Bioequivalence studies and regulatory aspects MCQs With Answer

Bioequivalence studies and regulatory aspects MCQs With Answer

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Bioequivalence studies and regulatory aspects MCQs With Answer

Bioequivalence studies assess whether two drug products (usually a generic and a reference) have comparable pharmacokinetics — mainly AUC and Cmax — ensuring equivalent rate and extent of absorption. B.Pharm students should understand study designs (crossover, replicate), statistical concepts (log-transformation, 90% CI, TOST), regulatory criteria (80–125% limits, EMA/FDA/CDSCO guidelines), biowaivers (BCS), and special cases (narrow therapeutic index, highly variable drugs, fed vs fasting). This concise review emphasizes practical and regulatory considerations, sample size, analytical requirements, and dissolution correlation to support approval of generics. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary definition of bioequivalence?

  • Two products have identical inactive ingredients
  • Two products have no significant difference in the rate and extent of absorption
  • Two products are manufactured in the same facility
  • Two products cost the same

Correct Answer: Two products have no significant difference in the rate and extent of absorption

Q2. Which pharmacokinetic parameters are most commonly used as primary endpoints in BE studies?

  • Tmax and half-life
  • AUC and Cmax
  • Volume of distribution and clearance
  • Protein binding and bioavailability percentage

Correct Answer: AUC and Cmax

Q3. What is the usual regulatory acceptance range for the 90% confidence interval of the geometric mean ratio for AUC and Cmax?

  • 70%–140%
  • 80%–125%
  • 90%–110%
  • 85%–115%

Correct Answer: 80%–125%

Q4. Which confidence interval is typically used to demonstrate bioequivalence?

  • 95% CI
  • 99% CI
  • 90% CI
  • 80% CI

Correct Answer: 90% CI

Q5. Why are AUC and Cmax data usually log-transformed before statistical analysis?

  • To normalize skewed PK data and make ratios interpretable
  • To simplify plotting
  • To avoid using ANOVA
  • To change units from mg to μg

Correct Answer: To normalize skewed PK data and make ratios interpretable

Q6. What is the most common clinical study design for single-dose BE studies in healthy volunteers?

  • Parallel design with multiple arms
  • Randomized two-period crossover
  • Open-label single-arm
  • Case-control design

Correct Answer: Randomized two-period crossover

Q7. When is a fed BE study required in addition to a fasting study?

  • Only when the drug is an injectable
  • When food significantly affects the bioavailability of the drug
  • For all topical products
  • Never; fasting studies are always sufficient

Correct Answer: When food significantly affects the bioavailability of the drug

Q8. Which AUC measure is typically considered primary if AUC extrapolation is minimal?

  • AUC0–t
  • AUC0–inf only
  • AUC between Tmax and tlast
  • Partial AUC only

Correct Answer: AUC0–t

Q9. What statistical method is commonly used to compare Tmax between products?

  • Parametric ANOVA on log-transformed Tmax
  • Nonparametric tests such as the Wilcoxon signed-rank test
  • Chi-square test
  • Kaplan–Meier survival analysis

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

Q10. How are narrow therapeutic index (NTI) drugs usually handled in regulatory BE assessments?

  • Same 80–125% limits as all drugs
  • Tighter bioequivalence limits such as 90–111% or other tightened criteria
  • No BE studies are required
  • Only in vitro tests are accepted

Correct Answer: Tighter bioequivalence limits such as 90–111% or other tightened criteria

Q11. Which BCS classes are commonly eligible for a biowaiver for immediate-release oral solid dosage forms?

  • BCS Class II and IV
  • BCS Class I and sometimes Class III
  • Only BCS Class IV
  • All four BCS classes

Correct Answer: BCS Class I and sometimes Class III

Q12. What product is typically used as the reference in a bioequivalence study?

  • Any marketed generic product
  • The innovator (originator) marketed reference product
  • A locally compounded formulation
  • A laboratory placebo

Correct Answer: The innovator (originator) marketed reference product

Q13. Which factors primarily determine the sample size for a BE study?

  • Color of the tablet and branding
  • Within-subject variability, desired power, and expected ratio
  • Study budget only
  • Number of investigators

Correct Answer: Within-subject variability, desired power, and expected ratio

Q14. Why are replicate crossover designs used in BE studies?

  • To reduce drug costs
  • To estimate within-subject variability and allow scaled approaches for highly variable drugs
  • To avoid blood sampling
  • To randomize more treatments

Correct Answer: To estimate within-subject variability and allow scaled approaches for highly variable drugs

Q15. How is carry-over effect minimized in crossover BE studies?

