Anticipating and Closing Out FDA Warning Letters

  • By: Staff Editor
  • Date: November 20, 2015
  • Source: ComplianceOnline
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 Anticipating and Closing Out FDA Warning Letters

How can an FDA regulated company know that a Warning Letter is definitely on its way? What are the signs that can help firms anticipate a letter from the regulator? What is the groundwork that can be done before the receipt of the Warning Letter so that when it indeed arrives, the company is ready for it and implements the close-out process quickly and effectively? The answers to these questions are vital in ensuring the FDA Warning Letter response and close-out program is handled in a thorough manner that leaves nothing to chance.

What is a Warning Letter?

A Warning Letter is issued by the FDA to a regulated manufacturer if it is found that any significant regulatory violations have occurred.

Violations identified in the Warning Letter can include:

·          nonconformance with Good Manufacturing Practices (GMP) or

·          false claims about a product or

·          inadequate training for personnel or

·          wrong directions for use and so on

Once the manufacturer receives the Warning Letter, it has to correct the violations noted by the agency. The manufacturer has to provide a clear timeframe to the FDA in which the corrections will be done and the regulatory will follow up to check that these have been accomplished.

What is a Closeout Letter?

Once the FDA has checked and verified that corrective actions have been done to rectify the violations noted in the Warning Letter, it will issue a “close-out” letter. The Warning Letter Close-Out Program applies to Warning Letters issued after September 1, 2009.

It must be noted that if the Warning Letter includes violations that cannot be corrected, then no close-out letter will be issued. The FDA office which issued the Warning Letter will issue the close-out letter as well.

How to Effectively Handle Warning Letter Close-Out Process

The companies can handle the Warning Letter, its implications and resolution without unnecessary delays and loss in revenue or reputation by carrying out following best practices:


Watch Out for Warning Letter Signs

The following can help in foreseeing the advent of a Warning Letter and fixing them in advance can prevent the actual enforcement action:


-           Long standing internal problems that have not yet caught the attention of the FDA but are known within the company

-           Form 483 notifications (the most obvious predictor of Warning Letters)

-           Red flags from the quality unit

-           Adverse events

-           High volume of customer complaints

-           Prior investigations about the same issue or same type of issue

-           FDA responses to communications from the company that do not signal satisfaction with issue resolution and so on

-           Product contamination

-           Off-label promotional activities that have caught the attention of the FDA

-           DDMAC letters

Repeated FDA inspections of facilities

Set Post-Inspection Deadlines and Adhere to Them 

It is important for companies that receive citations in the form of 483s or Warning Letters to ensure they respond within the set deadlines. In the case of Form 483s, companies should respond within the 15 day timeline to the significant FDA findings.

If the Warning Letter is issued and the FDA does expect corrective actions to be taken within certain time frames, the imperative is on the company to set deadlines to achieve these and adhere to them.

Do a Proper Internal Audit

The audit will help to find the faults that led to the observations and Warning Letter citations, making it easier to devise and implement corrective actions. A methodical internal audit is a key part of a fast and trouble-free close-out program.

Retain and Provide Proper Documentation

The FDA follows the mantra “If it isn’t documented, it didn’t happen”. So records play a very important role in the Warning Letter close-out process. The FDA shouldn’t be left with an unclear view of whether remediation activities have taken place or not.

The proper close-out of a Warning Letter will boost not just the company, but also most importantly, consumer confidence in its products.

Additional Resource:


FDA Inspectional and Regulatory Enforcement Trends: Key Focus on Trends in Consent Decree   

Introduction to the FDA and Your First FDA Meeting

FDA Inspection Lessons Learned: Lack of Trial Oversight

How to Survive FDA's New Inspection and Enforcement Practices

FDA Regulatory Compliance Training

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