode do not deviate from the warmest temperature specified on the storage
temperature range on HD labels (see 1079 Good Storage and Distribution Practices
for Drug Products). Compounding personnel should communicate directly with the
couriers to learn shipping durations and exposure conditions that HDs may encounter.
Refer to 795 and 797 for additional storage information.
Compounding facilities that ship HDs to patients and other recipients outside their own
premises shall ascertain or provide, whichever is appropriate, the following assurances:
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Delivery performance of couriers to ascertain that HDs are being efficiently and
properly transported.
Labels and accessory labeling for HDs include clearly readable BUDs, storage
instructions, disposal instructions for out-of-date units, and HD category labels
that shall be consistent with the carriers policies.
Each facility, patient, or other recipient can store the HD properly; including the
use of a properly functioning refrigerator or freezer if the HD is labeled for such
storage.
11. DISPENSING HD DOSAGE FORMS NOT REQUIRING ALTERATION
HDs in unit-dose or unit-of-use packaging that do not require any further alteration
before delivery to the patient or the patients caregiver may be dispensed without any
further requirements for containment unless required by the manufacturer.
If the entitys SOPs permit, non-antineoplastic HDs that require only transfer from the
manufacturers package to a prescription container may be dispensed without any
further requirements for containment unless required by the manufacturer. Counting of
HDs should be done carefully, and clean equipment should be dedicated for use with
these drugs.
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Tablet and capsule forms of HDs shall not be placed in automated counting machines,
which subject them to stress and may introduce powdered contaminants into the work
area. Counting coated tablets and capsules does not require a C-PEC, as long as they
are not altered or broken.
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Compounding personnel are responsible for ensuring that HDs are accurately
identified, measured, diluted, and mixed and are appropriately sterilized (when
appropriate), packaged, sealed, labeled, stored, dispensed, and distributed. These
performance responsibilities include maintaining clean conditions and providing labeling
and supplementary instructions for the proper administration of HDs.
Work practices for compounding nonsterile HD dosage forms shall include:
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appropriate for use, e.g., using an injection rather than a bulk powder.
Appropriately preparing materials used in compounding before introduction into
for
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
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809
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811
812
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815
816
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818
819
820
821
822
823
824
needleless and closed systems) and techniques (such as spiking and priming of
IV tubing by pharmacy personnel inside a C-PEC, and/or priming in-line with
nondrug solutions).
Using CSTDs when administering HDs, when the dosage form allows.
Complying with hand hygiene practices before and after manipulation of the HDs.
Wearing PPE (including two pairs of ASTM-tested gloves and protective gowns)
for activities associated with drug administrationopening the outer bag,
assembling the delivery system, delivering the drug to the patient, and
disposing of all equipment used to administer drugs. Wear eye protection where
splashing is possible.
Removing outer gloves and gowns and bagging them for disposal in the
approved chemotherapy waste container at the site of drug administration.
Remembering that HDs administered in locations, such as the surgical suite,
present challenges to training and containment. Intracavitary administration of
HDs (e.g., into the bladder, peritoneal cavity, or chest cavity) frequently requires
equipment for which locking connections may not be readily available or
possible.
Ensuring that all staff members who handle HDs receive safety training that
includes recognition of HDs and appropriate spill response. HD spill kits,
containment bags, and disposal containers shall be available in all areas where
HDs are handled.
Using techniques and ancillary devices that minimize the risk of open systems
when administering HDs through unusual routes or in non-traditional locations.
The Oncology Nursing Society (ONS) Safe Handling of Hazardous Drugs publication
contains additional details that may be incorporated into SOPs (see Appendix B).
14. CLEANING: DEACTIVATION, DECONTAMINATION, CLEANING, AND
DISINFECTION
Personnel performing cleaning activities (including compounding, direct care,
environmental services, laundry, waste handling, and others) shall be protected from
inadvertent exposure to HDs.
