The Office of Generic Drugs issues new DRAFT Question based Review (QbR) Chemistry Questions
Written by Garth Boehm • July 18, 2014
On July 14 OGD issued a revised list of DRAFT Chemistry Questions. These questions are not intended to be implemented but have been issued specifically to get comments from Industry about the proposed questions. They cover BOTH Active Ingredient DMFs and Finished Dose Form Applications (ANDAs). The first 24 questions relate to DMFs and the following 38 questions relate to dosage form.
The specific purpose is to solicit comments from Industry which in this case is both the API industry and the FDF industry. Now when FDA goes to great lengths to get input from industry, it usually means the some of the questions or information sought might be “controversial”, in other words questions might difficult to answer (or unclear) or seeking information that industry may not believe is appropriate. As a general rule, the more times FDA asks for industry comment, the more important it is for industry to CAREFULLY read the questions and to be sure that you understand EXACTLY what is being asked and that you can answer all questions in every circumstance. If you now, or in the future propose to, file DMFs and/or ANDAs it is your responsibility to comment NOW, or as the saying goes, to forever hold your silence.
Some of the questions are quite broad and far reaching, for example:
“What are the critical process parameters (CPPs) and how are they linked to drug substance quality?”
This question does not have a short answer. Imagine exactly how you are going to answer this question for an API DMF. If it is not clear, then say so in a comment. If you feel confident that you can answer that question, then how about this one:
“What is the proposed control strategy for the drug substance manufactured at commercial scale? What are the residual risks upon implementation of the control strategy at commercial scale?”
Similar proposed questions exist for ANDA filers. For example:
“What are the Quality Attributes of the finished product? Which quality attributes are considered Critical Quality Attributes (CQAs)? For each CQA, what is the target and how is it justified?”
If you find that easy to answer, then you should be confident you know exactly what is required for this question:
“What is the approach for meeting the CQAs related to clinical performance? If applicable, what in vitro bioperformance evaluations (i.e., dissolution method, flux assay, etc.) were used during pharmaceutical development to ensure clinical performance?”
Although these draft questions for comment seem to be issued seeking generic drug company input, it is apparent that they can apply to all FDF applications, NDAs and ANDAs.
If you do comment, can somebody do me a favor and ask what are the "mechanical" properties of a drug substance? Apparently they differ from the physical, chemical, and biological properties of the drug substance.
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法规指南解读：FDA MAPP 5015.10 Chemistry Review of Question-based Review (QbR) Submissions
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