Cleaning method development MCQs With Answer

Introduction: Cleaning method development is a crucial component of pharmaceutical validation, ensuring that manufacturing equipment is free from product residues, cleaning agents, and potential contaminants. For M.Pharm students, mastering cleaning method development involves understanding sampling strategies (swab vs. rinse), selection of worst‑case products, design of extraction procedures, analytical method validation (specificity, accuracy, precision, LOD/LOQ), and calculation of acceptance limits using health‑based or dose‑based approaches. Regulatory expectations from agencies like FDA, EMA and PIC/S emphasize scientific justification, robustness and documented recovery. This blog provides targeted multiple‑choice questions with answers to reinforce conceptual depth, practical decision‑making and exam readiness in cleaning validation.

Q1. Which primary objective drives cleaning method development in pharmaceutical validation?

• To document cleaning procedures without analytical testing
• To ensure reproducible removal of residues, prevention of cross‑contamination and compliance with regulatory limits
• To maximize use of solvents regardless of residue type
• To perform only visual inspections after cleaning

Correct Answer: To ensure reproducible removal of residues, prevention of cross‑contamination and compliance with regulatory limits

Q2. Which guideline is considered the principal reference for analytical method validation used in cleaning method development?

• WHO Technical Report Series only
• ICH Q2(R1) — Validation of Analytical Procedures
• ISO 9001
• ICH Q7A — Good Manufacturing Practice

Correct Answer: ICH Q2(R1) — Validation of Analytical Procedures

Q3. When is swab sampling preferred over rinse sampling during cleaning validation?

• For bulk solution monitoring only
• When sampling small, defined surface locations or areas difficult to rinse
• When equipment is cleaned in closed CIP systems only
• For monitoring airborne contamination

Correct Answer: When sampling small, defined surface locations or areas difficult to rinse

Q4. Which factors should be considered when selecting the worst‑case product for cleaning validation?

• Highest daily production volume only
• Lowest therapeutic dose and low solubility in cleaning media
• Packaging color and label design
• Product marketing priority rather than physicochemical properties

Correct Answer: Lowest therapeutic dose and low solubility in cleaning media

Q5. Which approach is the preferred hierarchical method to establish a cleaning acceptance limit?

• Arbitrarily set 10 ppm for all products
• Use a health‑based limit (e.g., occupational exposure limit or toxicology‑based limit)
• Divide the previous product batch weight by 1000
• Use visual cleanliness as the acceptance criterion

Correct Answer: Use a health‑based limit (e.g., occupational exposure limit or toxicology‑based limit)

Q6. Which formula correctly converts a mass‑based acceptance limit to an area‑based acceptance limit (µg/cm²)?

• Acceptance (µg/cm²) = (Acceptance mass (mg) × Surface area (cm²)) / 1000
• Acceptance (µg/cm²) = (Acceptance mass (mg) × 1000 µg/mg) / Equipment surface area (cm²)
• Acceptance (µg/cm²) = Acceptance mass (mg) / 1000
• Acceptance (µg/cm²) = Equipment surface area (cm²) / Acceptance mass (mg)

Correct Answer: Acceptance (µg/cm²) = (Acceptance mass (mg) × 1000 µg/mg) / Equipment surface area (cm²)

Q7. What is an acceptable target for swab recovery during cleaning method development?

• Swab recovery is not required to be measured
• Demonstrated experimentally and typically at least 50%
• Exactly 100% recovery is mandatory for all methods
• Less than 10% is acceptable if LOQ is low

Correct Answer: Demonstrated experimentally and typically at least 50%

Q8. Which analytical term describes the lowest concentration that can be measured with acceptable accuracy and precision?

• Limit of Detection (LOD)
• Limit of Quantitation (LOQ)
• Instrument Resolution
• Sensitivity Index

Correct Answer: Limit of Quantitation (LOQ)

Q9. When is a non‑specific method such as Total Organic Carbon (TOC) appropriate in cleaning validation?