14.1 Routine Cleaning, Decontaminating, and Waste Disposal
Work practices for environmental services and other personnel who handle HDs shall
include:
Wearing two pairs of ASTM-tested chemotherapy gloves that are chemically
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
The entity shall establish cleaning routines consistent with this chapter and with
recommendations from the C-PEC manufacturer. The routines shall include periodic
cleaning of all work surfaces and equipment that may become contaminated, including
administration carts and trays. Details shall be included in the entitys SOPs (see
Appendix B), including processes, solutions and dilutions used, and documentation
requirements.
Personnel shall wear eye protection and ASTM-tested chemotherapy gloves for
deactivating, decontaminating, cleaning, and disinfecting. Gloves used shall be
chemically resistant to the cleaning agents used. Face shields shall be worn if splashing
is possible.
The choice of cleaning products shall be related to the product and preparation, time,
and application of the decontamination product, equipment used, and resistance
patterns.
The equipment used for compounding HDs shall be dedicated for HDs and shall be
chosen so that the equipment can be effectively cleaned (and sterilized, if necessary, by
steam, dry heat, or other methods). Perform cleaning in areas that are sufficiently
ventilated to prevent build-up of hazardous airborne drug concentrations and
decontamination agents. Cleaning of nonsterile compounding equipment shall not be
done when sterile compounding is underway in the same room.
847
14.4 Cleaning C-PEC and Other Devices Used for Compounding HDs
848
849
850
851
852
853
854
855
856
Cleaning C-PEC, other devices and equipment, and areas used for compounding HDs
involves several steps that are discussed below:
857
858
859
860
861
862
863
864
865
866
867
868
14.4.1 DEACTIVATION
Chemical deactivation of a hazardous substance is preferred, but no single process
has been found to deactivate all currently available HDs. Deactivation shall occur when
an appropriate agent is identified. Note that alcohol is not a deactivation agent, and the
use of alcohol before deactivating and decontamination may result in the spread of
contamination rather than any actual cleaning. A multi-component deactivation system
is theoretically more efficient than a single-agent system because of the diverse nature
of HDs.
The SDSs of some HDs recommend use of sodium hypochlorite; generally, this should
be a 2% solution. Note that sodium hypochlorite will pit stainless steel surfaces;
therefore, the sodium hypochlorite must be removed with sodium thiosulfate or followed
by use of a germicidal detergent in sterile water.
14.4.1 Deactivation
14.4.2 Decontamination
14.4.3 Cleaning
14.4.4 Disinfecting
The entitys SOPs shall include the procedure, the components and dilutions (if
applicable) used, and the documentation requirements for all four steps.
869
870
871
872
873
874
875
876
877
878
14.4.2 DECONTAMINATION
Decontamination occurs by removing HD residue from surfaces, and transferring them
to a low-lint wipe, which is then contained and discarded as contaminated waste. The
amount of HD contamination introduced into the BSC or CACI may be reduced by
surface decontamination (i.e., wiping down) of HD containers. Although no wipe-down
procedures have been studied, the use of low-lint wipes moistened with alcohol, sterile
water, peroxide, or sodium hypochlorite solutions may be effective. The solvent used for
wiping vials must not alter the product label. The BSC or CACI should be
decontaminated at least weekly, any time a spill occurs, before and after certification,
voluntary interruption, or if the ventilation tool is moved.
879
880
881
882
883
884
14.4.3 CLEANING
The Cleaning section in chapter 797 is appropriate for both nonsterile and sterile
HDs. The products used for cleaning shall not contaminate the compounding equipment
with substances that are toxic, volatile, corrosive, or otherwise harmful to the surface.
To clean C-PECs, refer to manufacturers information and appropriate references for
guidance in developing the entitys cleaning procedures.
885
886
887
888
889
890
891
892
893
894
14.4.4 DISINFECTING
The products used for disinfecting shall not contaminate the compounding equipment
with substances that are toxic, volatile, corrosive, or otherwise harmful to the surface. CPECs used for compounding HDs shall be disinfected at the beginning of the workday,
between batches of compounding medications, at the beginning of each subsequent
shift (if compounding takes place over an extended period of time), routinely during
compounding, and after anytime the C-PEC has been powered off. The area under the
work tray shall be cleaned at least monthly to reduce the contamination level in the
BSCs and CACIs. Clean as much as possible before opening the area under the work
tray. When cleaning a CACI, don a respirator when opening the front of the cabinet.
