Out-of-specification (OOS) investigation MCQs With Answer

Introduction

This quiz collection on Out-of-Specification (OOS) investigations is designed specifically for M.Pharm students studying Good Regulatory Practices. It covers practical and regulatory aspects of handling analytical results that fall outside established acceptance criteria. Questions focus on laboratory investigations, root-cause analysis, retesting principles, documentation, CAPA, data integrity, sampling, stability failures, and interactions between QC and QA during investigations. The aim is to deepen understanding beyond definitions — emphasizing when to escalate, how to document findings, and how regulators expect firms to respond. Use these MCQs to test knowledge, identify learning gaps, and prepare for real-world regulatory inspection scenarios.

Q1. What best defines an Out-of-Specification (OOS) result in pharmaceutical analysis?

• A result that is slightly different from historical lab values
• A result that fails to meet pre-established acceptance criteria for a test
• A result that is within specification but unexpected
• A result obtained from an expired analytical method

Correct Answer: A result that fails to meet pre-established acceptance criteria for a test

Q2. According to regulatory guidance, what is the appropriate first action when an OOS result is obtained?

• Immediately discard the batch and inform regulatory authorities
• Perform an immediate initial laboratory investigation to determine potential laboratory or analytical errors
• Automatically perform a full recall of distributed product
• Retest the sample repeatedly until a passing result is obtained

Correct Answer: Perform an immediate initial laboratory investigation to determine potential laboratory or analytical errors

Q3. How does an Out-of-Trend (OOT) result differ from an OOS result?

• OOT indicates the result is outside specification limits; OOS is within limits
• OOT is a trend deviation that may still be within specification; OOS is outside specification limits
• OOT relates only to stability studies; OOS relates only to release testing
• OOT always requires regulatory reporting, OOS does not

Correct Answer: OOT is a trend deviation that may still be within specification; OOS is outside specification limits

Q4. When is retesting permissible after observing an OOS result?

• Retesting is always permissible until a passing result is achieved
• Retesting is allowed only after a documented initial laboratory investigation that does not identify an assignable laboratory error and per predefined retest criteria
• Retesting is never allowed under any circumstance
• Retesting is allowed only if the analyst requests it informally

Correct Answer: Retesting is allowed only after a documented initial laboratory investigation that does not identify an assignable laboratory error and per predefined retest criteria

Q5. Who should be involved in a full-scale OOS investigation for a manufacturing batch?

• The laboratory analyst alone
• Only Quality Assurance (QA)
• A cross-functional team including QC, QA, production, and technical experts
• The regulatory inspector only

Correct Answer: A cross-functional team including QC, QA, production, and technical experts

Q6. Which of the following is NOT a common root-cause category for OOS results?

• Sampling error
• Analytical method failure
• Manufacturing process deviation
• Regulatory agency policy changes

Correct Answer: Regulatory agency policy changes

Q7. What is the appropriate immediate action if an OOS microbiological limit test indicates contamination?

• Ignore the result if the product looks normal
• Quarantine the batch, notify QA, initiate a full-scale investigation, and assess patient safety risk
• Immediately dispose of all raw materials without investigation
• Release the product but increase the release frequency

Correct Answer: Quarantine the batch, notify QA, initiate a full-scale investigation, and assess patient safety risk

Q8. Which documentation must be retained as part of an OOS investigation file?

• Only the final conclusion and CAPA
• All raw data, investigation findings, root cause analysis, corrective/preventive actions, and final conclusion
• Only the analyst’s notes
• Only electronic data summaries without raw chromatograms

Correct Answer: All raw data, investigation findings, root cause analysis, corrective/preventive actions, and final conclusion

Q9. Under what circumstances is invalidation of an OOS result acceptable?

• Whenever the result is inconvenient for batch release
• Only when there is clear documented evidence of a laboratory error, sample mix-up, or analytical anomaly that invalidates the result
• Whenever production requests it
• When trending shows similar values historically

Correct Answer: Only when there is clear documented evidence of a laboratory error, sample mix-up, or analytical anomaly that invalidates the result

Q10. Which of the following is an inappropriate practice when handling an initial OOS result?

