How Companies Should Respond to FDA-483: Consultant

Former FDA special assistant to the associate commissioner for regulatory affairs Martin Browning, now president of EduQuest, says that an inspected company’s response to an FDA-483 observation “is your last and best opportunity to tell your side of the story before higher-ups in the agency (including enforcement officials in Washington) become involved.” Writing in an online GxP Lifeline post, Browning reminds companies of FDA’s position that firms have a responsibility to work with agency investigators before they leave the facility to remove, or at least address, what the firm believes are incorrect points on the FDA-483.

It also is imperative that the firm provide a formal written response, he says, and that it be submitted immediately. He notes that FDA inspectors have a maximum of 10 working days to submit an Establishment Inspection Report to their supervisors summarizing their findings. The agency’s chain of decisions about whether to issue a Warning Letter or take other enforcement action begins when the report is submitted. While FDA suggests that companies respond to FDA-483 observations within 15 days, Browning says he recommends that the response come within 10 days to match the time given the inspector to finish the report, giving the company the maximum opportunity to have its input heard at the agency’s next levels.

Written responses, he says, should contain a restatement of the investigator’s observations to show that company officials understand the issue, the possible reason for the observation, what has been done to ensure that the observed situation did not and will not affect product specifications, and how and when the observation will be addressed.

He recommends that companies not argue over regulation interpretation and not simply acknowledge receiving an FDA-483 without outlining specific corrective actions that will be taken.

“Demonstrate to FDA that you recognize the agency’s concerns, and are working to resolve them without the need for further legal action,” Browning concludes. “Then the agency may move on to a ‘bigger problem’ company while continuing to monitor your progress. What’s certain is this: no response, a tardy response, or a poor response to a 483 inspection observation can increase the likelihood of a Warning Letter landing on your CEO’s desk.”