Sei sulla pagina 1di 40

GMP Requirements in Packaging Materials Science

YUB RAJ NEUPANE M.PHARM- SEM II 2012 (PHARMACEUTICS) JAMIA HAMDARD ,NEW DELHI

What is the purpose of a


packaging a pharmaceutical product ?
To contain a convenient quantity of the product. To protect the product during storage, transport and distribution To identify the product (what it is, its batch number, who manufactured it, and so on) To provide other information

GMP is.
.. that part of Quality Assurance which ensure that products are consistently produced and controlled to the quality standards appropriate to their use. GMP is an integral part of Quality Assurance

QA

GMP

QC

Basic Principle of GMP


Quality, safety and efficacy must be designed and built in the product. Testing alone cannot be relied on to ensure quality. Each step in the manufacturing process must be controlled to ensure that the final product lies within limits and specifications.

Why is GMP necessary?


Customer Protection & Satisfaction

Employee Protection
Fulfilling Legal Requirements Good Business Practice Pride in Workplace

Basic Requirements for GMP


Clearly defined and systematically reviewed processes. Critical steps validated. Appropriate resources: personnel, buildings, equipment, materials. Clearly written procedures. Trained operators. Complete records, failure investigations. Recall system. Complaint handling.

Food and Drug Administration : GMP


Code of Federal Regulations (Title 21)
Title 21, Code of Federal Regulations (21 CFR) is updated April 1 of each year.

The current edition contains nine volumes.


1) 21 CFR 1-99. General regulations for enforcement of the FFDC (Federal Food, Drug and Cosmetic ) Act and the Fair Packaging and Labeling Act. Color additives.

2) 21 CFR 100-169. General regulations for food labeling (contains the new regulations for nutrition labeling). Infant formula quality control procedures and labeling. Food standards and quality standards for bottled drinking water. The CGMP regulations for food, bottled drinking water, low-acid canned foods, and acidified foods.

3) 21 CFR 170-199. Food additives.


4) 21 CFR 200-299. General regulations for drugs.

5) 21 CFR 300-499. Drugs for human use. 6) 21 CFR 500-599. Animal drugs, feeds, and related products. 7) 21 CFR 600-799. Biologics and cosmetics.

8) 21 CFR 800-1299. Medical devices, radiological health, and control of communicable diseases. Import Milk Act, Federal Tea Importation Act, and Federal Caustic Poison Act.
9) 21 CFR 1300-End. Regulations implementing the Controlled Substances Act and the Controlled Substances Import and Export Act.

Under the 4 th volume:


Part 210: GMP in Manufacturing, Processing, Packing, or Holding of Drugs; General

Part 211: GMP for Finished Pharmaceuticals.

INTRODUCTION (PACKAGING MATERIAL)


In pharmaceutical industry , it is vital that the package selected adequately preserve the integrity of the product. The selection of package therefore depends upon: Physical characteristics. Chemical characteristics. Photosensitivity Hygroscopicity Its marketing requirement

DESIRED CHARACTERISTICS
It must protect the preparation from environmental conditions. ( MOISTURE, LIGHT, GAS ) It must not be reactive with the product. It must not impart odors or traces to the product. It must be FDA approved. It must meet applicable tamper-resistance requirement. It must be adaptable to high speed packaging equipment

Subparts of Schedule-M
Subpart: A Finished Pharmaceuticals: General Provision B Organization and Personnel C Building and Facilities D Equipments E Control of Components and Drug Product Container and Closure F Production and Process Control G Packaging and Labeling Control H Holding and Distribution I Laboratory Control J Records and Report

SUBPART-G

SUBPART-G
(PACKAGING AND LABELLING CONTROL)

Topics covered : Materials examination and usage criteria. Labeling issuance. Packaging and labeling operations. Temper resistant packaging requirements for OTC human drug products. Drug product Inspection. Expiration dating.

Materials Examination and Usage Criteria

(Sec. 211.122 )
There should be written procedures describing in sufficient detail for the: Receipt Identification Storage Handling Sampling Examination Testing of labeling and packaging materials. Any labeling or packaging material meeting appropriate written specifications may be approved and released for use.

