Medical Packaging Regulations
Drug Packaging
The regulations for pharmaceutical products require premarket approval. This means that a manufacturer wishing to produce and sell a drug must provide the FDA with evidence that the drug is safe and effective. In particular, the package for the drug is considered part of the drug. One of the requiremets is that suclt29prlduct be labeled with an expiration date, and stability testing must be done to verify that the drug remains acceptable during that period. The requirements for stability testing require that the drug be tested "in the same container-closure system as that in which the drug product is marketed" (21CFR211.166).This standard nomenclature for referring to the CFR means Section 210f the Code of Federal Regulations, Part 211, Section166. The FDA works closely with the United States Pharmacopoeia (USP) in developing regulations, as U.S. law requires that any drug sold that is listed in the USPmust conform to USP standards. The USP is also a source for regulations in some countries outside the U.S.
If, after a drug is on the market, the manufacturer wishes to change the packaging in any significant way, it is necessary both to carry out stability testing in the new package, and to submit a supplementary new-drug application (NDA) to FDA for approval before the package can be used. There are provisions for accelerated testing at high temperature and relative humidity. Accelerated testing is done at severe conditions to speed up changes that may occur at a slower rate under normal storage conditions. However, even if approval to market the drug in a particular package is issued based on accelerated testing, stability tests under normal storage conditions must continue for the full labeled life of the product. Thus, changing the package for a drug product is a major undertaking.
The FDA does provide for some interchangeability of plastic resins. While in general testing "in the same container-closure system" is interpreted ~ mean not just the same generic plastic, but rather the same precise container, including the resin formulation, FDA has accepted procedures developed by the USP for allowing manufacturers to change packaging without requiring prior FDA approval. These test protocols provide for a determination that a new plastic resin is equivalent to the one already approved if the tests so indicate. Currently such test protocols are available for HDPE, LDPE, PET, and glycol-modified PET (PETG). If, for example, both HDPE bottles satisfy the test protocol, then they can be used interchangeably, and if one has been approved for a specific application, the other can be used as well. However, the approval conditional on successful completion of stability testing in /the new package.