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EduQuest, a global team of FDA compliance experts, answers industry’s pressing questions. In this round, Martin Browning, President and Co-Founder of EduQuest, explains how to best respond to FDA Form 483 observations.
Question: We are reviewing our FDA inspection preparation procedures, and several questions have come up about how best to respond to Form 483 observations—especially those we don’t agree with (which has happened in the past).
Given your experience as FDA investigators and additional years of helping clients handle FDA inspections, what would you advise?
Answer: FDA believes that it’s your responsibility to work with its investigators before they leave your facility to remove—or at least address—what you believe are incorrect points on Form 483.
In the wrap-up meeting with you after an inspection, FDA investigators should review each Form 483 observation, one by one, and annotate them with your responses and any corrective actions you’ve made during the inspection. When you can verbally respond to an observation with 100% confidence, do so. But if you are uncertain how to respond, it’s better to tell the investigator that you will send FDA a written response about the observation.
Even if you respond verbally to each point, it’s still imperative for you to provide FDA with a follow-up, written response immediately. This assures that your response is seen by all interested parties, including the investigators’ supervisor (who is usually a district compliance officer) and to other higher-ups in the Agency.
In general, your response—especially the written one—should contain a restatement of the investigators’ observations (from your perspective) to show that you understand the issue, possible reason for the observation, what you have done to ensure that the observed situation did not (and will not) affect product specifications, and how and when you will address the observation.If you disagree with an observation, your response should offer background information on the point, indicate why you think the investigator made the observation and explain why you believe that it’s not valid.
In your written response:
- Discuss your experience with the process or item. Use sound, scientific reasoning as much as possible.
- Don’t demean the investigators’ experience or inspection process; that won’t win you any friends at the Agency.
- Your response will be read by FDA officials who work in higher levels of the Agency, and they likely won’t be familiar with your operations. So I also suggest that you include a paragraph or two with an overview of your company and its history, products and operations.
- In your response, it’s critical to show FDA that you are in control of the situation and are attempting to comply voluntarily by doing everything possible and reasonable to ensure that your products meet Agency specifications.
- Don’t argue over an interpretation of the regulation. Odds are that FDA investigators know the finer points of the regulations better than you do. Keep in mind that you usually won’t win a regulatory interpretation clash with the Agency.
- Don’t just simply acknowledge that you received the Form 483 without outlining specific corrective actions you have planned. That approach raises eyebrows at the Agency, which may believe that you don’t truly understand the problems or appreciate their significance.
Remember that Form 483 observations are just the investigators’ opinions. Their observations are not always supported for additional legal action (such as a Warning Letter) by the district office or at FDA headquarters.
Your response is your last, best chance to tell your side of the story. Will it help? Maybe, maybe not—but you can be certain that no response, a tardy response or a poor response will increase the possibility of a Warning Letter coming your way.
For further reading, FDA’s website features a page of frequently asked questions about Form 483s. Also, I think it’s useful to be familiar with Chapter 4-1 of FDA’s Regulatory Procedures Manual, which outlines the Agency’s policies and procedures for the issuance of Warning Letters.
Mr. Browning, President and Co-Founder of EduQuest, served as an expert field investigator and Special Assistant to the Associate Commissioner for Regulatory Affairs during his 22-year career at FDA. EduQuest can be reached by email.
