Validation in pharmaceutical manufacturing ensures processes, analytical methods, and cleaning procedures consistently produce safe, effective, and high-quality medicines. This resource for B.Pharm students explains major types of validation — process validation (process design, IQ/OQ/PQ, and continued process verification), analytical validation (specificity, accuracy, precision, linearity, LOD/LOQ, robustness), and cleaning validation (worst-case selection, swab vs rinse, acceptance limits, health-based/TTC approaches). You will also review Validation Master Plans, validation protocols, documentation, bracketing and matrixing, critical quality attributes (CQAs), critical process parameters (CPPs), and relevant regulatory guidance (FDA, ICH). Mastery of these topics supports compliant manufacturing and quality assurance. ‘Now let’s test your knowledge with 30 MCQs on this topic.’
Q1. What is the primary objective of validation in pharmaceutical manufacture?
- To reduce production costs
- To ensure processes consistently produce products meeting predefined quality criteria
- To optimize marketing strategies
- To increase production speed regardless of quality
Correct Answer: To ensure processes consistently produce products meeting predefined quality criteria
Q2. Which of the following lists the three stages of process validation as described by regulatory guidance?
- Design qualification, performance qualification, release testing
- Process design, process qualification, continued process verification
- Installation qualification, operational qualification, analytical qualification
- Prospective validation, concurrent validation, retrospective validation
Correct Answer: Process design, process qualification, continued process verification
Q3. What is the purpose of a Validation Master Plan (VMP)?
- To list marketed products only
- To describe the overall validation strategy, scope, responsibilities and schedule
- To replace batch production records
- To provide marketing authorization
Correct Answer: To describe the overall validation strategy, scope, responsibilities and schedule
Q4. Which qualification confirms that equipment has been installed according to manufacturer and design specifications?
- Operational Qualification (OQ)
- Performance Qualification (PQ)
- Installation Qualification (IQ)
- Process Validation (PV)
Correct Answer: Installation Qualification (IQ)
Q5. Which analytical validation parameter measures the closeness of test results to the true value?
- Precision
- Accuracy
- Linearity
- Robustness
Correct Answer: Accuracy
Q6. What does specificity in analytical validation evaluate?
- Ability to produce identical results over time
- Ability to measure the analyte distinctly in presence of other components
- Ability to detect very low concentrations only
- Ability to perform under extreme temperature fluctuations
Correct Answer: Ability to measure the analyte distinctly in presence of other components
Q7. Which term describes the lowest concentration that can be reliably detected but not necessarily quantified?
- Limit of Quantitation (LOQ)
- Limit of Detection (LOD)
- Range
- Linearity
Correct Answer: Limit of Detection (LOD)
Q8. What is the purpose of system suitability testing in chromatographic methods?
- To validate the final product stability
- To check that the chromatographic system is working properly before sample analysis
- To determine acceptance limits for cleaning validation
- To replace method validation
Correct Answer: To check that the chromatographic system is working properly before sample analysis
Q9. What is the primary objective of cleaning validation?
- To increase cleaning frequency
- To demonstrate that cleaning procedures effectively remove product residues, cleaning agents and potential contaminants to acceptable limits
- To validate analytical methods only
- To speed up production cycles
Correct Answer: To demonstrate that cleaning procedures effectively remove product residues, cleaning agents and potential contaminants to acceptable limits
Q10. Which approach is widely accepted for setting cleaning acceptance limits when toxicological data is available?
- Arbitrary ppm limits
- Health-based approach using PDE or TTC
- Visual inspection only
- Using the smallest batch size only
Correct Answer: Health-based approach using PDE or TTC
Q11. In cleaning validation, a “worst-case” product for selection is usually one that:
- Has the most attractive packaging
- Is most difficult to clean, most potent, or has the lowest acceptable residue limit
- Is produced in the smallest batch size
- Has the shortest shelf life
Correct Answer: Is most difficult to clean, most potent, or has the lowest acceptable residue limit
Q12. Which sampling technique is most appropriate for assessing internal surfaces of closed equipment like hoses and filters?
- Swab sampling
- Rinse or rinse-recovery sampling
- Visual inspection only
- Air sampling
Correct Answer: Rinse or rinse-recovery sampling
Q13. What does TTC stand for in the context of cleaning validation?
- Total Toxic Clearance
- Threshold of Toxicological Concern
- Toxicity Transfer Coefficient
- Target Trace Contamination
Correct Answer: Threshold of Toxicological Concern
Q14. What does “bracketing” mean in validation design?
- Testing each and every batch exhaustively
- Testing only the extremes of a design space or parameter range to infer intermediate conditions
- Testing random samples regardless of risk assessment
- Testing only placebo batches
Correct Answer: Testing only the extremes of a design space or parameter range to infer intermediate conditions
Q15. Which biological indicator organism is commonly used to validate steam sterilization (autoclave)?
