Cleaning validation MCQs With Answer

Introduction:

Cleaning validation is a critical component of Good Regulatory Practices, ensuring that manufacturing equipment is free from harmful residues that could affect subsequent batches. This blog provides focused multiple-choice questions (MCQs) with answers specifically designed for M.Pharm students studying cleaning validation. The questions cover fundamental concepts such as acceptance criteria, sampling techniques (swab and rinse), analytical methods, worst-case selection, risk assessment, revalidation triggers, and regulatory expectations. By practicing these questions, students will strengthen their understanding of practical and theoretical aspects of cleaning validation, preparing them for exams and real-world quality assurance challenges in pharmaceutical manufacturing.

Q1. Which statement best defines cleaning validation in pharmaceutical manufacturing?

• Documenting the quantity of detergents used during cleaning
• Establishing objective evidence that cleaning processes consistently remove residues to acceptable levels
• Scheduling routine maintenance for cleaning equipment
• Training personnel to operate cleaning machines

Correct Answer: Establishing objective evidence that cleaning processes consistently remove residues to acceptable levels

Q2. What is considered the primary goal when setting acceptance limits in cleaning validation?

• Minimizing water consumption during cleaning
• Ensuring residues do not pose a safety risk to patients or affect product quality
• Keeping cleaning cycle time under a predefined duration
• Reducing labor costs associated with cleaning

Correct Answer: Ensuring residues do not pose a safety risk to patients or affect product quality

Q3. Which sampling technique is most appropriate for quantifying surface residues in localized areas?

• Rinse sampling of bulk liquid from the system
• Swab sampling from defined surface area
• Air monitoring for particulates
• Visual inspection only

Correct Answer: Swab sampling from defined surface area

Q4. When selecting a worst-case product for cleaning validation, which characteristic is most important?

• Highest production volume regardless of potency
• Lowest therapeutic dose and/or highest toxicity that is hardest to clean
• Newest product introduced in the portfolio
• Product with the most appealing color

Correct Answer: Lowest therapeutic dose and/or highest toxicity that is hardest to clean

Q5. Which analytical method is commonly used for specific detection and quantification of API residues during cleaning validation?

• Gravimetric analysis
• High-performance liquid chromatography (HPLC)
• Turbidity measurement
• Simple pH test

Correct Answer: High-performance liquid chromatography (HPLC)

Q6. What does “TOC” measurement in cleaning validation stand for and why is it used?

• Total Oxygen Content; to measure oxidative potential of residues
• Total Organic Carbon; to estimate overall organic contamination when specific assays are not available
• Typical Operational Cycle; to document cleaning duration
• Temperature of Cleaning; to monitor heat applied during cleaning

Correct Answer: Total Organic Carbon; to estimate overall organic contamination when specific assays are not available

Q7. Which of the following is a valid reason to revalidate a cleaning procedure?

• Change in the color of the product packaging
• Change in cleaning agent formulation or supplier
• Hiring a new operator without process change
• Routine annual review without any process changes

Correct Answer: Change in cleaning agent formulation or supplier

Q8. What is the primary advantage of rinse sampling compared to swab sampling?

• Higher sensitivity for trace-level residues on small surfaces
• Ability to sample internal surfaces and entire system rinses more representatively
• Less requirement for validated analytical methods
• Rinse sampling is always cheaper than swabbing

Correct Answer: Ability to sample internal surfaces and entire system rinses more representatively

Q9. In a cleaning validation study, what is matrixing or bracketing used for?

• Selecting only the smallest equipment to validate
• Reducing number of analytical tests by selecting representative combinations of products, equipment, and surfaces
• Determining cleaning agent toxicity
• Measuring cleaning time variations across shifts

Correct Answer: Reducing number of analytical tests by selecting representative combinations of products, equipment, and surfaces

Q10. Which factor should NOT be used alone to establish cleaning validation acceptance criteria?