Records should be maintained for each of above activities. Homeopathic drug products are subject to the same labeling provisions of the Food, Drug, and Cosmetic Act as other drug products. Labels and labeling errors have been among the top ten reasons for product recall in recent years.*

Labels and other labeling materials for each different drug product, strength, dosage form, or quantity of contents shall be stored separately with suitable identification.
Access to the storage shall be limited to authorized personnel. Obsolete and outdated labels, labeling, and other packaging materials shall be destroyed.

Market recall example:


New Delhi, Mon Mar 28, 2011, 16:13 hrs Pfizer Inc. recall in the US market of two drugs, which were contract manufactured by Aurobindo Pharma due to labelling error. The recall involves Citalopram 10mg tablets (100-count bottle), used in treatment of depression and Finasteride 5mg tablets (90-count bottle) prescribed for treating prostrate enlargement. "The recall is due to incorrect labels have been placed on the bottles by a third-party manufacturer. This is the only lot number being recalled and no other lots or markets are believed to be impacted," Pfizer said in a statement on its website. Hyderabad-based Aurobindo Pharma is the third party manufacturer of the two drugs, which have been recalled.

Reacting to the recall news, shares of Aurobindo Pharma on Monday tanked 5.84 per cent from its previous close on the Bombay Stock Exchange, ending the day at Rs 186.30 per share. Pfizer, had entered into a large supply contract with the Hyderabad-based firm in 2009. It had acquired the rights from the Indian firm for 39 generic solid oral dose products in the US and 20 in Europe, plus an additional 11 in France. Pfizer said its recall is for a particular lot under number 'FI0510058-A' on the label. "Bottles labelled as Citalopram Lot # FI0510058-A may contain Finasteride. Patients who believe they may have ingested the wrong medication should contact their physician as soon as possible," said. Bottles of either Citalopram or Finasteride with the same lot number should be returned to the pharmacist, he added. (http://www.indianexpress.com/news/pfizer-recalls-twodrugs-in-the-us-on-labell/768367/)

Labeling Issuance (Sec. 211.125 )


Strict control should be exercised over labels issued for use in drug product labeling operations. Labeling material issued for a batch should be carefully examined for identity and conformity to the labeling specified in the master or batch production record.

Procedure should be written, describing insufficient detail the control procedure employed for the issuance of labeling; such written procedures must be followed.

Procedure should be utilized to reconcile the quantities of labels issued, used and returned and shall require evaluation of discrepancies found between quantity of drug product finished and the quantity of labeling issued. All excess labels bearing lot of control no. should be destroyed.

Returned labeling should be maintained and stored in a manner to prevent mix-ups and provides proper identification.

Packaging and Labeling Operations


(Sec. 211.130)

There should be written procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products. It incorporate the following feature:

Prevention of mix-ups and cross contamination by physical or spatial separation from operation on other drug products. Identification need to be applied to each individual container, sufficient to determine name, strength, quantity, lot no of each container.

Identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch.

Examination of packaging and labeling materials for suitability and correctness before packaging operations, and documentation of such examination in the batch production record. Inspection of the packaging and labeling facilities immediately before use to assure that all drug products have been removed from previous operations. ( line clearance)

Master Batch Packaging Formula


Contains the Following Data Field
1. 2. Drug product name, identification no. and strength. Name, identification no. and quantities of each packaging component:
I. II. III. IV. V. VI. VII. Primary container: bottle, closure and liner, foil, laminate, etc. Label Carton Inserts Tamper-evident feature Child resistant feature Shipper, divider, other protective packaging.

3. 4.
5. 6.

Complete description of the equipment to be utilized for the packaging operation. Characteristics to be monitored during filling and packaging (e.g., Temperature, fill, clarity, pH, specific gravity, color, cap tightness, seal integrity). Sample requirements and frequency. For the specific batch being packaged:
I. II. III. IV. V. Batch number of the bulk drug product. Packaging lot or control no. assigned Quantities of packs expected and action level value. Quantities of each packaging component issued (if different from item 2) Expiry date to be assigned

VI.

Item 6a e are sometimes incorporated into a separate document, the packaging order.

Temper Resistant Packaging Requirements for OTC Human Drug Products (Sec. 211.132 )

Product tampering is not a new occurrence. However, as a direct result of several deaths in 1982 resulting from the malicious addition of cyanide to Tylenol Capsules, this section was introduced into the CGMP regulations.

