subject to section 505 of the act if it is a drug licensed under the Public Health Service Act of July 1, 1944 (58 Stat. 682, as amended (42 U.S.C. 201 et seq.)) or under the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832 (21 U.S.C. 151 et seq.)).

(b) A radioactive biological product (as defined in § 600.3(ee) of this chapter) intended for human use is subject to section 505 of the act. Any license for such a radioactive biological product which is issued under the Public Health Service Act of July 1, 1944 (58 Stat. 682, as amended (42 U.S.C. 201 et seq.)) and which has not been revoked or suspended as of August 25, 1975 shall constitute an approved new drug application in effect under the same terms and conditions as set forth in such license and such portions of the establishment license relating to such product, which include data and information required under Part 314 of this chapter for a new drug application. Any such radioactive biological product for which licensure under the Public Health Service Act is pending on August 25, 1975 shall, upon determination that it is acceptable for licensure, be approved as a new drug application in lieu of issuance of a biological product license.

[40 FR 31312, July 25, 1975]

§ 310.6 Applicability of “new drug" or safety or effectiveness findings in drug efficacy study implementation notices and notices of opportunity for hearing to identical, related, and similar drug products.

(a) The Food and Drug Administration's conclusions on the effectiveness of drugs are currently being published in the FEDERAL REGISTER as Drug Efficacy Study Implementation (DESI) Notices and as Notices of Opportunity for Hearing. The specific products listed in these notices include only those that were introduced into the market through the new drug procedures from 1938-62 and were submitted for review by the National Academy of Sciences-National Research Council (NAS-NRC), Drug Efficacy Study Group. Many products which are identical to, related to, or similar to the products listed in these notices have been marketed under different

names or by different firms during this same period or since 1962 without going through the new drug procedures or the Academy review. Even though these products are not listed in the notices, they are covered by the new drug applications reviewed and thus are subject to these notices. All persons with an interest in a product that is identical, related, or similar to a drug listed in a drug efficacy notice or a notice of opportunity for a hearing will be given the same opportunity as the applicant to submit data and information, to request a hearing, and to participate in any hearing. It is not feasible for the Food and Drug Administration to list all products which are covered by an NDA and thus subject to each notice. However, it is essential that the findings and conclusions that a drug product is a “new drug" or that there is a lack of evidence to show that a drug product is safe or effective be applied to all identical, related, and similar drug products to which they are reasonably applicable. Any product not in compliance with an applicable drug efficacy notice is in violation of section 505 (new drugs) and/or section 502 (misbranding) of the act.

(b)(1) An identical, related, or similar drug includes other brands, potencies, dosage forms, salts, and esters of the same drug moiety as well as of any drug moiety related in chemical structure or known pharmacological properties.

(2) Where experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs would conclude that the findings and conclusions, stated in a drug efficacy notice or notice of opportunity for hearing, that a drug product is a "new drug" or that there is a lack of evidence to show that a drug product is safe or effective are applicable to an identical, related, or similar drug product, such product is affected by the notice. A combination drug product containing a drug that is identical, related, or similar to a drug named in a notice may also be subject to the findings and conclusions in a notice that a drug product is a "new drug" or that there is a lack of evidence to show that a drug product is safe or effective.

(3) Any person may request an opinion on the applicability of such a notice to a specific product by writing to the Food and Drug Administration at the address shown in paragraph (e) of this section.

(c) Manufacturers and distributors of drugs should review their products as drug efficacy notices are published and assure that identical, related, or similar products comply with all applicable provisions of the notices.

(d) The published notices and summary lists of the conclusions are of particular interest to drug purchasing agents. These agents should take particular care to assure that the same purchasing policy applies to drug products that are identical, related, or similar to those named in the drug efficacy notices. The Food and Drug Administration applies the same regulatory policy to all such products. In many instances a determination can readily be made as to the applicability of a drug efficacy notice by an individual who is knowledgeable about drugs and their indications for use. Where the relationships are more subtle and not readily recognized, the purchasing agent may request an opinion by writing to the Food and Drug Administration at the address shown in paragraph (e) of this section.

