Form FDA-483s and Warning Letters

At the conclusion of an inspection, FDA investigators issue a form FDA-483 which lists the adverse observations made during the inspection. Following review of the 483 and the establishment inspection report (EIR), the FDA District Office may elect to send the inspected company a Warning Letter.

The FDA inspection team communicates its observations to the inspected company via Form FDA-483 (or simply, “483”). The top 10 FDA warning letter findings for finished pharmaceuticals are listed below:

  1. Lack of a written stability program to assess the stability characteristics of drug products.
  2. Cleaning, sanitizing, or maintenance of equipment and utensils not performed adequately to prevent contamination.
  3. Procedures designed to prevent microbial contamination of sterile drug products not established.
  4. Testing for release for distribution not satisfactory.
  5. Routine calibration, inspection, or checking of equipment not adequately performed according to written programs designed to assure proper performance.
  6. Environmental monitoring systems not adequate in aseptic processing areas.
  7. Inadequate procedures for production and process controls to assure the identity, strength, quality, and purity purported.
  8. failure to thoroughly investigate discrepancies.
  9. Laboratory controls not scientifically sound.
  10. Quality control procedures not in writing or fully followed.

Both the 483 and the Warning Letter are serious documents which warrant a prompt and thoughtful reply. Companies often tend to rush replies, at the expense of careful consideration of the issues. Many companies believe that a rapid response to a 483 will prevent a Warning Letter. In certain cases this may be true, but a rapid 483 reply is no guarantee that a Warning Letter will not follow. A poorly written 483 response, on the other hand, may very well increase the likelihood of a subsequent Warning Letter.

A 483 or a Warning Letter from the FDA are never welcome events, but they do not have to be disasters. By focusing communication with the FDA on the factors the agency considers important, developing well thought out corrective action plans, and by following through to make certain actions have been carried out as promised, companies can achieve genuine improvements in quality practice and thus reduce or eliminate the risk of further regulatory action. If your company has the task of responding to a 483 or Warning Letter and want to ensure success, Kymanox is well versed in FDA audits and 483 or Warning Letter responses, so please contact us and we can assist you with your needs, no matter how urgent.