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(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. Each Radioactive Drug Research Committee shall be specifically approved by the Center for Drug Evaluation and Research of the Food and Drug Administration. Applications shall be submitted to the Food and Drug Administration, Center for Drug Evaluation and Research, HFD-160, 5600 Fishers Lane, Rockville, MD 20857, and shall contain the names and qualifications of the members of the committee, and a statement that the committee agrees to comply with the requirements set forth in this section. Ap

proval shall be based upon an assessment of the qualifications of the members of the committee, and the assurance that all necessary fields of expertise are covered. Approval of a committee may be withdrawn at any time for failure of the committee to comply with any of the requirements of this section. Approval of a committee shall remain effective unless and until the FDA withdraws such approval. Changes in membership and applications for new members shall be submitted to the Food and Drug Administration as soon as, or before, vacancies occur on the committee,

(5) Monitoring. The Food and Drug Administration shall conduct periodic reviews of approved committees. Monitoring of the activities of the committee shall be conducted through review of its annual report, through review of minutes and full protocols for certain studies, and through on-site inspections.

(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. To assure that the radiation dose to research subjects is as low as practicable to perform the study and meet the criteria of 8361.1(b)(3), the Radioactive Drug Research Committee shall require that:

(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 halflife, 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. To determine that the amount of active ingredients to be administered does not exceed the limitations set forth in paragraph (b)(2) of this section, the committee shall require that the investigator provide pharmacological dose calculations based on data available from published literature or from other valid human studies.

(3) Qualifications of investigators. Each investigator shall be qualified by training and experience to conduct the proposed research studies.

(4) License to handle radioactive materials. The responsible investigator or institutions shall, in the case of reactor-produced isotopes, be licensed by the Nuclear Regulatory Commission or Agreement State to possess and use the specific radionuclides for research use or be a listed investigator under a broad license, or in the case of non-reactor-produced isotopes, be licensed by other appropriate State or local authorities, when required by State or local law, to possess and use the specific radionuclides for research use.

(5) Human research subjects. Each investigator shall select appropriate human subjects and shall obtain the review and approval of an institutional review committee that conforms to the requirements of part 56 of this chapter, and shall obtain the consent of the subjects or their legal representatives in accordance with part 50 of this chapter. The research subjects shall be at least 18 years of age and legally competent. Exceptions are permitted only in those special situations when it can be demonstrated to the committee that the study presents a unique opportunity to gain information not currently available, requires the use of research subjects less than 18 years of age, and is without significant risk to the subject. Studies involving minors shall be supported with review by qualified pediatric consultants to the Radioactive Drug Research Committee. Each female research subject of childbearing potential shall state in writing that she is not pregnant, or, on the basis of a pregnancy test be confirmed as not pregnant, before she may participate in any study.

(6) Quality of radioactive drug. The radioactive drug used in the research

study shall meet appropriate chemical, pharmaceutical, radiochemical, and radionuclidic standards of identity, strength, quality, and purity as needed for safety and be of such uniform and reproducible quality as to give significance to the research study conducted. The Radioactive Drug Research Committee shall determine that radioactive materials for parenteral use are prepared in sterile and pyrogen-free form.

(7) Research protocol. No matter how small the amount of radioactivity, no study involving administration of a radioactive drug, as defined in $310.3(n) of this chapter, to research subjects under this section, shall be permitted unless the Radioactive Drug Research Committee concludes, in its judgment, that scientific knowledge and benefit is likely to result from that study. Therefore, the protocol shall be based upon a sound rationale derived from appropriate animal studies or published literature and shall be of sound design such that information of scientific value may result. The radiation dose shall be both sufficient and no greater than necessary to obtain valid measurement. The projected number of subjects shall be sufficient but no greater than necessary for the purpose of the study. The number of subjects shall also reflect the fact that the study is intended to obtain basic research information referred to in paragraph (a) of this section and 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., to carry out a clinical trial).