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
Spills shall be contained and cleaned immediately by trained workers. Signs shall be
available to restrict access to the spill area. Only trained workers with appropriate PPE
shall manage an HD spill. All workers who may be required to clean up a spill of HDs
shall receive proper training in spill management and in the use of PPE and NIOSHcertified respirators (see 6. Personal Protective Equipment).
Policies and procedures shall be developed to prevent spills and to govern clean-up of
HD spills. Written procedures shall specify who is responsible for spill management and
shall address the size and scope of the spill. Spill kits containing all of the materials
needed to clean HDs spills shall be readily available in all areas where HDs are
routinely handled. If HDs are being prepared or administered in a non-routine area (e.g.,
home setting, unusual patient care area), a spill kit and respirator shall be available.
The circumstances and handling of spills shall be documented. Workers who are
contaminated during the spill or spill clean-up, or who have direct skin or eye contact
with HDs, require immediate treatment. Staff and nonemployees exposed to an HD spill
should also complete an incident report or exposure form and report to the designated
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
emergency service for initial evaluation. All spill materials shall be disposed of as
hazardous waste.
SOPs (see Appendix B) shall be developed to include:
Management of HD spills.
Assurances that clean-up of a spill according to its size and type is handled by
932
933
16. DISPOSAL
934
935
936
937
938
Disposal of all HD waste (including unused and unusable HDs) shall comply with all
applicable federal and state regulations. All personnel who perform routine custodial
waste removal and cleaning activities in storage and preparation areas for HDs shall be
trained in appropriate procedures to protect themselves and the environment and to
prevent contamination.
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
Examples of improving engineering controls include implementing use of CSTDs or reassessing the types of C-PEC used.
956
957
18. DOCUMENTATION
958
959
960
961
962
963
964
965
966
967
The entity shall establish policies and procedures to ensure that compounding and
dispensing records meet the requirement of this chapter, chapters 795 and 797 ,
entity policy, and federal and state laws and regulations.
Activities that shall be documented include but are not limited to the acquisition,
preparation, and dispensing of a compounded HD, personnel training, and the use and
maintenance of equipment and supplies. These records shall be available for review by
the applicable authorities.
Policies and procedures shall be reviewed at least annually by the compounding
supervisor, and the review shall be documented. Revisions in forms or records shall be
made as needed and communicated to all compounding personnel.
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
Exposure assessment of all employees who have worked with HDs is important,
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
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1044
1045
1046
1047
1048
1049
1050
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1053
1054
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1056
1057
1058
1059
1060
1061
1062
1063
1064
1065
1066
ACRONYMS
1067
ACOEM American College of Occupational and Environmental Medicine
ACPH
ASHP
ASTM
BSC
BUD
Beyond-use date
CACI
CAI
CDC
CETA
CFR
CSTD
CVE
EPA
GHS
HCS
HD
Hazardous drug
HEPA
IV
Intravenous
LAFW
OSHA
PEC
PPE
RCRA
SDS
SOP
ULPA
USP
1068
1069
1070
1071
1072
1073
1074
1075
Alternative duty:
of HDs.
1076
1077
1078
1079
1080
1081
Anteroom: Transition area between the general area and the room containing the CPEC. Hand hygiene, garbing, staging of components, order entry, and other particlegenerating activities are performed in the anteroom. For sterile compounding, the
anteroom shall meet ISO Class 7 (for all references to ISO classification, see Table 1)
and also provides assurance that pressure relationships between rooms are constantly
maintained.
1082
1083
1084
Batch: More than one unit of a compounded preparation that is intended to have
uniform character and quality within specified limits, prepared in a single process, and
completed during the same and limited time period.
1085
1086
Beyond-use date (BUD): The date or time after which a compounded preparation
shall not be used, stored, or transported (see 795 and 797 for additional details).
1087
1088
1089
1090
1091
1092
1093
Biological safety cabinet (BSC): A ventilated cabinet often used for preparation of
hazardous drugs. BSCs shall be NSF/ANSI listed. These cabinets are divided into three
general classes (Class I, Class II, and Class III). Class II BSCs are further divided into
types (Type A1, Type A2, Type B1, and Type B2). See Appendix C for details.