Temper resistant packaging: having one or more indicators or barriers to entry which, if breached or missing, can reasonably be expected to provide visible evidence to consumer that temper has occurred.

FDA has the authority under the Federal Food, Drug and Cosmetics Act to establish a uniform national requirement for temper-resistant packaging of OTC drug products that will improve the security, assure safety and effectiveness of OTC drug products.

An OTC drug product (except a dermatological, dentifrice, insulin, or throat lozenge product) for retail sale that is not packaged in a tamperresistant package or that is not properly labeled considered an adulterated under section 501 of the act, or misbranded under section 502 of the act, or both.

A tamper-resistant package may involve an immediate-container and closure system, or secondary-container or carton system, or any combination of systems intended to provide a visual indication of package integrity. Any two-piece, hard gelatin capsule covered by this section must be sealed using an acceptable tamper-evident technology.

Request for exemption packaging and labeling requirements: a request for an exemption is required to be submitted in the form of a citizen petition under $10.30 of this chapter and should be clearly identified on the envelop as a Request for Exemption from Tamper-resistant Rule. the petition is require to contain:
The name of the drug product The reason that the drug products compliance with TRpackaging of this section is unnecessary or can not be achieved. A description of alternative steps that are available, or that the petitioner has already taken Other information justifying an exemption

In 1992, the FDA published Compliance Policy Guide 7132a.17 (Sec 450.500) TamperResistant Packaging Requirements for certain OTC Human Drug Products. Examples of packaging technologies capable of meeting the TRP requirements are listed below: A. PACKAGING SYSTEMS: The TRP requirements are intended to assure that the products packaging can reasonably be expected to provide visible evidence to consumers that tampering has occurred. Examples of packaging technologies capable of meeting the TRP requirements are:

Film Wrappers: Blister or Strip Packs. Bubble Packs Heat Shrink Bands or Wrappers Foil, Paper, or Plastic Pouches Container Mouth Inner Seals. Tape Seals Breakable Caps. Sealed Metal Tubes or Plastic Blind-End Heat-Sealed Tubes. Sealed Cartons Aerosol Containers. Cans (Both All-Metal and Composite).

B. CAPSULE SEALING TECHNOLOGIES: currently in use include sonic welding, banding, and sealing techniques employing solvents and/or low temperature heating.

The TRP requirements are part of the CGMP regulations. Regulatory actions for deviations from these requirements should be handled in the same manner as any other deviation from the GMP regulations.

Drug Product Inspection(Sec. 211.134 )


Packed and labeled products should be examined during finishing operation to provide assurance that containers and packages in the lot have the correct label. A representative sample units should be collected at the completion of finishing operations and be visually examined for correct labeling. Results of these examinations shall be recorded in the batch production or control records.

Expiration Dating (Sec. 211.137 )


To assure that a drug product meets applicable standards of identity, strength, quality and purity at the time of use, it should bear an expiration date, determined appropriately by stability testing described in sect.-211.166. Exp. Date should be related to any storage conditions stated on the label. If the product is to be reconstituted at the time of dispensing , its label should bear expiration information for both the reconstituted and unrecontituted drug product

Expiration dates shall appear on labeling in accordance with the requirements of 201.17 of this chapter. Homoeopathic drug products shall be exempted from the requirements of this section. Allergic extracts that are labeled No U.S. Standards of Potency are exempted from the requirements of this section. New drug products for investigational use are exempted from the requirements of this section

References.
Good Manufacturing Practices for Pharmaceuticals Sixth Edition edited by Joseph D. Nally, Nallianco LLC ,New Vernon, New Jersey, U.S.A. 2007, James .R . Stoker, Sidney H. Willing; Good Manufacturing Practices for Pharmaceutics A Plan for Total Quality Control 4th Edition, Revised and Expanded, Vol.-78, page no.-85-133.
L.Lachman, H. A. Liberman, The Theory and Practice of Industrial Pharmacy, 3rd-Edition, 686,733,829833,869-870

Good manufacturing practices (GMP), guidelines - 2009 edition, GUI-0001

Quality assurance of pharmaceuticals, Volume 2, 2nd updated edition, World Health Organization 2007

Potrebbero piacerti anche