Out-of-Specification (OOS) Investigations – GMP Compliance & Practical Implementation
Course Description This course provides in-depth knowledge and practical guidance on managing Out-of-Specification (OOS) results in accordance with FDA, EU GMP, and ICH expectations. Participants will learn how to properly identify, investigate, document, conclude, and trend OOS results while ensuring data integrity and regulatory compliance.
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Course Description This course provides in-depth knowledge and practical guidance on managing Out-of-Specification (OOS) results in accordance with FDA, EU GMP, and ICH expectations. Participants will learn how to properly identify, investigate, document, conclude, and trend OOS results while ensuring data integrity and regulatory compliance.
2. Module 1: Introduction to OOS
Definition of Out-of-Specification (OOS)
Difference between:
OOS
Out-of-Trend (OOT)
Atypical / Aberrant results
Why OOS management is critical for GMP compliance
Impact of OOS on product quality, patient safety, and business
3. Module 2: Regulatory Expectations
FDA Guidance for Industry: Investigating OOS Test Results
EU GMP expectations (Chapter 1, Chapter 6)
ICH Q7, Q9, Q10 relevance
Warning letters and inspection trends related to OOS
Data integrity considerations in OOS investigations
4. Module 3: Types of OOS Results
Laboratory-related OOS
Manufacturing-related OOS
Stability study OOS
Raw material and packaging material OOS
In-process vs finished product OOS
5. Module 4: Initial OOS Assessment
Immediate actions after observing an OOS
Phase I investigation overview
Checking:
Calculation errors
Instrument calibration
System suitability
Sample preparation errors
Role of analyst, supervisor, and QA
Documentation requirements at this stage
6. Module 5: Laboratory Investigation (Phase I)
• Analyst self-check requirements
• Review of:
o Test method
o SOP compliance
o Instrument logs
o Chromatograms / raw data
• Invalidating test results – when is it justified?
• Retesting vs resampling: regulatory expectations
7. Module 6: Full-Scale Investigation (Phase II)
• When to escalate to Phase II
• Manufacturing process review
• Review of:
o Batch manufacturing records
o Environmental monitoring data
o Equipment logs and cleaning records
• Role of cross-functional teams
• Scientific justification vs speculation
8. Module 7: Root Cause Analysis (RCA)
• Importance of true root cause identification
• RCA tools:
o 5 Why analysis
o Fishbone (Ishikawa) diagram
o Fault Tree Analysis
• Common root causes in OOS investigations
• Linking root cause to CAPA
9. Module 8: Retesting, Resampling & Averaging
• FDA position on retesting
• Invalid practices (testing into compliance)
• When re-sampling is acceptable
• Prohibition of result averaging
• Proper documentation and approvals
10. Module 9: Batch Disposition Decisions
• Impact of OOS on batch release
• QA responsibilities
• Scientific rationale for:
o Batch rejection
o Reprocessing
o Reworking
• Handling distributed batches
11. Module 10: CAPA Management
• Designing effective CAPA
• Preventive vs corrective actions
• CAPA effectiveness checks
• Linking OOS trends to continuous improvement
• Integration with QMS (Change Control, Risk Management)
12. Module 11: OOS Documentation & Reporting
• OOS investigation report structure
• Required elements:
o Description
o Investigation summary
o Root cause
o CAPA
o Conclusion
• Data integrity and ALCOA+ principles
• QA review and approval
13. Module 12: Trending and Periodic Review
• OOS and OOT trending requirements
• Statistical tools for trend analysis
• Management review and escalation criteria
• Regulatory expectations for periodic review
14. Module 13: Common Deficiencies & Inspection Findings
• Frequent FDA 483 observations related to OOS
• Examples of poor investigations
• How to defend OOS investigations during audits
• Best practices for inspection readiness
15. Module 14: Practical Case Studies
• Laboratory error vs true product failure
• Stability OOS case study
• Manufacturing deviation leading to OOS
• Interactive decision-making scenarios
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