27 September 2022
Dr Joachim Ermer, Ermer Quality Consulting, Germany
Out-of-specification (OOS) test results and their appropriate management is an important topic in pharmaceutical Quality Control and inevitably in the focus of any inspection and audit. The purpose of the seminar is providing an overview on regulatory expectations, which are mainly based on the FDA Guidance for Industry “Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production”, as well as practical recommendations for a GMP-conform investigation.
Although the FDA-Guidance on OOS-results provides detailed instructions how to manage results outside specification, observations and deficiencies dealing with OOS results is still a major issue in inspections, FDA 483s and Warning Letters.
In the speaker’s experience, an important aspect is to establish a clear terminology to facilitate understanding of the investigation phases and the appropriate testing approaches.
Of course, “prevention is better than cure”. For this purpose, it is important to avoid OOS-results, for example by means of a suitable identification of atypical or out-of-trend (OOT) results. The participants will learn how to identify OOT-results and how to establish suitable OOT-limits
This Live Online Training is aimed at executives and employees from quality control, quality assurance, production, regulatory and audit functions who want to gain a better understanding of the GMP requirements for the management of OOS-results and how to establish OOT-limits to better prevent OOS-results.
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
Evaluation and commenting of OOS examples
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