Clinical significance of bioequivalence studies MCQs With Answer

Clinical significance of bioequivalence studies MCQs With Answer

Introduction: This quiz collection is designed for M.Pharm students studying Modern Bio-Analytical Techniques (MPA 202T). It focuses on the clinical importance of bioequivalence (BE) studies, emphasizing how BE ensures therapeutic interchangeability between generic and reference products. Questions cover pharmacokinetic endpoints, study designs, statistical approaches, regulatory acceptance criteria, special cases like highly variable drugs and narrow therapeutic index drugs, and practical considerations such as washout periods, in vitro–in vivo correlations and biowaivers. These MCQs aim to deepen conceptual understanding and prepare students for examinations and real-world BE study interpretation, helping link analytical data to clinical outcomes.

Q1. What is the primary clinical significance of conducting a bioequivalence study for a generic drug?

• To demonstrate identical excipient composition between formulations
• To confirm the generic product has the same marketing authorization holder
• To show therapeutic equivalence through comparable systemic exposure of active moiety
• To assess local tissue concentrations at the administration site

Correct Answer: To show therapeutic equivalence through comparable systemic exposure of active moiety

Q2. Which pharmacokinetic parameters are routinely used as primary endpoints in standard single-dose BE studies?

• Tmax and Tlag
• AUC and Cmax
• Volume of distribution and clearance
• Half-life and protein binding

Correct Answer: AUC and Cmax

Q3. What is the commonly accepted regulatory criterion for declaring average bioequivalence for AUC and Cmax?

• 95% confidence interval of mean difference within ±20% on arithmetic scale
• 90% confidence interval for the geometric mean ratio within 80–125%
• Two-sided p-value < 0.05 comparing means
• 99% confidence interval for geometric mean ratio within 70–143%

Correct Answer: 90% confidence interval for the geometric mean ratio within 80–125%

Q4. Why are PK data usually log-transformed before statistical analysis in BE studies?

• To simplify calculation of arithmetic means
• To convert ratios to differences and stabilize variance, producing approximate normality
• To remove units from concentration data
• To make Tmax values comparable across subjects

Correct Answer: To convert ratios to differences and stabilize variance, producing approximate normality

Q5. Which study design is most commonly employed for single-dose BE assessment of immediate-release oral products?

• Parallel-group design with many subjects per arm
• Two-period, two-sequence crossover design
• Open-label uncontrolled single-arm study
• Single-period repeated dosing without washout

Correct Answer: Two-period, two-sequence crossover design

Q6. For highly variable drugs (within-subject CV > ~30%), which approach is often used to improve chances of demonstrating BE?

• Switch from crossover to parallel design
• Use replicate crossover designs or reference-scaled average BE methods
• Ignore variability and increase sampling frequency
• Require only point estimate without confidence interval

Correct Answer: Use replicate crossover designs or reference-scaled average BE methods

Q7. What is the primary purpose of including an adequate washout period between treatment periods in crossover BE studies?

• To allow blinding of subjects
• To avoid carryover of drug from the first period into the next period
• To save costs by reducing sampling needs
• To permit re-randomization of treatment sequences

Correct Answer: To avoid carryover of drug from the first period into the next period

Q8. Which Biopharmaceutics Classification System (BCS) classes are commonly eligible for regulatory biowaivers for immediate-release solid oral dosage forms?

• BCS Class I (high solubility, high permeability) and sometimes Class III (high solubility, low permeability)
• BCS Class II and IV only
• All four BCS classes are always eligible
• Only BCS Class IV

Correct Answer: BCS Class I (high solubility, high permeability) and sometimes Class III (high solubility, low permeability)

Q9. What does reference-scaled average bioequivalence adjust for when assessing BE?

• Inter-subject variability regardless of reference variability
• Within-subject variability of the reference product to widen or tighten BE limits
• Manufacturing differences like tablet hardness
• Demographic differences between study sites

Correct Answer: Within-subject variability of the reference product to widen or tighten BE limits

Q10. Which factor most strongly influences the sample size required for a BE study?

