Nonclinical development of radiopharmaceuticals: regulatory considerations for the United States Food and Drug Administration.

Abstract

In general, the nonclinical studies conducted to support the development of radiopharmaceuticals should be consistent with current International Conference on Harmonization (ICH) Guidelines. The United States Food and Drug Administration (FDA), however, has recognized that certain characteristics of radiopharmaceuticals necessitate an adaptation of the type and scope of the nonclinical studies that are typically utilized in the development of drugs. From a regulatory perspective, the nonclinical studies that are recommended by the FDA to support the development of radiopharmaceutical drugs are dependent on the intended indication of the drug as either a radiodiagnostic or a radiotherapeutic. There is an overlap of safety and toxicology issues for radiodiagnostics and radiotherapeutics because of the presence of the radionuclide. There are, however, usually significant differences between the two general categories of radiopharmaceuticals with respect to dose, frequency and duration of dosing, and pharmacological activity. Consequently, the regulatory considerations for the nonclinical development of radiodiagnostics are considerably different from radiotherapeutics. The FDA has recently released a revised draft guidance document (“Guidance for Industry: Medical Imaging Drug and Biological Products — Part 1: Conducting Safety Assessment — May 2003”) that specifically addresses the development of medical imaging agents including radiodiagnostics. At this time, however, there is no FDA or ICH guidance that expressly outlines considerations for the nonclinical studies to support the development of radiotherapeutics. The following discussion will address regulatory considerations for nonclinical studies for radiodiagnostics and radiotherapeutics separately, describing the recommended studies, timing of the studies, and the rationale for the recommended studies.