Impurities: Definitions, classification and ICH reporting requirements MCQs With Answer

Introduction: This quiz collection on “Impurities: Definitions, classification and ICH reporting requirements” is designed for M.Pharm students preparing for advanced pharmaceutical analysis. It covers core definitions (impurity, related substance, degradation product, genotoxic impurity), classification schemes (by origin, chemical nature, safety), analytical identification techniques, and international regulatory expectations—particularly ICH guidance (Q3A, Q3B, Q3C, Q3D and M7). Questions emphasize practical decision-making: threshold concepts (reporting, identification, qualification), control strategies, and appropriate analytical methods. Use these MCQs to test and deepen your conceptual understanding and to prepare for exams and regulatory problem-solving in drug substance and drug product impurity control.

Q1. Which of the following best defines an “impurity” in a pharmaceutical substance according to ICH guidance?

• A substance produced intentionally during synthesis that enhances efficacy
• A component of the final drug product that guarantees consistency
• Any substance present in the drug substance or drug product that is not the desired active ingredient
• A solvent used during manufacturing and fully removed in the final product

Correct Answer: Any substance present in the drug substance or drug product that is not the desired active ingredient

Q2. Which term specifically refers to impurities that form from the active pharmaceutical ingredient (API) during storage or shelf life?

• Process impurities
• Degradation products
• Residual solvents
• Elemental impurities

Correct Answer: Degradation products

Q3. Which classification groups impurities by their origin in the manufacturing process?

• Organic, inorganic, and elemental
• Process-related, degradation-related, and interaction-related
• Toxic, non-toxic, and inert
• Volatile, semi-volatile, and non-volatile

Correct Answer: Process-related, degradation-related, and interaction-related

Q4. Which ICH guideline primarily addresses impurities in new drug substances (i.e., thresholds and identification/qualification criteria)?

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

Correct Answer: ICH Q3A

Q5. In ICH impurity control terminology, what is the difference between “reporting threshold” and “identification threshold”?

• Reporting threshold is higher and triggers structural identification; identification threshold is lower and requires listing only
• Reporting threshold triggers listing the impurity in regulatory submissions; identification threshold requires structural elucidation or provisional identification
• Reporting threshold relates to safety qualification; identification threshold relates to potency measurement
• They are synonymous and used interchangeably in ICH documents

Correct Answer: Reporting threshold triggers listing the impurity in regulatory submissions; identification threshold requires structural elucidation or provisional identification

Q6. Which set of thresholds (reporting/identification/qualification) is consistent with common ICH Q3A tables for drug substances at relatively high maximum daily dose (≥2 g/day)?

• Reporting 0.5%, Identification 1.0%, Qualification 1.5%
• Reporting 0.05%, Identification 0.10%, Qualification 0.15%
• Reporting 0.005%, Identification 0.01%, Qualification 0.015%
• Reporting 0.2%, Identification 0.4%, Qualification 0.6%

Correct Answer: Reporting 0.05%, Identification 0.10%, Qualification 0.15%

Q7. ICH M7 guidance focuses on which specific category of impurities?

• Residual solvents
• Genotoxic (mutagenic) impurities
• Elemental impurities
• Unknown organic impurities over 1% w/w

Correct Answer: Genotoxic (mutagenic) impurities

Q8. Under ICH M7, what is the conservative TTC (threshold of toxicological concern) commonly used as a control limit for genotoxic impurities for lifetime exposure?

• 1.5 micrograms per day
• 15 micrograms per day
• 150 micrograms per day
• 0.15 micrograms per day

Correct Answer: 1.5 micrograms per day

Q9. Which ICH guideline categorizes residual solvents into Class 1, 2 and 3 based on toxicity and provides limits?

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

Correct Answer: ICH Q3C

Q10. Which analytical technique is most appropriate for detecting and identifying volatile organic residual solvents in a drug product?

