Developing specifications – ICH Q6A/Q6B MCQs With Answer

Introduction: Developing specifications – ICH Q6A/Q6B MCQs With Answer is designed for M.Pharm students to deepen understanding of how pharmaceutical product specifications are created and justified under ICH guidance. This blog focuses on the principles of ICH Q6A for chemical drug substances and products and ICH Q6B for biotechnology-derived biologicals. You will learn about specification attributes, acceptance criteria, selection and validation of analytical methods, reference materials, impurities and stability considerations. The following multiple-choice questions test theoretical knowledge and practical application relevant to quality control, regulatory submissions and routine QA activities in a pharmaceutical setting.

Q1. What is the primary purpose of ICH Q6A?

• To provide global harmonized guidance on specifications for new drug substances and drug products of chemical origin
• To define clinical trial design and statistical endpoints for efficacy studies
• To give recommendations on pharmacovigilance reporting requirements
• To establish manufacturing site inspection procedures

Correct Answer: To provide global harmonized guidance on specifications for new drug substances and drug products of chemical origin

Q2. Which products are specifically covered by ICH Q6B?

• Chemical small-molecule drug substances and their formulations
• Over-the-counter herbal preparations
• Biotechnology-derived therapeutic proteins, peptides and other biological products
• Medical devices and combination products

Correct Answer: Biotechnology-derived therapeutic proteins, peptides and other biological products

Q3. According to ICH Q6A/Q6B, which item is not normally considered a specification attribute?

• Assay (potency or content)
• Related substances / impurities
• Manufacturing cost per unit
• Identity

Correct Answer: Manufacturing cost per unit

Q4. How does ICH define a “specification” for a drug substance or drug product?

• A marketing description and promotional claims for the product
• A list of tests, analytical procedures and acceptance criteria to determine quality of the drug substance or product
• A manufacturing protocol including process parameters and equipment lists
• A clinical protocol for post-marketing surveillance

Correct Answer: A list of tests, analytical procedures and acceptance criteria to determine quality of the drug substance or product

Q5. What is the key difference between release specifications and shelf-life (stability) specifications?

• Release specifications apply to raw materials only while shelf-life specifications apply to finished products only
• Release specifications are used at batch release; shelf-life specifications are acceptance criteria applied after storage to support the claimed expiry
• Release specifications are numeric while shelf-life specifications are descriptive
• There is no difference; both terms are interchangeable

Correct Answer: Release specifications are used at batch release; shelf-life specifications are acceptance criteria applied after storage to support the claimed expiry

Q6. When selecting analytical methods for specifications, which principle is emphasized by ICH Q6A/Q6B?

• Use the cheapest available method regardless of performance
• Methods should be scientifically validated and demonstrated suitable for their intended purpose; compendial methods are preferred when appropriate
• Only non-instrumental techniques are acceptable for regulatory purposes
• Analytical methods need not be documented if the lab is accredited

Correct Answer: Methods should be scientifically validated and demonstrated suitable for their intended purpose; compendial methods are preferred when appropriate

Q7. According to ICH Q6B, what is the recommended use of reference materials for biological products?

• Reference materials are unnecessary if in-house assays are used
• Well-characterized primary and secondary reference materials should be used to support assay calibration, potency determination and comparability
• Only international pharmacopoeial standards may be used and no in-house materials are allowed
• Reference materials should be renewed for every batch release

Correct Answer: Well-characterized primary and secondary reference materials should be used to support assay calibration, potency determination and comparability

Q8. On what basis should acceptance criteria for impurities be established?

• Arbitrary values chosen at the convenience of the manufacturer
• Based on toxicological qualification, regulatory thresholds, degradation studies and clinical safety considerations
• Exactly equal to the LOQ of the analytical method used
• Always set to zero for any impurity

Correct Answer: Based on toxicological qualification, regulatory thresholds, degradation studies and clinical safety considerations

Q9. For a biotherapeutic product, which specification attribute assesses biological activity?

• Related substances by HPLC
• Dissolution
• Potency determined by a validated biological assay
• Residual solvent content

Correct Answer: Potency determined by a validated biological assay

Q10. What characterizes a stability-indicating analytical method as required for specifications?

