Accelerated stability testing: ICH/WHO guidelines and data interpretation MCQs With Answer

Introduction:

This quiz set on accelerated stability testing follows ICH and WHO principles and focuses on practical data interpretation for M.Pharm students. It covers accelerated study design, recommended conditions, statistical methods, degradation kinetics, Arrhenius extrapolation, photostability, forced degradation, and regulatory considerations. Questions emphasize how to interpret accelerated results for shelf-life estimation, when accelerated data are acceptable for extrapolation, and how to recognize changes in degradation mechanisms. These MCQs will help you consolidate concepts needed for designing studies, analyzing rate constants, and applying guidelines during product development and regulatory submissions.

Q1. What is the standard accelerated stability condition most commonly recommended by ICH for drug products in many climatic zones?

• 25°C / 60% RH
• 30°C / 65% RH
• 40°C / 75% RH
• 5°C / 60% RH

Correct Answer: 40°C / 75% RH

Q2. According to ICH Q1A(R2), how long is a typical accelerated stability study performed to support initial evaluation?

• 1 month
• 3 months
• 6 months
• 24 months

Correct Answer: 6 months

Q3. Which statement best describes the Arrhenius approach used in accelerated stability analysis?

• Plot percent remaining versus time to get activation energy directly
• Plot ln(k) versus 1/T to derive the activation energy from slope
• Use humidity alone to calculate shelf-life
• Use photostability data to estimate thermal degradation rates

Correct Answer: Plot ln(k) versus 1/T to derive the activation energy from slope

Q4. For a drug that follows first-order degradation, which formula gives the time to 90% label claim (t90)?

• t90 = 0.1053 / k
• t90 = (0.9 × C0) / k
• t90 = ln(2) / k
• t90 = k / 0.1053

Correct Answer: t90 = 0.1053 / k

Q5. Which condition must be met before using accelerated data to extrapolate shelf-life to long-term conditions?

• Accelerated study must always show no degradation
• Degradation mechanism and pathway must be the same at accelerated and real-time conditions
• Accelerated temperature must be lower than long-term temperature
• Only a single batch is required for extrapolation

Correct Answer: Degradation mechanism and pathway must be the same at accelerated and real-time conditions

Q6. Which ICH guideline specifically addresses photostability testing requirements?

• Q1A(R2)
• Q1B
• Q1E
• Q3B

Correct Answer: Q1B

Q7. ICH photostability testing requires exposure to what minimum light energy for visible light?

• 1.2 million lux hours
• 200 lux hours
• 100,000 lux hours
• 10 million lux hours

Correct Answer: 1.2 million lux hours

Q8. Which of the following describes “forced degradation” studies?

• Long-term stability testing under recommended storage conditions
• Stress testing under exaggerated conditions to identify degradation pathways
• Photostability testing only
• Microbiological challenge testing

Correct Answer: Stress testing under exaggerated conditions to identify degradation pathways

Q9. When using Arrhenius extrapolation, what does the slope of the ln(k) vs 1/T plot represent?

• Rate constant at standard temperature
• Activation energy divided by the gas constant with a negative sign
• Half-life value
• Intercept for zero-order kinetics

Correct Answer: Activation energy divided by the gas constant with a negative sign

Q10. Which kinetic order is commonly assumed when percent potency loss is proportional to concentration?

• Zero-order kinetics
• First-order kinetics
• Second-order kinetics
• Mixed-order kinetics only

Correct Answer: First-order kinetics

Q11. In stability data analysis, why is it important to check whether accelerated data show new degradation products not seen in real-time studies?

• New degradants indicate method sensitivity is insufficient
• New degradants may indicate a change in degradation mechanism and make extrapolation invalid
• New degradants always mean the product is unsafe
• New degradants are ignored for regulatory submissions

Correct Answer: New degradants may indicate a change in degradation mechanism and make extrapolation invalid

Q12. What is the primary purpose of bracketing and matrixing designs in accelerated stability testing?

• To reduce the number of analytical methods required
• To allow reduced testing by selecting representative strengths, presentations or storage conditions
• To increase the sample size for statistical power
• To determine microbiological stability

Correct Answer: To allow reduced testing by selecting representative strengths, presentations or storage conditions

Q13. Which statistical method is typically used to estimate shelf-life and provide confidence intervals from stability data?

• Non-linear regression with bootstrapping only
• Simple arithmetic averaging of measurements
• Linear regression of ln(concentration) (for first-order) and calculation of confidence limits
• ANOVA without regression

Correct Answer: Linear regression of ln(concentration) (for first-order) and calculation of confidence limits

Q14. A product shows linear ln(concentration) vs time at both 25°C and 40°C with the same degradation products. Which is a valid next step to estimate shelf-life at 25°C?

• Use the 40°C k value directly as the 25°C shelf-life
• Apply Arrhenius extrapolation using k values at multiple temperatures to determine k at 25°C
• Assume shelf-life is twice that at 40°C
• Ignore 40°C data and use only photostability results

Correct Answer: Apply Arrhenius extrapolation using k values at multiple temperatures to determine k at 25°C

Q15. What is the ICH/WHO recommended action if accelerated conditions produce irreversible physical changes (e.g., melting, phase separation) not seen at long-term conditions?

• Use accelerated data for shelf-life without modification
• Do not use accelerated data for extrapolation and investigate cause and appropriate packaging or formulation changes
• Discard long-term data and rely solely on accelerated results
• Assume packaging is adequate and proceed to market

Correct Answer: Do not use accelerated data for extrapolation and investigate cause and appropriate packaging or formulation changes

Q16. Which of the following is a WHO-specific consideration for stability testing of multi-source (generic) products?

• WHO requires only accelerated testing and never real-time studies
• WHO emphasizes testing relevant climatic zones and critical excipient equivalence for generics
• WHO does not recognize ICH guidelines
• WHO requires photostability only for injectables

Correct Answer: WHO emphasizes testing relevant climatic zones and critical excipient equivalence for generics

Q17. The Q10 rule is sometimes used for rough estimation. What does Q10 represent?

• The percent RH increase per 10°C
• The factor by which the reaction rate increases when temperature increases by 10°C
• The number of degradation products formed per 10°C
• The shelf-life in months at 10°C

Correct Answer: The factor by which the reaction rate increases when temperature increases by 10°C

Q18. In accelerated stability studies, why is container-closure system evaluation essential?

• Because container-closure has no impact on stability
• Because container-closure can interact with product or affect moisture ingress resulting in altered degradation
• Only aesthetics are assessed by container-closure testing
• Container-closure testing is only needed for clinical trials

Correct Answer: Because container-closure can interact with product or affect moisture ingress resulting in altered degradation

Q19. Which outcome from an accelerated study would most likely invalidate simple Arrhenius extrapolation to predict shelf-life?

• Consistent first-order kinetics at each temperature with identical degradants
• Non-linear Arrhenius plot indicating a change in activation energy across temperatures
• Parallel ln(k) plots across stresses
• Reversible physical changes that revert at room temperature

Correct Answer: Non-linear Arrhenius plot indicating a change in activation energy across temperatures

Q20. When analyzing accelerated stability results statistically, what is the regulatory-recommended confidence level often used for shelf-life estimation?

• 50% confidence interval
• 80% confidence interval
• 90% confidence interval
• 95% confidence interval

Correct Answer: 95% confidence interval

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