1178 GOOD REPACKAGING PRACTICES

INTRODUCTION
This chapter is intended to provide guidance to those engaged in repackaging of oral solid drug products; and the chapter provides information to any person who removes drugs from their original container–closure system (new primary package) and repackages them into a different container–closure system for sale and/or for distribution.
This chapter does not apply to pharmacists engaged in dispensing prescription drugs in accordance with state practice of pharmacy. The pharmacist needs to apply
  1. the principal information provided in the USP general information chapter Packaging—Unit-of-Use 1136 and
  2. other beyond-use date references in the subsection Expiration Date and Beyond-Use Date in the Labeling section under General Notices and Requirements.

DEFINITIONS
659 Packaging and Storage Requirements provides definitions related to repackaging. For the purposes of this chapter, a repackager, a contract packager, and an equivalent container–closure system are defined as follows:
  1. Repackager—A repackager is an establishment that repackages drugs and sends them to a second location in anticipation of a need. Repackaging firms repackage preparations for distribution (e.g., for resale to distributors, hospitals, or other pharmacies), a function that is beyond the regular practice of a pharmacy. Distribution is not patient-specific in that there are no prescriptions. Unlike dispensers, repackaging firms are required to register with the FDA and to comply with the Current Good Manufacturing Practice Regulations in 21 CFR 210 and 211.
  2. Contract Packager—A contract packager is an establishment that is contracted to package or repackage a drug product into a single- or multi-unit container. These containers should meet all of the applicable requirements in this chapter. A contract packager does not take ownership from the manufacturer and generally receives the assigned expiration date from the contractor.
  3. Equivalent Container–Closure System—This term refers to a container–closure system that is at least as protective or more protective than the original container–closure system in terms of moisture vapor transmission rate (MVTR), oxygen transmission, light transmission, and compatibility of the container–closure system with the drug product. System equivalency extends to any special protective materials, such as for light transmission, seals, or desiccants associated with the original container–closure system. These values may be determined by the repackager, or they may be obtained from the container–closure vendor for the specific container–closure system under consideration.

ESTABLISHING EXPIRATION DATE
In the absence of stability data, the following criteria should be considered by repackagers when assigning an expiration date.
Unit-Dose Packaging
  1. The original container–closure system of the drug product to be used for repackaging must be received un-opened and show no outward signs of having been previously opened.
  2. The unit-dose container–closure system must meet the testing requirements under Containers—Performance Testing 671 for either Class A or Class B containers.
  3. The contents of the original bulk drug product to be repackaged are repackaged at one time unless the repackager has data and/or other scientific information from literature sources demonstrating that the drug product is not sensitive to exposure to moisture, oxygen, or light.
  4. The unit-dose container–closure system must meet or exceed the original container's specification for light resistance.
  5. The conditions of storage must meet the storage specifications provided in the USP General Notices and as described in the labeling of the original container–closure system received for repackaging. Where no specific storage conditions are specified, the product must be maintained at controlled room temperature and in a dry place during the repackaging process, including storage.
  6. The expiration dating period used for the repackaged product does not exceed (1) 6 months from the date of repackaging; or (2) the manufacturer's expiration date; or (3) 25% of the time between the date of repackaging and the expiration date shown on the manufacturer's bulk article container of the drug being repackaged, whichever is earlier.
  7. Nitroglycerin Sublingual Tablets or any other drug product known to have stability problems should not be repackaged. This would include any drug known to be oxygen-sensitive or one that exhibits extreme moisture or light sensitivity. In deciding whether a particular drug product is suitable for repackaging, the repackager should take into consideration any available information from the manufacturer, published literature, the USP, and the FDA.
  8. Documentation must be maintained to demonstrate that the preceding criteria are met.
  9. Documentation must be maintained that specifies the container–closure packaging material used in repackaging operations.
Multiple-Unit Packaging
  1. A repackager may use the manufacturer's original expiration date without additional stability testing if the drug product is repackaged into an equivalent container–closure system that is at least as protective as, or more protective than, the original system and complies with criteria established for equivalency.
  2. The original container–closure system of the drug product to be used for repackaging must be received un-opened and shows no outward signs of having been previously opened.
  3. The contents of the original bulk drug product to be repackaged are repackaged at one time unless the repackager has data and/or other scientific information from literature sources demonstrating that the drug product is not sensitive to exposure to moisture, oxygen, or light.
  4. The conditions of storage meet the storage specifications in the USP General Notices and as described in the labeling of the original container–closure system received for repackaging. When no specific storage conditions are specified, the product should be maintained at controlled room temperature and in a dry place during repackaging operations.
  5. The type of container–closure system used for repackaging must be at least as protective or more protective than the original container–closure system in terms of moisture vapor transmission rate (MVTR), oxygen transmission, light transmission, and compatibility of the container–closure system with the drug product. System equivalency extends to any special protective materials, such as for light transmission, seals, or desiccants associated with the original container–closure system.
  6. The container–closure system must meet or exceed the original container–closure system's results for light transmission.
  7. Nitroglycerin Sublingual Tablets or any other drug product known to have stability problems should not be repackaged. This would include any drug known to be oxygen-sensitive or one that exhibits extreme moisture or light sensitivity. In deciding whether a particular drug product is suitable for repackaging, the repackager should take into consideration any available information from the manufacturer, published literature, the USP, and the FDA.
  8. Documentation must be maintained to demonstrate that the preceding criteria are met.
  9. Documentation must be maintained that specifies the container–closure packaging material used in repackaging operations.

REFERENCES FOR REPACKAGING REGULATIONS AND GUIDANCES
The references listed below are not meant to be all inclusive: specific repackaging operations may have additional requirements.
  • Food, Drug, and Cosmetic Act
  • Food and Drug Administration Regulations and Guidances

Enforcement Policy: 21 CFR, Part 7
General Labeling Provisions: 21 CFR, Part 201, Subpart A
Drug Establishment Registration and Listing: 21 CFR, Part 207.20
Current Good Manufacturing Regulations: 21 CFR, Parts 210–211
Special Requirements for Specific Human Drugs: 21 CFR, Part 250
Controlled Substances: 21 CFR, Part 1300
Potable Water: 40 CFR, Part 141
FDA Compliance Policy Guides, including the following:

Sub Chapter 430 Labeling and Repackaging
Sub Chapter 460 Pharmacy Issues
Sub Chapter 480 Stability/Expiration Dating
  • Applicable USP Chapters
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
General Chapter Desmond G. Hunt, Ph.D.
Senior Scientific Liaison
(301) 816-8341		 (GCPS2010) General Chapters - Packaging Storage and Distribution
USP38–NF33 Page 1335
Pharmacopeial Forum: Volume No. 32(5) Page 1523