Out-of-Specification (OOS) investigations MCQs With Answer

Out-of-Specification (OOS) investigations MCQs With Answer are essential for B. Pharm students to understand regulatory expectations, good manufacturing practice (GMP) compliance, and laboratory quality systems. This introduction covers key concepts such as OOS definition, root cause analysis, sampling, analytical method validity, documentation, CAPA, retesting, lot disposition, trend analysis, and regulatory guidance from authorities like FDA and EMA. Knowing how to assess analyst error, instrument malfunction, method suitability, and manufacturing deviations is critical for robust OOS investigation and patient safety. These MCQs will deepen your practical and theoretical knowledge for exams and industrial practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary definition of an Out-of-Specification (OOS) result?

• A result that exceeds the validated limit of detection
• A laboratory result that does not conform to predefined acceptance criteria
• A manufacturing batch with lower yield
• An instrument calibration report outside tolerance

Correct Answer: A laboratory result that does not conform to predefined acceptance criteria

Q2. Which regulatory document is most commonly referenced for OOS laboratory investigations?

• ICH Q8 Pharmaceutical Development
• FDA’s CGMP for Finished Pharmaceuticals guidance
• WHO GMP Annex 2
• European Pharmacopoeia monographs

Correct Answer: FDA’s CGMP for Finished Pharmaceuticals guidance

Q3. What is the first step after obtaining an OOS result in the lab?

• Release the batch with deviation
• Initiate a formal OOS investigation and quarantine the sample/batch
• Perform an immediate CAPA
• Discard the sample and repeat the test

Correct Answer: Initiate a formal OOS investigation and quarantine the sample/batch

Q4. Which of the following is NOT a common phase in OOS investigation?

• Laboratory investigation
• Hypothesis testing and root cause analysis
• Regulatory submission of the method validation report
• Corrective and preventive action (CAPA)

Correct Answer: Regulatory submission of the method validation report

Q5. When investigating OOS, reanalysis of the retained sample is performed to:

• Assure the analyst’s identity
• Confirm whether the original result can be replicated under the same conditions
• Replace the need for root cause analysis
• Generate a new specification

Correct Answer: Confirm whether the original result can be replicated under the same conditions

Q6. Which factor is LEAST likely to cause an analytical OOS result?

• Improper sample preparation
• Instrument malfunction
• Authorized procedural deviation recorded in SOP
• Contaminated reagents

Correct Answer: Authorized procedural deviation recorded in SOP

Q7. In OOS investigations, the term “root cause” refers to:

• The most probable manufacturing defect only
• The underlying reason why the nonconformity occurred and must be addressed
• A statistical outlier to be ignored
• The final disposition of the batch

Correct Answer: The underlying reason why the nonconformity occurred and must be addressed

Q8. Which technique is commonly used for structured root cause analysis in OOS cases?

• Fishbone (Ishikawa) diagram
• Colorimetric analysis
• High-performance liquid chromatography
• Stability testing

Correct Answer: Fishbone (Ishikawa) diagram

Q9. How should outliers be handled during OOS investigations?

• Automatically discard them to calculate mean values
• Investigate their cause and justify any exclusion with documented rationale
• Always include them without comment
• Replace outliers with the closest valid value

Correct Answer: Investigate their cause and justify any exclusion with documented rationale

Q10. Which action is acceptable before a formal OOS investigation concludes?

• Releasing the batch to market
• Retesting using a validated alternative method if justified
• Changing the specification to include the result
• Deleting the original data to avoid confusion

Correct Answer: Retesting using a validated alternative method if justified

Q11. What role does method validation play in OOS investigations?

• It is irrelevant once the method is implemented
• It provides evidence that the analytical method is suitable and helps interpret OOS results
• It guarantees no OOS results will ever occur
• It is only needed for registration dossiers

Correct Answer: It provides evidence that the analytical method is suitable and helps interpret OOS results

Q12. Which documentation is essential when initiating an OOS investigation?

• Only the analyst’s resume
• Complete raw data, chromatograms, sample logs, and instrument logs
• Only the final test report
• Marketing authorization letters

Correct Answer: Complete raw data, chromatograms, sample logs, and instrument logs

Q13. What is a “repeat test” and when is it justified?

• Performing the exact same test on a fresh aliquot; justified when procedural errors are suspected
• Using a different method on a new sample; always justified
• Combining two samples and testing; justified for stability concerns
• Immediate disposal of the sample

Correct Answer: Performing the exact same test on a fresh aliquot; justified when procedural errors are suspected

Q14. Which outcome indicates an acceptable conclusion of an OOS laboratory investigation?

• Root cause cannot be determined, but the batch is released without CAPA
• Identified root cause with documented corrective actions and appropriate disposition
• No investigation performed and results ignored
• Spec limits are widened to include the result

Correct Answer: Identified root cause with documented corrective actions and appropriate disposition

Q15. What is the significance of a “retained sample” in OOS scenarios?

• It is used for routine QC only
• It provides material for repeat analysis and confirmatory tests during investigation
• It must be discarded immediately after testing
• It is used as a calibration standard

Correct Answer: It provides material for repeat analysis and confirmatory tests during investigation

Q16. Which statistical tool is helpful for detecting trends that may lead to OOS results?

