Approaches to drug discovery and IND submission MCQs With Answer

Introduction: This question set focuses on approaches to drug discovery and the Investigational New Drug (IND) submission process, tailored for M.Pharm students studying Clinical Research (MPP 104T). It covers core topics such as target identification and validation, lead discovery strategies (high-throughput screening, structure-based design, fragment-based and phenotypic approaches), ADME/Tox profiling, preclinical safety pharmacology, and regulatory requirements for IND dossiers including CMC, nonclinical studies, and clinical protocol elements. These MCQs emphasize applied understanding needed for designing preclinical packages, selecting appropriate animal models, determining starting human dose (MRSD/MABEL), and assembling a compliant IND for first-in-human trials. Answers include concise, accurate choices to prepare you for exams and practical regulatory tasks.

Q1. Which method is primarily used for rapidly testing large chemical libraries against a biological target to identify initial ‘hits’?

• Structure-based drug design
• High-throughput screening
• Fragment-based lead discovery
• Phenotypic screening

Correct Answer: High-throughput screening

Q2. In drug discovery, target validation aims to:

• Discover chemical starting points without biological rationale
• Confirm that modulation of a biomolecule produces the desired therapeutic effect
• Optimize pharmacokinetic properties of a lead compound
• Scale up manufacturing under GMP

Correct Answer: Confirm that modulation of a biomolecule produces the desired therapeutic effect

Q3. Fragment-based lead discovery is characterized by:

• Screening large molecules (>600 Da) for immediate potency
• Using very small libraries of low molecular weight fragments to build potent ligands
• Relying exclusively on whole-cell assays
• Bypassing structural biology techniques

Correct Answer: Using very small libraries of low molecular weight fragments to build potent ligands

Q4. Which approach directly measures a compound’s effect on disease-relevant phenotypes without knowing the molecular target?

• Target-based screening
• Phenotypic screening
• In silico docking
• ADME profiling

Correct Answer: Phenotypic screening

Q5. Structure-based drug design most critically relies on:

• Animal efficacy models only
• High-resolution structural information of the target (e.g., X-ray, cryo-EM)
• Randomized clinical trial data
• Large fragment libraries without target information

Correct Answer: High-resolution structural information of the target (e.g., X-ray, cryo-EM)

Q6. Which in vitro assay panel is essential early to predict metabolic stability and potential drug-drug interactions?

• Genotoxicity battery (Ames, micronucleus)
• CYP450 inhibition and metabolic stability assays
• Reproductive toxicity studies
• Chronic carcinogenicity bioassays

Correct Answer: CYP450 inhibition and metabolic stability assays

Q7. For IND-enabling toxicology, which regulatory requirement is typically expected by FDA?

• Only one acute toxicity study in any species
• Good Laboratory Practice (GLP) compliant repeat-dose toxicity studies in two species when clinically relevant
• No animal data if in vitro data look promising
• Only chronic toxicity studies are required before first-in-human trials

Correct Answer: Good Laboratory Practice (GLP) compliant repeat-dose toxicity studies in two species when clinically relevant

Q8. When converting animal NOAEL to a human starting dose, the commonly used calculation involves:

• Direct mg/kg translation without scaling
• Human Equivalent Dose (HED) using body surface area conversion and safety factors
• Using maximum tolerated dose in animals as starting human dose
• Scaling by organ weight only

Correct Answer: Human Equivalent Dose (HED) using body surface area conversion and safety factors

Q9. MABEL (Minimum Anticipated Biological Effect Level) is especially useful when:

• A drug has a well-defined safety margin from animal data
• The compound is first-in-class with high pharmacological potency and uncertain translation from animals to humans
• Only chronic toxicity studies are available
• Starting dose can be based solely on NOAEL without pharmacology

Correct Answer: The compound is first-in-class with high pharmacological potency and uncertain translation from animals to humans

Q10. Which section of the IND dossier details drug substance and drug product information including manufacturing, specifications, and stability?

