The most common reasons an FDA warning letter is issued. Are you prepared to avoid these risks?

Posted on March 23, 2014 · Posted in Medical Device Legal Trends

We can all imagine the pressure associated with receiving an FDA 483 (observations made by FDA during a site inspection) or an FDA Warning letter (violations FDA has documented based on its site inspection).

To avoid these problems down the road, how can your firm remain proactive to prevent such risks from occurring in the first place? By maintaining & documenting your quality management system and knowing how the FDA “thinks”.

In a study completed by Invensys Operations Management (pertaining to 87 warning letters issued), useful information was revealed about why the FDA sends warning letters to firms.

The most common reasons for receiving an FDA warning letter:

Out-of-Spec (OOS) investigations
Just over 8% of the letters warned manufacturers that their out-of-spec investigations were lax. Some had not thoroughly investigated OOS results or performed investigations in a timely manner. Others had not even acknowledged a need to investigate OOS results.

Inadequate stability testing
About 11% of warning letters addressed stability testing problems. Some testing was inadequate to assess the stability characteristics of drug products or for determining appropriate storage conditions and expiration dates. In other cases appropriate stability testing could not determine expiration dates on drug product labeling and still others were warned for having no stability testing program at all.

Lack of scientifically sound specs, sampling plans, or test procedures
Almost 13% of the warnings cited inadequate laboratory test procedures for microbial products or for test methods that didn’t document accuracy, sensitivity, specificity and reproducibility.

Lax microbial contamination/sterility procedures
Just over 15% of the letters called out lax procedures for managing microbial contamination. Some manufacturers had no written procedures to prevent microbial contamination or for validation of sterilization process. Others had no sterility testing on a product that was actually labeled sterile. Others were warned for incomplete microbial contamination testing.

Inadequate QC unit
About a quarter of the letters warned of inadequacies in the QC unit. In these letters, inspectors observed that the Quality Control Unit had failed its responsibility to reject off-spec products. Or they observed that the unit had failed to review production records to assure there were no errors or if there were, that they were fully investigated. In at least one case the QC director was not even familiar with cGMPs; and in others the QC unit was not following established procedures or did not have clearly defined responsibilities and procedures.

The TOP FDA warning letter observation:

Inadequate batch record investigation
Almost 33% of the observations revealed inadequate batch record investigation. Even though electronic records have been allowed since 1997, inspection teams found many firms still using pencil-based batch record-keeping. They also found inadequate batch failure investigation and in some cases the QC unit did not even investigate batch discrepancies and failures.

Work to create a documenting process that is simply put, a part of your manufacturing culture. When the QA/QC and other departments across the business understand the importance and need for accuracy in your documentation, you minimize the fear and uncertainty of how the FDA will “rate” your company the next time they walk in the door.

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