• Control charts (e.g., Shewhart X-bar chart)
• Simple counts without time axis
• Only visual inspection of chromatograms
• Mass balance calculations only

Correct Answer: Control charts (e.g., Shewhart X-bar chart)

Q17. If an analyst records a transcription error that led to an OOS, the investigation should:

• Ignore the error because the instrument was working
• Document the error, retrain as needed, and implement CAPA if systemic
• Terminate the analyst immediately without further review
• Alter the raw data to match expected values

Correct Answer: Document the error, retrain as needed, and implement CAPA if systemic

Q18. Which of the following is an acceptable confirmatory action for dissolution OOS?

• Changing the dissolution medium without validation
• Performing dissolution on retained units and checking apparatus performance
• Assuming manufacturing caused the issue without lab checks
• Releasing product based on visual inspection

Correct Answer: Performing dissolution on retained units and checking apparatus performance

Q19. What does CAPA stand for and why is it important in OOS investigations?

• Corrective Action and Preventive Action; to address root causes and prevent recurrence
• Calibration and Preventive Action; for instruments only
• Corrective Assessment of Process Ability; for process yield
• Critical Analysis of Performance Attributes; for marketing

Correct Answer: Corrective Action and Preventive Action; to address root causes and prevent recurrence

Q20. When should the Quality Unit (QU) be involved in an OOS investigation?

• Only after the investigation is complete
• Immediately upon identification of an OOS to oversee and approve the investigation
• Only for final product release, not investigations
• Never, investigations are purely laboratory tasks

Correct Answer: Immediately upon identification of an OOS to oversee and approve the investigation

Q21. Which instrument-related documentation is most relevant during an OOS investigation?

• Instrument service history, calibration certificates, and maintenance logs
• Only the instrument model number
• Vendor marketing brochures
• Employee payroll records

Correct Answer: Instrument service history, calibration certificates, and maintenance logs

Q22. How should a company handle a confirmed OOS that affects product safety?

• Immediately notify regulatory authorities as required and initiate recalls if necessary
• Keep information internal to avoid regulatory scrutiny
• Wait for quarterly review before action
• Issue a press release without investigation

Correct Answer: Immediately notify regulatory authorities as required and initiate recalls if necessary

Q23. Which is an appropriate confirmatory test strategy after an OOS for assay by HPLC?

• Use an unrelated method without validation
• Perform assay on retained sample using the same validated method and, if needed, an orthogonal validated method
• Only check the instrument with a service engineer and skip retesting
• Adjust chromatogram peak integration arbitrarily

Correct Answer: Perform assay on retained sample using the same validated method and, if needed, an orthogonal validated method

Q24. Which personnel action is appropriate if an analyst is repeatedly associated with OOS results?

• Ignore trends to protect staff
• Conduct performance review, retraining, and investigate for systemic issues
• Terminate without investigation
• Transfer responsibility to another department without root cause analysis

Correct Answer: Conduct performance review, retraining, and investigate for systemic issues

Q25. What is the importance of chain-of-custody records in OOS investigations?

• They are unnecessary if samples are labeled
• They document sample handling, custody, and ensure integrity during investigation
• They are only required for controlled substances
• They replace raw analytical data

Correct Answer: They document sample handling, custody, and ensure integrity during investigation

Q26. Which scenario suggests a manufacturing rather than laboratory cause for an OOS result?

• Instrument failure during analysis
• Multiple units from the same batch failing specification during independent retesting
• Analyst handwriting errors in the logbook
• Degraded reagent lot used only in the lab

Correct Answer: Multiple units from the same batch failing specification during independent retesting

Q27. In documentation of OOS investigations, what is critical for regulatory inspection readiness?

• Brief verbal summaries only
• Complete, contemporaneous records with rationale, corrective actions, and approvals
• Only final conclusions without raw data
• Separate undocumented investigator notes

Correct Answer: Complete, contemporaneous records with rationale, corrective actions, and approvals

Q28. How should stability OOS findings be addressed compared to release testing OOS?

• Stability OOS can be ignored if release tests pass
• Stability OOS require investigation, possible shelf-life reassessment, and notification if safety is impacted
• Only release testing OOS need CAPA
• Stability OOS only affect packaging

Correct Answer: Stability OOS require investigation, possible shelf-life reassessment, and notification if safety is impacted

Q29. What is an “investigation hypothesis” in the OOS process?

• An untestable accusation against the analyst
• A proposed explanation for the OOS that can be tested and confirmed or rejected
• A regulatory citation
• A finalized CAPA plan

Correct Answer: A proposed explanation for the OOS that can be tested and confirmed or rejected

Q30. Which practice helps reduce frequency of OOS results in a quality lab?

• Skipping routine maintenance to save time
• Robust training, regular instrument calibration, validated methods, and trend monitoring
• Not documenting deviations to avoid bureaucracy
• Using unqualified reagents to minimize costs

Correct Answer: Robust training, regular instrument calibration, validated methods, and trend monitoring

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com