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Wisconsin companies regularly and eagerly await responses from the FDA to requests for authorization of clinical trials involving investigational products, submissions for premarket clearance of medical devices, and other submissions and applications. But a different type of FDA letter -- a warning letter -- is much less welcome.
Warning letters provide written notice that the FDA has identified significant regulatory violations involving drugs, biologics, devices, radiation-emitting products, foods, dietary supplements or cosmetics.
Last month's column
discussed FDA inspections, and explained the importance of providing timely and thorough written responses to notices of inspectional observations. If the FDA deems the response inadequate, it may issue a warning letter. Sometimes, the FDA issues warning letters even when an individual or company provided what it believes to be a thorough response.
The FDA also issues warning letters based on information from sources other than inspections. Its staff review of websites or consumer complaints may bring to the agency's attention a medical device being marketed without the required authorization or approval, or a dietary supplement with claims that trigger the regulatory requirements for drugs.
What a warning letter is (and is not)
The FDA issues warning letters for significant regulatory violations. That means violations that would warrant enforcement action if they are not adequately corrected. A key goal of warning letters is voluntary compliance. The FDA issues warning letters to provide individuals and companies with an opportunity to take voluntary and prompt corrective action.
To be considered an official warning letter, a letter from the FDA must include the words "warning letter" in the title. For example, a letter from the FDA requesting additional information after a manufacturer files an adverse event report is not a warning letter.
A warning letter can come from one of the FDA's district offices, such as the Minneapolis District, or one of its product-based centers, such as the Center for Drug Evaluation and Research.
Warning letters generally are sent to the highest known official in an organization (e.g., president or CEO). Warning letters usually require a response within 15 working days of receipt. Failure to respond could cause the FDA to bring an enforcement action in federal court, such as a seizure or injunction.
The agency also issues warning letters to establish prior notice before enforcement action. But it takes the position that prior notice is not required, and no one should assume that a warning letter will be issued before the FDA takes enforcement action. The FDA can and does move immediately to enforcement action if the violation is flagrant, presents a reasonable possibility of serious injury, reflects a history of repeated conduct, or involves a felony.
The FDA routinely posts warning letters on its website (with confidential or protected information removed). Other federal agencies are advised of warning letters and they may take this information into account when considering the award of contracts.
The agency issues a different type of letter, usually referred to as an "untitled letter," for less significant regulatory violations. Those letters are untitled, and tend to request a written response from the company within 30 days. Although an inadequate response to an untitled letter is unlikely to bring the severe consequences that a failure to respond to a warning letter can bring, companies still should consider the points below when evaluating and responding to an untitled letter.
What to do if a warning letter arrives
An FDA warning letter provides an opportunity for you to respond and work with the agency to achieve compliance. Because warning letter responses should be as specific as possible, and explain what actions the company has taken and plans to take, it is important to follow these steps if a warning letter arrives:
¥ Review the warning letter very carefully. Evaluate the specific violation or violations alleged, and what action is demanded.
¥ If the letter seems unclear, contact the listed FDA contact person for clarification.
¥ A carefully prepared response can make the difference in whether the FDA pursues enforcement action. It may be useful to obtain advice from an attorney or consultant experienced in FDA matters.
¥ In preparing a response, consider both what the FDA would like to hear and what the company is willing to do.
¥ The response should clearly and specifically state the corrective actions the company is willing to take.
¥ Do not promise a correction and then fail to take corrective action. Assume the FDA will do a follow-up inspection or otherwise confirm that corrective action has been implemented.
¥ If you disagree with the FDA's fact-finding or interpretations-or believe that changes are not needed or not possible in a particular area-make sure that the response explains why. Before doing so, evaluate the potential consequences of declining to make requested changes.
¥ Consider whether a meeting with the FDA should be requested in the response.
¥ In any event, be sure to send a complete written response to the warning letter within the requested timeframe (usually 15 working days). Recipients can request that the FDA post the response on the FDA website.
From the FDA's perspective, warning letters serve three functions: they document the FDA's position that violation exists, establish that notice of violations has been provided, and promote voluntary compliance. Recipients of warning letters should utilize the opportunity presented for voluntary compliance and provide a thorough response. Failure to do so will not only hamper a company's working relationship with the agency, but also leave the company particularly vulnerable to an FDA enforcement action.
Patricia Kaeding, an attorney, was an associate chief counsel at the FDA in Rockville, Md from 1993 to 2003. FDA & Your Business appears monthly on WTN.
The opinions expressed herein or statements made in the above column are solely those of the author and do not necessarily reflect the views of The Wisconsin Technology Network, LLC. (WTN). WTN, LLC, accepts no legal liability or responsibility for any claims made or opinions expressed herein.