FDA Mulls More Post-Inspection Feedback: Cavazzoni
FDA is considering more opportunities for sponsors to learn about inspection issues that arise during pre-approval/pre-licensure inspections before an application review is completed. Speaking at a joint Parenteral Drug Association/FDA regulatory conference in Washington, DC 9/9, CDER director Patrizia Cavazzoni acknowledged that there is a “desire” by sponsors and contract manufacturing organizations to have more communications after an inspection, but sometimes meetings may not be necessary or possible depending on where an application is in the review cycle.
Cavazzoni said that generally companies find out the outcome of the inspection at the time a complete response letter is issued or at the time of approval, and when an Establishment Inspection Report (EIR) is released. She emphasized that when the FDA-483 is given to the manufacturing facility on the day the inspection ends, the remediation should start then as opposed to waiting for the EIR or the complete response letter.
“There may be some opportunity to have more dialog, but I've seen some companies think that a meeting will solve all issues, and FDA will be persuaded that everything is fine and the drug should be approved,” Cavazzoni said. “And if things are not fine, and if things are the opposite of fine in the facility, then there’s no amount of meetings or calls or interactions that will fix that within a matter of months or weeks that are left after an inspection during the review of an application.”
Regarding Warning Letters, about 20% of those issued in fiscal year 2024 were not based on physical inspections, rather the findings came from remote assessments and document requests, Cavazzoni told the conference attendees. She said investigators are documenting recurring compliance issues in drug manufacturing, which include these top issues:
- Sterility assurance and aseptic processing
- Selection of ingredient suppliers and appropriate testing
- Quality management related to contract manufacturing arrangements
- Data integrity, transparency, and record retention
Cavazzoni paid particular attention to data integrity issues, such as document shredding incidents and other “egregious situations… When it comes to data integrity, we're still seeing too many problems. We’re seeing about one in five cGMP Warning Letters that reference data integrity issues, and that is not a good number this day and age. You know, with digitization, we should be in a much better place when it comes to records management and documentation.”
Looking ahead to 2025, Cavazzoni predicted that FDA is going to continue to see pre-approval inspections that continue to uncover cGMP and facility issues, which is not optimal. “The user fee programs do not fund surveillance inspections for new drugs or new biologics/biosimilars, which, of course, means that we are likely to continue, unless we change that in the next user fee cycle, to see this pattern,” she told the conference. “This is not a good situation for FDA, and it’s not a good situation for sponsors, because I think that more surveillance inspections in the drug, biologics and biosimilar facilities would actually prevent these issues from being found at the time of the pre-approval inspection, which should be very focused and really looking at the manufacturing, the [chemistry, manufacturing and controls] and these sort of processes.”