6 Rules for Responding To FDA 483s And Warning Letters
1. Immediately secure executive leadership support and the right expertise.
While your head of RA/QA is tasked with leading the response, he or she cannot do it alone. Identify leaders within each function area that pertains to the 483. This team will be responsible for overseeing the response.
2. Set the emotional tone: calm and supportive.
Remain calm. Once people understand management is committed and in control, they’re likely to stick around and contribute to remediation. Listen, engage, and respond to concerns and comments, as your staff may offer useful information for your response to FDA.
3. Organize: Open the communication channels and keep them open.
Inform the members of the teams about needs to be done, who is going to do what, how everyone will be kept on the same page, and what the timeline is. It is critical to hold a regular team meeting — typically weekly.
4. Write a thorough, proactive response.
Issuing the initial response to a 483 is one of the most critical regulatory responses you will ever have to provide to FDA. A well-constructed cover letter that emphasizes your company’s (and its executive team’s) commitment to quality and compliance sets a positive stage for responding to any FDA findings. The more comprehensive the response, the more FDA will be assured that your company takes its concerns seriously. Every observation should have a thorough root cause analysis performed and, if necessary, one or more corrective and preventive actions (CAPAs) identified, along with a CAPA reference.
5. Engage a range of internal and external stakeholders to thoroughly review the response.
External reviewers can provide a second or third opinion to identify gaps in the response or tweak key messages. Regulatory advisors or consultants experienced with FDA communication should review the response.
6. Timing is everything.
Remediation should start the day after receiving a notice of 483 or a warning letter. FDA requires a response to most compliance notices within 15 business days. Monthly updates often make sense, but for warning letters, bi-monthly is recommended. Whatever schedule you choose, it is important to demonstrate your company’s commitment by sticking to the schedule.
The final element of a successful response is the description of a set of actions or programs to correct and prevent recurrence of FDA observations. Instill confidence in the remediation plan with realistic due dates, competent people to lead them, and specific outcomes that can be measured and documented.