PART 361—PRESCRIPTION DRUGS FOR HUMAN USE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED: DRUGS USED IN RESEARCH Authority: 21 U.S.C. 321, 351, 352, 353, 355, 371; 42 U.S.C. 262. § 361.1 Radioactive drugs for certain research uses. (a) Radioactive drugs (as defined in § 310.3(n) of this chapter) are generally recognized as safe and effective when administered, under the conditions set forth in paragraph (b) of this section, to human research subjects during the course of a research project intended to obtain basic information regarding the metabolism (including kinetics, distribution, and localization) of a radioactively labeled drug or regarding human physiology, pathophysiology, or biochemistry, but not intended for immediate therapeutic, diagnostic, or similar purposes or to determine the safety and effectiveness of the drug in humans for such purposes ( i.e. (b) The conditions under which use of radioactive drugs for research are considered safe and effective are: (1) Approval by Radioactive Drug Research Committee. (i) The pharmacological dose is within the limits set forth in paragraph (b)(2) of this section; (ii) The radiation dose is within the limits set forth in paragraph (b)(3) of this section; (iii) The radiation exposure is justified by the quality of the study being undertaken and the importance of the information it seeks to obtain; (iv) The study meets the other requirements set forth in paragraph (d) of this section regarding qualifications of the investigator, proper licensure for handling radioactive materials, selection and consent of research subjects, quality of radioactive drugs used, research protocol design, reporting of adverse reactions, and approval by an appropriate Institutional Review Committee; and (v) The use of the radioactive drug in human subjects has the approval of the Radioactive Drug Research Committee. (2) Limit on pharmacological dose. (3) Limit on radiation dose. (i) Under no circumstances may the radiation dose to an adult research subject from a single study or cumulatively from a number of studies conducted within 1 year be generally recognized as safe if such dose exceeds the following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual and total dose commitment 5 Other organs: Single dose 5 Annual and total dose commitment 15 (ii) For a research subject under 18 years of age at his last birthday, the radiation dose shall not exceed 10 percent of that set forth in paragraph (b)(3)(i) of this section. (iii) All radioactive material included in the drug either as essential material or as a significant contaminant or impurity shall be included when determining the total radiation doses and dose commitments. Radiation doses from x-ray procedures that are part of the research study ( i.e. (iv) Numerical definitions of dose shall be based on an absorbed fraction method of radiation absorbed dose calculation, such as the system set forth by the Medical Internal Radiation Dose Committee of the Society of Nuclear Medicine, or the system set forth by the International Commission on Radiological Protection. (c) A Radioactive Drug Research Committee, in order to comply with paragraph (b)(1) of this section, shall be composed, shall function, and shall obtain and maintain approval of the Food and Drug Administration in conformity with the following: (1) Membership. (2) Function. (3) Reports. Report on Research Use of Radioactive Drug 1. Title of the research project. 2. Brief description of the purpose of the research project. 3. Name of the investigator responsible. 4. Pharmacological dose: a. Active ingredients. b. Maximum amount administered per subject. 5. Name of the radionuclide(s) used, including any present, as significant contaminants or impurities. 6. Radiation absorbed dose. Provide the maximum dose commitement to the whole body and each organ specified in 21 CFR 361.1(b)(3)(i) that was received by a representative subject and the calculations or references that were used to estimate these maximum dose commitments. The report shall include the dose contribution of both the administered radionuclide(s) and any X-ray procedures associated with the study. If the study elicits data on the uptake or excretion of the radioactive drug pertinent to the estimation of dose commitment, report the mean value and range of values. For each subject provide: (a) Age, sex, and approximate weight. (b) Total activity of each radionuclide administered for each radioactive drug used in the study. Report each X-ray procedure used in conjunction with the study. (c) If the subject has participated in other radioactive drug research studies, report the name of the radioactive drug used in these other studies, the date of administration, and the total activity of each radionuclide administered. If any X-ray procedures were used, identify the X-ray procedure(s) and include an estimate of the absorbed radiation doses. (d) If more than one administration of a radioactive drug per subject, cumulative radiation dose and dose commitment, expressed as whole body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered radionuclides. 