Bioequivalence and its significance MCQs With Answer

Introduction: This quiz collection on Bioequivalence and its Significance is designed for M.Pharm students preparing for exams and practical application in regulatory pharmaceutics. It covers core concepts — definitions, pharmacokinetic parameters (AUC, Cmax, Tmax), study designs (crossover, replicate), statistical approaches (log-transformation, 90% confidence intervals), regulatory acceptance criteria, BCS-based biowaivers, food effects, analytical methods and special topics such as highly variable and narrow therapeutic index drugs. Each question aims to reinforce understanding needed for designing, analyzing and interpreting bioequivalence studies and for appreciating their role in generic drug approval, therapeutic interchangeability and patient safety. Test yourself and use explanations to identify areas for deeper study.

Q1. What is the standard regulatory definition of bioequivalence?

• Two products have identical excipients and manufacturing processes
• Two products show no difference in in vitro dissolution profile only
• Two products produce equivalent rate and extent of absorption of the active ingredient
• Two products have the same labeling and packaging

Correct Answer: Two products produce equivalent rate and extent of absorption of the active ingredient

Q2. What are the commonly accepted bioequivalence limits for the 90% confidence interval of the geometric mean ratio for AUC and Cmax?

• 70%–130%
• 80%–125%
• 90%–111%
• 50%–150%

Correct Answer: 80%–125%

Q3. Which confidence interval is typically used to assess bioequivalence?

• 95% confidence interval
• 99% confidence interval
• 90% confidence interval
• 80% confidence interval

Correct Answer: 90% confidence interval

Q4. Which pharmacokinetic parameter is the primary measure of the extent of absorption?

• Cmax (maximum plasma concentration)
• Tmax (time to reach Cmax)
• AUC (area under the plasma concentration–time curve)
• t1/2 (elimination half-life)

Correct Answer: AUC (area under the plasma concentration–time curve)

Q5. Which parameter is most commonly used as an indicator of the rate of absorption?

• AUC0–t
• Clearance
• Cmax
• AUC0–inf

Correct Answer: Cmax

Q6. Which study design is most commonly used for single-dose bioequivalence trials in healthy volunteers?

• Parallel-group randomized design
• Randomized two-period two-sequence crossover design (2×2)
• Single-arm open-label design
• Case–control observational design

Correct Answer: Randomized two-period two-sequence crossover design (2×2)

Q7. On which scale are primary pharmacokinetic parameters usually analyzed statistically for bioequivalence?

• Arithmetic scale without transformation
• Log-transformed scale (natural log of PK parameters)
• Rank-transformed nonparametric scale
• Square-root transformed scale

Correct Answer: Log-transformed scale (natural log of PK parameters)

Q8. For which Biopharmaceutics Classification System (BCS) class is a biowaiver most commonly granted for immediate-release oral products?

• BCS Class II (low solubility, high permeability)
• BCS Class IV (low solubility, low permeability)
• BCS Class I (high solubility, high permeability)
• BCS Class III (high solubility, low permeability)

Correct Answer: BCS Class I (high solubility, high permeability)

Q9. Which analytical requirement is essential for concentration measurement in bioequivalence studies?

• Use of a non-validated immunoassay
• Validated sensitive and specific bioanalytical method (e.g., LC-MS/MS)
• Visual colorimetric assay without validation
• External literature values for concentrations

Correct Answer: Validated sensitive and specific bioanalytical method (e.g., LC-MS/MS)

Q10. For narrow therapeutic index drugs, regulatory agencies may require tightened bioequivalence limits. Which example illustrates such tighter limits?

• Tighter limits are never required
• Tighter limits such as 90%–111% for AUC
• Wider limits such as 70%–143% for AUC
• Use of 99% confidence interval instead of 90%

Correct Answer: Tighter limits such as 90%–111% for AUC

Q11. When is it necessary to conduct both fasting and fed bioequivalence studies?

• Only when the reference product is labeled to be taken with food
• When food has no impact on drug absorption
• When regulatory guidance or product labeling requires assessment of food effect (e.g., reference labeled with food)
• Always, even for parenteral products

Correct Answer: When regulatory guidance or product labeling requires assessment of food effect (e.g., reference labeled with food)

Q12. What is the purpose of a replicate crossover design in bioequivalence studies?

• To avoid randomization
• To increase formulation variability intentionally
• To allow estimation of within-subject variability and enable reference-scaled approaches for highly variable drugs
• To shorten the washout period

Correct Answer: To allow estimation of within-subject variability and enable reference-scaled approaches for highly variable drugs

Q13. Which statistical ANOVA effect is commonly inspected to detect potential carryover in a 2×2 crossover BE study?

• Subject nested within sequence effect
• Period effect only
• Sequence effect (significant sequence suggests possible carryover)
• Residual error only

Correct Answer: Sequence effect (significant sequence suggests possible carryover)

Q14. How long should blood sampling continue in a single-dose BE study to reliably estimate AUC0–inf?

• Until one terminal half-life only
• At least 3–5 terminal half-lives and such that AUC extrapolated portion is acceptably small (e.g., <20%)
• Only until Cmax is observed
• Until the first measurable concentration

Correct Answer: At least 3–5 terminal half-lives and such that AUC extrapolated portion is acceptably small (e.g., <20%)

Q15. Which statement best describes why PK parameters are log-transformed before statistical comparison in BE studies?

• Log-transformation makes the data integer values
• Log-transformation corrects for subject dropouts
• Log-transformation stabilizes variance and makes ratios of geometric means appropriate for inference
• Log-transformation eliminates the need for ANOVA

Correct Answer: Log-transformation stabilizes variance and makes ratios of geometric means appropriate for inference

Q16. Which advantage is specifically associated with replicate designs compared to a simple 2×2 crossover?

• They eliminate the need for bioanalytical validation
• They allow direct estimation of within-subject variability for each treatment
• They require fewer subjects than any other design always
• They remove the requirement for washout periods

Correct Answer: They allow direct estimation of within-subject variability for each treatment

Q17. Which AUC measure is most commonly used as the primary extent parameter in BE trials when sampling covers the dosing interval adequately?

• AUC extrapolated from last measurable concentration to infinity only
• AUC0–t (area under the curve from zero to last measurable concentration)
• Only AUC0–inf when extrapolated portion is >50%
• Trough concentration (Cmin)

Correct Answer: AUC0–t (area under the curve from zero to last measurable concentration)

Q18. How can formulation excipients affect bioequivalence?

• Excipients are always inert and have no effect on bioavailability
• Excipients can alter drug dissolution, permeability or gastric residence and thus change bioavailability
• Excipients only affect color and have no clinical relevance
• Excipients only influence stability during storage, not PK

Correct Answer: Excipients can alter drug dissolution, permeability or gastric residence and thus change bioavailability

Q19. Which observation would most likely indicate an immediate-release formulation compared to a modified-release formulation?

• Markedly delayed Tmax and lower Cmax
• Earlier Tmax and higher initial slope of absorption
• Complete absence of Cmax
• Longer apparent half-life without change in absorption

Correct Answer: Earlier Tmax and higher initial slope of absorption

Q20. Which method is typically used in noncompartmental analysis to calculate AUC in bioequivalence studies?

• Compartmental modeling using Bayesian priors only
• Trapezoidal rule applied to observed concentration–time data
• Visual estimation from plotted curves only
• Fourier transform analysis

Correct Answer: Trapezoidal rule applied to observed concentration–time data

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