ICH Q3 – Impurity testing and limits MCQs With Answer

Introduction:
This blog provides M.Pharm students with a focused set of multiple-choice questions on ICH Q3 — the suite of guidelines addressing impurities in pharmaceuticals. It summarizes the intent of ICH Q3A/B/C/D and explains practical aspects of impurity testing, thresholds, identification and qualification, and control strategies. The questions emphasize regulatory expectations, analytical approaches for detection and quantification, and risk-based assessment for elemental and residual solvents. Designed to deepen conceptual understanding and exam preparedness, the MCQs help students link guideline principles to laboratory practice and specification setting, promoting correct decision-making for impurity evaluation and regulatory compliance.

Q1. What is the primary objective of ICH Q3 guidelines for impurities?

• To provide stability testing protocols only
• To define the regulatory framework for impurity control, identification, qualification and limits for drug substances and products
• To prescribe manufacturing steps for process optimization
• To set pharmacopoeial assay limits for potency

Correct Answer: To define the regulatory framework for impurity control, identification, qualification and limits for drug substances and products

Q2. Which ICH guideline specifically addresses residual solvents in pharmaceuticals?

• ICH Q3A
• ICH Q3B
• ICH Q3C
• ICH Q3D

Correct Answer: ICH Q3C

Q3. Which document in the Q3 series covers elemental (inorganic) impurities and their control?

• ICH Q3A
• ICH Q3B
• ICH Q3C
• ICH Q3D

Correct Answer: ICH Q3D

Q4. Which of the following best describes the common categories of organic impurities addressed by ICH Q3?

• Microbial, endotoxin and heavy metal impurities
• Related organic impurities, degradation products and process-related impurities
• Residual solvents, elemental impurities and counter-ions
• Packaging-derived, photolytic and microbial impurities

Correct Answer: Related organic impurities, degradation products and process-related impurities

Q5. How do the reporting, identification and qualification thresholds relate to each other?

• Identification threshold < Qualification threshold < Reporting threshold
• Qualification threshold < Reporting threshold < Identification threshold
• Reporting threshold < Identification threshold < Qualification threshold
• All thresholds are equal by definition

Correct Answer: Reporting threshold < Identification threshold < Qualification threshold

Q6. What is the primary factor used to set impurity thresholds in ICH Q3A for a new drug substance?

• Maximum daily dose of the drug substance
• Cost of analytical method development
• Molecular weight of the drug substance
• Solubility of the drug substance

Correct Answer: Maximum daily dose of the drug substance

Q7. In the context of ICH Q3, what does “qualification” of an impurity mean?

• Determining the impurity’s chromatographic retention time
• Performing toxicological evaluation and providing safety data to justify the impurity limit
• Assigning a CAS number to the impurity
• Reporting the impurity without further action

Correct Answer: Performing toxicological evaluation and providing safety data to justify the impurity limit

Q8. When is structural identification of an impurity typically required under ICH Q3 principles?

• Only when the impurity is visible as a colored spot
• When an impurity exceeds the identification threshold and requires characterization
• For every detectable peak regardless of size
• Only after product registration is complete

Correct Answer: When an impurity exceeds the identification threshold and requires characterization

Q9. The ICH Q3C classification of residual solvents groups solvents based on which primary consideration?

• Manufacturing cost and availability
• Toxicity and potential risk to patient safety
• Chromatographic behavior and polarity
• Odor and color

Correct Answer: Toxicity and potential risk to patient safety

Q10. What approach does ICH Q3D recommend for controlling elemental impurities?

• A fixed single limit for all elements across all products
• Risk-based assessment using permitted daily exposure (PDE) values and control strategies
• Relying solely on supplier certificates of analysis
• No control is required if the manufacturing process is documented

Correct Answer: Risk-based assessment using permitted daily exposure (PDE) values and control strategies

Q11. Which analytical technique is commonly used and acceptable for profiling low-level organic impurities in drug substances?

• HPLC with appropriate detector, often coupled to MS for identification
• Simple UV spectrophotometry without chromatography
• Titration methods only
• Visual color comparison

Correct Answer: HPLC with appropriate detector, often coupled to MS for identification

Q12. How is an “unspecified impurity” best defined in impurity control?

• An impurity whose structure, origin and route of formation are unknown or not confirmed
• A known related compound with a defined synthetic route
• A specified degradation product with an established assay
• An impurity intentionally added as an excipient

Correct Answer: An impurity whose structure, origin and route of formation are unknown or not confirmed

Q13. What is the role of forced degradation (stress) studies in impurity evaluation?

• To intentionally generate degradation products to aid in identification and to establish degradation pathways and stability-indicating methods
• To improve manufacturing yield
• To determine product color stability only
• To establish solubility limits in water

Correct Answer: To intentionally generate degradation products to aid in identification and to establish degradation pathways and stability-indicating methods

Q14. According to ICH Q3 principles, how should unspecified impurities be handled during product development and registration?

• Ignore them if they are present at trace levels
• Report them and, if above thresholds, identify and qualify them based on established criteria
• Replace them with another unknown impurity
• Always set acceptance limits at 5% for all unspecified impurities

Correct Answer: Report them and, if above thresholds, identify and qualify them based on established criteria

Q15. Which class of impurities typically demands genotoxicity assessment and may require applying the TTC approach (e.g., ICH M7) rather than standard qualification thresholds?

• Bulk solvent impurities with high boiling points
• Potentially genotoxic (DNA-reactive) impurities
• Common process-related inorganic salts
• All degradation products irrespective of structure

Correct Answer: Potentially genotoxic (DNA-reactive) impurities

Q16. Which validation characteristics are most critical when developing an analytical method for low-level impurity quantification?

• Specificity and limit of quantitation (LOQ)
• Bulk density and flow rate
• Color and odor detection limits
• Melting point and refractive index

Correct Answer: Specificity and limit of quantitation (LOQ)

Q17. What does “carryover” mean in the context of impurity testing by chromatographic methods?

• A phenomenon where previous sample residues contaminate subsequent runs, producing false peaks
• Intentional addition of an internal standard
• Complete separation of all peaks in a chromatogram
• Loss of analyte during sample filtration only

Correct Answer: A phenomenon where previous sample residues contaminate subsequent runs, producing false peaks

Q18. Which analytical technique is most appropriate and sensitive for trace-level determination of elemental impurities?

• Gas chromatography with FID
• ICP-MS (Inductively Coupled Plasma Mass Spectrometry)
• UV-Visible spectrophotometry
• Polarimetry

Correct Answer: ICP-MS (Inductively Coupled Plasma Mass Spectrometry)

Q19. If an impurity is found above the qualification threshold during development, what is the expected regulatory action?

• Ignore the impurity if product potency is within limits
• Conduct appropriate qualification (toxicology) studies or provide adequate justification for safety at observed levels
• Never proceed to market under any circumstances
• Automatically recall all batches

Correct Answer: Conduct appropriate qualification (toxicology) studies or provide adequate justification for safety at observed levels

Q20. What is the main purpose of setting impurity specifications in the drug development and regulatory submission process?

• To limit manufacturing costs by reducing testing
• To define acceptable limits and control strategy for impurities to ensure patient safety and consistent product quality
• To replace stability testing requirements
• To ensure the product has a pleasant taste

Correct Answer: To define acceptable limits and control strategy for impurities to ensure patient safety and consistent product quality

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