7. A claim of confidentiality, if any. Note: Contents of this report are available for public disclosure unless confidentiality is requested by the investigator and it is adequately shown by the investigator that the report constitutes a trade secret or confidential commercial information as defined in 21 CFR 20.61. Investigator Chairman, Radioactive Drug Research Committee At any time a proposal is approved which involves exposure either of more than 30 research subjects, or of any research subject under 18 years of age, the committee shall immediately submit to the Food and Drug Administration a special summary of information in the format shown in this paragraph. Contents of these reports are available for public disclosure, unless confidentiality is requested by the investigator and it is adequately shown by the investigator that the report constitutes a trade secret or confidential commercial information as defined in § 20.61 of this chapter. (4) Approval. (5) Monitoring. (d) In making the determination required in paragraph (b)(1) of this section, a Radioactive Drug Research Committee shall consider the following requirements and assure that each is met: (1) Radiation dose to subjects. (i) The investigator provide absorbed dose calculations based on biologic distribution data available from published literature or from other valid studies. (ii) The investigator provide for an acceptable method of radioassay of the radioactive drug prior to its use to assure that the dose calculations actually reflect the administered dose. (iii) The radioactive drug chosen for the study has that combination of half-life, types of radiations, radiation energy, metabolism, chemical properties, etc., which results in the lowest dose to the whole body or specific organs with which it is possible to obtain the necessary information. (iv) The investigator utilize adequate and appropriate instrumentation for the detection and measurement of the specific radionuclide. (2) Pharmacological dosage. (3) Qualifications of investigators. (4) License to handle radioactive materials. (5) Human research subjects. (6) Quality of radioactive drug. (7) Research protocol. i.e. (8) Adverse reactions. (9) Approval by an institutional review board. (e) The results of any research conducted pursuant to this section as part of the evaluation of a drug pursuant to part 312 of this chapter shall be included in the submissions required under part 312 of this chapter. (f) A radioactive drug prepared, packaged, distributed, and primarily intended for use in accordance with the requirements of this section shall be exempt from section 502(f)(1) of the act and §§ 201.5 and 201.100 of this chapter if the packaging, label, and labeling are in compliance with Federal, State, and local law regarding radioactive materials and if the label of the immediate container and shielded container, if any, either separate from or as part of any label and labeling required for radioactive materials by the Nuclear Regulatory Commission or by State or local radiological health authorities bear the following: (1) The statement “Rx only”; (2) The statement “To be administered in compliance with the requirements of Federal regulations regarding radioactive drugs for research use (21 CFR 361.1)”; (3) The established name of the drug, if any; (4) The established name and quantity of each active ingredient; (5) The name and half-life of the radionuclide, total quantity of radioactivity in the drug product's immediate container, and amount of radioactivity per unit volume or unit mass at a designated referenced time; (6) The route of administration, if it is for the other than oral use; (7) The net quantity of contents; (8) An identifying lot or control number from which it is possible to determine the complete manufacturing history of the package of the drug; (9) The name and address of the manufacturer, packer, or distributor; (10) The expiration date, if any; (11) If the drug is intended for parenteral use, a statement as to whether the contents are sterile; (12) If the drug is for other than oral use, the names of all inactive ingredients, except that: (i) Trace amounts of harmless substances added solely for individual product identification need not be named. (ii) If the drug is intended for parenteral use, the quantity or proportion of all inactive ingredients, except that ingredients added to adjust pH or to make the drug isotonic may be declared by name and a statement of their effect; if the vehicle is water for injection, it need not be named. Provided, however, [40 FR 31308, July 25, 1975, as amended at 40 FR 44543, Sept. 29, 1975; 42 FR 15674, Mar. 22, 1977; 43 FR 14646, Apr. 7, 1978; 46 FR 8955, Jan. 27, 1981; 49 FR 44460, Nov. 7, 1984; 50 FR 8996, Mar. 6, 1985; 55 FR 11582, Mar. 29, 1990; 56 FR 10806, Mar. 14, 1991; 67 FR 4907, Feb. 1, 2002]