FDA requirements on oos investigation in pharmaceutical industry

The FDA outlines expectations for investigating Out-of-Specification (OOS) test results in the pharmaceutical industry through its guidance document: 

"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigating-out-specification-oos-test-results-pharmaceutical-production-level-2-revision".

Here's a breakdown of the key requirements:

Whenever an OOS result is obtained, an investigation must be conducted (§ 211.192). An OOS result refers to any test result falling outside the established specifications or acceptance criteria. This applies to:

• Tests on active pharmaceutical ingredients (APIs)
• Excipients and other components
• In-process materials
• Finished drug products

The investigation should determine the source of the OOS result:

• Was it an error in the measurement process (analytical aberration)?
• Did it originate from an aberration in the manufacturing process?

The investigation should be:

• Scientifically sound: Based on scientific principles and methodologies.
• Thorough: Comprehensively evaluate all potential factors.
• Timely: Investigate promptly to minimize delays and potential impact.
• Unbiased: Objectively assess all available data.
• Well-documented: Maintain detailed records of the investigation process and findings.

The FDA recommends a two-phased approach:

• Phase I: Laboratory Investigation

  • Review the test method with laboratory personnel.
  • Verify the analyst's performance of the test procedure.
  • Examine raw data and identify anomalies.
  • Confirm calculations and absence of unauthorized changes.
  • Ensure proper use of reference standards, solvents, and reagents.
  • Evaluate the test method's performance compared to validation data.

• Phase II: Full-Scale OOS Investigation (if necessary)

  • This may involve a production process review and/or additional laboratory work.
  • The goal is to identify the root cause of the OOS and take corrective and preventive actions (CAPA).
  • The investigation may need to expand beyond the laboratory if the cause is suspected to originate in the manufacturing process.
  • The impact of the OOS result on already distributed batches needs to be evaluated.

Overall, the focus of the OOS investigation is to:

• Understand the cause of the OOS result.
• Prevent similar occurrences in the future.
• Ensure the quality and safety of the drug product.

Additional Notes:

• The specific requirements for OOS investigations may vary depending on the complexity of the product and the severity of the OOS result.
• Pharmaceutical companies should have established procedures for conducting OOS investigations.
• Consulting the full FDA guidance document is recommended for a more comprehensive understanding of the expectation.

Also Read:

Investigating Out-of-Specification (OOS) Test Results: A Comprehensive Guide

OOT (Out-of-trend) in Pharma : Identification, Investigation, Overview

OOS In Pharma: OOS Investigation, Laboratory Investigation, Detailed Review