(8) Adverse reactions. The investigator shall immediately report to the Radioactive Drug Research Committee all adverse effects associated with the use of the radioactive drug in the research study. All adverse reactions probably attributable to the use of the radioactive drug in the research study shall be immediately reported by the Radioactive Drug Research Committee to the Food and Drug Administration, Center for Drug Evaluation and Research, HFD-160, 5600 Fishers Lane, Rockville, MD 20857.

(9) Approval by an institutional review board. The investigator shall obtain the

review and approval of an institutional review board that conforms to the requirements of part 56 of this chapter.

(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 88 201.5 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 “Caution: Federal law prohibits dispensing without prescription";

(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,

(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, That in the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, the information required by paragraphs (f) (1) and (12) of this section may be placed on the shielded container only.

(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)

PART 369-INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND DEVICES FOR OVER-THECOUNTER SALE

Subpart A-Definitions and Interpretations

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;

Sec. 369.1 Purpose of issuance. 369.2 Definitions. 369.3 Warnings required on drugs exempted

from prescription-dispensing require

ments of section 503(b)(1)(C). 369.4 Warnings suggested for drugs by for

mal or informal statements of policy. 369.5 Warnings required on insulin intended

for over-the-counter sale. 369.6 (Reserved) 369.7 Warnings required by official compen

dia. 369.8 Warning statements in relation to

conditions for use. 369.9 General warnings re accidental inges

tion by children. 369.10 Conspicuousness of warning state

ments.

Subpart B-Warning and Caution

Statements for Drugs

369.20 Drugs; recommended warning and

caution statements.

369.21 Drugs; warning and caution state

ments required by regulations. 369.22 Drugs; warning and caution state

ments specifically required by law.

AUTHORITY: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 371.

SOURCE: 39 FR 11745, Mar. 29, 1974, unless otherwise noted.

Subpart A-Definitions and

Interpretations

8 369.3 Warnings required on drugs ex

empted from prescription-dispensing requirements of section

503(b)(1)(C). Drugs exempted from prescriptiondispensing requirements under section 503(b)(1)(C) of the act are subject to the labeling requirements prescribed in 8310.201(a) of this chapter. Although, for convenience, warning and caution statements for a number of the drugs named in $310.201 of this chapter (cross-referenced in the text of this part) are included in subpart B of this part, the inclusion of such drugs in $$ 369.20, 369.21, 369.22 in no way affects the requirements for compliance with $310.201(a) of this chapter, or the provisions of an effective application pursuant to section 505(b) of the act.

8369.4 Warnings suggested for drugs

by formal or informal statements of

policy. The warning and caution statements included in subpart B of this part in no way affect any warning statement suggested for such drugs or devices by any statement of policy or interpretation in subchapter C of this chapter.

8 369.1 Purpose of issuance.

The warning and caution statements suggested in subparts B and C of this part, for inclusion in the label or labeling of drugs and devices subject to section 502(d) and (f)(2) and other relevant provisions of the Federal Food, Drug, and Cosmetic Act are issued for the purpose of assisting industry in preparing proper labeling for these articles for over-the-counter sale and in meeting the legal requirements of the act that the label or labeling of drugs and devices bear adequate warnings, in such manner and form as are necessary for the protection of users. Only section 502(d) of the act requires use of the specific language included in these suggested warning and caution statements. These suggested warning or caution statements are illustrative of those that may be necessary or desirable. It is the responsibility of the manufacturer, packer, shipper, or distributor in interstate commerce to see that such statements are adequate for compliance with the provisions of the law. Omission of any article from this suggested list does not relieve drugs and devices subject to provisions of the act from bearing adequate warning or caution statements where such statements are necessary or desirable for the protection of the user.

[39 FR 11745, Mar. 29, 1974, as amended at 40 FR 13496, Mar. 27, 1975)

8 369.5 Warnings required on insulin

intended for over-the-counter sale.