• Health-based limit such as PDE or TTC
• Analytical method limit of quantitation (LOQ)
• Historical visual inspection outcomes only
• Therapeutic daily dose of the previous product

Correct Answer: Historical visual inspection outcomes only

Q11. Which is a critical performance characteristic of analytical methods used in cleaning validation?

• High noise in the baseline to enhance peaks
• Demonstrated specificity, accuracy, precision, and appropriate sensitivity (LOD/LOQ)
• Only linearity across 2 concentration points
• No requirement for system suitability tests

Correct Answer: Demonstrated specificity, accuracy, precision, and appropriate sensitivity (LOD/LOQ)

Q12. Which calculation approach is widely accepted for setting an acceptance limit for carryover based on patient safety?

• Using visual color match between batches
• Health-based limit approach using PDE, maximum daily dose of next product, and safety factors
• Applying a fixed ppm limit for all products regardless of potency
• Setting limits based on the cost of cleaning agents

Correct Answer: Health-based limit approach using PDE, maximum daily dose of next product, and safety factors

Q13. What is the typical surface area to batch size consideration in cleaning validation?

• Surface area is irrelevant; only batch size matters
• Residue limits may be normalized per surface area (e.g., µg/cm2) to account for different equipment sizes
• Batch size always exceeds surface area numerically
• Surface area is only used for visual inspection

Correct Answer: Residue limits may be normalized per surface area (e.g., µg/cm2) to account for different equipment sizes

Q14. Which of the following best describes a “microbial cleaning validation”?

• Validation that focuses solely on detergent effectiveness against viruses
• Assessment ensuring bioburden and endotoxin levels are controlled where microbial contamination is critical
• Visual confirmation that surfaces look clean
• Measuring pH change after cleaning

Correct Answer: Assessment ensuring bioburden and endotoxin levels are controlled where microbial contamination is critical

Q15. Which swab material is commonly preferred for cleaning validation swab sampling due to low extractables and good recovery?

• Cotton ball
• Polyester tip swab with synthetic shaft
• Wooden applicator stick with cotton tip
• Unspecified household tissue

Correct Answer: Polyester tip swab with synthetic shaft

Q16. What is an appropriate acceptance criterion when using TOC as a surrogate measurement in cleaning validation?

• Any TOC reduction is acceptable as long as it decreases from baseline
• Predefined TOC limit based on risk assessment and correlation to specific residue levels
• TOC value must be zero in all cases
• TOC should be higher after cleaning to indicate residue solubilization

Correct Answer: Predefined TOC limit based on risk assessment and correlation to specific residue levels

Q17. Which documentation is essential to demonstrate a successful cleaning validation program?

• Only raw analytical data without protocol or conclusions
• Cleaning validation protocol, execution reports, analytical data, acceptance criteria, and final report
• Only photographs of cleaned equipment
• Only the list of cleaning agents used

Correct Answer: Cleaning validation protocol, execution reports, analytical data, acceptance criteria, and final report

Q18. In a cross-contamination risk assessment, which factor most strongly influences the potential for harm?

• Color of the product formulation
• Potency/toxicity of the residual compound relative to the next product
• Brand popularity of the product
• Time of day when cleaning occurs

Correct Answer: Potency/toxicity of the residual compound relative to the next product

Q19. Which validation sampling strategy helps demonstrate consistent cleaning performance over time?

• Single one-time sample during initial commissioning only
• Periodic verification sampling as part of routine monitoring following initial qualification
• Sampling only when a customer complains
• Sampling only at the end of a year

Correct Answer: Periodic verification sampling as part of routine monitoring following initial qualification

Q20. Which regulatory expectation is commonly emphasized for cleaning validation by agencies like FDA and EMA?

• That cleaning validation should be proprietary and not documented
• That cleaning processes are scientifically justified, risk-based, and supported by appropriate documentation and data
• That only visual cleanliness is necessary for approval
• That cleaning validation can be skipped for non-sterile products

Correct Answer: That cleaning processes are scientifically justified, risk-based, and supported by appropriate documentation and data

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