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If an FDA investigation results in a Form 483 then it is important to prove that earlier issues have been resolved upon re-inspection. The following steps using your Corrective and Preventive Action (CAPA) program are crucial to appropriately handling and responding to an FDA Form 483 in helping avoid a Warning Letter.
There are significant steps needed to prepare and ensure high likelihood of successful navigation through an FDA inspection. If the inspection results in an FDA Form 483, the pressure is on to escalate the findings to a high priority organization-wide process improvement program because there will be a re-inspection, and it is imperative to demonstrate that the findings in the earlier inspection have been resolved in order to get off the path of escalation to a Warning Letter. Your Corrective and Preventive Action (CAPA) program is a critical tool in your response to an FDA Form 483 and can prevent a Warning Letter. Here are some tips for using CAPA in your response: 1. Use your CAPA form and a cover letter instead of a memo. If you have an electronic system with an easy-to-follow output format, use a cover letter and copies of the forms instead of starting from scratch with a memo. This makes it easier to read and demonstrates a robust CAPA program. 2. Document the investigation that was conducted for each observation with a concisely stated root cause. Document how you determined the root cause. Look beyond the immediate scope of the FDA 483 to ensure that a similar problem cannot occur elsewhere in a different study. 3. Identify containment measures and corrections to address each specific observation noted by the FDA inspector. Identify if immediate containment is necessary and how you can correct the problem, then attempt to implement the containment and corrections during your FDA inspection. The new CAPA issued from this inspection should identify containment and corrections that have been or will be implemented. 4. Identify corrective actions planned and the date(s) you expect to complete implementation. Ensure your corrective actions are clear and brief; timelines are realistic (be sure you can achieve the target dates); and there is a responsible person and role for each action. 5. Include documentation of containment and corrective actions already completed when you submit your response to the FDA. Show the Agency that you are taking action. If you revised a SOP and scheduled a group training, then provide the FDA a copy of the revised procedure and a copy of the agenda for your planned training session. Remember to only commit to actions you are certain you will implement and do not forget to include target dates. 6. Follow-up with a memo confirming that all the corrective actions are complete and include all related documentation, including any necessary training for new procedures or corrective actions. Follow-up before FDA does. If the verification of effectiveness is compelling and received in a timely fashion after the inspection, you may convince the compliance office to hold off on a planned Warning Letter. These straightforward steps are critical to steering the organization to appropriately handling the organizational response to a 483. The organizational changes and improvements a 483 response requires should be expeditiously addressed, however, the pace of change combined with the pressure a regulatory timeline brings can result in staff turnover or morale issues that impact company performance. The responses to a regulatory inspection often define the relationship with the Agency for years to come, so external expertise may be required to supplement an internal team. Laurie Halloran is the founder, president and CEO of Halloran Consulting Group