OOS培训教材-2003-en.ppt

Out of Specification (OOS) Test Results ????? ????? ? ?? 2003? 8? 25? OOS (Out of Specification) The failure of a batch or any of its components to meet any of its specifications OOS indicates non-compliance with specifications Outliers Statistically invalid individual test result Can be eliminated OOS – General Principles How should we handle OOS results? OOS cannot be ignored or discounted without basis When does testing stop (accept the result) First test failure? Second test failure? Tenth test failure? Barr Decision (1993) cGMP regulations are vague about exactly how to handle OOS 1993? Barr Laboratories, Inc United States District Court for the District of New Jersey Jurdge Wolin made it clear what is acceptable and what is not acceptable in handling OOS What does the cGMP Regulation say about Handling OOS Results? cGMP Part 211.192 The failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated… The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure of discrepancy… cGMP Part 211.194 A written record of the investigation shall include the conclusions and follow-up… A complete record of all data secured in the course of each test… Complete records shall be maintained of all stability testing performed… Barr Decision Failure investigation is central Failure investigation Immediate Timely follow-up Appropriate resolution Documented FDA: Interpretation of investigation results Batch acceptance or rejection must be based on scientific justification Overall body of data must be considered in judging the batch Essence of Barr Labs Decision Include all suspect results that fall outside established specifications Drug testing Drug companies must Validate their processes and Ensure the quality of the batch for release Out-of-Specification Better word than “failure” for non-passing results Essence of Barr Labs Dec