FDA-483 Observations
Q&A With David L. Chesney, Vice President, Strategic Compliance, PAREXEL Consulting. Contact Mr. Chesney
In the Federal Register Tuesday August 11, 2009, the FDA established a policy concerning written responses to FDA-483 observations. The policy gives companies 15 days to respond in writing to the FDA after a 483 is issued, if they wish their comments to be taken into consideration when the FDA is deciding whether or not to issue a warning letter.
What is an FDA-483?
It is the form an FDA investigator issues to a company at the conclusion of a GMP, GCP or GLP inspection (or any inspection) setting forth the observations the FDA employee finds objectionable, and considers to be possible violations of the law.
Is a written reply to a 483 required by law?
No. Companies are not required to reply at all, but nearly everyone does, and it is expected. Failure to respond is unusual, and could be taken as a sign of indifference by the FDA. A prompt, proper response is essential to avoid further action by the FDA.
Do warning letters always follow an FDA-483?
No, not at all. In fact, the vast majority of 483s do not lead to warning letters. Warning letters are sent when the FDA feels the observations made during the inspection are significant, and a stronger warning than the 483 itself is warranted.
What is different under this policy from the past policy?
In the past, FDA did not set a specific time frame for companies to respond to 483s. As the announcement explains, practice in this regard varies, and many companies do not respond promptly or efficiently. The new FDA Commissioner has placed a high degree of importance on a timely, effective enforcement response by the FDA as part of her overall agenda to make enforcement more effective. This is a step in that process.
What is the purpose of a warning letter, and what are the consequences of receiving one?
There are two purposes: (1) obtain prompt, voluntary correction of the issues cited by the FDA and (2) establish a background of prior warning so that if the FDA has to seek court intervention, they can show that they exhausted their administrative options before asking the court to intervene through formal litigation.
The primary consequences of a warning letter are the publicity (since warning letters are posted on FDA’s web site), and the time and expense to take the necessary corrective actions, and deal with the FDA.
How can a written response to a 483 help prevent a warning letter?
If the FDA sees that the company is taking prompt, reasonable steps that are likely to take care of the issues on the 483, they may conclude that a warning letter is not necessary. Timeliness is important, but getting it “right” is even more important.
How can PAREXEL Consulting help?
We have many years of experience helping our clients respond to 483s effectively. We have a team of former FDA investigators, Center scientists and reviewers, and compliance experts, plus highly experienced former industry scientists and executives who know what the FDA expects, and how to effectively word 483 responses to make sure they are proper and are understood by the FDA.
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