Calibration and validation as per ICH guidelines MCQs With Answer

Calibration and validation are core topics in pharmaceutical quality systems, central to ICH guidelines and vital for B.Pharm students entering analytical and quality assurance roles. Calibration ensures instruments deliver accurate, traceable measurements via IQ/OQ/PQ, routine checks, and documented calibration certificates. Validation—especially analytical method validation as per ICH Q2(R1)—confirms methods are fit for purpose by assessing accuracy, precision, specificity, linearity, range, LOD/LOQ, and robustness. Understanding system suitability, measurement uncertainty, revalidation triggers, GMP/GLP expectations, and risk-based approaches links theory to practical SOPs and regulatory compliance. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which ICH guideline primarily addresses analytical method validation?

• ICH Q1A(R2)
• ICH Q2(R1)
• ICH Q9
• ICH Q7

Correct Answer: ICH Q2(R1)

Q2. What is the main purpose of instrument calibration in a pharmaceutical laboratory?

• To validate the analytical method
• To ensure instruments provide accurate, traceable measurements
• To reduce sample preparation time
• To establish product stability

Correct Answer: To ensure instruments provide accurate, traceable measurements

Q3. Which validation characteristic assesses the closeness of measured values to the true value?

• Precision
• Specificity
• Accuracy
• Robustness

Correct Answer: Accuracy

Q4. In calibration terminology, what does IQ/OQ/PQ stand for?

• Initial Qualification / Operational Qualification / Performance Qualification
• Instrument Quality / Operational Quality / Performance Quality
• Installation Qualification / Operational Qualification / Performance Qualification
• Installation Quality / Optimal Qualification / Performance Qualification

Correct Answer: Installation Qualification / Operational Qualification / Performance Qualification

Q5. Which validation parameter evaluates the method’s ability to measure the analyte in presence of other components?

• Linearity
• Specificity
• Precision
• Range

Correct Answer: Specificity

Q6. What is the best definition of Limit of Detection (LOD)?

• The highest concentration the method can accurately measure
• The lowest concentration that can be reliably quantified with acceptable precision
• The lowest concentration that can be detected but not necessarily quantified
• The concentration at the midpoint of the calibration curve

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

Q7. Which parameter describes the method’s ability to produce similar results under the same conditions?

• Accuracy
• Specificity
• Precision
• Robustness

Correct Answer: Precision

Q8. Which of the following is a typical system suitability test for HPLC?

• Retention time stability, theoretical plates, tailing factor
• Melting point determination
• pH indicator strip test
• Friability testing

Correct Answer: Retention time stability, theoretical plates, tailing factor

Q9. When is revalidation of an analytical method required?

• Only when the lab gets a new analyst
• After any change that may affect method performance, such as new equipment or formulation changes
• Never, once validated it is permanent
• Only when specified by the client

Correct Answer: After any change that may affect method performance, such as new equipment or formulation changes

Q10. Which statistical measure is commonly used to express precision?

• Mean recovery
• Standard deviation or relative standard deviation (RSD)
• Correlation coefficient
• Bias

Correct Answer: Standard deviation or relative standard deviation (RSD)

Q11. In calibration, traceability refers to:

• Linking measurements to national or international standards through an unbroken chain of comparisons
• Tracking instrument usage over time
• Documenting who performed the test
• Storing calibration certificates digitally

Correct Answer: Linking measurements to national or international standards through an unbroken chain of comparisons

Q12. Which validation characteristic assesses linear response across a specified range?

• Linearity
• Robustness
• Specificity
• System suitability

Correct Answer: Linearity

Q13. Robustness testing examines:

• The method’s resistance to small deliberate variations in method parameters
• The method’s absolute accuracy
• System suitability only
• Calibration certificate validity

Correct Answer: The method’s resistance to small deliberate variations in method parameters

Q14. Which document typically contains calibration intervals, acceptance criteria, and responsibility?

• Analytical method validation report
• Calibration procedure or calibration SOP
• Batch manufacturing record
• Drug master file

Correct Answer: Calibration procedure or calibration SOP

Q15. What is measurement uncertainty?

• The guaranteed exactness of a result
• A quantitative estimate of the doubt about the measurement result
• The difference between two analysts’ results
• The bias measured during validation

Correct Answer: A quantitative estimate of the doubt about the measurement result

Q16. Which of the following is not typically a part of analytical method validation?

