Reduced testing of Active Pharmaceutical Ingredients (API), excipients, and other raw materials can be a valid approach to gaining overall efficiencies in the pharmaceutical quality control laboratory. However, the choice of tests to perform and the justification for choosing those tests are key elements of operating a compliant Reduced Testing Program that is also scientifically sound.
The key to a scientifically sound Reduced Testing Program is a documented understanding of the links between the tests performed on the raw materials and the critical quality attributes of the drug product. For example, if the performance of the drug product is known to be dependent on the particle size of the API, then it is important that particle-size testing against scientifically sound specifications be performed for every batch as part of the Reduced Testing Program. Now, everyone reading this is probably saying, “this is obvious.” However, gaps in the understanding of these key links to product quality are most often revealed during OOS investigations. For example, if an OOS occurs during dissolution testing, and the investigation team seeks to eliminate the API particle-size variation as a potential root cause but there is no discriminating particle-size testing data for the API, then it is not possible to justify eliminating the API as a potential OOS root cause.
So, a scientifically sound Reduced Testing Program is based on a robust Quality by Design (QbD) program and a full understanding of the critical raw material attributes (API particle size in the example above) and their contribution to product quality. Without such an understanding, a Reduced Testing Program lacks a sound scientific basis and may contribute to future regulatory compliance issues.
For further information or questions relating to Reduced Testing and QbD, please contact James Davidson, Ph.D. at firstname.lastname@example.org.