Regulatory aspects of BA/BE studies MCQs With Answer

Introduction

This blog provides a focused set of multiple-choice questions on the regulatory aspects of bioavailability (BA) and bioequivalence (BE) studies tailored for M.Pharm students preparing for exams and regulatory practice. It covers international and Indian regulatory guidance, study designs, statistical acceptance criteria, bioanalytical validation, study conduct requirements (GCP/GLP), special populations, and practical issues such as food effect, washout, and narrow therapeutic index considerations. Each question is crafted to deepen conceptual understanding and application of regulations to real-world BA/BE study planning, execution, and dossier preparation for generic drug approval. Answers are provided to enable self-assessment and targeted revision.

Q1. Which statistical criterion is most commonly used by regulatory agencies to conclude bioequivalence for AUC and Cmax in a standard two-period crossover study?

• Point estimate of the ratio within 90–110%
• 90% confidence interval for the geometric mean ratio within 80–125%
• P-value less than 0.05 for paired t-test
• 95% confidence interval for arithmetic means within 85–115%

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

Q2. For which scenario is a replicate design (e.g., four-period) preferred over a standard two-period crossover in bioequivalence studies?

• When the test product is an immediate-release tablet
• When within-subject variability of the reference is high and scaled average BE is considered
• When sample size needs to be minimized regardless of variability
• When only a single-dose fasting study is required

Correct Answer: When within-subject variability of the reference is high and scaled average BE is considered

Q3. According to common regulatory guidance, which pharmacokinetic parameter is considered the primary measure of extent of absorption in BA/BE studies?

• Cmax
• Tmax
• AUC (area under the concentration–time curve)
• Half-life (t1/2)

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

Q4. Which of the following is a key requirement for bioanalytical methods used in regulatory BA/BE studies?

• Only qualitative identification of analyte is required
• Validation demonstrating accuracy, precision, selectivity, sensitivity, and stability
• Calibration using a single concentration standard only
• No need to assess matrix effects for LC-MS/MS methods

Correct Answer: Validation demonstrating accuracy, precision, selectivity, sensitivity, and stability

Q5. What regulatory concept allows waiver of in vivo bioequivalence studies for certain immediate-release solid oral dosage forms?

• Adaptive licensing
• Biowaiver under the Biopharmaceutics Classification System (BCS)
• Orphan drug designation
• Emergency use authorization

Correct Answer: Biowaiver under the Biopharmaceutics Classification System (BCS)

Q6. For narrow therapeutic index (NTI) drugs, how do regulatory agencies typically modify bioequivalence acceptance criteria?

• Wider acceptance limits of 70–143% for 90% CI
• Use only Tmax for equivalence assessment
• Narrower acceptance limits (e.g., 90–111% for 90% CI) or stricter requirements
• Exemption from bioequivalence studies

Correct Answer: Narrower acceptance limits (e.g., 90–111% for 90% CI) or stricter requirements

Q7. Which document is usually required by regulators to justify conducting a BA/BE study in India for an investigational generic product?

• Investigator’s brochure only
• Clinical trial registry entry without dossier
• Regulatory submission dossier including protocol, manufacturing details, and CMC information
• Marketing authorization for the innovator product only

Correct Answer: Regulatory submission dossier including protocol, manufacturing details, and CMC information

Q8. In a fed vs fasting bioequivalence study, which regulatory position is generally correct?

• Fed studies are never required if a fasting study is done
• Fed study is required if the label states dosage with food or if food significantly affects PK
• Only fed studies are acceptable; fasting studies are obsolete
• Food effect studies are only required for parenteral products

Correct Answer: Fed study is required if the label states dosage with food or if food significantly affects PK

Q9. Which parameter is most sensitive to differences in rate of absorption between test and reference products?

• AUC0–∞
• Cmax
• Apparent volume of distribution
• Elimination rate constant (kel)

Correct Answer: Cmax

Q10. What is the common regulatory requirement regarding subjects in a BA/BE crossover study?

• Patients with the target disease only
• Healthy volunteers are typically used unless safety or therapeutic considerations require patients
• Only elderly subjects are acceptable
• Subjects must be of the same gender

Correct Answer: Healthy volunteers are typically used unless safety or therapeutic considerations require patients

Q11. In the context of regulatory reporting, what is the significance of the power calculation performed before a BA/BE study?

