title: Manufacturing of [(14)C]-Labeled Drug Substance and Drug Product Utilized in Clinical Research: A Case Study of Omecamtiv Mecarbil.
abstract: 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.
authors.affiliation: Drug Substance Technologies, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States. scott.roberts@amgen.com.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Roberts
authors.forename: Jeroen M
authors.initials: JM
authors.lastname: Bezemer
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kennedy
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Correll
authors.forename: Raju
authors.initials: R
authors.lastname: Subramanian
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Walker
mesh_terms: D065567:Absorption, Physiological; D002250:Carbon Radioisotopes / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004339:Drug Compounding; D065546:Drug Liberation; D006801:Humans; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; C547293:omecamtiv mecarbil; D014508:Urea