IND-enabling studies: required studies and submissions MCQs With Answer

Introduction: IND-enabling studies: required studies and submissions MCQs With Answer is a focused quiz set designed for M.Pharm students preparing for advanced pharmacology and toxicology roles. This collection clarifies the nonclinical data required to support an Investigational New Drug (IND) application — including GLP toxicology, safety pharmacology, genotoxicity, ADME, reproductive toxicology, and species selection — and highlights regulatory expectations such as ICH guidances, pre-IND interactions, and dossier formats. Each question targets decision-making and interpretation skills needed to design, evaluate, and submit IND-enabling programs. Use these MCQs to reinforce practical knowledge and prepare for both examinations and regulatory practice in drug development.

Q1. What is the primary objective of IND-enabling nonclinical studies?

• To demonstrate commercial viability of the drug
• To provide nonclinical safety, pharmacology and exposure data to support safe initiation of human clinical trials
• To optimize marketing strategies for the drug
• To replace clinical trials by exhaustive animal testing

Correct Answer: To provide nonclinical safety, pharmacology and exposure data to support safe initiation of human clinical trials

Q2. Which ICH guidance is the principal document describing timing and scope of nonclinical safety studies to support human clinical trials?

• ICH S7A
• ICH S2(R1)
• ICH M3(R2)
• ICH S9

Correct Answer: ICH M3(R2)

Q3. According to ICH S7A, the core battery of safety pharmacology studies should evaluate which physiological systems?

• Renal, hepatic and gastrointestinal systems
• CNS, cardiovascular and respiratory systems
• Endocrine, metabolic and immune systems
• Skeletal, muscular and integumentary systems

Correct Answer: CNS, cardiovascular and respiratory systems

Q4. Which statement best describes GLP expectations for IND-enabling toxicity studies?

• All PK and in vitro ADME studies must be GLP-compliant
• Pivotal repeat-dose toxicology and safety pharmacology studies intended to support an IND should be conducted under GLP
• GLP is optional for pivotal toxicology studies if sponsor documents good intent
• GLP only applies to clinical chemistry analyses and not to necropsy findings

Correct Answer: Pivotal repeat-dose toxicology and safety pharmacology studies intended to support an IND should be conducted under GLP

Q5. How is the recommended starting dose for first-in-human studies typically derived?

• Direct transfer of the highest animal dose tested
• From the Maximum Tolerated Dose (MTD) in animals without safety margins
• By converting the animal NOAEL to a Human Equivalent Dose (HED) and applying an appropriate safety factor
• By using the therapeutic dose in the most sensitive animal species

Correct Answer: By converting the animal NOAEL to a Human Equivalent Dose (HED) and applying an appropriate safety factor

Q6. What does NOAEL stand for and indicate?

• No Observable Adverse Effect Level — highest dose at which no adverse effects are observed
• New Observational Acute Exposure Limit — lowest toxic dose in acute studies
• No Observable Acute Effect Limit — highest safe dose for acute toxicity only
• Normalized Observed Adverse Exposure Limit — a pharmacokinetic parameter

Correct Answer: No Observable Adverse Effect Level — highest dose at which no adverse effects are observed

Q7. Which best defines Maximum Tolerated Dose (MTD) as used in IND-enabling studies?

• The dose producing no pharmacological activity
• The dose that causes 100% lethality in the treated animals
• The highest dose that produces acceptable, non-lethal toxicity and is tolerated by the test species
• The dose used for long-term carcinogenicity studies only

Correct Answer: The highest dose that produces acceptable, non-lethal toxicity and is tolerated by the test species

Q8. For a clinical trial program intended to last up to one month, what is the typical duration of repeat-dose toxicity studies recommended by ICH M3(R2) in rodent and non-rodent species?

• Single-dose toxicity studies only
• 7 days in rodent and 14 days in non-rodent
• 28 days (approximately 1 month) in both a rodent and a non-rodent species
• 6 months in both species

Correct Answer: 28 days (approximately 1 month) in both a rodent and a non-rodent species

Q9. Which tests form the core genotoxicity battery per ICH S2(R1)?

• In vitro receptor-binding assay, in vivo PK study, Ames test
• Ames bacterial reverse mutation test, in vitro mammalian cell genotoxicity assay, and in vivo micronucleus or chromosomal aberration test
• Dermal sensitization, local tolerance, and Ames test
• Two in vivo carcinogenicity studies in different species

Correct Answer: Ames bacterial reverse mutation test, in vitro mammalian cell genotoxicity assay, and in vivo micronucleus or chromosomal aberration test

Q10. What is the primary objective of carcinogenicity studies in IND-enabling programs?