Warning and caution statements for insulin products sold over the counter must comply with the specific labeling provisions of the act and $429.11 of this chapter.

8 369.6 [Reserved]

$369.7 Warnings required by official

compendia. Any drug included in the official compendia defined by the act shall bear such warning or caution statement as may be required by such compendia, and no statement in subpart B or subpart of this part is intended to alter, modify, or permit the omission of any such statement required by such compendia.

8 369.2 Definitions.

(a) As used in this part, the term act means the Federal Food, Drug, and Cosmetic Act.

(b) The terms drugs and devices are defined in section 201(g) and (k) of the act.

(c) Official compendia are defined in section 201(j) of the act.

8 369.8 Warning statements in relation

to conditions for use. The mention in any warning or caution statement included in subparts A, B, and C of this part, of a disease condition does not imply a finding on the part of the Food and Drug Administration that any drug or device is efficacious in such condition; nor is any drug or device bearing labeling referring to such disease condition precluded from regulatory action under the applicable provisions of the act if such claim is considered to be misbranding.

§ 369.9 General warnings re accidental

ingestion by children. Section 369.20 includes under certain items, but not all medicines, the statement: “Warning-Keep this and all medicines out of children's reach. In case of accidental overdose, contact a physician immediately”, or "Warning-Keep out of the reach of children". However, in view of the possibility of accidental ingestion of drugs, it is not only suggested but is recommended that one of these statements be used on the label of all drug products.

Warning--This medication may damage the kidneys when used in large amounts or for a long period of time. Do not take more than the recommended dosage, nor take regularly for longer than 10 days without consulting your physician. ANESTHETICS FOR EXTERNAL USE (LOCAL ANESTHETICS). (See also $310.201(a)(19) and (23) of this chapter.)

Caution-Do not use in the eyes. Not for prolonged use. If the condition for which this preparation is used persists or if a rash or irritation develops, discontinue use and consult physician. ANTIHISTAMINICS FOR EXTERNAL USE (EXCEPT PREPARATIONS FOR OPHTHALMIC USE).

Caution-Do not use in the eyes. If the condition for which this preparation is used persists or if a rash or irritation develops, discontinue use and consult physician.

§ 369.10 Conspicuousness of warning

statements.

of age

Necessary warning statements should appear in the labeling prominently and conspicuously as compared to other words, statements, designs, and devices, and in bold type on clearly contrasting background, in order to comply with the provisions of section 502(c) and (f)(2) of the act. The warning statements should be placed in the labeling in juxtaposition with the directions for use and, in any case, should appear on the label when there is sufficient label space in addition to mandatory label information.

ANTIHISTAMINICS, ORAL. (See also 8310.201(a)(4) and (a)(24) of this chapter.)

Caution—This preparation may cause drowsiness. Do not drive or operate machinery while taking this medication. Do not give to children under 6 years

or exceed the recommended dosage unless directed by physician.

The reference to drowsiness is not required on preparations for the promotion of sleep or on preparations that are shown not to produce drowsiness. ANTIPERSPIRANTS.

Do not apply to broken skin. If a rash develops, discontinue use. ANTIPYRINE.

Warning-DO not exceed recommended dosage. If skin rash appears, discontinue use and consult physician. ANTISEPTICS FOR EXTERNAL USE.

Caution—In case of deep or puncture wounds or serious burns, consult physician. If redness, irritation, swelling, or pain persists or increases or if infection occurs discontinue use and consult physician.

The reference to wounds and burns is not required on preparations intended solely for diaper rash. ARSENIC PREPARATIONS.

Subpart B-Warning and Caution

Statements for Drugs

$369.20 Drugs; recommended warning

and caution statements.

ACETANILID.

Warning-Do not exceed recommended dosage. Overdosage or continued use may result in serious blood disturbances.

ACETOPHENETIDIN CONTAINING PREPARATIONS. (See $201.309 of this chapter.)

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