1094
1095
1096
Buffer room: Part of the HD compounding area under negative pressure where the
C-PEC is physically located. Activities that occur in this area are limited to the
preparation and staging of components and supplies used when compounding HDs.
1097
1098
1099
Chemotherapy glove: A medical glove that meets the ASTM Standard Practice
(D6978-05-2013) for Assessment of Resistance of Medical Gloves to Permeation by
Chemotherapy Drugs.
1100
1101
1102
Cleaning: The removal of soil (e.g., organic and inorganic material) from objects and
surfaces, normally accomplished manually or mechanically using water with detergents
or enzymatic products.
1103
1104
1105
1106
1107
1108
1109
1110
1111
1112
1113
1114
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
1125
1126
1127
1128
1129
1130
1131
1132
1133
1134
1135
1136
1137
1138
1139
1140
1141
1142
1143
1144
1145
1146
1147
1148
cabinet
The use of HEPA filtration on all potentially contaminated exhaust streams
1149
1150
1151
1152
Examples of C-PECs include Class I, II, or III BSCs, CACIs, and CVE (e.g., powder
hood).
C-PECs used for nonsterile compounding do not need to have ISO Class 5 air quality.
C-PECs used for sterile compounding shall have ISO Class 5 air quality (see Table 2).
1153
1154
1155
1156
1157
1158
1159
1160
1161
1162
1163
1164
1165
1166
Critical area:
1167
1168
1169
1170
Critical site: A location that includes any component or fluid pathway surfaces (e.g.,
vial septa, injection ports, beakers) or openings (e.g., opened ampules, needle hubs)
exposed and at risk of direct contact with the air (e.g., ambient room or HEPA filtered),
moisture (e.g., oral and mucosal secretions) or touch contamination.
1171
1172
1173
1174
Decontamination:
chemical means.
1175
1176
1177
1178
1179
1180
1181
1182
1183
1184
1185
1186
1187
1188
Expiration/expiry date: The expiration date identifies the time during which the
article may be expected to meet the requirements of the compendia monograph,
provided it is kept under the prescribed storage conditions (see General Notices and
Requirements10.40.100).
1189
1190
1191
1192
1193
1194
Goggles: Tight-fitting eye protection that completely covers the eyes, eye sockets,
and the facial area that immediately surrounds the eyes and that provide protection from
impact, dust, and splashes. Some goggles will fit over corrective lenses.
1195
1196
1197
1198
1199
1200
1201
1202
1203
1204
1205
Carcinogenicity
Teratogenicity or developmental toxicity
Reproductive toxicity in humans
Organ toxicity at low doses in humans or animals
Genotoxicity
New drugs that mimic existing hazardous drugs in structure or toxicity
1206
1207
1208
1209
1210
1211
1212
1213
1214
Labeling: A term that designates all labels and other written, printed, or graphic
matter on an immediate container of an article or preparation, or on, or in, any package
or wrapper in which it is enclosed, except any outer shipping container. The term label
designates that part of the labeling on the immediate container [see General Notices
and Requirements and 21 USC 321 (k) and (m)].
1215
1216
1217
Laminar air flow workbench (LAFW): A primary engineering control designed for
use when compounding sterile non-HDs. An LAFW shall not be used for the
manipulation of HDs.
1218
1219
1220
1221
1222
1223
1224
1225
1226
1227
1228
1229
1230
1231
1232
1233
1234
1235
1236
1237
the environment from exposure to the compounds under manipulation. PECs used for
manipulation of HDs shall be designed for containment (see also Containment primary
engineering control).
1238
1239
1240
1241
Resource conservation and recovery act (RCRA) empty: A vial, ampule, IV bag,
or other container that once held a drug regulated under the Resource Conservation
and Recovery Act, if all the contents have been removed that can be removed by
normal means and no more than 3% of the contents by weight remain.
1242
1243
1244
Safety data sheet (SDS): An informational document that provides written or printed
material concerning a hazardous chemical that is prepared in accordance with the HCS
[previously known as a Material Safety Data Sheet (MSDS)].
