Following the release of the report “Final Report on Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach” in 2003, the Office of Generic Drugs (OGD) recognized that its process for review of ANDAs needed an update to meet the new risk-based approach and to handle a significant increase in submitted ANDAs since 2002 (in 2017 the OGD received 2,849 original ANDAs and CR responses/amendments, up from 346 in 2002). The new process, known as Question-based Review (QbR), was developed during 2005-2006 and released in 2007. 

The process involves a set of standardized questions available to sponsors as a guide for preparing their Quality Overall Summary and to reviewers as a guide for their review. There’s a general outline QbR, as well as model QbR for extended release capsules and immediate release tablets. Of particular interest for sponsors and manufacturers of aseptic drug products is the Question-based Review (QbR) for Sterility Assurance of Aseptically Processed Products, which gives a nice overview of the critical parameters for microbiological control of aseptically processed products. There are also a couple of other CMC microbiology QbR for terminally sterilized drug products on the main QbR page. In my experience review of these microbiology QbR could help when preparing for a Prior Approval Inspection or educating quality practitioners on the elements necessary to a microbiological control strategy.

A QbR helps sponsors understand exactly what the reviewers are looking for when assessing the Chemistry, Manufacturing, and Controls (CMC) for the proposed generic drug product. QbR also guides reviewers toward the right questions to emphasize quality by design principles and critical drug product attributes, as well as helping them adjust their review based on the level of risk the drug product presents. By clarifying the expectations for CMC content, the QbR are expected to lead to more first-cycle approvals and focus review effort on more complex drug products that represent a greater potential patient risk. QbR are mentioned in the new guidance on CTD standards for ANDAs (see my previous post), which I hope means the OGD will publish more QbR to clarify the requirements for additional types of generic drug products.

Text Copyright © 2018 Katrina Rogers