How to Respond to an FDA 483 and Warning Letter – Precautionary Measures

The FDA themselves state it is industry’s responsibility to work with investigators before they leave the company to remove all incorrect points on the 483. The FDA is also supposed to annotate the 483 concerning your corrective actions that were accomplished during the inspection.

From latest experience with the new FDA investigators, this advice doesn’t appear to hold any weight when they are trying to prove themselves while still on the learning curve. Some seem to think the longer the list on the FD483, the better their chances for advancement — though, that is not always the case (in fact, FDA promotions are based on the candidate’s actions not just the number of issued 483’s or Warning Letters).

Why try to prevent inaccuracies on the FD483?

1. The FDA483 is a legal document, and inspectional observations could be construed as deviations from the GMPs. These GMP violations can be used as counts against you in legal proceedings.
2. The FDA483 is part of the company’s regulatory history. If future problems arise, past FDA483’s could be caused to enhance legal actions against you.
3. The FDA483 is available via the Freedom of Information Act so the competition could get a copy and use it against you in the market.

The issuance of the FDA 483

You have just been issued an FDA483 — now what? The investigator will try to elicit your response to each point, one by one. In cases where your responses can be made without any uncertainty as to the outcome and conclusion, definitely provide them to the investigator at the close out meeting. But, if you are not sure of your response, it would be better to explain to the investigator that you will supply a written response to the FDA483 directly to the FDA district office.

Even if you respond verbally to the investigator on each point, it is crucial, let me repeat, it is crucial, that you also send in a written response as soon as possible. This assures your response is accurately given to all interested parties which could include the investigator’s supervisor, the compliance officer assigned to your case (yes, you will now be considered a “case”) and the branch director ─ all those who could be a part of the decision as to whether a Warning Letter should be issued.

The nature of your response to the FDA has changed over the years. Simply stating you received the FDA483 and will address all issues, without outlining the specific corrective actions you have planned and their implementation time frames will not fly with the FDA any longer. Such response could be interpreted as a poor attitude on the part of the company and the agency will definitely issue a Warning Letter to assure that the corrective actions are taken.

Remember the observations on the FDA 483 are just the investigator’s opinions. These observations are not always supported for additional legal action by the district office or the Division of Compliance in Washington. But, the investigator is the main advocate for additional action, though they may have the least amount of input on whether additional regulatory action would be taken.

You must understand that the issuance of the 483 is an initial FDA’s regulatory action as a result of their inspection and the issuance of a WARNING LETTER is the next level of FDA regulatory action.

The FDA is now setting up a case against companies to take additional legal actions if proper correctives actions are not taken and in the appropriate period of time.

For more information on dealing with a 483 and Warning letter contact mdi at info@mdiconsultants.com and RE: 483/WL

How to Respond to an FDA 483 — and Prevent a Warning Letter

A COMPLETE GUIDE