Degradation products: Rationale for reporting, control and specification setting MCQs With Answer

Introduction

This MCQ set on Degradation products: Rationale for reporting, control and specification setting is designed for M.Pharm students studying Advanced Pharmaceutical Analysis (MPA 102T). The questions focus on regulatory rationale, analytical strategies, forced degradation studies, stability-indicating methods, identification/qualification principles, and formulation/control decisions. Emphasis is placed on linking toxicological considerations to specification setting, the role of mass balance, and practical laboratory approaches (LC-MS, NMR, photostability). Use these questions to deepen conceptual understanding, prepare for exams, and sharpen decision-making skills when establishing impurity control strategies for drug products.

Q1. What is the primary regulatory rationale for reporting degradation products in a finished pharmaceutical product?

• To meet labeling requirements for excipients
• To monitor manufacturing equipment wear
• To ensure patient safety and maintain drug quality throughout shelf life
• To reduce production cost by eliminating stability studies

Correct Answer: To ensure patient safety and maintain drug quality throughout shelf life

Q2. Which definition best describes a degradation product (DP)?

• A deliberately added preservative to improve shelf life
• A compound formed by chemical, photolytic, hydrolytic or oxidative transformation of the active substance or excipients over time
• An impurity introduced only during synthesis and not formed later
• An inert excipient breakdown product that has no chemical relation to the API

Correct Answer: A compound formed by chemical, photolytic, hydrolytic or oxidative transformation of the active substance or excipients over time

Q3. Forced degradation studies are primarily performed to:

• Accelerate manufacturing processes
• Identify likely degradation pathways and develop a stability-indicating analytical method
• Replace real-time stability studies entirely
• Find the cheapest storage conditions for the product

Correct Answer: Identify likely degradation pathways and develop a stability-indicating analytical method

Q4. What does “mass balance” refer to in stability and degradation studies?

• The financial accounting of raw material usage
• The ratio of drug substance to excipients in formulation
• The quantitative reconciliation of the loss of parent drug with the sum of assay, known degradation products and unidentified components
• The pH balance of a formulation under stress

Correct Answer: The quantitative reconciliation of the loss of parent drug with the sum of assay, known degradation products and unidentified components

Q5. A stability-indicating method must primarily demonstrate which analytical characteristic?

• High throughput sample processing without separation
• Specificity: clear separation and quantitation of the API in presence of degradation products and excipients
• Lowest possible detection limits regardless of selectivity
• Only suitability for formulation assays, not stability samples

Correct Answer: Specificity: clear separation and quantitation of the API in presence of degradation products and excipients

Q6. Which techniques are most appropriate for structural identification of unknown degradation products?

• Bulk density measurement and pH paper
• High-resolution mass spectrometry (HRMS), tandem MS and NMR spectroscopy
• Visual inspection and melting point apparatus
• Karl Fischer titration and refractive index

Correct Answer: High-resolution mass spectrometry (HRMS), tandem MS and NMR spectroscopy

Q7. Why is qualification of a degradation product necessary?

• To determine the product’s solubility in different solvents
• To generate toxicological and safety data if the DP is present above thresholds that could impact patient safety
• To reduce the analytical method validation requirements
• To allow substitution of the API with the DP in formulation

Correct Answer: To generate toxicological and safety data if the DP is present above thresholds that could impact patient safety

Q8. The Threshold of Toxicological Concern (TTC) concept in impurity assessment is used to:

• Replace all toxicology studies for new chemical entities
• Provide a conservative human exposure level below which no appreciable risk is expected for certain low-level impurities
• Determine the exact pharmacological activity of an impurity
• Set manufacturing acceptance criteria for raw materials

Correct Answer: Provide a conservative human exposure level below which no appreciable risk is expected for certain low-level impurities

Q9. When setting a specification limit for a degradation product, which factors should be considered?

• Only the chromatographic peak area regardless of toxicology
• Safety/toxicology data, clinical exposure, analytical capability and process variability
• The cost of standards and availability of reagents only
• Marketing preferences for easier shelf disposal

Correct Answer: Safety/toxicology data, clinical exposure, analytical capability and process variability

Q10. An effective control strategy for degradation products typically includes:

• Only final product visual inspection
• Identification/qualification thresholds, routine release testing or stability monitoring, manufacturing controls, and packaging/storage conditions
• Random batch testing once per year
• Excluding degradation product testing if manufacturing is GMP certified

Correct Answer: Identification/qualification thresholds, routine release testing or stability monitoring, manufacturing controls, and packaging/storage conditions

Q11. Which ICH guideline specifically addresses degradation products in new drug products?