  • By using unmatched products
  • By an adequate washout period before the next period
  • By not randomizing sequence
  • By increasing dose each period

Correct Answer: By an adequate washout period before the next period

Q16. The 80–125% bioequivalence limits apply to which statistical measure?

  • Arithmetic mean difference
  • Ratio of geometric means of the test/reference
  • Median of absolute differences
  • Standard deviation ratio

Correct Answer: Ratio of geometric means of the test/reference

Q17. If an initial BE study fails due to high variability, what is an appropriate regulatory strategy?

  • Ignore results and market the product
  • Conduct a replicate study and consider scaled average bioequivalence or increase sample size
  • Change the reference product
  • Reduce the dose

Correct Answer: Conduct a replicate study and consider scaled average bioequivalence or increase sample size

Q18. When is reference-scaled average bioequivalence applied?

  • For drugs with low within-subject variability
  • For highly variable drugs with high within-subject CV typically >30%
  • Only for injectables
  • For topical products

Correct Answer: For highly variable drugs with high within-subject CV typically >30%

Q19. What FDA therapeutic equivalence code indicates a therapeutically equivalent generic?

  • AA
  • AB
  • BC
  • CC

Correct Answer: AB

Q20. For modified-release oral dosage forms, what type of BE study is often required?

  • Single-dose fasting only
  • Multiple-dose steady-state or special design justified for release characteristics
  • Topical irritation study
  • Inhalation challenge test

Correct Answer: Multiple-dose steady-state or special design justified for release characteristics

Q21. Which ethical and quality standard is essential for conducting BE studies in human volunteers?

  • Good Laboratory Practice only
  • Informed consent and compliance with ICH-GCP
  • No documentation required
  • Only animal ethics are needed

Correct Answer: Informed consent and compliance with ICH-GCP

Q22. What is a recommended minimum washout period between periods in a crossover BE study?

  • At least 1 half-life
  • At least 5 half-lives of the drug
  • No washout is needed
  • At least 24 hours regardless of half-life

Correct Answer: At least 5 half-lives of the drug

Q23. When calculating AUC0–inf, what is the acceptable percentage of AUC extrapolated beyond tlast?

  • Less than 5%
  • Generally less than 20%
  • More than 50% is acceptable
  • Extrapolation percentage is not relevant

Correct Answer: Generally less than 20%

Q24. Which factors are typically included in the ANOVA model for BE studies?

  • Treatment only
  • Sequence, subject(sequence), period, and treatment
  • Investigator and site only
  • Age and gender only

Correct Answer: Sequence, subject(sequence), period, and treatment

Q25. How are biological products (biologics) treated differently from small-molecule generics in regulatory pathways?

  • They follow the same BE rules as small molecules
  • They require biosimilarity demonstration including analytical comparability and clinical/immunogenicity data
  • No regulatory oversight is needed
  • Only in vitro tests are required

Correct Answer: They require biosimilarity demonstration including analytical comparability and clinical/immunogenicity data

Q26. Which hypothesis testing approach is commonly used to demonstrate equivalence in BE studies?

  • Two one-sided t-tests (TOST)
  • Single two-sided t-test
  • One-sided chi-square test
  • Kaplan–Meier test

Correct Answer: Two one-sided t-tests (TOST)

Q27. When should a fed BE study be performed even if the label does not require food administration?

  • If the drug has a narrow therapeutic index
  • If the test formulation’s absorption is likely altered by food or the reference is labeled to be taken with food
  • Only for pediatric formulations
  • Fed studies are never required unless requested by sponsor

Correct Answer: If the test formulation’s absorption is likely altered by food or the reference is labeled to be taken with food

Q28. What role does in vitro dissolution testing play in BE and regulatory submissions?

  • It has no regulatory value
  • It supports quality, can predict in vivo behavior, and may support biowaivers
  • It replaces clinical studies in all cases
  • It only measures tablet hardness

Correct Answer: It supports quality, can predict in vivo behavior, and may support biowaivers

Q29. Which parameter best reflects the extent of drug absorption and which reflects the rate?

  • Extent = Cmax; Rate = AUC
  • Extent = AUC; Rate = Cmax
  • Extent = Tmax; Rate = half-life
  • Extent = bioavailability percentage only; Rate = volume of distribution

Correct Answer: Extent = AUC; Rate = Cmax

Q30. Which Indian regulatory authority oversees approval of BE studies and generic drug approvals?

  • FDA (United States)
  • European Medicines Agency (EMA)
  • Central Drugs Standard Control Organization (CDSCO)
  • World Health Organization (WHO)

Correct Answer: Central Drugs Standard Control Organization (CDSCO)

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