Evaluation of safety.

§ 601.35 Evaluation of safety. (a) Factors considered in the safety assessment of a diagnostic radiopharmaceutical include, among others, the following: (1) The radiation dose; (2) The pharmacology and toxicology of the radiopharmaceutical, including any radionuclide, carrier, or ligand; (3) The risks of an incorrect diagnostic determination; (4) The adverse reaction profile of the drug; (5) Results of human experience with the radiopharmaceutical for other uses; and (6) Results of any previous human experience with the carrier or ligand of the radiopharmaceutical when the same chemical entity as the carrier or ligand has been used in a previously studied product. (b) The assessment of the adverse reaction profile includes, but is not limited to, an evaluation of the potential of the diagnostic radiopharmaceutical, including the carrier or ligand, to elicit the following: (1) Allergic or hypersensitivity responses, (2) Immunologic responses, (3) Changes in the physiologic or biochemical function of the target and nontarget tissues, and (4) Clinically detectable signs or symptoms. (c)(1) To establish the safety of a diagnostic radiopharmaceutical, FDA may require, among other information, the following types of data: (A) Pharmacology data, (B) Toxicology data, (C) Clinical adverse event data, and (D) Radiation safety assessment. (2) The amount of new safety data required will depend on the characteristics of the product and available information regarding the safety of the diagnostic radiopharmaceutical, and its carrier or ligand, obtained from other studies and uses. Such information may include, but is not limited to, the dose, route of administration, frequency of use, half-life of the ligand or carrier, half-life of the radionuclide, and results of clinical and preclinical studies. FDA will establish categories of diagnostic radiopharmaceuticals based on defined characteristics relevant to risk and will specify the amount and type of safety data that are appropriate for each category (e.g., required safety data may be limited for diagnostic radiopharmaceuticals with a well established, low-risk profile). Upon reviewing the relevant product characteristics and safety information, FDA will place each diagnostic radiopharmaceutical into the appropriate safety risk category. (d) Radiation safety assessment. The radiation safety assessment must establish the radiation dose of a diagnostic radiopharmaceutical by radiation dosimetry evaluations in humans and appropriate animal models. The maximum tolerated dose need not be established.