The FDA Just Completed Its Inspection...Now What?

""And this 483 item right here basically says your quality system is about to implode.""

Even after an FDA investigator has completed an inspection at your facility, there’s still plenty of work that remains. At the conclusion of an audit, the inspector will hold an exit interview to discuss observations and present significant findings on a Form 483. What do you do next? In the second installment of an ongoing webinar series on FDA inspections, ARC Experts President and CEO Walt Murray, a consultant with more than 30 years of experience in quality management and regulatory affairs, recently offered some ideas about what steps to take after an FDA investigator has finished an inspection, issued a 483 and left your facility. (Recap of the first webinar in this series can be found here.)

1) Review All FDA Findings Immediately.

When an FDA investigator holds an exit interview to discuss findings and deficiencies, staff should take extensive notes during the interview, specifically documenting observations, comments and commitments. The investigator will cite deficiencies observed during the inspection on a 483. Everyone should understand the issues around all 483 items. ""It is of great importance that you go over these observations very carefully,” Murray, who is certified in quality systems auditing and problem solving, said. “Make sure there’s no ambiguity about the particulars that you don’t want to have come up after you’ve supplied a response.” During the exit interview, you may discuss noted infractions with the FDA investigator and ask clarifying questions. If you take issue with any 483 item, believing the observation is in error, inform the investigator of your concern on the spot. If any observed issues have been remedied during the course of the FDA inspection, be sure to have that duly noted during the exit interview.

For medical device inspections, you can annotate the observations to support the company’s position if there is information that didn’t come out during the investigation; many companies do this so that the 483 has their comments noted. Keep in mind that a 483 will eventually become a public document, available through the Freedom of Information Act (FOIA). To protect against potential disclosure of trade secrets to competitors or other third parties, you should request that any trade secrets be deleted from the inspection report in case the report is later sought in an FOIA inquiry. The FDA will typically honor a request of this nature.

2) Respond to the FDA Within 15 Days.

The observations cited on the 483 should be addressed in writing within 15 days to avoid escalation to a warning letter. After 15 days, the FDA can escalate a 483 to a warning letter if the agency believes the infractions are marginally aggressive and if it is inclined to provide an especially strong sense of urgency. Your reply within the 15-day window shows the FDA you take the issues seriously. You are entitled to list any exceptions you have to the observations. Then explain how you intend to overcome the cited problems, and of course change your procedures to overcome these problems in the future.

The written response should include specifics, restating each observation and providing your response and action plan. Murray advised breaking long observations into smaller parts, addressing each infraction point by point and listing any exceptions you have to the observations. Then explain how you intend to overcome the cited problems. Describe how you plan to correct not just the cited problems, but also their underlying root cause and systemic issues. Set expectations for a realistic timeline for corrections, and supply evidence that corrections are occurring. “And, of course, change your procedures to overcome these problems in the future,” Murray said. Put together an effective action plan, and be consistent about how you resolve the problems. To ensure confidence in the verification of root cause of the failure(s) cited during the investigation, you must determine whether a finding was a single occurrence or a systematic problem requiring a change to the process/procedure. Conducting corrective and preventive actions (CAPAs) is a good way to handle infractions systematically, according to Murray.

3) Follow Through to Resolution – and Beyond.

The FDA can bring injunctions, consent decrees, fines, seizures and criminal prosecution depending on how the actions are addressed. To avoid causing the FDA to take legal action following an inspection, you must not take for granted the FDA’s findings and your responsiveness. Indicate in your original response (within the 15-day window) that you will be giving the FDA updates during the timeline of improvements and when those updates will occur. Then, as you respond aggressively to 483s with corrective actions, regularly provide the FDA District Office with reporting and supporting documentation that could mitigate any further action from the district. “If supporting documentation is not yet available, give the District an expected plan, stick to the plan and follow through with subsequent documentation,” Murray advises. “The compliance person at the district [office] only knows and understands the activity and nature of improvements that are occurring through your communication, so err on the side of [providing] more information, not less information.”

Always feel free to discuss matters with the District to ensure your corrective action plan will meet their expectations, Murray says. But understand that FDA agents are not consultants and will usually not act as such. Your problems – how long corrections will take, how many people you will need, how much it will cost, etc. – are usually not of concern to regulators. You will know the matters have been resolved if you receive an establishment inspection report (EIR), which summarizes the FDA findings. Even then, you aren’t done. To avoid repeating the same mistakes later, Murray stressed the importance of not only employing an integrated approach to your corrective action plan relative to the findings, but also periodically following up with internal and mock audits to ensure that the same issues don’t return.