Failures in Handling OOS Results cited in FDA Warning Letters 2013

Recommendation

12-14 December 2023

Stability by Design - Live Online Training
- Stability Testing in Product Design and Method Development- Focus mainly on small-molecule APIs and drug products

A review of the 2013 FDA Warning Letters shows that the incorrect handling of OOS results is still a hot topic in FDA inspections and inspection follow up activities (483s, etc.). In total 9 companies received a FDA Warning Letter relating to OOS investigations in the calendar year 2013. Here are some examples of these OOS citations:

• Your firm did not identify, report, or investigate out-of-specification (OOS) results,
  
• Your firm released multiple lots of finished products despite the failure of these lots to meet acceptance criteria,
  
• Your firm selectively reported only the passing retest values in the final assay results,
  
• Provide a summary report of all OOS results that your firm disregarded without conducting an investigation. Thoroughly investigate all OOS results, including testing of the reserve samples if necessary, and provide your conclusions in the report,
  
• Describe the corrective actions you will take against all batches for which a non-conforming result was obtained,
  
• Your reponse is inadequate because your retrospective investigations lacked scientific evidence to support your hypotheses. 

According to these citations giving adequate attention to out-of-specification (OOS) results in batch release decision continues as one of the dominant themes in 2013 FDA Warning Letters.

In order to assist the pharmaceutical industry in a FDA/GMP-compliant handling of OOS Results the ECA Quality Control Working Group established a general SOP for the handling of OOS results. This SOP will be presented in the ECA OOS Training Course on 11-12 March 2014 in Vienna, Austria