• It measures only the label claim without detecting impurities
• It can separate and quantify the active from its degradation products and detect changes in the product over time
• It relies on microbiological culture methods exclusively
• It requires no validation if used in stability studies

Correct Answer: It can separate and quantify the active from its degradation products and detect changes in the product over time

Q11. When should product specifications generally be established according to ICH guidance?

• Only after commercialization has started
• Prior to regulatory submission/approval and justified during development; initial specifications should be in place before significant clinical or commercial use
• After the first five commercial batches are produced
• Only when requested by local inspectors

Correct Answer: Prior to regulatory submission/approval and justified during development; initial specifications should be in place before significant clinical or commercial use

Q12. What is an appropriate statistical approach when setting specification limits from batch data?

• Using historical production data with scientifically justified statistical methods and understanding of product variability
• Always setting limits at mean ± 5 standard deviations without justification
• Selecting the most permissive limit observed in historical data to avoid rejections
• Relying solely on a single pilot batch to define permanent limits

Correct Answer: Using historical production data with scientifically justified statistical methods and understanding of product variability

Q13. How should an out-of-specification (OOS) result be handled according to good QA practice?

• Automatically reject the batch without investigation
• Immediately report, initiate a thorough investigation, evaluate method performance, and perform validated retesting as appropriate before concluding
• Ignore the result if most other tests pass
• Change the specification retrospectively to include the result

Correct Answer: Immediately report, initiate a thorough investigation, evaluate method performance, and perform validated retesting as appropriate before concluding

Q14. Which of the following is a product-related impurity of particular concern for biologicals per ICH Q6B?

• Host cell proteins and DNA remnants
• Sulphated ash content
• Tablet hardness variation
• Residual packaging glue

Correct Answer: Host cell proteins and DNA remnants

Q15. For an immediate-release oral tablet, when is dissolution testing generally expected in the product specification?

• Only if the product is enteric-coated
• When dissolution is needed to ensure consistent release and to support bioavailability or to detect manufacturing differences
• Never; dissolution is only needed for parenteral products
• Only during clinical studies, not for release

Correct Answer: When dissolution is needed to ensure consistent release and to support bioavailability or to detect manufacturing differences

Q16. Which ICH guideline is most relevant for setting limits on residual solvents in specifications?

• ICH Q3A(R2) on impurities in new drug substances
• ICH Q3C on residual solvents
• ICH Q2(R1) on analytical method validation
• ICH Q6B on biologicals

Correct Answer: ICH Q3C on residual solvents

Q17. Which guideline should be consulted for identification and qualification thresholds for impurities in new drug substances and products?

• ICH Q3A and Q3B
• ICH Q8 on pharmaceutical development only
• ICH M7 for environmental monitoring
• ICH Q10 on quality systems

Correct Answer: ICH Q3A and Q3B

Q18. What is an important requirement for reference standards used in specification testing?

• They may be used without documentation as long as analysts are experienced
• They should be well-characterized, traceable, and stored under defined conditions with established expiry or retest periods
• Only bulk drug substance batches can serve as reference standards
• Reference standards do not need purity assessment for biologics

Correct Answer: They should be well-characterized, traceable, and stored under defined conditions with established expiry or retest periods

Q19. Which validation parameters are typically required when validating an analytical procedure used in a specification?

• Specificity, accuracy, precision, linearity, range, detection and quantitation limits, and robustness as applicable
• Only precision and appearance
• Only linearity and run time
• No validation is required for compendial methods

Correct Answer: Specificity, accuracy, precision, linearity, range, detection and quantitation limits, and robustness as applicable

Q20. Which ICH guideline should be followed for analytical procedure validation supporting specifications?

• ICH Q1A(R2) on stability testing
• ICH Q2(R1) on validation of analytical procedures
• ICH Q5C on quality of biotechnological products: stability testing only
• ICH Q8 on pharmaceutical development exclusively

Correct Answer: ICH Q2(R1) on validation of analytical procedures

Download