Team: Review and approve the investigation reports and corrective actions for OOS results.

Laboratory Manager: Ensure proper execution of tests and initial review of OOS results.

Procedure

1. Initial Identification of OOS Results:
   • Immediately document any result that falls outside the predefined specifications or shows abnormal trends.
   • Notify the Stability
     

     “Mastering Stability Testing for Pharmaceutical Excellence – A Comprehensive Guide for Optimum Drug Development”

     Manager and Laboratory Manager of the OOS result.
   • Quarantine the affected batch or sample to prevent further testing or use until the investigation is complete.
2. Preliminary Investigation:
   • Review the test method, equipment calibration, and analyst’s training records to identify any immediate errors or issues.
   • Examine raw data, including chromatograms, instrument printouts, and calculations, to verify accuracy.
   • Interview the analyst to understand any procedural deviations or unusual observations during testing.
   • Document all findings from the preliminary investigation.
3. Hypothesis Testing:
   • Formulate potential causes for the OOS result based on the preliminary investigation.
   • Design and conduct additional tests to confirm or refute each hypothesis, such as retesting the original sample or testing a new sample from the same batch.
   • Ensure that all retesting follows the same protocol as the original test.
   • Document the results and conclusions of hypothesis testing.
4. Comprehensive Investigation:
   • If the preliminary and hypothesis testing do not resolve the OOS result, initiate a comprehensive investigation.
   • Examine broader factors such as raw material quality, manufacturing processes, and storage conditions.
   • Conduct a thorough review of batch records, stability protocols, and environmental controls.
   • Document all steps, findings, and conclusions of the comprehensive investigation.
5. Corrective and Preventive Actions (CAPA):
   • Based on the investigation findings, identify root causes and implement corrective actions to address the specific issue.
   • Develop preventive actions to avoid recurrence, such as revising SOPs, retraining personnel, or updating equipment maintenance schedules.
   • Document the CAPA plan and obtain approval from the Stability Manager and QA Team.
   • Monitor the effectiveness of CAPA through follow-up testing and audits.
6. Reporting and Documentation:
   • Prepare a comprehensive investigation report that includes:
     • Description of the OOS result and initial observations
     • Details of the preliminary and comprehensive investigations
     • Hypotheses tested and their outcomes
     • Root cause analysis and CAPA plan
     • Approval signatures from the Stability Manager and QA Team
   • Ensure that the final report is reviewed and approved by the Stability Manager and QA Team.
   • Store the investigation report in the stability study records and ensure it is accessible for regulatory review.

Abbreviations Used

• OOS: Out-of-Specification
• QA: Quality Assurance
• SOP: Standard Operating Procedure
• CAPA: Corrective and Preventive Actions

Documents

• Stability Protocol
• Laboratory Notebooks/Electronic Data Systems
• Investigation Reports
• CAPA Records
• Audit Reports

References

• ICH Q1A(R2) Stability Testing of New Drug Substances and Products
• FDA Guidance for Industry: Investigating OOS Test Results for Pharmaceutical Production

SOP Version

Version 1.0 – Effective Date: [Insert Date]