Premarketing and Clinical Development Flashcards

Which nonclinical study package is minimally required before first-in-human (FIH) single-dose administration of a new small molecule according to ICH M3(R2)?

Answer: Single-dose toxicity, dose-range-finding, and safety pharmacology core battery

ICH M3(R2) requires single-dose toxicity data, a safety pharmacology core battery, and preliminary repeat-dose data supporting the FIH exposure duration.

Under FDA's Pediatric Research Equity Act (PREA), when must a sponsor submit a Pediatric Study Plan (PSP)?

Answer: No later than 60 days after an end-of-Phase II meeting

PREA requires sponsors to submit an initial PSP (iPSP) no later than 60 days after the end-of-Phase II meeting with FDA.

A sponsor is developing a biologic and conducts an immunogenicity assessment. Which regulatory guidance is most directly applicable to this assessment?

Answer: FDA guidance on Immunogenicity Testing of Therapeutic Protein Products

FDA's guidance on immunogenicity testing for therapeutic proteins provides a framework for assessing anti-drug antibodies and their clinical impact.

What is the primary regulatory purpose of an End-of-Phase II (EOP2) meeting with FDA?

Answer: To reach agreement on the Phase III design, endpoints, and data needed to support an NDA/BLA

The EOP2 meeting allows sponsors and FDA to align on the Phase III program design, statistical approaches, and evidence requirements before major investment.

In adaptive clinical trial design, an interim analysis that allows sample size re-estimation based on unblinded effect size data is regulated under which FDA guidance framework?

Answer: FDA guidance on Adaptive Designs for Clinical Trials of Drugs and Biologics (2019)

FDA's 2019 adaptive design guidance addresses unblinded sample size re-estimation, response-adaptive randomization, and other adaptive elements.

A sponsor terminates a Phase II trial due to futility. Under 21 CFR 312.38, the sponsor must notify FDA:

Answer: Within 30 days of the termination decision

21 CFR 312.38 requires sponsors to notify FDA within 30 days when all clinical investigations under an IND are discontinued.

Which phase of clinical development is specifically designed to evaluate dose-response relationships and identify the dose regimen for Phase III confirmatory trials?

Answer: Phase II

Phase II trials evaluate therapeutic activity, dose-response, and identify an optimal dose and regimen to carry forward into pivotal Phase III studies.