1245
1246
Spill kit: A container of supplies, warning signage, and related materials used to
contain the spill of an HD.
1247
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1249
1250
1251
1252
1253
1254
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1256
1257
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1259
1260
1261
1262
1263
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1265
1266
1267
1268
1269
1270
1271
1272
Policies and procedures for the safe handling of HDs shall be in place for all
situations in which these drugs are used throughout a facility. Chapters 795
and 797 list SOPs recommended for use for nonsterile and sterile
compounding. Additionally, the following HD-related procedures should be
considered:
- Comprehensive hazardous drug safety program
- Hazard communication program
1273
1274
1275
- Procurement of HDs
1276
- Use of C-PECs, including work practices specific to the type of device used
1277
1278
1279
1280
1281
- Spill control, including use and contents of spill kit, cleaning, and notification
1282
1283
- Medical surveillance
1284
1285
1286
1287
1288
1289
1290
1291
1292
1293
1294
1295
1296
1297
1298
1299
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
Class I: A BSC that protects personnel and the environment but does not protect the
product/preparation. Personnel protection is provided as a minimum velocity of 75
linear feet/min of unfiltered room air is drawn through the front opening and across the
work surface. The air is then passed through a HEPA/ULPA filter either into the room
or to the outside in the exhaust plenum, providing environmental protection.
Class II: Class II (Types A1, A2, B1, and B2) BSCs are partial barrier systems that
rely on the movement of air to provide personnel, environmental, and
product/preparation protection. Personnel and product/preparation protection is
provided by the combination of inward and downward airflow captured by the front
grille of the cabinet. Side-to-side cross-contamination of products/preparations is
minimized by the internal downward flow of HEPA/ULPA filtered air moving toward the
work surface and then drawn into the front and rear intake grilles. Environmental
protection is provided when the cabinet exhaust air is passed through a HEPA/ULPA
filter.
Type A1 (formerly, Type A): These Class II BSCs maintain a minimum inflow
velocity of 75 ft/min, have HEPA-filtered, down-flow air that is a portion of the mixed
down-flow and inflow air from a common plenum, may exhaust HEPA-filtered air
back into the laboratory or to the environment through an exhaust canopy, and may
have positive-pressure contaminated ducts and plenums that are not surrounded by
negative-pressure plenums. They are not suitable for use with volatile toxic
chemicals and volatile radionucleotides.
Type A2 (formerly, Type B3): These Class II BSCs maintain a minimum inflow
velocity of 100 ft/min, have HEPA-filtered, down-flow air that is a portion of the mixed
down-flow and inflow air from a common exhaust plenum, may exhaust HEPAfiltered air back into the laboratory or to the environment through an exhaust canopy,
and have all contaminated ducts and plenums under negative pressure or
surrounded by negative-pressure ducts and plenums. If these cabinets are used for
minute quantities of volatile toxic chemicals and trace amounts of radionucleotides,
they must be exhausted through properly functioning exhaust canopies.
Type B1: These Class II BSCs maintain a minimum inflow velocity of 100 ft/min,
have HEPA-filtered down-flow air composed largely of uncontaminated, recirculated
inflow air, exhaust most of the contaminated down-flow air through a dedicated duct
exhausted to the atmosphere after passing it through a HEPA filter, and have all
contaminated ducts and plenums under negative pressure or surrounded by
negative-pressure ducts and plenums. If these cabinets are used for work involving
minute quantities of volatile toxic chemicals and trace amounts of radionucleotides,
the work must be done in the directly exhausted portion of the cabinet.
Type B2 (total exhaust): These Class II BSCs maintain a minimum inflow velocity of
100 ft/min, have HEPA-filtered down-flow air drawn from the laboratory or the
outside, exhaust all inflow and down-flow air to the atmosphere after filtration through
a HEPA filter without recirculation inside the cabinet or return to the laboratory, and
have all contaminated ducts and plenums under negative pressure or surrounded by
directly exhausted negative-pressure ducts and plenums. These cabinets may be
used with volatile toxic chemicals and radionucleotides.
