Stability Testing Guidance Finalized

Rockville, MD (Feb. 25)-The US Food and Drug Administration released a final guidance on a protocol for testing sterile products. Rather than using sterility testing as part of the stability protocol, sterile product manufacturers can use container and closure system integrity tests, and therefore avoid validation tests for individual products with the same type of container.

“If you manufacture a number of products that use the same type of container and closure system, you may validate your integrity test method using a bracketing matrix,” reads the final guidance. “It is not necessary to perform validation studies on each product.”

The guidance, “Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products,” provides for final clarification of the January 1998 draft guidance of the same name.

The guidance recommends that manufacturers include container and closure system integrity tests in stability protocols for new marketing applications. Recommended tests include: validated physical or chemical container and closure system integrity methods such as bubble tests, pressure/vacuum decay, trace-gas permeation/leak tests, dye penetration tests, seal force or electrical conductivity and capacitance tests. Microbiological container and closure system integrity tests include microbial challenge or immersion tests. For media-filled containers, the guidance says, “It may be acceptable to use media-filled containers instead of product-filled containers for testing during the product’s shelf life or dating period if the product contains a material, such as a preservative, which would bias the results of the container and closure system integrity test.”

“If you currently perform sterility testing as a stability-indicating test as part of a stability protocol, you may continue to do so,” reads the guidance. FDA states that the advantages of using container and closure system integrity tests in lieu of sterility tests include:

• Such alternate methods may detect a breach of the container and/or closure system prior to product contamination

• Some of the alternate methods used to evaluate container and closure integrity can conserve samples that may be used for other stability tests

• Alternative test methods may require less time than sterility test methods which require at least seven days incubation

• The potential for false positive results may be reduced with some alternative test methods when compared to sterility tests.

Companies that incorporate a validated container and closure system integrity test to demonstrate the continued capability of containers to maintain sterility for an approved product, need to submit a “Special Supplement–Changes Being Effected (CBE)” drugs or a “Supplement–CBE” for biologics.

Read the full guidance.