(e) Interested parties may submit to the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Compliance, HFD300, 5600 Fishers Lane, Rockville, MD 20857, the names of drug products, and of their manufacturers or distributors, that should be the subject of the same purchasing and regulatory policies as those reviewed by the Drug Efficacy Study Group. Appropriate action, including referral to purchasing officials of various government agencies, will be taken.

(f) This regulation does not apply to OTC drugs identical, similar, or related to a drug in the Drug Efficacy Study unless there has been or is notification in the FEDERAL REGISTER that a drug will not be subject to an OTC panel review pursuant to §§ 330.10, 330.11, and 330.5 of this chapter.

[39 FR 11680, Mar. 29, 1974, as amended at 48 FR 2755, Jan. 21, 1983; 50 FR 8996, Mar. 6, 1985; 55 FR 11578, Mar. 29, 1990]

Subpart B-Specific Administrative Rulings and Decisions

§ 310.100 New drug status opinions; statement of policy.

(a) Over the years since 1938 the Food and Drug Administration has given informal advice to inquirers as to the new drug status of preparations. These drugs have sometimes been identified only by general statements of composition. Generally, such informal opinions were incorporated in letters that did not explicitly relate all of the necessary conditions and qualifications such as the quantitative formula for the drug and the conditions under which it was prescribed, recommended, or suggested. This has contributed to misunderstanding and misinterpretation of such opinions.

(b) These informal opinions that an article is "not a new drug" or "no longer a new drug" require reexamination under the Kefauver-Harris Act (Public Law 87-781; 76 Stat. 788-89). In particular, when approval of a new drug application is withdrawn under provisions of section 505(e) of the Federal Food, Drug, and Cosmetic Act, a drug generally recognized as safe may become a "new drug" within the meaning of section 201(p) of said act as amended by the Kefauver-Harris Act on October 10, 1962. This is of special importance by reason of proposed actions to withdraw approval of new drug applications for lack of substantial evidence of effectiveness as a result of reports of the National Academy of Sciences-National Research Council on its review of drug effectiveness; for example, see the notice published in the FEDERAL REGISTER of January 23, 1968 (33 FR 818), regarding rutin, quercetin, et al.

(c) Any marketed drug is a "new drug" if any labeling change made after October 9, 1962, recommends or suggests new conditions of use under which the drug is not generally recognized as safe and effective by qualified experts. Undisclosed or unreported side effects as well as the emergence of new knowledge presenting questions with respect to the safety or effectiveness of a drug may result in its becoming a "new drug" even though it

was previously considered “not a new drug." Any previously given informal advice that an article is "not a new drug" does not apply to such an article if it has been changed in formulation, manufacture control, or labeling in a way that may significantly affect the safety of the drug.

(d) For these reasons, all opinions previously given by the Food and Drug Administration to the effect that an article is "not a new drug" or is "no longer a new drug" are hereby revoked. This does not mean that all articles that were the subjects of such prior opinions will be regarded as new drugs. The prior opinions will be replaced by opinions of the Food and Drug Administration that are qualified and current on when an article is "not a new drug," as set forth in this subchapter.

[39 FR 11680, Mar. 29, 1974]

§ 310.101 FD&C Red No. 4; procedure for discontinuing use in new drugs for ingestion; statement of policy.

(a) Section 81.10(d) of this chapter published December 11, 1964 (29 FR 16983), terminated the provisional listing of FD&C Red No. 4 for use in drugs that may be ingested and canceled the effectiveness of certificates for this color additive and mixtures containing it as of June 9, 1965 (§ 81.30(c) of this chapter), insofar as ingested drugs are concerned. On August 19, 1965 (30 FR 10289), FD&C Red No. 4 was restored to provisional listing by amendment to § 81.1(a) of this chapter, which restricted the use of color to the terms of § 81.25 of this chapter. The use of FD&C Red No. 4 or mixtures containing it in the manufacture of ingested drugs (except for limited use as provided in § 81.25 of this chapter) will result in adulteration and may constitute grounds for withdrawing approval of drugs for which a new drug approval is in effect.

