Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hi!

The recently-released FDA draft guidance, "Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies" details that mass balance studies should be conducted early in drug development, at the latest before initiating any late-phase clinical trials. I interpret this to mean that mass balance studies should be initiated before Phase 3 trials.

However, I've been told that FDA likes to see the safety of major human circulatory metabolites be established before the start of any large clinical study, and in some cases a Phase 2b study may qualify as a large study.

May I ask what constitutes a "large study" for a Phase 2b? Is enrolling over 100 subjects considered large?

Appreciate any help!! Thank you!!

There are no absolutes that can be used to answer your questions. My philosophy is that the more facts you have and the earlier in the development process you have them the better your development program will be and the safer subjects in your clinical trials will be. 100 exposed subjects could be considered a "large" Phase 2b study.  However, there are many factors that go into the decision on when to conduct a mass balance study. Generally, they are expensive and can be technically challenging from labeling the compound to identifying metabolites. If there is the potential to require qualification of one or metabolites, the earlier that is done the better.

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Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States
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Original Message:
Sent: 22-Jul-2022 18:42
From: Anonymous Member
Subject: Timing of Mass Balance (ADME) Studies

This message was posted by a user wishing to remain anonymous

Hi!

The recently-released FDA draft guidance, "Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies" details that mass balance studies should be conducted early in drug development, at the latest before initiating any late-phase clinical trials. I interpret this to mean that mass balance studies should be initiated before Phase 3 trials.

However, I've been told that FDA likes to see the safety of major human circulatory metabolites be established before the start of any large clinical study, and in some cases a Phase 2b study may qualify as a large study.

May I ask what constitutes a "large study" for a Phase 2b? Is enrolling over 100 subjects considered large?

Appreciate any help!! Thank you!!