Concept of bioequivalence MCQs With Answer

Introduction: Concept of Bioequivalence MCQs With Answer

This collection of multiple-choice questions is tailored for M.Pharm students studying Modern Bio-Analytical Techniques (MPA 202T). The quiz covers core bioequivalence concepts including pharmacokinetic metrics (AUC, Cmax, Tmax), study designs (cross-over, replicate), regulatory acceptance criteria (80–125% and 90% confidence intervals), statistical approaches (log-transformation, ANOVA), biowaiver principles, and special topics such as highly variable drugs, narrow therapeutic index drugs, and reference-scaled average bioequivalence. Questions are designed to deepen understanding, reinforce calculations and study planning considerations, and link theoretical knowledge with regulatory expectations from agencies like FDA and EMA. Use these MCQs to assess and strengthen your applied bioequivalence skills.

Q1. Which pharmacokinetic parameter primarily reflects the extent of drug absorption in a bioequivalence study?

• Maximum plasma concentration (Cmax)
• Time to reach maximum concentration (Tmax)
• Area under the plasma concentration–time curve (AUC)
• Elimination half-life (t1/2)

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

Q2. Regulatory bioequivalence acceptance limits for AUC and Cmax for most immediate-release generics are typically expressed as which of the following?

• 90% confidence interval within 70–130%
• 95% confidence interval within 80–125%
• 90% confidence interval within 80–125%
• One-sided 97.5% confidence interval within 75–133%

Correct Answer: 90% confidence interval within 80–125%

Q3. Why are pharmacokinetic metrics typically log-transformed before statistical analysis in bioequivalence studies?

• To linearize elimination kinetics for half-life estimation
• To normalize distribution and stabilize variance for ratio-based comparisons
• To alter Tmax distribution to a normal form
• To convert concentration units to percentage differences

Correct Answer: To normalize distribution and stabilize variance for ratio-based comparisons

Q4. Which study design is most commonly used for single-dose bioequivalence trials?

• Parallel-group design
• Two-period two-sequence crossover design
• Multiple ascending dose open-label study
• Population pharmacokinetic pooled design

Correct Answer: Two-period two-sequence crossover design

Q5. In a crossover bioequivalence study, the washout period is chosen primarily to:

• Ensure carryover effects are negligible by allowing >5 half-lives before next period
• Reduce variability by giving subjects a drug holiday for several months
• Permit sampling for Tmax over an extended time
• Allow subjects to develop tolerance to the drug

Correct Answer: Ensure carryover effects are negligible by allowing >5 half-lives before next period

Q6. Which parameter is most sensitive to differences in the rate of absorption between test and reference products?

• AUC0–t
• AUC0–inf
• Cmax
• Elimination rate constant (ke)

Correct Answer: Cmax

Q7. For drugs categorized under the Biopharmaceutics Classification System (BCS), which condition can allow a biowaiver for in vivo bioequivalence studies?

• BCS Class IV with documented clinical equivalence
• BCS Class I with high solubility and high permeability and rapid dissolution of the test product
• BCS Class II with slow dissolution but high permeability
• Any class if formulation excipients are identical

Correct Answer: BCS Class I with high solubility and high permeability and rapid dissolution of the test product

Q8. Which statistical method is commonly used to assess bioequivalence after log-transformation of AUC and Cmax?

• Paired t-test on raw values
• ANOVA followed by calculation of 90% confidence intervals for geometric mean ratios
• Mann–Whitney U test
• Chi-square test for proportions

Correct Answer: ANOVA followed by calculation of 90% confidence intervals for geometric mean ratios

Q9. Which regulatory approach is used when dealing with highly variable drugs to avoid large sample sizes?

• Parallel design equivalence testing
• Reference-scaled average bioequivalence (RSABE)
• Use of a stricter 75–133% fixed acceptance range
• Replacing AUC with Tmax as the primary metric

Correct Answer: Reference-scaled average bioequivalence (RSABE)

Q10. What is the main objective of conducting a replicate design in bioequivalence studies?

