Definition of OOT and OOS Results
- Regulatory “out-of” definitions
- atypical, suspect, out-of-trend, out-of-expectation, out-of-specification
- Reportable value
- Error types (random, systematic)
- How can they be distinguished?
- Normal or abnormal?
- (Normal) distribution of data
Establishing OOT Limits for Release Testing
- Statistical approaches
- Empirical approaches
- Control charts
Establishing OOT Limits for Stability Testing
- Impact of OOT results in stability studies (ICH studies, ongoing stability)
- Introducing a second dimension (“normal” stability trend)
- Statistical approaches
- 95% prediction interval of the linear regression
- Regression control chart
- Time-point method
Management of OOT and OOS Results in the Quality Control Laboratory
- FDA Guidance and European requirements (EU GMP Guide, MHRA, PIC/S)
- Importance of a clear terminology (reportable value, re-analysis, retest, re-sampling)
- Investigation pathway: OOS identification & decisions
- Phase I: Initial laboratory investigation
- Phase II: Full scale investigation
- Phase IIA: Review in production
- Phase IIB: Additional laboratory testing (retests, averaging)
- Variability and OOS
- Reporting and documentation
- Appropriate response to OOS observations in inspections
Workshop
Evaluation and commenting of OOS examples