RAC Premarketing and Clinical Development 2 — Questions and Answers
Question 1: Which IND type allows a sponsor to ship an investigational drug to clinical investigators without a 30-day FDA review period?
- Treatment IND
- Emergency IND (Correct answer)
- Exploratory IND
- Investigator-initiated IND
Correct answer: Emergency IND
An Emergency IND allows FDA to authorize use over the phone before submission, bypassing the standard 30-day waiting period.
Question 2: In a Phase I dose-escalation oncology trial, what is the primary endpoint typically used to determine the Maximum Tolerated Dose (MTD)?
- Overall survival
- Dose-Limiting Toxicity (DLT) (Correct answer)
- Pharmacokinetic AUC
- Tumor response rate
Correct answer: Dose-Limiting Toxicity (DLT)
DLTs observed during the first treatment cycle define the MTD boundary in classic 3+3 and modified dose-escalation designs.
Question 3: Under 21 CFR Part 312, which section requires sponsors to report unexpected serious adverse events from foreign clinical studies to the IND within 15 calendar days?
- 312.32 (Correct answer)
- 312.50
- 312.60
- 312.81
Correct answer: 312.32
21 CFR 312.32 governs IND safety reporting, requiring 15-day expedited reports for unexpected serious adverse drug reactions from any source.
Question 4: A sponsor wants to conduct a single-dose PK study in six healthy volunteers using a microdose (≤100 mcg) to characterize absorption without triggering full IND requirements. Which IND category applies?
- Commercial IND
- Exploratory IND (Correct answer)
- Treatment IND
- Emergency IND
Correct answer: Exploratory IND
Exploratory INDs (Phase 0) permit very limited human exposure with microdoses primarily to obtain early pharmacokinetic or pharmacodynamic data.
Question 5: What is the purpose of a Special Protocol Assessment (SPA) agreement between a sponsor and FDA for a Phase III trial?
- To waive IRB review requirements
- To secure FDA agreement that the protocol design is acceptable to support a future NDA/BLA (Correct answer)
- To allow expedited enrollment without informed consent
- To grant automatic Breakthrough Therapy designation
Correct answer: To secure FDA agreement that the protocol design is acceptable to support a future NDA/BLA
An SPA provides sponsors with FDA's binding agreement that the protocol design, endpoints, and statistical analysis plan are acceptable for regulatory approval.
Question 6: Which ICH guideline addresses the timing and extent of carcinogenicity studies needed to support clinical development of pharmaceuticals?
- ICH S1A (Correct answer)
- ICH E6
- ICH M3(R2)
- ICH S7A
Correct answer: ICH S1A
ICH S1A provides recommendations on the need for carcinogenicity studies, specifying criteria based on treatment duration and patient population.
Question 7: During clinical development, a sponsor discovers that an investigational product lot used in an ongoing trial fails a stability specification. What is the immediate regulatory obligation?
- Terminate the trial immediately
- Notify FDA in the next annual IND report
- Report as an IND safety report if the failure poses a risk to subjects (Correct answer)
- Quarantine the lot and continue enrollment uninterrupted
Correct answer: Report as an IND safety report if the failure poses a risk to subjects
If a stability failure creates a reasonable possibility of risk to subjects, it must be reported as an IND safety report under 21 CFR 312.32.
RAC Premarketing and Clinical Development 2
Which IND type allows a sponsor to ship an investigational drug to clinical investigators without a 30-day FDA review period?