Dealing With FDA Warning Letters

By Casper E. Uldriks

The FDA issues Warning Letters to provide firms notice that unless they achieve voluntary correction of the violations noted in the letter, the agency is prepared to initiate an enforcement action without further notice.  Enforcement actions may include, for example, the seizure of goods, injunction and/or prosecution.  Other administrative actions may be taken, such as the automatic detention of foreign products presented for entry into the U.S. or issuing a mandatory recall order.  The FDA expects a response to a Warning Letter within 15 working days of the firm’s receipt of the letter.  It can be a challenge for some firms to meet this deadline.

Who really issues the Warning Letter?

For certain types of violations, such as manufacturing regulations, a Warning Letter may be issued by the FDA District Office in which the recipient is located. If the firm is located in Cambridge, Massachusetts, then the New England District Office would issue the Warning Letter to the firm.  If the firm is located in Houston, Texas, then the Dallas District Office would issue the Warning Letter to the firm. For certain other types of violations, such as for a product that lacks premarket approval or for not complying with advertising and promotion requirements, the FDA Center with jurisdiction over the product would issue the Warning Letter.  If a drug was involved, the Warning Letter would be issued by the Center for Drug Evaluation and Research. If a medical device is involved, then the Warning Letter would be issued by the Center for Devices and Radiological Health. A response to the Warning Letter should be sent to the point of contact identified in the letter for further communication.

Basic practical factors

Regardless of the particular issues raised in the Warning Letter, there are practical steps that can be taken to facilitate the response process.  The response should be well reasoned, address how each immediate problem will be resolved and how such violations will be prevented in the future. Each response should provide sufficient and concrete detail so the FDA can objectively determine whether or not the proposed corrective action is adequate.  Documentation provided in the initial and subsequent responses should be cross-referenced to the Warning Letter and, where appropriate, any related FDA Form 483 observations.  This will help to ensure that the FDA and you are “on the same page” when you are discussing a particular issue during a meeting or a telephone conversation with the Agency.  The purpose is to avoid confusion at this stage of the interactive process.

Meeting deadlines

Developing a meaningful response is usually a daunting task.  The content and tone of the FDA’s Warning Letter can instill a sense of alarm. Meeting the 15-day deadline makes it difficult to provide a well-reasoned and realistic response. The initial promise and plan of correction in the response may indicate that the firm is headed down a constructive successful path or traveling in a misguided direction.  In addition to the regulatory issues, the response should provide a detailed corrective action plan with a prompt, but reasonably achievable, timeline. In some cases implementing adequate corrections is bound by certain time frames.  The nature of the correction or corrective action often takes longer than the 15-day time frame allows.  For example, sterilization validation necessarily requires weeks to accomplish. If the 15 day response states that required sterilization validation has been completed, the FDA has prima facie evidence that the firm fails to understand how to meet its regulatory obligations.  A request by the firm for additional time to make corrections without providing FDA a reasonable basis for the request can work to a firm’s disadvantage in the process. In all probability, the FDA’s view of an unsupported request would not merit any special accommodations from the agency. In any case, timeframes proposed in the firm’s response should reflect the shortest time possible to provide the best possible result given the nature and risk of the issue at hand.

Promise of correction

Making a promise and keeping a promise will create the foundation for the FDA’s follow-up action.  A response deemed “adequate” by the FDA will in all likelihood prompt a follow-up inspection to verify whether or not the firm has fulfilled its promises.  If the same or similar types of violations continue, then the FDA will collect evidence of a firm’s failure.  Likewise, the firm will struggle with a loss of credibility and foster an expectation that the firm is not able to achieve compliance. Consequently, the FDA is motivated to act promptly.  A firm’s ability to negotiate with FDA may be adversely affected if the firm is suffering a credibility crisis with the Agency.

The FDA will expect rigorous adherence to the corrective action plan and sufficient evidence to demonstrate the plan is or will be effective.  In that regard, unrealistic or empty promises work to characterize the firm as a chronic bad actor that presents a significant risk to the public health and safety. The firm’s discussions during or after the inspection and the adequacy of the Warning Letter response may lead the FDA to the conclusion that, “They don’t get it.”  Salvaging one’s image becomes an uphill effort.  What you promise and what you actually accomplish should coincide.

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