PII-108 - HUMAN RADIOLABELED MASS BALANCE STUDIES SUPPORTING NEW DRUGS APPROVAL BY THE FDA BETWEEN 2019 TO JUNE 2022.

A. Ramamoorthy¹, A. Chen², E. Chow¹, D. Jean¹, S. Pahwa¹, Y. Ren¹, C. Shukla¹, S. Doddapaneni¹, Z. Yan Danielsen¹; ¹US Food and Drug Administration, Silver Spring, MD, USA, ²University of Pittsburgh, Pittsburgh, PA, USA.

Background: Recently, US FDA published a draft guidance for the industry to provide recommendations for conducting human radiolabeled mass balance (MB) studies. During drug development, MB studies help characterize the absorption, distribution, metabolism, and excretion of the parent drug and its metabolite(s) in human body. Previously, we evaluated MB studies supporting new drug applications (NDAs) approval by the FDA between 2014 and 2018 (Ramamoorthy A et al., 2022), which also informed the development of the FDA MB draft guidance. Herein, we summarize recent trends in the conduct of MB studies.

Methods: Documents (e.g., labeling, MB clinical study reports, clinical pharmacology reviews) supporting NDAs approval by the FDA between 2019 to June 2022 were reviewed to collect information related to MB studies.

Results: Of the 126 NDAs approved in this timeframe, 68% had conducted MB studies prior to approval. On an average, the studies had about 6 evaluable subjects, and most studies were conducted in healthy volunteers (98%). Majority of the studies were in males (89%) while some were in both males and females (9%) or in females (2%). Most MB studies were single dose studies (97%) and used the final approved route of administration (100%). These results are similar to our previous research, except that more MB studies included evaluation of absolute bioavailability (19% vs. 13%) and fewer MB studies used a dose within the range of the final approved dose (43% vs. 54%) in 2019-2022 vs. 2014-2018.

Conclusion: Our survey on the recent MB studies supports the recommendations outlined in the FDA MB draft guidance. Compared with previous MB studies, recent MB studies show differences in the dose used and inclusion of absolute bioavailability evaluation in the MB study.

Ramamoorthy A, Bende G, Chow E, Dimova H, Hartman N , Jean D, Pahwa S, Ren Y, Shukla C, Yang Y, Doddapaneni D, Danielsen Z. Human Radiolabeled Mass Balance Studies Supporting the FDA Approval of New Drugs. ePub 06 September 2022. doi:10.1111/cts.13403