Calibration and validation as per USFDA guidelines MCQs With Answer

Calibration and validation are core quality activities in pharmaceutical analysis, and USFDA guidelines frame expectations for reliable equipment and validated methods. This concise primer offers B.Pharm students clear insight into instrument calibration, analytical method validation, IQ/OQ/PQ equipment qualification, validation protocols, and key parameters like accuracy, precision, specificity, linearity, range, LOD/LOQ, robustness, and system suitability. Emphasis on documentation, SOPs, traceability, risk-based calibration frequency, and regulatory compliance (USFDA, ICH) prepares students for lab practice, audits, and batch release. Practical MCQs reinforce understanding of validation lifecycle, revalidation triggers, and computerized system validation. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary purpose of calibration in a pharmaceutical laboratory?

• To change the method procedure to fit the instrument
• To establish the relationship between instrument readings and known standards
• To validate a new analytical method
• To document batch release

Correct Answer: To establish the relationship between instrument readings and known standards

Q2. Which activity is described as “validation” under USFDA expectations?

• Routine maintenance of instruments
• Demonstrating that a process or method produces results meeting predetermined acceptance criteria
• Calibration of measurement standards
• Issuing calibration certificates

Correct Answer: Demonstrating that a process or method produces results meeting predetermined acceptance criteria

Q3. Which document outlines the three stages of process validation as per USFDA guidance?

• 21 CFR Part 11
• USFDA Process Validation guidance (Process Design, Process Qualification, Continued Process Verification)
• ICH Q3A
• USP General Chapter on Sterility

Correct Answer: USFDA Process Validation guidance (Process Design, Process Qualification, Continued Process Verification)

Q4. What does IQ/OQ/PQ stand for in equipment qualification?

• Installation Qualification, Operational Qualification, Performance Qualification
• Initial Qualification, Ongoing Qualification, Periodic Qualification
• Instrument Quick-test, Operational Quick-test, Performance Quick-test
• Integrity Qualification, Optimization Qualification, Protocol Qualification

Correct Answer: Installation Qualification, Operational Qualification, Performance Qualification

Q5. Which parameter assesses closeness of measured value to true value in analytical validation?

• Precision
• Specificity
• Accuracy
• Robustness

Correct Answer: Accuracy

Q6. Precision in analytical validation commonly includes which of the following?

• Linearity and range
• Repeatability, intermediate precision and reproducibility
• LOD and LOQ only
• Specificity and selectivity

Correct Answer: Repeatability, intermediate precision and reproducibility

Q7. Which guidance is typically referenced for analytical method validation parameters like linearity, accuracy and precision?

• ICH Q2(R1)
• ICH Q8
• 21 CFR Part 211
• WHO GMP Annex 1

Correct Answer: ICH Q2(R1)

Q8. What is the purpose of system suitability tests in chromatography?

• To calibrate the instrument detector wavelength
• To confirm the system performance is adequate for the intended analysis before sample testing
• To determine expiry of reagents
• To certify analyst qualification

Correct Answer: To confirm the system performance is adequate for the intended analysis before sample testing

Q9. Limit of Detection (LOD) is best defined as:

• The highest concentration reliably measured
• The lowest analyte concentration that can be detected but not necessarily quantified
• The validated calibration range
• The amount used for system suitability

Correct Answer: The lowest analyte concentration that can be detected but not necessarily quantified

Q10. Which factor is NOT typically part of method robustness testing?

• Small deliberate variations in pH
• Minor changes in mobile phase composition
• Changing the active pharmaceutical ingredient
• Temperature variations

Correct Answer: Changing the active pharmaceutical ingredient

Q11. When should revalidation be considered according to good practice?

• Only when equipment is replaced
• After significant changes to process, method, equipment, or when trending indicates drift
• Every ten years regardless of changes
• Only during regulatory inspections

Correct Answer: After significant changes to process, method, equipment, or when trending indicates drift

Q12. Traceability of standards means:

• Standards are kept in a locked cabinet
• Results can be linked to national or international reference materials through an unbroken chain of calibrations
• Standards have no documented source
• Standards are prepared fresh weekly

Correct Answer: Results can be linked to national or international reference materials through an unbroken chain of calibrations

Q13. Which document typically initiates a validation activity in a laboratory?

• Validation Master Plan (VMP) or Validation Protocol
• Purchase order for reagents
• Analyst training certificate
• Daily equipment logbook

Correct Answer: Validation Master Plan (VMP) or Validation Protocol

Q14. In calibration certificates, which information is essential?

• Instrument model only
• Calibration date, calibration results, uncertainty, and traceability to standards
• Analyst salary
• Lab cleanliness rating

Correct Answer: Calibration date, calibration results, uncertainty, and traceability to standards

Q15. Which is the best approach to determine calibration frequency?