- Escherichia coli
- Geobacillus stearothermophilus (Bacillus stearothermophilus)
- Bacillus subtilis var. niger for steam
- Staphylococcus aureus
Correct Answer: Geobacillus stearothermophilus (Bacillus stearothermophilus)
Q16. What is the purpose of a media fill (process simulation) test in aseptic manufacturing?
- To validate sterilization cycle efficiency
- To simulate aseptic operations and detect process contamination risk
- To clean equipment
- To measure preservative effectiveness
Correct Answer: To simulate aseptic operations and detect process contamination risk
Q17. Which event would typically trigger revalidation of a validated process?
- Minor change in office stationery
- Significant change in formulation, equipment, process parameters, or a validated change control affecting quality
- Routine cleaning at scheduled times
- Completion of every batch
Correct Answer: Significant change in formulation, equipment, process parameters, or a validated change control affecting quality
Q18. What does robustness testing evaluate in analytical method validation?
- The precision between different laboratories only
- The capacity of the method to remain unaffected by small deliberate variations in method parameters
- The method’s ability to detect extremely low analyte levels only
- The long-term stability of reference standards
Correct Answer: The capacity of the method to remain unaffected by small deliberate variations in method parameters
Q19. Which term best describes repeatability in analytical method validation?
- Variation observed between different laboratories
- Variation under the same conditions: same analyst, same equipment, short interval
- Variation due to different reagents only
- Long-term stability of the instrument
Correct Answer: Variation under the same conditions: same analyst, same equipment, short interval
Q20. Linearity in an analytical method refers to:
- The method’s ability to remain stable over months
- The proportional relationship between instrument response and analyte concentration within a given range
- The lowest concentration that can be detected
- The difference between two analysts’ results
Correct Answer: The proportional relationship between instrument response and analyte concentration within a given range
Q21. How is accuracy commonly expressed in analytical method validation?
- As percent recovery of the known amount of analyte
- As the number of theoretical plates
- As the tailing factor only
- As the signal-to-noise ratio
Correct Answer: As percent recovery of the known amount of analyte
Q22. What is a stability-indicating method?
- A method that measures impurities only
- A method that can accurately quantify the active pharmaceutical ingredient in presence of degradation products
- A method used exclusively for cleaning validation
- A method that does not separate degradation products from the main peak
Correct Answer: A method that can accurately quantify the active pharmaceutical ingredient in presence of degradation products
Q23. Which of the following is NOT typically part of validation documentation?
- Validation protocol and acceptance criteria
- Validation reports and raw data
- Validation Master Plan (VMP)
- Supplier marketing brochures
Correct Answer: Supplier marketing brochures
Q24. Computerized System Validation (CSV) primarily ensures that:
- All software licenses are paid
- Computerized systems are fit for intended use and comply with regulatory and data integrity requirements
- Hardware components are physically secure only
- Only personnel have access to the system
Correct Answer: Computerized systems are fit for intended use and comply with regulatory and data integrity requirements
Q25. Which sampling method gives a direct measurement of residue on a specific equipment surface?
- Air sampling
- Rinse sampling only
- Swab sampling
- Visual inspection only
Correct Answer: Swab sampling
Q26. In chromatographic LOD/LOQ determination, which signal-to-noise ratio is commonly used as an approximate criterion for LOQ?
- 1:1
- 3:1
- 10:1
- 100:1
Correct Answer: 10:1
Q27. What is the main purpose of method transfer between laboratories?
- To increase laboratory workload
- To ensure the receiving laboratory can perform the method and obtain comparable results
- To modify the method completely for new instrumentation
- To avoid validation
Correct Answer: To ensure the receiving laboratory can perform the method and obtain comparable results
Q28. Critical Process Parameters (CPPs) are best described as:
- Parameters that have no effect on product quality
- Process variables that should be monitored and controlled because they affect Critical Quality Attributes (CQAs)
- Only environmental conditions like temperature and humidity
- Parameters used solely for documentation purposes
Correct Answer: Process variables that should be monitored and controlled because they affect Critical Quality Attributes (CQAs)
Q29. Which ICH guideline specifically provides guidance for analytical method validation?
- ICH Q9
- ICH Q8
- ICH Q2(R1)
- ICH Q10
Correct Answer: ICH Q2(R1)
Q30. Which of the following is typically NOT a system suitability parameter in HPLC?
- Tailing factor
- Theoretical plates (efficiency)
- Resolution between peaks
- Cleaning limit for worst-case product
Correct Answer: Cleaning limit for worst-case product
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