(a) On January 8, 1963 (28 FR 183), the Commissioner of Food and Drugs exempted investigational radioactive new drugs from part 312 of this chapter provided they were shipped in complete conformity with the regulations issued by the Nuclear Regulatory Commission. This exemption also applied to investigational radioactive biologics.
(b) It is the opinion of the Nuclear Regulatory Commission, and the Food and Drug Administration that this exemption should not apply for certain specific drugs and that these drugs should be appropriately labeled for uses for which safety and effectiveness can be demonstrated by new drug applications or through licensing under the Public Health Service Act (42 U.S.C. 262 et seq.) in the case of biologics. Continued distribution under the investigational exemption when the drugs are intended for established uses will not be permitted.
(c) Based on its experience in regulating investigational radioactive pharmaceuticals, the Nuclear Regulatory Commission has compiled a list of reactor-produced isotopes for which it considers that applicants may reasonably be expected to submit adequate evidence of safety and effectiveness for use as recommended in appropriate labeling. Such use may include, among others, the uses in this tabulation:
| Isotope
| Chemical form
| Use
|
|---|
| Chromium 51 | Chromate | Spleen scans.
|
| Do | ......do | Placenta localization.
|
| Do | ......do | Red blood cell labeling and survival studies.
|
| Do | Labeled human serum albumin | Gastrointestinal protein loss studies.
|
| Do | ......do | Placenta localization.
|
| Do | Labeled red blood cells | Do.
|
| Cobalt 58 or Cobalt 60 | Labeled cyanocobalamin | Intestinal absorption studies.
|
| Gold 198 | Colloidal | Liver scans.
|
| Do | ......do | Intracavitary treatment of pleural effusions and/or ascites.
|
| Do | ......do | Interstitial treatment of cancer.
|
| Iodine 131 | Iodide | Diagnosis of thyroid functions.
|
| Do | ......do | Thyroid scans.
|
| Do | ......do | Treatment of hyperthyroidism and/or cardiac dysfunction.
|
| Do | ......do | Treatment of thyroid carcinoma.
|
| Do | Iodinated human serum albumin | Blood volume determinations.
|
| Do | ......do | Cisternography.
|
| Do | ......do | Brain tumor localization.
|
| Do | ......do | Placenta localization.
|
| Do | ......do | Cardiac scans for determination of pericardial effusions.
|
| Do | Rose Bengal | Liver function studies.
|
| Do | ......do | Liver scans.
|
| Do | Iodopyracet, sodium iodohippurate, sodium diatrizoate, diatrizoate methylglucamine, sodium diprotrizoate, sodium acetrizoate, or sodium iothalamate | Kidney function studies and kidney scans.
|
| Do | Labeled fats and/or fatty acids | Fat absorption studies.
|
| Do | Cholografin | Cardiac scans for determination of pericardial effusions.
|
| Do | Macroaggregated iodinated human serum albumin | Lung scans.
|
| Do | Colloidal microaggregated human serum albumin | Liver scans.
|
| Iodine 125 | Iodide | Diagnosis of thyroid function.
|
| Do | Iodinated human serum albumin | Blood volume determinations.
|
| Do | Rose Bengal | Liver function studies.
|
| Do | Iodopyracet, sodium iodohippurate, sodium diatrizoate, diatrizoate methyl-glucamine, sodium diprotrizoate, sodium acetrizoate, or sodium iothalamate | Kidney function studies.
|
| Do | Labeled fats and/or fatty acids | Fat absorption studies.
|
| Iron 59 | Chloride, citrate and/or sulfate | Iron turnover studies.
|
| Krypton 85 | Gas | Diagnosis of cardiac abnormalities.
|
| Mercury 197 | Chlormerodrin | Kidney scans.
|
| Do | ......do | Brain scans.
|
| Mercury 203
1 | ......do | Kidney scans.
|
| Do | ......do | Brain scans.
|
| Phosphorus 32 | Soluble phosphate | Treatment of polycythemia vera.
|
| Do | ......do | Treatment of leukemia and bone metastasis.
|
| Do | Colloidal chromic phosphate | Intracavitary treatment of pleural effusions and/or ascites.
|
| Do | ......do | Interstitial treatment of cancer.
|
| Potassium 42 | Chloride | Potassium space studies.
|
| Selenium 75 | Labeled methionine | Pancreas scans.
|
| Strontium 85 | Nitrate or chloride | Bone scans on patients with diagnosed cancer.
|
| Technetium 99m | Pertechnetate | Brain scans.
|
| Do | ......do | Thyroid scans.
|
| Do | Sulfur colloid | Liver and spleen scans.
|
| Do | Pertechnetate | Placenta localization.
|
| Do | ......do | Blood pool scans.
|
| Do | ......do | Salivary gland scans.
|
| Do | Diethylenetri-amine pentaacetic acid (DTPA) | Kidney scans.
|
| Xenon 133 | Gas | Diagnosis of cardia abnormalities. Cerebral bloodflow studies. Pulmonary function studies. Muscle bloodflow studies.
|
(d)(1) In view of the extent of experience with the isotopes listed in paragraph (c) of this section, the Nuclear Regulatory Commission and the Food and Drug Administration conclude that such isotopes should not be distributed under investigational-use labeling when they are actually intended for use in medical practice.
(2) The exemption referred to in paragraph (a) of this section, as applied to any drug or biologic containing any of the isotopes listed in paragraph (c) of this section, in the “chemical form” and intended for the uses stated, is terminated on March 3, 1972, except as provided in paragraph (d)(3) of this section.
