Don’t Let an FDA 483 Become an Intimidating Warning Letter

Robert Romanchuk, Schulman IRB Vice Chair

Robert Romanchuk, Schulman IRB Vice Chair

After visiting clinical trial sites for more than 10 years, Schulman IRB Vice Chair Robert Romanchuk has a simple message: When you get a Food and Drug Administration (FDA) 483, consider your response to it seriously. It’s your best opportunity to address the situation and get back to business.

It sounds like common sense, Romanchuk allows, yet it’s perhaps not as common a practice as it should be. “Sometimes a site will get a 483 and almost forget about it,” says Romanchuk, BS, CIP, CCRC. That’s when an FDA Warning Letter will arrive. “FDA [staff] can’t read your mind. All they know is what you tell them in a response.”

In the vast majority of cases, a 483 citation is over a relatively minor issue. That said, failure to respond to even the most minor of infractions can become trouble down the road.

Romanchuk will provide more tips for responding to FDA Form 483s during his ACRP 2017 Meeting & Expo session, Mastering Your Responses to the Dreaded FDA Form 483, on Saturday, April 29.

View the ACRP 2017 Preliminary Program

Each year, some 250 FDA Bioresearch Monitoring Program (BIMO) inspections result in a 483. Only a small fraction of 483s result in a Warning Letter, Romanchuk notes, but failing to respond is one sure way to receive one. “It can ruin a site” if it is hit with one, Romanchuk says. Thereafter, it has to answer “yes” to any questionnaire asking if the site has ever received a Warning Letter. That’s not exactly good for winning new business.

On the other end of the spectrum, Romanchuk has observed turmoil at research sites after getting a 483. That kind of overreaction doesn’t help things either, he notes.

Instead, sites should recognize that 483 responses tend to fail in a few areas, notably in terms of supplying Corrective and Preventive Action (CAPA) plans, providing evidence of compliance, and presenting a robust series of documents and standard operating procedures with milestones that clearly demonstrate the concrete steps you are taking to address shortcomings alleged by the FDA inspector.

FDA isn’t in the business of shutting down sites. “FDA is not out to get anybody,” says David C. Burrow, PharmD, JD, acting director of the Office of Scientific Investigations, which is part of the Office of Compliance within the Center for Drug Evaluation and Research.

It’s up to sites to leverage that opportunity to their best advantage, stresses Romanchuk.

Author: Michael Causey