USA – FDA sheds light on conducting human radiolabeled mass balance studies

The US Food and Drug Administration (FDA) has issued draft guidance outlining the clinical pharmacology considerations for human radiolabeled mass balance studies for investigational drugs, including when to conduct the study, the study design, and what elements to include in the study report.

The draft guidance, issued on 5 May, does not cover animal mass balance studies, safety testing of drug metabolites or recommendations for selecting the radioactive dose. (RELATED: CDER unveils 30 planned guidance documents in 2022 agenda, Regulatory Focus 07 February 2022)

FDA said mass balance studies are generally needed for all new molecular entities but if a study is not conducted, the sponsor should provide the agency with an “adequate justification.” The agency noted that a mass balance study might not be recommended in cases in which mass balance study results can obtained from the literature for existing product labeling. Additionally, some drugs, such as monoclonal antibodies, have known metabolism and elimination pathways. Mass balance studies also may not be needed for drugs where 90% or more of the dose is received in the urine as the unchanged parent drug with minimum metabolism or for drugs with no or negligible systemic exposures…