(b) An approved supplemental new drug application will not be required to provide for discontinuing the use of FD&C Red No. 4 in the manufacture of articles that are the subject of approved new drug applications, provided that the applicant submits to the Food and Drug Administration a written notice of the date on which the

change in formulation will be put into effect.

(c) It will be the policy of the Food and Drug Administration to take no action against a drug or applicant where a permitted color additive is substituted for FD&C Red No. 4 in the manufacture of a drug prior to receipt of a written notice of approval of a supplemental new drug application, provided that the applicant submits a satisfactory supplemental application meeting all the following conditions:

(1) The applicant submits a full list of the components and a full statement of the composition of the drug.

(2) The date when the composition of the drug will be changed is stated.

(3) The applicant submits data showing that the change in composition does not interfere with any assay or other control procedures used in manufacturing the drug, or that the assay and other control procedures are revised to make them adequate.

(4) The data available to establish the stability of the revised formulation are included, and if the data are too limited to support a conclusion that the drug will retain its declared potency for a reasonable marketing period, a commitment from the applicant:

(i) To test the stability of marketed batches at reasonable intervals;

(ii) To submit the data as they become available; and

(iii) To recall from the market any batch found to fall below the approved specifications for the drug.

(d) When a supplemental application proposes the change prescribed in paragraph (c) of this section and the applicant informs the Food and Drug Administration that the changes have been put into effect, such notification will be regarded as an agreement by the applicant to an extension of the time for formal action on the supplemental application.

(e) Except as provided in paragraph (c) of this section, no provision of this statement of policy shall limit the authority of the Secretary of Health and Human Services or of the Commissioner of Food and Drugs to suspend or withdraw approval of a new-drug application as prescribed by section 505(e) of the act or to initiate any

other regulatory proceedings with respect to a drug or applicant under the provisions of the act.

[39 FR 11680, Mar. 29, 1974, as amended at 42 FR 15674, Mar. 22, 1977]

§ 310.103 New drug substances intended for hypersensitivity testing.

(a) The Food and Drug Administration is aware of the need in the practice of medicine for the ingredients of a new drug to be available for tests of hypersensitivity to such ingredients and therefore will not object to the shipment of a new drug substance, as defined in § 310.3(g), for such purpose if all of the following conditions are met:

(1) The shipment is made as a result of a specific request made to the manufacturer or distributor by a practitioner licensed by law to administer such drugs, and the use of such drugs for patch testing is not promoted by the manufacturer or distributor.

(2) The new drug substance requested is an ingredient in a marketed new drug and is not one that is an ingredient solely in a new drug that is legally available only under the investigational drug provisions of this part.

(3) The label bears the following prominently placed statements in lieu of adequate directions for use and in addition to complying with the other labeling provisions of the act:

(i) "Caution: Federal law prohibits dispensing without a prescription"; and

(ii) "For use only in patch testing". (4) The quantity shipped is limited to an amount reasonable for the purpose of patch testing in the normal course of the practice of medicine and is used solely for such patch testing.

(5) The new drug substance is manufactured by the same procedures and meets the same specifications as the component used in the finished dosage form.

(6) The manufacturer or distributor maintains records of all shipments for this purpose for a period of 2 years after shipment and will make them available to the Food and Drug Administration on request.

(b) When the requested new drug substance is intended for investigational use in humans or the substance

is legally available only under the investigational drug provisions of part 312 of this chapter, the submission of an "Investigational New Drug Application" (IND) is required. The Food and Drug Administration will offer assistance to any practitioner wishing to submit an Investigational New Drug Application.

(c) This section does not apply to drugs or their components that are subject to the licensing requirements of the Public Health Service Act of 1944, as amended. (See Subchapter F— Biologies, of this chapter.)