• The study site location
• The within-subject variability of the measured PK parameter
• The brand recognition of the reference product
• The number of blood draws only

Correct Answer: The within-subject variability of the measured PK parameter

Q11. Which statistical method is most appropriate for comparing Tmax between test and reference in many BE studies?

• Parametric t-test on log-transformed Tmax
• Nonparametric tests such as the Wilcoxon rank-sum or signed-rank test
• Chi-square test
• ANOVA on untransformed Tmax with equal variances assumed

Correct Answer: Nonparametric tests such as the Wilcoxon rank-sum or signed-rank test

Q12. Why might partial AUC metrics be included in BE evaluation for modified-release formulations?

• Partial AUCs are easier to compute than total AUC
• They assess exposure in specific time windows important for therapeutic effect or safety
• They replace the need for Cmax assessment entirely
• They eliminate the need for statistical analysis

Correct Answer: They assess exposure in specific time windows important for therapeutic effect or safety

Q13. Which level of in vitro–in vivo correlation (IVIVC) can predict the entire plasma concentration–time profile and support dissolution-based BE waivers?

• Level D IVIVC
• Level A IVIVC
• Level B IVIVC
• Level C IVIVC

Correct Answer: Level A IVIVC

Q14. Which statistical indicator in an ANOVA model can suggest a carryover effect in a crossover BE study?

• Significant sequence-by-period interaction only
• Significant period effect only
• Significant sequence (or carryover) effect
• Significant treatment effect

Correct Answer: Significant sequence (or carryover) effect

Q15. How are bioequivalence requirements typically changed for narrow therapeutic index (NTI) drugs?

• They allow wider BE limits than 80–125%
• They often mandate stricter (narrower) BE acceptance limits and/or additional study requirements
• BE is not required for NTI drugs
• Only in vitro tests are used for NTI drugs

Correct Answer: They often mandate stricter (narrower) BE acceptance limits and/or additional study requirements

Q16. The reference-scaled average BE approach requires which of the following estimates to scale the BE limits?

• Inter-subject variance of the test product only
• Within-subject variance of the reference product
• Overall mean difference between formulations without variance
• Between-period variance only

Correct Answer: Within-subject variance of the reference product

Q17. For a prodrug that is inactive until converted to an active metabolite, what is usually the appropriate analyte to compare in a BE study?

• Only the parent prodrug concentrations
• Active moiety (active metabolite) concentrations, if clinically relevant
• Urinary excretion of unchanged prodrug only
• Concentration of excipients

Correct Answer: Active moiety (active metabolite) concentrations, if clinically relevant

Q18. Why are equivalence margins in BE studies defined based on ratios rather than absolute differences?

• Ratios reflect proportional differences in exposure and are scale-independent for PK metrics
• Absolute differences are easier to interpret clinically
• Regulators prefer arithmetic means only
• Absolute differences cannot be calculated from concentration data

Correct Answer: Ratios reflect proportional differences in exposure and are scale-independent for PK metrics

Q19. When measuring both parent drug and an active metabolite, what is a key consideration for BE interpretation?

• The metabolite is always ignored in BE assessment
• Which analyte (parent or metabolite) best reflects clinical activity and systemic exposure relevant to safety and efficacy
• Only urinary metabolite levels matter
• Only Cmax of metabolite should be compared

Correct Answer: Which analyte (parent or metabolite) best reflects clinical activity and systemic exposure relevant to safety and efficacy

Q20. Under which circumstances is a multiple-dose (steady-state) BE study preferred over a single-dose study?

• For drugs with very short half-lives that do not accumulate
• When the drug accumulates, has nonlinear kinetics, or when steady-state exposure is clinically relevant
• When only Cmax is of interest
• For immediate-release BCS Class I drugs with no accumulation

Correct Answer: When the drug accumulates, has nonlinear kinetics, or when steady-state exposure is clinically relevant

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