Quality assurance planning for Actinium-225: Layering current good manufacturing practice requirements onto US department of energy/nuclear safety quality systems to support medical isotope production suitable for clinical trial use.

Abstract

Oak Ridge National Laboratory (ORNL) operates under multiple quality frameworks using a graded approach for research operations, hazardous radioactive and nuclear material handling, and nuclear reactor facility management. This publication describes the quality management plan (QMP) ORNL developed to provide Current Good Manufacturing Practice (CGMP)-quality ²²⁵Ac for clinical trial use. The effort involved evaluating existing DOE and American Society of Mechanical Engineers (ASME) Nuclear Quality Assurance (NQA-1) QMS elements against Title 21 of the US Code of Federal Regulations (CFR), Parts 210 and 211 and associated CGMP guidance. The resulting CGMP-specific QMP leverages existing ORNL and NQA-1 QMS controls while adding targeted US Food and Drug Administration (FDA) CGMP requirements needed to assure medical isotope product quality. This approach supports radionuclide drug substance intermediate (DSI) production for clinical trials without imposing unnecessary CGMP rigor on nonmedical, industrial-grade isotope production. The CGMP program was then evaluated and further improved through customer supplier audits and internal reviews by FDA quality compliance experts.