• Inductively coupled plasma mass spectrometry (ICP-MS)
• Gas chromatography with suitable detector (GC-FID or GC-MS)
• High-performance liquid chromatography with UV detection (HPLC-UV)
• Nuclear magnetic resonance spectroscopy (NMR)

Correct Answer: Gas chromatography with suitable detector (GC-FID or GC-MS)

Q11. Which ICH guideline deals primarily with elemental impurities (metals) and their permitted daily exposures (PDEs)?

• ICH Q3A
• ICH Q3C
• ICH Q3D
• ICH M7

Correct Answer: ICH Q3D

Q12. What is a common analytical method used for quantifying elemental impurities at trace levels in pharmaceuticals?

• High-performance liquid chromatography (HPLC)
• Gas chromatography-mass spectrometry (GC-MS)
• Inductively coupled plasma mass spectrometry (ICP-MS)
• Thin-layer chromatography (TLC)

Correct Answer: Inductively coupled plasma mass spectrometry (ICP-MS)

Q13. Which of the following is an example of a process-related impurity?

• A degradation product formed during shelf storage of the drug
• A metal catalyst residue remaining after synthesis
• An impurity formed by interaction with packaging materials after release
• An impurity generated during dissolution testing

Correct Answer: A metal catalyst residue remaining after synthesis

Q14. According to ICH recommendations, when should an impurity be qualified (i.e., subjected to toxicological evaluation)?

• When its level is above the reporting threshold only
• When its level exceeds the qualification threshold or when there is structural concern (e.g., genotoxicity)
• Only when it is present at trace levels below the reporting threshold
• Qualification is not required if the impurity is process-related

Correct Answer: When its level exceeds the qualification threshold or when there is structural concern (e.g., genotoxicity)

Q15. Which analytical approach is most suitable for identifying unknown organic impurities at low level in a drug substance?

• UV-Visible spectroscopy alone
• LC-MS/MS combined with high-resolution mass spectrometry and, if needed, NMR
• Titration with standard reagents
• Melting point determination

Correct Answer: LC-MS/MS combined with high-resolution mass spectrometry and, if needed, NMR

Q16. Which statement about “related substances” in impurity profiling is correct?

• Related substances are unrelated environmental contaminants
• Related substances are structurally related to the API, often formed in synthesis or degradation
• Related substances always refer only to inorganic salts present in formulations
• Related substances are only considered for parenteral products

Correct Answer: Related substances are structurally related to the API, often formed in synthesis or degradation

Q17. Which of the following best describes the regulatory expectation for reporting unknown impurities detected above the reporting threshold?

• Unknown impurities above the reporting threshold may be listed in submissions with concentration but do not need identification
• Unknown impurities above the reporting threshold should be reported, and those above the identification threshold should be structurally characterized where feasible
• Unknown impurities are only relevant if they exceed 1% w/w
• Unknown impurities are ignored until stability studies are complete

Correct Answer: Unknown impurities above the reporting threshold should be reported, and those above the identification threshold should be structurally characterized where feasible

Q18. Which control strategy is most appropriate for a known genotoxic impurity that cannot be eliminated from the process?

• Ignore it if below 1% w/w because it is known
• Apply risk assessment, limit the impurity using process optimization, and control to levels at or below the M7 TTC or justified limits
• Convert it to a different impurity by adding more solvent
• Rely solely on finished product release testing without process control

Correct Answer: Apply risk assessment, limit the impurity using process optimization, and control to levels at or below the M7 TTC or justified limits

Q19. Which of the following is a primary reason to perform stress testing of a drug substance when assessing impurities?

• To increase the potency of the drug substance
• To force degradation and reveal likely degradation products for characterization and to develop stability-indicating methods
• To determine the best packaging colors
• To measure the taste profile of the API

Correct Answer: To force degradation and reveal likely degradation products for characterization and to develop stability-indicating methods

Q20. Which of the following describes the role of a stability-indicating analytical method in impurity control?

• A method that quantifies only the API without resolving impurities
• A method capable of detecting, separating, and quantifying the API and its degradation products formed during stability studies
• An in vivo assay for toxicity evaluation of impurities
• A method that intentionally masks degradation peaks to simplify chromatograms

Correct Answer: A method capable of detecting, separating, and quantifying the API and its degradation products formed during stability studies

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