FDA suggests new shelf-life testing practices
By Myron Struck
Washington, DC — New guidance from the Food and Drug Administration (FDA) suggests that the pharmaceutical and biotech industries consider the use of container and closure integrity testing as an alternative to sterility testing for monitoring product shelf-life integrity. Although the six-page proposal was designed to serve as the basis of industry comment, and is specifically marked “not for implementation,” it is being widely circulated by the agency.
Sterility tests have been used by the FDA to verify that a product maintains its integrity through the entire shelf life, or dating period, on the package. However, the FDA ac knowledges that there are limitations on the current system and that alternatives may need to be considered.
The new guidance, the FDA says, is “intended to provide recommendations and offer alternative methods for the sterility test for sterile biological products, human and veterinary drugs and medical devices.” Prepared by an FDA working group, the research focuses only on the means of confirming expiration dating and “represents the agency`s current thinking” on integrity testing. Industry comments were due to the agency by March 30.
As early as 1993 (Federal Register December 3, 1993 — 58 FR 63996), the FDA crafted a report — jointly written by the Center for Drug Evaluation and Research and the Center for Veterinary Medicine — called a “Guideline for Submitting Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products.” That guidance states that the ability of a container closure system to maintain the integrity of its microbial barrier, and hence, the sterility of the drug product through its shelf life, must be demonstrated to be considered effective.
From 1993 through 1996, the FDA published two supplemental reports addressing related issues. One focused on the quality of biotechnological products, primarily stability testing (61 FR 36466). The other was a guideline on stability testing as it applied specifically to new drug substances and drug products (59 FR 48754).
The FDA now says the alternative to sterility testing as part of the stability program, could result in replacing the traditional sterility test with a container and closure integrity test. The new tests “could more fully address all contamination potential over the shelf-life of a product, including efforts to detect a breach of the container unrelated to microbial contamination.”
The FDA also said in the guidance that, although some manufacturers have proposed using antimicrobial preservative effectiveness tests in lieu of the traditional sterility test for products containing preservatives, this method cannot confirm product sterility. “It does not confirm the presence or absence of contamination, but demonstrates only that the microbiological preservative systems are effective when used against the test contaminant organisms.”
The FDA has recommended that container and closure integrity tests should be considered in the stability testing protocols for sterile product license applications or premarket notifications for in vitro diagnostic devices.
For more information, contact Valerie A. Butler, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or call (301) 827-6210.
Myron Struck is a freelance writer based in Alexandria, VA.