• Nonclinical Pharmacology/Toxicology
• Clinical Protocols
• Chemistry, Manufacturing, and Controls (CMC)
• Investigator Brochure

Correct Answer: Chemistry, Manufacturing, and Controls (CMC)

Q11. The Investigator’s Brochure primarily provides investigators with:

• Detailed manufacturing batch records
• Comprehensive clinical and nonclinical safety and pharmacology data relevant to clinical study conduct
• Marketing approval letters
• Only efficacy data from phase III trials

Correct Answer: Comprehensive clinical and nonclinical safety and pharmacology data relevant to clinical study conduct

Q12. Which toxicology study is specifically intended to assess potential effects on fertility and early embryonic development?

• Chronic carcinogenicity study
• Genotoxicity in vitro assays
• Reproductive and developmental toxicity studies (segment I–III)
• Safety pharmacology battery (cardio/respiratory/CNS)

Correct Answer: Reproductive and developmental toxicity studies (segment I–III)

Q13. Which of the following is a core component of the FDA IND clinical protocol submission?

• Marketing plan for post-approval launch
• Study objectives, design, inclusion/exclusion criteria, dose and safety monitoring plan
• Only animal efficacy data
• Final labeling for commercial product

Correct Answer: Study objectives, design, inclusion/exclusion criteria, dose and safety monitoring plan

Q14. In safety pharmacology, which organ systems are part of the ICH S7A core battery?

• Hematology and clinical chemistry
• Cardiovascular, respiratory, and central nervous systems
• Reproductive and developmental systems
• Dermatologic and ocular systems

Correct Answer: Cardiovascular, respiratory, and central nervous systems

Q15. Genotoxicity testing for INDs typically includes which initial assays?

• Ames test and an in vitro mammalian cell assay (e.g., micronucleus or chromosomal aberration)
• Two-year rodent carcinogenicity studies only
• Reproductive toxicity battery
• In vivo chronic toxicity in non-rodent species only

Correct Answer: Ames test and an in vitro mammalian cell assay (e.g., micronucleus or chromosomal aberration)

Q16. Which regulatory concept allows limited emergency use of an investigational drug before full IND clearance?

• New Drug Application (NDA)
• Emergency Use Authorization (EUA)
• Expanded Access / Compassionate Use (single patient IND or expanded IND)
• Abbreviated IND

Correct Answer: Expanded Access / Compassionate Use (single patient IND or expanded IND)

Q17. Toxicokinetic (TK) data in preclinical studies are important because they:

• Are only needed after phase III trials
• Link systemic exposure in animals to observed toxicity and support dose selection for humans
• Replace the need for any GLP studies
• Only assess compound purity

Correct Answer: Link systemic exposure in animals to observed toxicity and support dose selection for humans

Q18. Which document provides the FDA with contact information, investigator list, and commitments for monitoring and informed consent in an IND?

• Investigator’s Brochure
• Form FDA 1571 (IND cover sheet) and protocol submissions
• Manufacturing batch record
• Final NDA labeling

Correct Answer: Form FDA 1571 (IND cover sheet) and protocol submissions

Q19. Which preclinical efficacy models are most relevant to demonstrate pharmacodynamic proof-of-concept prior to IND?

• In vitro target engagement assays and relevant in vivo disease models showing functional benefit
• Only single-dose acute toxicity studies
• Stability-indicating HPLC methods
• Human clinical epidemiology studies

Correct Answer: In vitro target engagement assays and relevant in vivo disease models showing functional benefit

Q20. For biological products, which additional IND submission element is often critical compared to small molecules?

• Nonclinical genotoxicity assays only
• Detailed characterization of the product (potency assay, purity, immunogenicity risk, cell substrate information)
• Only one species toxicology requirement irrespective of relevance
• No CMC section is required

Correct Answer: Detailed characterization of the product (potency assay, purity, immunogenicity risk, cell substrate information)

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