• When residues are inorganic salts only
• When residues are organic, specific analyte methods are not feasible, and TOC is scientifically justified
• For quantifying metals and elemental impurities
• When chromatography is mandatory by regulation

Correct Answer: When residues are organic, specific analyte methods are not feasible, and TOC is scientifically justified

Q10. Which criterion is most important when selecting an extraction solvent for swab recovery studies?

• Maximum flammability to ensure quick evaporation
• Compatibility with the analyte and swab material and non‑interference with the analytical detection
• Highest possible polarity regardless of analyte chemistry
• Color matching the swab to avoid visual detection

Correct Answer: Compatibility with the analyte and swab material and non‑interference with the analytical detection

Q11. Which system suitability characteristics are typically evaluated for an HPLC method used in cleaning validation?

• Resolution between peaks, theoretical plates and tailing factor
• Column length only
• Mobile phase color exclusively
• Ambient room décor

Correct Answer: Resolution between peaks, theoretical plates and tailing factor

Q12. How should swabs be handled after sampling to ensure validity of results?

• Store indefinitely at room temperature without documentation
• Process within a validated stability period and store under defined conditions until analysis
• Discard after 1 hour without analysis
• Expose to sunlight to dry samples faster

Correct Answer: Process within a validated stability period and store under defined conditions until analysis

Q13. When the target analyte is unavailable, what is the appropriate approach for spike‑recovery experiments in cleaning validation?

• Do not perform recovery studies
• Use a surrogate compound with similar physicochemical properties and demonstrate comparable recovery
• Use water as a surrogate analyte
• Estimate recovery from literature without experimental work

Correct Answer: Use a surrogate compound with similar physicochemical properties and demonstrate comparable recovery

Q14. Rinse sampling is particularly suitable for which of the following situations?

• Sampling isolated small valves that are inaccessible by rinse
• Large internal surfaces and equipment cleaned by CIP (clean‑in‑place)
• Only when swab materials are unavailable
• For visual cleanliness assessment

Correct Answer: Large internal surfaces and equipment cleaned by CIP (clean‑in‑place)

Q15. In the context of cleaning method development, what does analytical specificity mean?

• The method measures total organic carbon only
• The method can accurately determine the target residue in presence of other residues, detergents and matrix components
• The method uses the most expensive reagents
• Specificity is irrelevant for cleaning methods

Correct Answer: The method can accurately determine the target residue in presence of other residues, detergents and matrix components

Q16. What is a typical requirement for the LOQ relative to the cleaning acceptance limit?

• LOQ may be higher than the acceptance limit
• LOQ should be less than or equal to one tenth (10%) of the acceptance limit
• LOQ must equal the acceptance limit
• LOQ is not related to the acceptance limit

Correct Answer: LOQ should be less than or equal to one tenth (10%) of the acceptance limit

Q17. What is meant by analytical carryover in cleaning validation and how should it be controlled?

• Carryover is irrelevant if blanks are analyzed
• Carryover is residual signal from a previous high concentration sample and should be shown to be below the acceptance limit by appropriate blank or carryover checks
• Carryover refers to the physical movement of equipment only
• Carryover can be ignored if the system is calibrated daily

Correct Answer: Carryover is residual signal from a previous high concentration sample and should be shown to be below the acceptance limit by appropriate blank or carryover checks

Q18. Which swab material is generally recommended for cleaning validation sampling?

• Cotton swabs (unbleached) without qualification
• Polyester or other synthetic swabs with verified low extractables and good recovery
• Any material available in the laboratory
• Wooden applicators only

Correct Answer: Polyester or other synthetic swabs with verified low extractables and good recovery

Q19. In ICH terminology, which precision parameter describes variability between different laboratories?

• Repeatability
• Intermediate precision
• Reproducibility
• Accuracy

Correct Answer: Reproducibility

Q20. Under which circumstances is revalidation of a cleaning method required?

• Only if the product label color changes
• Whenever there are significant changes in product formulation, manufacturing process, equipment, cleaning procedure, or analytical method, or during periodic reviews as defined in the quality system
• Never after initial validation
• Only after a regulatory inspection

Correct Answer: Whenever there are significant changes in product formulation, manufacturing process, equipment, cleaning procedure, or analytical method, or during periodic reviews as defined in the quality system

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