• Accuracy
• Specificity
• Market price analysis
• Limit of Quantitation (LOQ)

Correct Answer: Market price analysis

Q17. What does system suitability ensure before running sample analyses?

• The system is capable of producing reliable data for that analytical run
• The samples are stable at room temperature
• All reagents are within shelf life
• The instrument has been used recently

Correct Answer: The system is capable of producing reliable data for that analytical run

Q18. Which acceptance criterion is commonly used for method accuracy during recovery studies?

• 90–110% recovery depending on the guideline and matrix
• Exactly 100% recovery
• Below 50% recovery
• No recovery required

Correct Answer: 90–110% recovery depending on the guideline and matrix

Q19. Specificity can be demonstrated by which experiment?

• Forced degradation studies to show analyte separation from degradation products
• Only calibration curve linearity
• Measuring pH of the sample
• Checking instrument temperature

Correct Answer: Forced degradation studies to show analyte separation from degradation products

Q20. Which of the following best describes method validation vs system suitability?

• Validation is a one-time demonstration; system suitability is performed on each analytical run
• System suitability replaces validation
• Validation is performed daily; system suitability is occasional
• They are identical activities

Correct Answer: Validation is a one-time demonstration; system suitability is performed on each analytical run

Q21. Which parameter helps determine the working range of an assay?

• Accuracy only
• Linearity, precision, and accuracy across concentrations
• Only robustness studies
• Calibration frequency

Correct Answer: Linearity, precision, and accuracy across concentrations

Q22. Which practice improves calibration reliability?

• Using uncertified reference materials
• Documenting traceability to national standards and using certified reference materials
• Calibrating only when results look wrong
• Relying solely on manufacturer claims without records

Correct Answer: Documenting traceability to national standards and using certified reference materials

Q23. During method validation, intermediate precision evaluates:

• Variability within the same analyst on the same day only
• Reproducibility across different days, analysts, and equipment within the same lab
• Only the robustness to pH changes
• The stability of calibration standards

Correct Answer: Reproducibility across different days, analysts, and equipment within the same lab

Q24. Which of the following is a common acceptance limit for RSD in precision studies for assay methods?

• Less than 2% for many assay methods, depending on concentration and guideline
• Greater than 50%
• Exactly 10% only
• No limit specified

Correct Answer: Less than 2% for many assay methods, depending on concentration and guideline

Q25. What is the role of documentation in calibration and validation per ICH and GMP?

• Documentation is optional for internal use
• Provides evidence of control, traceability, acceptance criteria, and compliance
• Only required for production equipment, not analytical
• Is only used for training purposes

Correct Answer: Provides evidence of control, traceability, acceptance criteria, and compliance

Q26. Which of the following changes would most likely require partial or full revalidation?

• Minor spelling corrections in SOPs
• Change in the critical detection wavelength for a UV assay
• Changing analyst gloves brand
• Reordering the same reagents from same supplier and lot

Correct Answer: Change in the critical detection wavelength for a UV assay

Q27. What statistical tool is commonly used to assess linearity?

• Regression analysis and correlation coefficient (r or r²)
• Control charts only
• ANOVA for system suitability only
• Kaplan-Meier curves

Correct Answer: Regression analysis and correlation coefficient (r or r²)

Q28. Which activity verifies that calibration remains valid over time?

• Routine calibration checks and periodic calibration with standards
• Once-only validation
• Discarding all calibration records monthly
• Only performing full recalibration after five years

Correct Answer: Routine calibration checks and periodic calibration with standards

Q29. In method validation, selectivity differs from specificity in that selectivity:

• Is a broader term that may include matrix effects and interference evaluation
• Is identical to specificity
• Refers only to instrument performance
• Is unrelated to analytical methods

Correct Answer: Is a broader term that may include matrix effects and interference evaluation

Q30. Which record should be retained to demonstrate calibration history and compliance?

• Calibration certificates, calibration logs, and maintenance records
• Only verbal confirmation by the analyst
• Just the last calibration certificate, discarding earlier ones
• Only purchase invoices for instruments

Correct Answer: Calibration certificates, calibration logs, and maintenance records

Download