Preclinical regulatory requirements MCQs With Answer

Introduction

This quiz collection on Preclinical Regulatory Requirements is designed specifically for M.Pharm students preparing for advanced studies and professional roles in drug development. It covers essential regulatory frameworks, study designs, required test batteries, and interpretation of preclinical safety data that support Investigational New Drug (IND) or Clinical Trial Applications (CTA). Questions emphasize international guidance such as ICH and OECD, practical considerations like dose selection, toxicokinetics, GLP compliance, and humane use of animals including the 3Rs. Use these carefully formulated MCQs to deepen your understanding, identify knowledge gaps, and practice applying regulations to real-world preclinical decision-making in pharmaceutical development.

Q1. Which international guidance specifically outlines the core battery of safety pharmacology studies to evaluate potential undesirable pharmacodynamic effects on vital functions?

• ICH M3(R2)
• OECD Test Guideline 401
• ICH S7A
• ICH S1A

Correct Answer: ICH S7A

Q2. In preclinical toxicology, the term NOAEL stands for and is used to determine what?

• New Observational Adverse Event Level; final clinical dose
• No Observed Adverse Effect Level; basis for human dose selection and safety margins
• Nominal Observed Acute Exposure Limit; toxicokinetic modeling
• Normalized Oncogenic Activity Estimate Level; carcinogenic risk

Correct Answer: No Observed Adverse Effect Level; basis for human dose selection and safety margins

Q3. Which of the following tests is part of the standard genotoxicity battery recommended by regulatory guidance?

• Two-year rodent carcinogenicity study
• Ames bacterial reverse mutation assay
• Subchronic 28-day repeated dose toxicity in non-rodent
• ICH S9 embryo-fetal development study

Correct Answer: Ames bacterial reverse mutation assay

Q4. For a small-molecule drug intended for chronic human use, which preclinical study duration in rodents is typically expected to support long-term clinical trials?

• Single-dose acute toxicity only
• 14-day repeated dose study
• 6-month subchronic study
• 2-year carcinogenicity study

Correct Answer: 2-year carcinogenicity study

Q5. Good Laboratory Practice (GLP) primarily ensures which of the following in nonclinical studies?

• That all animals are housed in sterile isolators
• Quality, reliability and integrity of safety data and records
• Faster timelines for study completion
• Regulatory approval of the clinical trial

Correct Answer: Quality, reliability and integrity of safety data and records

Q6. Which guideline provides recommendations for reproductive toxicity testing including embryo-fetal development and fertility studies?

• ICH M7
• ICH S5(R3)
• OECD TG 420
• ICH Q3A

Correct Answer: ICH S5(R3)

Q7. The primary purpose of toxicokinetic (TK) studies in preclinical safety assessment is to:

• Determine therapeutic efficacy in disease models
• Measure systemic exposure and relate dose to toxicity
• Assess only tissue distribution without plasma concentrations
• Replace the need for safety pharmacology studies

Correct Answer: Measure systemic exposure and relate dose to toxicity

Q8. Which principle describes replacing, reducing, and refining the use of animals in preclinical research?

• GMP principles
• The 3Rs
• Good Clinical Practice
• Risk-Benefit Analysis

Correct Answer: The 3Rs

Q9. When converting animal NOAEL to a human equivalent dose (HED) for first-in-human trials, which factor is commonly used by regulators?

• Animal body weight divided by human height
• Body surface area (BSA) scaling using Km factors
• Direct mg/kg conversion without correction
• Plasma protein binding ratio only

Correct Answer: Body surface area (BSA) scaling using Km factors

Q10. Which OECD test guideline is most relevant for acute dermal toxicity evaluation?

• OECD TG 401 (acute oral toxicity)
• OECD TG 402 (acute dermal toxicity)
• OECD TG 408 (subchronic toxicity)
• OECD TG 421 (reproductive/developmental toxicity)

Correct Answer: OECD TG 402 (acute dermal toxicity)

Q11. In the context of IND/CTA submissions, which document primarily summarizes all nonclinical pharmacology and toxicology data?

• Investigator’s Brochure (IB)
• Module 3 of the Common Technical Document (CTD)
• Clinical Study Report (CSR)
• Quality Target Product Profile (QTPP)

Correct Answer: Module 3 of the Common Technical Document (CTD)

Q12. For biologics, which preclinical assessment is essential to evaluate the potential for unintended immune responses?

• Chromatographic purity analysis only
• Immunogenicity assessment including anti-drug antibody (ADA) testing
• Acute oral toxicity in mice
• Phototoxicity testing

Correct Answer: Immunogenicity assessment including anti-drug antibody (ADA) testing

Q13. Which of the following best describes a Maximum Tolerated Dose (MTD) in preclinical toxicology?

• Highest dose that produces no biological effect
• Dose causing minimal lethal effects in all animals
• Highest dose that does not cause unacceptable toxicity or death
• Lowest dose that produces the intended pharmacodynamic effect

Correct Answer: Highest dose that does not cause unacceptable toxicity or death

Q14. ICH S6(R1) provides guidance mainly for which category of therapeutic agents?

• Small-molecule chemical drugs
• Herbal medicinal products
• Biotechnological/biological products
• Radiopharmaceuticals

Correct Answer: Biotechnological/biological products

Q15. Which nonclinical study is specifically targeted to detect potential effects on the developing embryo and fetus?

• Chronic toxicity study
• Developmental and reproductive toxicology—embryo-fetal development study (EFD)
• Toxicokinetic single-dose study
• Local tolerance test

Correct Answer: Developmental and reproductive toxicology—embryo-fetal development study (EFD)

Q16. What is the regulatory rationale for conducting two species (rodent and non-rodent) in repeat-dose toxicity testing?

• To comply with animal use quotas
• To capture species-specific and cross-species toxicity and increase predictivity for humans
• Because rodents do not metabolize drugs
• To reduce study costs by dividing animals

Correct Answer: To capture species-specific and cross-species toxicity and increase predictivity for humans

Q17. Which assay is commonly used to detect chromosomal damage in vivo as part of genotoxicity evaluation?

• In vitro hERG assay
• In vivo micronucleus test
• Acute dermal irritation test
• Local lymph node assay

Correct Answer: In vivo micronucleus test

Q18. According to regulatory guidance, which endpoint is specifically assessed in safety pharmacology to evaluate cardiac risk?

• Respiratory rate measurement only
• QT interval prolongation / hERG channel liability
• Memory and cognitive testing
• Subcutaneous tissue histology

Correct Answer: QT interval prolongation / hERG channel liability

Q19. Which document or committee approval is normally required before initiating animal studies at an institutional facility?

• Clinical trial protocol approval from regulatory authority
• Institutional Animal Care and Use Committee (IACUC) or equivalent ethical approval
• Marketing authorization from a regulatory agency
• Investigator’s financial disclosure

Correct Answer: Institutional Animal Care and Use Committee (IACUC) or equivalent ethical approval

Q20. Toxicokinetic bridging studies are most useful in which of the following scenarios?

• To replace all GLP toxicology studies
• To compare systemic exposure between formulations or species and support dose selection
• To determine the clinical efficacy endpoint
• To test photostability of a compound

Correct Answer: To compare systemic exposure between formulations or species and support dose selection

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