Warning letters are the FDA’s second level of enforcement actions after issuance of a form 483. The FDA determined that either the firm’s response to the form 483 was inadequate or the observations were serious enough to support issuance of a warning letter. Often it is possible to determine the corrective actions necessary and the impact that the warning letter will have on the business. To determine a letter’s impact on the business, I ask these questions:

  1. How many deficiencies does the warning letter identify? A large number of deficiencies identified in the warning letter suggests a broad scope of problems within the organization and quality system. More problems generally take longer to resolve and may have greater negative impact on the business, both finances and reputation.
  2. Does the warning letter cite that previously identified deficiencies were not effectively corrected? This citation suggests that the firm’s root cause analyses, corrective and preventive actions, and CAPA effectiveness evaluations may not be adequate.
  3. Does the warning letter indicate that inadequate investigations were conducted into quality events discovered after product was released to distribution? FDA may be suggesting that the firm recall the product(s). Again, corrective measures like a recall are disruptive and expensive ventures for the firm to perform. It is instructive to monitor the weekly recall reports to determine whether this happens.
  4. Does the warning letter state that a re-inspection will be necessary to confirm that appropriate and effective corrective actions have been put in place? This recommendation indicates the level of seriousness of the deficiencies or the potential risk of the deficiencies to threaten product quality and patient safety. It may also suggest that the agency does not have confidence in the ability of the firm to implement effective corrective and preventive actions without additional oversight. Not good.
  5. And finally, does the warning letter include additional requirements or issues that the company must address while responding to the identified deficiencies? Most recently, this has been common in warning letters issued for deficiencies in the areas of data integrity for electronic records. These appraisals may also cost time, money, and reputation.

The FDA is more frequently consolidating the outcome of inspections at multiple company sites in a single warning letter. It is prudent to consider that the same or similar deficiencies may be present at other sites owned and operated by the firm that were not covered by the inspections identified in the warning letter.

Even reasonably simple warning letters are time consuming and expensive to remediate, and the number and nature of the deficiencies contribute to the ultimate cost. Corrections frequently involve employing consultants or contractors and putting other projects on hold while remediation is completed.

This ‘lost opportunity’ is often difficult to assess regarding its impact on the business, but nonetheless negative impact is generally substantial. Depending on the nature of the deficiencies, capital expenses are often part of the solution. Thus, self-identification of potential deficiencies, along with an active continuous improvement program, is less expensive and disruptive to business than remediation after the receipt of a warning letter. “Benjamin Franklin said, “An ounce of prevention is worth a pound of a cure.” Access our database of warning letters here.