• To measure elimination half-life more accurately
• To allow estimation of within-subject variability for reference-scaling
• To shorten the overall study duration
• To avoid the need for washout periods

Correct Answer: To allow estimation of within-subject variability for reference-scaling

Q11. Which of the following best describes AUC0–t and AUC0–inf in bioequivalence evaluation?

• AUC0–t estimates extent up to last measurable concentration, AUC0–inf includes extrapolated terminal area
• AUC0–t is rate-related, AUC0–inf is absorption-related
• Both are measures of Tmax variability
• AUC0–inf is only used for IV formulations

Correct Answer: AUC0–t estimates extent up to last measurable concentration, AUC0–inf includes extrapolated terminal area

Q12. Which outcome could invalidate a crossover bioequivalence study interpretation due to sequence or carryover effects?

• Non-significant period effect in ANOVA
• Significant sequence effect suggesting residual carryover
• Identical mean AUC in both periods
• Low within-subject variability

Correct Answer: Significant sequence effect suggesting residual carryover

Q13. In assessing bioequivalence for a narrow therapeutic index (NTI) drug, regulators may:

• Widen the acceptance limits to 75–133% because variability is expected
• Apply tighter acceptance limits, for example 90–111% for AUC
• Ignore Cmax and focus only on Tmax
• Use population bioequivalence only

Correct Answer: Apply tighter acceptance limits, for example 90–111% for AUC

Q14. Which bioequivalence metric is most appropriate to assess partial absorption during a specific early time window (e.g., when early exposure is clinically relevant)?

• Partial AUC (pAUC)
• Total AUC (AUC0–inf)
• Elimination half-life (t1/2)
• Clearance (CL/F)

Correct Answer: Partial AUC (pAUC)

Q15. Which in vitro–in vivo correlation (IVIVC) level is considered the most predictive for regulatory biowaivers and formulation development?

• Level A — point-to-point correlation of in vitro dissolution and in vivo input rate
• Level B — statistical moment analysis correlation
• Level C — single-point correlation (e.g., percent dissolved at a single time)
• Level D — qualitative correlation

Correct Answer: Level A — point-to-point correlation of in vitro dissolution and in vivo input rate

Q16. Which factor is least likely to affect bioequivalence outcomes between test and reference oral formulations?

• Formulation excipients altering dissolution
• Differences in particle size distribution affecting dissolution
• Analytical method precision for PK sample assays
• Color of the tablet coating without affecting release

Correct Answer: Color of the tablet coating without affecting release

Q17. Population bioequivalence (PBE) differs from average bioequivalence (ABE) mainly because PBE:

• Requires only mean comparisons between formulations
• Assesses differences in means and variances to address switchability in the population
• Is used only for injectable drugs
• Does not consider within-subject variability

Correct Answer: Assesses differences in means and variances to address switchability in the population

Q18. When calculating sample size for a bioequivalence study, which parameter has the greatest influence on required subject numbers?

• Assumed within-subject coefficient of variation (CV)
• Color of capsules used in the study
• Number of blood sampling timepoints beyond those needed to define AUC
• Investigator site location

Correct Answer: Assumed within-subject coefficient of variation (CV)

Q19. Which of the following is a valid justification for using truncated AUC in a bioequivalence study?

• The drug has an extremely long half-life making AUC0–inf impractical within study constraints
• The drug shows identical Tmax for test and reference
• To avoid analysing Cmax altogether
• Regulators never accept truncated AUC

Correct Answer: The drug has an extremely long half-life making AUC0–inf impractical within study constraints

Q20. Which regulatory agency explicitly provides guidances on bioequivalence study design and statistical evaluation commonly used worldwide?

• World Health Organization (WHO) exclusively
• Food and Drug Administration (FDA) and European Medicines Agency (EMA)
• Local hospital ethics committees only
• International Air Transport Association (IATA)

Correct Answer: Food and Drug Administration (FDA) and European Medicines Agency (EMA)

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