As part of the FDA's Office of Generic Drugs' (OGD) ongoing effort to streamline the review process and reduce the number of deficiencies cited for the applications, a series of articles are being published to provide transparency and clarity to applicants submitting applications in the Question-based Review (QbR) format. The articles highlight the need and significance of science based justification in establishing drug substance (DS) and drug product (DP) specifications, in-process controls for both DS/DP, choice of formulation, selection of a product design and selection of the manufacturing processes. Part 1 of this series, which dealt with the deficiencies cited in the drug substance section, was published in January 2010 (1). Part 2 of the series dealing with drug product composition and excipients was published in August 2010 (2).
The current article is intended to provide clarification with respect to intent and criticality of common deficiencies cited in the control of the drug product (3.2.P.5) and stability (3.2.P.8) portions of abbreviated new drug application (ANDA) submissions using the Common Technical Document (CTD) and Question-based Review–Quality Overall Summary (QbR–QOS) format as a guide. Please refer to the sidebar for a list of some of the deficiencies and comments. This is not an all inclusive list of comments and deficiencies pertaining to the drug product specifications and drug product stability, but includes questions that are cited frequently.
Examples of commonly cited drug product and stability deficiencies and comments**