• To determine the elimination half-life of the drug
• To estimate required sample size to achieve desired probability of demonstrating BE given variability
• To validate the bioanalytical assay
• To set the washout period duration

Correct Answer: To estimate required sample size to achieve desired probability of demonstrating BE given variability

Q12. Which regulatory principle governs the duration of the washout period between periods in a crossover BA/BE study?

• At least one hour between doses
• Washout should be long enough to allow carryover negligible, typically ≥5 elimination half-lives of the drug
• Washout is unnecessary in replicate designs
• Washout period should equal Tmax

Correct Answer: Washout should be long enough to allow carryover negligible, typically ≥5 elimination half-lives of the drug

Q13. Which of the following is a regulatory expectation when submitting BE study data in a marketing authorization application?

• Only summary statements without raw data
• Complete study report including protocol, statistical analysis plan, raw data listings, and validated bioanalytical method details
• Photocopies of lab notebooks without method validation
• Only pharmacodynamic endpoints are necessary

Correct Answer: Complete study report including protocol, statistical analysis plan, raw data listings, and validated bioanalytical method details

Q14. What is the main regulatory rationale for performing BE studies for generic drug approval?

• To demonstrate identical manufacturing processes
• To demonstrate therapeutic equivalence by showing similar rate and extent of absorption compared to the reference
• To establish new indications for the drug
• To compare taste and color of formulations

Correct Answer: To demonstrate therapeutic equivalence by showing similar rate and extent of absorption compared to the reference

Q15. When can a single-dose BE study be considered sufficient instead of a multiple-dose study according to regulators?

• When drug exhibits nonlinear accumulation at clinical doses
• When drug is rapidly eliminated and reaches steady state without accumulation concerns, and guidelines allow single-dose studies
• When drug has a half-life longer than one month
• When the product is a parenteral depot formulation

Correct Answer: When drug is rapidly eliminated and reaches steady state without accumulation concerns, and guidelines allow single-dose studies

Q16. What is “scaled average bioequivalence” and when is it applied?

• A method to scale dose based on body weight for pediatrics
• A statistical approach that adjusts BE acceptance limits based on reference within-subject variability, applied for highly variable drugs
• An approach to scale bioanalytical concentrations using internal standards
• A method to combine fasting and fed study results into one metric

Correct Answer: A statistical approach that adjusts BE acceptance limits based on reference within-subject variability, applied for highly variable drugs

Q17. Which regulatory document provides harmonized recommendations for bioequivalence study conduct in the European Union?

• ICH Q7A
• EMA Guideline on the Investigation of Bioequivalence
• WHO GMP Annex 1
• FDA Orange Book

Correct Answer: EMA Guideline on the Investigation of Bioequivalence

Q18. For a locally acting nasal spray where systemic concentrations are negligible, regulators may accept which alternative to standard systemic BE studies?

• No data required at all
• Comparative in vitro performance, PK surrogate studies, or clinical endpoint studies demonstrating similar local effect
• Only animal studies
• Single-subject proof-of-concept trial

Correct Answer: Comparative in vitro performance, PK surrogate studies, or clinical endpoint studies demonstrating similar local effect

Q19. What is the typical regulatory expectation regarding protocol deviations in BE trials?

• All deviations can be ignored if study completes
• Major deviations should be documented, justified, and subjects with major deviations may be excluded from primary analysis (with sensitivity analyses)
• Deviations are acceptable without documentation for IA trials
• Only deviations affecting dosing time need recording

Correct Answer: Major deviations should be documented, justified, and subjects with major deviations may be excluded from primary analysis (with sensitivity analyses)

Q20. In submissions for BA/BE studies, what is the purpose of providing batch analysis and comparative dissolution data of test and reference batches?

• To confirm stability only after marketing
• To demonstrate consistent CMC quality, assure in vitro similarity, and support the batch used in the BE study representing commercial product
• To replace the need for bioanalytical validation
• To justify not conducting any clinical studies

Correct Answer: To demonstrate consistent CMC quality, assure in vitro similarity, and support the batch used in the BE study representing commercial product

Download