[39 FR 11680, Mar. 29, 1974, as amended at 55 FR 11578, Mar. 29, 1990]

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(b) Prescription-exemption dure for drugs limited by a new drug application. Any drug limited to prescription under section 503(b)(1)(C) of the act shall be exempted from prescription-dispensing requirements when the Commissioner finds such requirements are not necessary for the protection of the public health by reason of the drug's toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, and he finds that the drug is safe and effective for use in self-medication as directed in proposed labeling. A proposal to exempt a drug from the prescription-dispensing requirements of section 503(b)(1)(C) of the act may be initiated by the Commissioner or by any interested person. Any interested person may file a petition seeking such exemption, which petition may be pursuant to Part 10 of this chapter, or in the form of a supplement to an approved new drug application.

(c) New drug status of drugs exempted from the prescription requirement.

A drug exempted from the prescription requirement under the provisions of paragraph (b) of this section is a "new drug" within the meaning of section 201(p) of the act until it has been used to a material extent and for a material time under such conditions except as provided in paragraph (e) of this section.

(d) Prescription legend not allowed on exempted drugs. The use of the prescription caution statement quoted in section 503(b) (4) of the act, in the labeling of a drug exempted under the provisions of this section, constitutes misbranding. Any other statement or suggestion in the labeling of a drug exempted under this section, that such drug is limited to prescription use, may constitute misbranding.

§ 310.201 Exemption for certain drugs limited by new-drug applications to prescription sale.

(a) The prescription-dispensing requirements of section 503(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act are not necessary for the protection of the public health with respect to the following drugs subject to new drug applications:

(1) N-Acetyl-p-aminophenol (acetaminophen, p-hydroxy-acetanilid) preparations meeting all the following conditions:

(i) The N-acetyl-p-aminophenol is prepared, with or without other drugs, in tablet or other dosage form suitable for oral use in self-medication, and containing no drug limited to prescription sale under the provisions of section 503(b)(1) of the act.

(ii) The N-acetyl-p-aminophenol and all other components of the preparation meet their professed standards of identity, strength, quality, and purity. (iii) If the preparation is a new drug, an application pursuant to section 505 (b) of the act is approved for it.

(iv) The preparation contains not more than 0.325 gram (5 grains) of Nacetyl-p-aminophenol per dosage unit, or if it is in liquid form not more than 100 milligrams of N-acetyl-p-aminophenol per milliliter.

(v) The preparation is labeled with adequate directions for use in minor conditions as a simple analgesic.

(vi) The dosages of N-acetyl-p-aminophenol recommended or suggested in the labeling do not exceed: For adults, 0.65 gram (10 grains) per dose or 2.6 grams (40 grains) per 24-hour period: for children 6 to 12 years of age, onehalf of the maximum adult dose or dosage; for children 3 to 6 years of age, one-fifth of the maximum adult dose or dosage.

(vii) The labeling bears, in juxtaposition with the dosage recommendations, a clear warning statement against administration of the drug to children under 3 years of age and against use of the drug for more than 10 days, unless such uses are directed by a physician.

(viii) If the article is offered for use in arthritis or rheumatism, the labeling prominently bears a statement that the beneficial effects claimed are limited to the temporary relief of minor aches and pains of arthritis and rheumatism and, in juxtaposition with directions for use in such conditions, a conspicuous warning statement, such as "Caution: If pain persists for more than 10 days, or redness is present, or in conditions affecting children under 12 years of age, consult a physician immediately".

(2) Sodium gentisate (sodium-2, 5-dihydroxybenzoate) preparations meeting all the following conditions:

(i) The sodium gentisate is prepared, with or without other drugs, in tablet or other dosage form suitable for oral use in self-medication, and containing no drug limited to prescription sale under the provisions of section 503(b)(1) of the act.

(ii) The sodium gentisate and all other components of the preparation meet their professed standards of identity, strength, quality, and purity.

(iii) If the preparation is a new drug, an application pursuant to section 505(b) of the act is approved for it.