• To establish dosing for Phase I trials
• To evaluate the potential of a substance to cause tumors during chronic exposure and to inform risk assessment for long-term use
• To replace genotoxicity testing
• To determine acute toxicity endpoints

Correct Answer: To evaluate the potential of a substance to cause tumors during chronic exposure and to inform risk assessment for long-term use

Q11. What is the primary purpose of including satellite groups in repeat-dose toxicology studies?

• To increase group size for statistical power in clinical pathology
• To provide animals for additional toxicokinetic sampling and for recovery phase observations
• To evaluate different formulations of the drug simultaneously
• To serve as untreated controls for other unrelated studies

Correct Answer: To provide animals for additional toxicokinetic sampling and for recovery phase observations

Q12. Which parameters are typically assessed in the cardiovascular core safety pharmacology battery?

• QT interval, heart rate and arterial blood pressure
• Renal clearance, urine output and plasma electrolytes
• Glucose tolerance, insulin secretion and hepatic enzymes
• Bone density, muscle strength and reflexes

Correct Answer: QT interval, heart rate and arterial blood pressure

Q13. What is the primary rationale for species selection in IND-enabling toxicity studies?

• Select the cheapest and fastest breeding species available
• Choose species based on similarity to human target engagement, pharmacokinetics and metabolic pathways
• Always use rodents only because regulatory agencies prefer them
• Use only non-human primates for all small molecule programs

Correct Answer: Choose species based on similarity to human target engagement, pharmacokinetics and metabolic pathways

Q14. Which additional nonclinical concern is especially important for therapeutic proteins and other biologics compared with small molecules?

• Carcinogenicity potential is always absent for biologics
• Assessment of immunogenicity and species relevance due to target binding and immune responses
• Biologics do not require GLP studies
• Genotoxicity testing is more critical for biologics than for small molecules

Correct Answer: Assessment of immunogenicity and species relevance due to target binding and immune responses

Q15. Which developmental toxicity study specifically evaluates embryo-fetal development (EFD)?

• Segment I (fertility and early embryonic development)
• Segment II (embryo-fetal development)
• Segment III (pre- and postnatal development)
• Acute developmental screening assay

Correct Answer: Segment II (embryo-fetal development)

Q16. Why is validated bioanalytical method development important for nonclinical pharmacokinetic and toxicokinetic studies?

• Bioanalytical methods are not required for nonclinical studies
• To ensure accurate, precise and reproducible measurement of drug and metabolite concentrations for exposure–response and NOAEL interpretation
• To replace histopathology in determining toxicity
• To meet GLP requirements for toxicity endpoints only

Correct Answer: To ensure accurate, precise and reproducible measurement of drug and metabolite concentrations for exposure–response and NOAEL interpretation

Q17. What is the Maximum Recommended Starting Dose (MRSD) concept for first-in-human trials?

• The highest dose tested in animals without any safety margin
• The human dose obtained by converting animal NOAEL to HED and applying appropriate safety factors to define a safe starting dose
• The therapeutic dose predicted from in vitro potency alone
• A dose chosen arbitrarily by the clinical investigator

Correct Answer: The human dose obtained by converting animal NOAEL to HED and applying appropriate safety factors to define a safe starting dose

Q18. For calculation of Human Equivalent Dose (HED) from animal NOAEL, which parameter is commonly used for interspecies scaling?

• Body surface area (BSA) normalization using Km factors
• Direct mg/kg scaling without adjustment
• Age of the animal
• Organs weight to body weight ratio only

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

Q19. What is the primary purpose of a pre-IND meeting with a regulatory agency like the FDA?

• To obtain marketing approval
• To request funding for the development program
• To obtain agency feedback on nonclinical plans, clinical protocols and key CMC issues to align development strategy before filing an IND
• To register patents

Correct Answer: To obtain agency feedback on nonclinical plans, clinical protocols and key CMC issues to align development strategy before filing an IND

Q20. What does eCTD stand for and why is it important for IND submissions?

• electronic Clinical Trial Database — stores trial volunteers
• electronic Common Technical Document — standardized electronic format for regulatory submissions to facilitate review and lifecycle management
• enhanced Chemistry, Toxicology Document — for internal sponsor use only
• elective Clinical Trial Dossier — optional submission package for exploratory studies

Correct Answer: electronic Common Technical Document — standardized electronic format for regulatory submissions to facilitate review and lifecycle management

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