• Fixed annual schedule for all instruments
• Risk-based approach considering instrument criticality, usage, and historical drift
• Only when an instrument fails
• After every sample analysis

Correct Answer: Risk-based approach considering instrument criticality, usage, and historical drift

Q16. Specificity/selectivity in method validation means:

• Ability to measure the analyte response independent of other components
• Precision of replicate measurements
• Linearity over a narrow concentration range
• Speed of analysis

Correct Answer: Ability to measure the analyte response independent of other components

Q17. Which is a common acceptance criterion for method precision?

• Relative standard deviation (RSD) within predefined limits such as ≤2% or method-specific criteria
• Absolute difference of measurements must be zero
• Any variation is acceptable if mean is correct
• Precision is not evaluated in validation

Correct Answer: Relative standard deviation (RSD) within predefined limits such as ≤2% or method-specific criteria

Q18. Forced degradation studies are performed to:

• Reduce the shelf-life of the product
• Assess method specificity and to generate degradation products for stability-indicating methods
• Calibrate HPLC columns
• Determine instrument LOD

Correct Answer: Assess method specificity and to generate degradation products for stability-indicating methods

Q19. Which statement best differentiates qualification from validation?

• Qualification is for methods; validation is for equipment
• Qualification demonstrates equipment is installed and operates; validation demonstrates the process/method meets requirements consistently
• They are identical activities with different names
• Qualification is optional while validation is mandatory

Correct Answer: Qualification demonstrates equipment is installed and operates; validation demonstrates the process/method meets requirements consistently

Q20. Which regulatory requirement applies specifically to electronic records and signatures relevant to computerized validation?

• ICH Q2(R1)
• 21 CFR Part 11
• USP monograph numbering
• GMP Annex on Sterility

Correct Answer: 21 CFR Part 11

Q21. During analytical method transfer between labs, what is essential?

• No documentation is required
• Demonstration of equivalence through protocol, acceptance criteria, and comparative data
• Only a phone call confirmation
• Discarding validation data from the transferring lab

Correct Answer: Demonstration of equivalence through protocol, acceptance criteria, and comparative data

Q22. What role do SOPs play in calibration and validation?

• SOPs are not necessary if staff are trained
• SOPs provide standardized procedures, responsibilities, and documentation requirements to ensure consistent execution
• SOPs replace calibration certificates
• SOPs are used only for reagent preparation

Correct Answer: SOPs provide standardized procedures, responsibilities, and documentation requirements to ensure consistent execution

Q23. Which statistical tool is commonly used to monitor calibration drift over time?

• Control charts (e.g., Shewhart or Levey-Jennings charts)
• Kaplan-Meier plots
• Fourier transforms
• Venn diagrams

Correct Answer: Control charts (e.g., Shewhart or Levey-Jennings charts)

Q24. In validation reports, what is the importance of “uncertainty” stated for calibration?

• It indicates the analyst’s confidence interval and helps interpret if measurement differences are significant
• It is used to change the method SOP
• It is only useful for financial audits
• Uncertainty is not reported for calibrated instruments

Correct Answer: It indicates the analyst’s confidence interval and helps interpret if measurement differences are significant

Q25. Which is a trigger for revalidation of an analytical method?

• Minor change in document font
• Change in raw material supplier that may affect method performance
• Completion of routine calibration
• Weekly analyst rotations

Correct Answer: Change in raw material supplier that may affect method performance

Q26. Which of the following is TRUE about method linearity?

• Linearity assesses accuracy at a single concentration only
• Linearity evaluates the method response proportionality across a specified concentration range
• Linearity is unrelated to calibration curve
• Linearity is only required for dissolution testing

Correct Answer: Linearity evaluates the method response proportionality across a specified concentration range

Q27. Which element is essential in a validation protocol?

• Acceptance criteria and test plan with sampling and statistical approach
• Only a descriptive title with no test details
• Signature of the analyst only without dates
• List of unrelated SOPs

Correct Answer: Acceptance criteria and test plan with sampling and statistical approach

Q28. For chromatographic methods, which parameter is used to assess peak separation?

• Resolution (Rs)
• LOD
• Accuracy percentage
• Calibration certificate number

Correct Answer: Resolution (Rs)

Q29. Why is computerized system validation (CSV) important in modern labs?

• CSV is optional and rarely recommended
• To ensure software and systems reliably perform intended tasks, maintain data integrity, and comply with regulations
• To replace traditional method validation entirely
• Only to validate antivirus software

Correct Answer: To ensure software and systems reliably perform intended tasks, maintain data integrity, and comply with regulations

Q30. If an instrument fails calibration acceptance criteria, the immediate correct action is:

• Use the instrument anyway and note the failure in the report
• Quarantine the instrument, investigate cause, determine impact on results, and take corrective action before use
• Ignore and recalibrate later
• Change the calibration certificate date to pass

Correct Answer: Quarantine the instrument, investigate cause, determine impact on results, and take corrective action before use

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