(3) The exemption referred to in paragraph (a) of this section, as applied to any drug or biologic containing any of the isotopes listed in paragraph (c) of this section, in the “chemical form” and intended for the uses stated, for which drug a new drug application or a “Investigational New Drug Application” was submitted prior to March 3, 1972, or for which biologic an application for product license or “Investigational New Drug Application” was submitted prior to March 3, 1972, is terminated on August 20, 1976, unless an approvable notice was issued on or before August 20, 1976, in which case the exemption is terminated either upon the subsequent issuance of a nonapprovable notice for the new drug application or on November 20, 1976, whichever occurs first.
(e) No exemption from section 505 of the act or from part 312 of this chapter is in effect or has been in effect for radioactive drugs prepared from accelerator-produced radioisotopes, naturally occurring isotopes, or nonradioactive substances used in conjunction with isotopes.
(f)(1) Based on its experience in regulating investigational radioactive pharmaceuticals, the Nuclear Regulatory Commission has compiled a list of reactor-produced isotopes for which it considers that applicants may reasonably be expected to submit adequate evidence of safety and effectiveness for use as recommended in appropriate labeling; such use may include, among others, the uses in this tabulation:
| Isotope
| Chemical form
| Use
|
|---|
| Fluorine 18 | Fluoride | Bone imaging.
|
| Indium-113m | Diethylenetriamine pentaacetic acid (DTPA) | Brain imaging; kidney imaging.
|
| Do | Chloride | Placenta imaging; blood pool imaging.
|
| Technetium 99m | Human serum albumin microspheres | Lung imaging.
|
| Do | Diethylenetriamine pentaacetic acid (Sn) | Kidney imaging; kidney function studies.
|
| Do | ......do | Brain imaging.
|
| Do | Polyphosphates | Bone imaging.
|
| Do | Technetated aggregated albumin (human) | Lung imaging.
|
| Do | Disodium etidronate | Bone imaging. |
(2) In view of the extent of experience with the isotopes listed in paragraph (f)(1) of this section, the Nuclear Regulatory Commission and the Food and Drug Administration conclude that they should not be distributed under investigational-use labeling when they are actually intended for use in medical practice.
(3) Any manufacturer or distributor interested in continuing to ship in interstate commerce drugs containing the isotopes listed in paragraph (f)(1) of this section for any of the indications listed, shall submit, on or before August 25, 1975 to the Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, a new drug application or a “Investigational New Drug Application” for each such drug for which the manufacturer or distributor does not have an approved new drug application pursuant to section 505(b) of the act. If the drug is a biologic, a “Investigational New Drug Application” or an application for a license under section 351 of the Public Health Service Act shall be submitted to the Food and Drug Administration, Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002, in lieu of any submission to the Center for Drug Evaluation and Research.
(4) The exemption referred to in paragraph (a) of this section, as applied to any drug or biologic containing any of the isotopes listed in paragraph (f)(1) of this section, in the “chemical form” and intended for the uses stated, is terminated on August 26, 1975 except as provided in paragraph (f)(5) of this section.
(5)(i) Except as provided in paragraph (f)(5)(ii) of this section, the exemption referred to in paragraph (a) of this section, as applied to any drug containing any of the isotopes listed in paragraph (f)(1) of this section, in the “chemical form” and intended for the uses stated, for which drug a new drug application or “Investigational New Drug Application” was submitted to the Center for Drug Evaluation and Research on or before August 25, 1975 is terminated on August 20, 1976, unless an approvable notice was issued on or before August 20, 1976, in which case the exemption is terminated either upon the subsequent issuance of a nonapprovable notice for the new drug application or on November 20, 1976, whichever occurs first.
(ii) The exemption referred to in paragraph (a) of this section, as applied to any biologic containing any of the isotopes listed in paragraph (f)(1) of this section in the “chemical form” and intended for the uses stated, for which biologic an application for product license or “Investigational New Drug Application” was submitted to the Center for Biologics Evaluation and Research on or before August 25, 1975 is terminated on October 20, 1976, unless an approvable notice was issued on or before October 20, 1976, in which case the exemption is terminated either upon the subsequent issuance of a nonapprovable notice for the new drug application or on January 20, 1977, whichever occurs first.
(g) The exemption referred to in paragraph (a) of this section, as applied to any drug intended solely for investigational use as part of a research project, which use had been approved on or before July 25, 1975 in accordance with 10 CFR 35.11 (or equivalent regulation of an Agreement State) is terminated on February 20, 1976 if the manufacturer of such drug or the sponsor of the investigation of such drug submits on or before August 25, 1975 to the Food and Drug Administration, Bureau of Drugs, HFD-150, 5600 Fishers Lane, Rockville, MD 20857, the following information:
(1) The research project title;
(2) A brief description of the purpose of the project;
(3) The name of the investigator responsible;
(4) The name and license number of the institution holding the specific license under 10 CFR 35.11 (or equivalent regulation of an Agreement State);
(5) The name and maximum amount per subject of the radionuclide used;
(6) The number of subjects involved; and
(7) The date on which the administration of the radioactive drugs is expected to be completed.
(h) The exemption referred to in paragraph (a) of this section, as applied to any drug not referred to in paragraphs (d), (f), and (g) of this section, is terminated on August 26, 1975.
[39 FR 11680, Mar. 29, 1974, as amended at 40 FR 31307, July 25, 1975; 40 FR 44543, Sept. 29, 1975; 41 FR 35171, Aug. 20, 1976; 41 FR 42947, Sept. 29, 1976; 50 FR 8996, Mar. 6, 1985; 55 FR 11578, Mar. 29, 1990; 64 FR 56449, Oct. 20, 1999; 80 FR 18091, Apr. 3, 2015]