• Conducting an initial laboratory investigation to look for analytical errors
• Averaging multiple retest results to artificially bring the mean within specification without justification
• Documenting all analytical data and deviations
• Involving QA and production for a full-scale investigation if no lab error is found

Correct Answer: Averaging multiple retest results to artificially bring the mean within specification without justification

Q11. How should trending data be used in the context of OOS investigations?

• Trending is irrelevant to OOS investigations
• Trends should be monitored to detect systematic shifts, help identify root causes, and prevent recurrence of OOS
• Only final release dates should be trended
• Trend analyses should be performed only for stability studies

Correct Answer: Trends should be monitored to detect systematic shifts, help identify root causes, and prevent recurrence of OOS

Q12. Which sampling-related issue commonly causes false OOS results?

• Correct chain-of-custody documentation
• Representative sampling and proper sample handling
• Improper sample size, non-representative sampling, or contamination during sampling
• Using validated analytical methods

Correct Answer: Improper sample size, non-representative sampling, or contamination during sampling

Q13. If a stability test yields an OOS result for a released product, what should the manufacturer do first?

• Immediately recall all marketed product without assessment
• Initiate an investigation, evaluate the impact on product quality and patient safety, and determine whether regulatory notification or recall is required
• Ignore the result because the product was already released
• Change the specification to include the stability result

Correct Answer: Initiate an investigation, evaluate the impact on product quality and patient safety, and determine whether regulatory notification or recall is required

Q14. Why is maintaining chain-of-custody important for samples related to OOS investigations?

• It speeds up testing time
• It ensures sample identity, prevents unauthorized access, and supports data integrity during the investigation
• It allows anyone to alter data as needed
• It is only required for controlled substances

Correct Answer: It ensures sample identity, prevents unauthorized access, and supports data integrity during the investigation

Q15. What is the primary purpose of implementing CAPA following an OOS investigation?

• To assign blame to an individual
• To identify root cause(s), implement corrective actions to fix the current issue, and preventive actions to avoid recurrence
• To delay batch release indefinitely
• To satisfy auditors only with paperwork

Correct Answer: To identify root cause(s), implement corrective actions to fix the current issue, and preventive actions to avoid recurrence

Q16. Which finding during method validation suggests the analytical method may be unsuitable and could contribute to OOS results?

• High precision, good recovery, and linear response
• High variability, poor recovery, and lack of specificity
• Complete documentation of validation parameters
• Robustness across typical operating ranges

Correct Answer: High variability, poor recovery, and lack of specificity

Q17. Are all OOS results required to be reported immediately to regulatory authorities?

• Yes — every single OOS must be immediately reported to regulators
• No — not all OOS require immediate external reporting; reporting depends on impact, regulatory thresholds, and local requirements
• Only OOT results must be reported
• OOS results should never be reported to regulators

Correct Answer: No — not all OOS require immediate external reporting; reporting depends on impact, regulatory thresholds, and local requirements

Q18. Which of the following is a critical data integrity concern discovered during OOS investigations?

• Proper archiving of raw data
• Backdating, deletion of raw data, or unauthorized data manipulation
• Transparent audit trails
• Validated electronic systems

Correct Answer: Backdating, deletion of raw data, or unauthorized data manipulation

Q19. What is the difference between confirmation testing and invalidation during an OOS investigation?

• Confirmation testing verifies the result by repeat analysis under controlled conditions; invalidation is declaring the original result invalid due to proven analytical error
• Confirmation testing always uses the same analyst and conditions that produced the OOS
• Invalidation means the batch is released
• There is no difference — both are the same process

Correct Answer: Confirmation testing verifies the result by repeat analysis under controlled conditions; invalidation is declaring the original result invalid due to proven analytical error

Q20. Which combination represents best practices to prevent OOS occurrences in QC laboratories?

• Reducing method validation, minimal training, and no equipment maintenance
• Comprehensive method validation, competent training, representative sampling, routine equipment qualification and maintenance, and trending of results
• Only relying on historical analyst experience and infrequent audits
• Eliminating SOPs to speed up testing

Correct Answer: Comprehensive method validation, competent training, representative sampling, routine equipment qualification and maintenance, and trending of results

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