1310
1311
1312
1313
1314
1315
1316
1317
1318
1319
1320
1321
1322
1323
1324
1325
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1327
1328
1329
1330
1331
1332
1333
1334
1335
1336
1337
1338
1339
Class III: The Class III BSC is designed for work with highly infectious microbiological
agents and other hazardous operations. It provides maximum protection for the
environment and the worker. It is a gas-tight enclosure with a viewing window that is
secured with locks and/or requires the use of tools to open. Both supply and exhaust
air are HEPA/ULPA filtered. Exhaust air must pass through two HEPA/ULPA filters in
series before discharge to the outdoors.
1340
1341
1342
Activity
Location
Unpacking
HDs
Designated
receiving
area
Unpacking
damaged
shipping
containers
C-PEC
Class I device
designated for
this purpose or
Class I device
Pressure
(inches of
Minimum
water
HEPA filtration ACPH
column)
Activity
Location
C-PEC
Pressure
(inches of
Minimum
water
HEPA filtration ACPH
column)
Nonsterile
preparations
Sterile
preparations
1343
1344
1345
1346
Separate
room for
nonsterile
HDs
Negativepressure,
ventilated
enclosure, such
as a Class 1 BSC
or CVE
Not required if
hazardous
preparations
are handled
only in the CPEC
Negativepressure
ISO Class 7 Class II BSC or
room
CACI
Required in
supply to
maintain room
state of control
Negativepressure
SCA
Not required if
CACI meets
minimum
criteria
established in
the chapter
Class II BSC or
CACI
12
Minimum
0.01"
negative
30
Minimum
0.01"
negative
12
Minimum
0.01"
negative
1348
1349
1350
Activity
Description
Gloves
ASTM-tested
chemotherapy
gloves shall be
worn for all
handling of
HDs. Two
pairs are
required for
compounding,
administering,
managing a
spill, and
disposal of
HDs.
+a
If an industrial
glove is used
for receiving,
at least one
ASTM-tested
chemotherapy
glove shall be
Receiving
worn over the
suspected/broken industrial
supplies
glove.
Gown
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
Disposable,
long-sleeved
and cuffed
gowns, with a
solid front and
closure in the
back, made of
polyethylenecoated polypropylene or
other laminate
material
Not required
for routine use
when a CPEC is used.
Use eye and
face
protection
when
manipulating
HDs outside
of a C-PEC
and working at
or above eye
level, cleaning
a C-PEC, or
cleaning a
spill.
A NIOSHcertified N95
respirator is
generally
sufficient to
protect
against
particles.
Consult the
SDS for
respiratory
protection
information.
Receiving intact
supplies (remote
from
compounding
area)
Transporting
intact supplies or
compounded HDs
Receiving in
compounding
area
Stocking
Activity
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
Gloves
Gown
+
Outer glove
shall be sterile
(including
outer glove in
CACI).
compounding
area
Nonsterile
compounding
Sterile
compounding
Required
when
splashing or
aerosolization
is possible
Clean-up, routine
(such as following
compounding or
administration)
Collection and
disposal of
patient waste
Administering
Spills
Use an
appropriate,
fullfacepiece,
chemical
cartridgetype
respirator for
spills and
when there is
known or
suspected
airborne
exposure to
vapors or
gases.
Activity
a
Gloves
Gown
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
+ = Required.
1351
1352
APPENDIX G. BIBLIOGRAPHY
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1366
1367
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1371
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1373
1374
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1380
1381
1382
1383
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1393
1394
1395
1396
1397
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1399
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1401
1402
1403
1404
1405
1406
1407
1408
1409
1410
1411
1412
1413
1414
1415
1416
1417
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1420
1421
1422
1423
1424
1425
1426
1427
1428
1429
1430
1431
1432
1433
1434
1435
1436
1437
1438
1439
1440
1441
1442
1443
1444
1445
1446
1447
1448
1449
1450
1451
1452
1453
1454
1455
1456
1457
1458
1459
1460
1461
1462
1463
1464
1465
1466
1467
1468
1469
1470
1471
1472
1473
1474
1475
1476
1477
1478
1479
1480
1481
1482
1483
1484
1485
1486
1487
1488
1489
1490
1491
1492
1S (USP38)