GMP Update: CDER Official Explains, Advises, and Predicts

Francis Godwin, Director of the Office of Manufacturing Quality of the Office of Compliance at FDA’s Center for Drug Evaluation and Research provided useful information (presentation attached here) Tuesday at the GMP by the Sea Conference.  He talked about regulatory discretion being exercised for drug manufacturing facilities with serious compliance problems, about how firms should respond to FDA inspectional observations, and about an upcoming guidance that will be of interest to generic drug manufacturing firms that have received Warning Letters.

First, Mr. Godwin provided updated information on the presentation made the day before by another CDER official, Jennifer Maguire, the Director of the Office of Quality Surveillance within the Office of Pharmaceutical Quality at CDER,.  We summarized in a blog post yesterday  her comments about facilities with FDA inspections that had been classified as Official Action Indicated, the most serious classification for FDA inspections relating to current Good Manufacturing Practice compliance.  Mr. Godwin’s presentation made the same point, although with more data to back it up: so far this fiscal year (since October 1, 2022), the number of OAI inspections resulting in the exercise of regulatory discretion is unusually high.  Regulatory discretion, in this context, means basically that FDA has decided not to issue a Warning Letter, request a Regulatory Meeting, impose an Import Alert, or to take a more serious enforcement action.  There were 286 FDA GMP-related inspections of drug manufacturing facilities in this period with OAI classifications.  Of that number, 80 of the facilities were graced with FDA’s regulatory discretion (28%), 75 resulted in imposition of an import alert (26%), 66 resulted in Warning Letters (23%), and 62 prompted Regulatory Meetings (22%).

Mr. Godwin confirmed that the percentage of OAI facilities receiving regulatory discretion was unusually high, and stated that he believes (as we posited in the blogpost yesterday) that the higher percentage was due to COVID-related causes: there were more facilities making critically needed drugs, and the drug supply chain has not recovered from COVID shutdowns and delays, making shortages of important drugs much more likely.  FDA would not want to curtail supplies of vitally needed drugs by, for example, imposing an Import Alert.

Second, Mr. Godwin said he reads numerous responses to FDA Forms 483, the report that FDA issues at the end of a GMP inspection, and that it is critically important that the responses include a narrative summary of the major remedial actions that a company has made or intends to make, and discuss if a company contests a finding.  “Document dumps,” he said, are not helpful without the assistance of a narrative placing the documents in context.

Third, Mr. Godwin said that he expects FDA to issue soon a Guidance document that will address how generic drug manufacturers should request, and what they should present, at meetings with his office that will be held after the company receives a Warning Letter.  After his remarks, Mr. Godwin stated that the Guidance, and the necessity of FDA providing such a meeting is one of the commitments in the GDUFA III  Commitment Letter.