• ICH Q1A(R2) — Stability Testing of New Drug Substances and Products
• ICH Q3B(R2) — Impurities in New Drug Products
• ICH Q7 — Good Manufacturing Practice for APIs
• ICH Q8 — Pharmaceutical Development

Correct Answer: ICH Q3B(R2) — Impurities in New Drug Products

Q12. Photostability testing for degradation products is covered under which ICH guideline?

• ICH Q2(R1)
• ICH Q1B
• ICH Q3A(R2)
• ICH Q9

Correct Answer: ICH Q1B

Q13. Acceptance criteria for a degradation product limit should primarily be based on:

• How easy it is to measure by HPLC
• Available toxicological data and the clinical exposure (dose and duration)
• Historical levels observed in unrelated products
• Regulatory convenience rather than safety

Correct Answer: Available toxicological data and the clinical exposure (dose and duration)

Q14. Which statement correctly distinguishes identification from qualification of a degradation product?

• Identification requires toxicology studies; qualification requires only mass spectra
• Identification means the chemical structure has been elucidated; qualification means sufficient safety data exist to justify the proposed limit
• Identification is optional but qualification is mandatory for all DPs
• They are synonymous terms used interchangeably in guidelines

Correct Answer: Identification means the chemical structure has been elucidated; qualification means sufficient safety data exist to justify the proposed limit

Q15. If mass balance during a stability study is poor (significant loss of parent not accounted for), the most appropriate next step is:

• Ignore the discrepancy and publish the data
• Investigate further to detect/identify unknown degradation products and assess method specificity
• Reduce sample size to minimize perceived losses
• Assume loss is due to evaporation and report as such without testing

Correct Answer: Investigate further to detect/identify unknown degradation products and assess method specificity

Q16. Which approach is appropriate when a degradation product is observed at low levels but analytical variability is high?

• Set an arbitrary tight limit irrespective of variability
• Improve the analytical method (specificity/sensitivity/precision) and re-evaluate the control limit based on method performance and safety considerations
• Discontinue testing since variability obscures results
• Exclude the DP from reports if it’s below a random cut-off

Correct Answer: Improve the analytical method (specificity/sensitivity/precision) and re-evaluate the control limit based on method performance and safety considerations

Q17. During accelerated stability, a previously unseen DP appears above the established control threshold. The best course of action is to:

• Immediately recall all batches without investigation
• Conduct identification and toxicological assessment, reassess formulation/packaging, and update specifications or control strategy as needed
• Ignore it until real-time stability confirms the trend
• Adjust QC acceptance criteria upward for convenience

Correct Answer: Conduct identification and toxicological assessment, reassess formulation/packaging, and update specifications or control strategy as needed

Q18. High-resolution MS is particularly valuable for degradation product work because it:

• Is cheaper than UV detection
• Provides accurate mass measurements that help deduce elemental composition and likely structures
• Automatically provides toxicological safety data
• Does not require chromatography

Correct Answer: Provides accurate mass measurements that help deduce elemental composition and likely structures

Q19. Why are reporting thresholds used in impurity/degradation studies?

• To hide data from regulators
• To prioritize resources on impurities that are analytically detectable and potentially relevant to safety or quality
• To prevent method development work
• To limit the amount of required documentation arbitrarily

Correct Answer: To prioritize resources on impurities that are analytically detectable and potentially relevant to safety or quality

Q20. How do degradation products differ from extractables and leachables in the context of product safety assessment?

• Degradation products are always more toxic than leachables
• Degradation products are formed by chemical change of the drug or excipients; extractables/leachables originate from packaging or device materials and migrate into the product
• They are identical concepts used in different disciplines
• Extractables are only formed during photostability testing whereas degradation products are not

Correct Answer: Degradation products are formed by chemical change of the drug or excipients; extractables/leachables originate from packaging or device materials and migrate into the product

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