Antimicrobial Effectiveness Tests (AET) or challenge tests on drug products are typically performed during development studies supporting the Marketing Authorisation Holder to define the formulation, address microbial hurdles, and guarantee that the products meet their critical attributes for the entire shelf life.
Normally the shelf life for closed products is established during stability studies. Additionally, evaluations on multi-dose products, such as aqueous or reconstituted preparation, topical creams or ointments, solid dose tablets, or capsules packed in containers that could expose them to light, temperature, and humidity after
opening, should be performed as well. Consequently, in-use stability studies can be designed to assess intrinsic microbiological robustness of multi-dose drug products.
Even if there are no recent specific guidelines, in-use stability is more and more frequently being requested by regulatory agencies for all types of multi-dose products both preserved and self-preserved. It’s typically indicated to perform chemical tests, such as assay or preservative content, packaging tests, or tests similar to container integrity tests to assure the sterility of, for example, eye drops packaging when in-use, and microbiological tests such as AET.
Usually references for challenge tests are USP or Ph.Eur., but for in-use stability purposes, time points should be selected taking into consideration the real use of the products according to label instructions and the additional strain of a typical home environment, introducing for instance, Staphylococcus epidermidis in the protocol. An example of a sampling plan for a product diluted in an infusion bag may include testing at T0, T2, T4, T8, T24, and T48 (time expressed in hours) with storage at 5°C and 30°C. The test is then completed with the verification that microorganisms are able to grow if present or added to the product.
Eurofins BioPharma Product Testing partners with clients to work on defining protocols and running them in our laboratories and solving testing challenges that may arise when approaching these requirements. For more information, please visit us at: www.eurofins.it/biopharma/