Translation of Radiopharmaceuticals from Bench to Bedside: Regulatory and Manufacturing Issues

Abstract

Radiopharmaceuticals (RPhs) are unique pharmaceuticals which contain radioisotopes which emit ionizing radiation. Depending on the nature of the radioisotope and application, radiopharmaceuticals are used for diagnostic applications, using radioisotopes which emit photons which can be detected externally for diagnostic purposes. The second group of RPhs contains particle-emitting radioisotopes which are used as therapeutic tools for treating various diseases. In some case, the radionuclide can be administered in an ionic form directly, such as using 123I− for thyroid imaging, 131I− for thyroid therapy, and 89Sr+ for treatment of bone pain, as described in Chap. 12. Generally, however, radioisotopes are directly attached to pharmaceutical targeting agents which are then administered for various applications, as described in earlier chapters. In every case, RPhs must be manufactured, handled, dispensed, and administered under controlled conditions, which are regulated by the appropriate government agencies. RPhs are either manufactured or distributed in a ready-to-use form from a central commercial manufacturer or from a central radiopharmacy dispensing site or prepared locally in a hospital-based radiopharmacy from “cold kits” and often using radioisotopes available from radionuclide generators. In some cases, hospitals synthesize the necessary ligands (targeting compound) at the hospital radiopharmacy and also formulate the radiopharmaceuticals. In all cases, RPhs are required to be prepared in conformance with a legal framework that is suited for conventional drugs similar to those manufactured by large drug commercial companies. Regulatory procedures necessary to control the production, dispensing, and use of radiopharmaceuticals are primarily focused on production methods. Preparation and handling of RPhs involve adherence to regulations on radiation protection and are regulated by a number of generally federal/regional directives, regulations, and rules to ensure safety. Radiopharmaceuticals are thus prepared in hospital radiopharmacies, centralized radiopharmacies, nuclear centers and institutes, or by industrial manufacturers.