This mini-review describes the Chemistry, Manufacturing and Control activities associated with the manufacture of [(14)C]-labeled drug substance and subsequent drug compounding activities to generate clinical trial material utilized in human absorption, distribution, metabolism, and excretion clinical studies. Due to the unstable nature and increased decomposition rates observed with [(14)C]-labeled compounds, the manufacture, testing, release, formulation, and regulatory filings are uniquely challenging. A case study of the cardiac myosin activator AMG 423 (omecamtiv mercarbil), utilized in a dual oral/intravenous infusion clinical study is presented.