Sec.

PART 300-GENERAL

Subpart A [Reserved]

Subpart B-Combination Drugs

The Food and Drug Administration's policy in administering the new-drug, antibiotic, and other regulatory provisions of the Federal Food, Drug, and Cosmetic Act regarding fixed combination dosage form prescription drugs for humans is as follows:

(a) Two or more drugs may be combined in a single dosage form when each component makes a contribution to the claimed effects and the dosage of each component (amount, frequency, duration) is such that the combination is safe and effective for a significant patient population requiring such concurrent therapy as defined in the labeling for the drug. Special cases of this general rule are where a component is added:

(1) To enhance the safety or effectiveness of the principal active component; and

(2) To minimize the potential for abuse of the principal active component.

(b) If a combination drug presently the subject of an approved new-drug application has not been recognized as effective by the Commissioner of Food and Drugs based on his evaluation of the appropriate National Academy of Sciences-National Research Council panel report, or if substantial evidence of effectiveness has not otherwise been

presented for it, then formulation, labeling, or dosage changes may be proposed and any resulting formulation may meet the appropriate criteria listed in paragraph (a) of this section.

(c) A fixed-combination prescription drug for humans that has been determined to be effective for labeled indications by the Food and Drug Administration, based on evaluation of the NAS-NRC report on the combination, is considered to be in compliance with the requirements of this section.

[40 FR 13496, Mar. 27, 1975, as amended at 64 FR 401, Jan. 5, 1999]

Subpart D-Records and Reports

310.303 Continuation of long-term studies, records, and reports on certain drugs for which new drug applications have been approved.

310.305 Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications.

Subpart E-Requirements for Specific New Drugs or Devices

310.500 Digoxin products for oral use; conditions for marketing.

310.501 Patient package inserts for oral contraceptives.

310.502 Certain drugs accorded new drug status through rulemaking procedures. 310.503 Requirements regarding certain radioactive drugs.

310.509 Parenteral drug products in plastic

containers.

310.515 Patient package inserts for estrogens.

310.517 Labeling for oral hypoglycemic drugs of the sulfonylurea class.

310.518 Drug products containing iron or iron salts.

310.519 Drug products marketed as over-thecounter (OTC) daytime sedatives. 310.527 Drug products containing active ingredients offered over-the-counter (OTC) for external use as hair growers or for hair loss prevention.

310.528 Drug products containing active ingredients offered over-the-counter (OTC) for use as an aphrodisiac.

310.529 Drug products containing active ingredients offered over-the-counter (OTC) for oral use as insect repellents. 310.530 Topically

applied hormone-containing drug products for over-thecounter (OTC) human use.

310.531 Drug products containing active in

gredients offered over-the-counter (OTC) for the treatment of boils.

310.532 Drug products containing active ingredients offered over-the-counter (OTC) to relieve the symptoms of benign prostatic hypertrophy.

310.533 Drug products containing active ingredients offered over-the-counter (OTC) for human use as an anticholinergic in cough-cold drug products.

310.534 Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents.

310.536 Drug products containing active in

gredients offered over-the-counter (OTC) for use as a nailbiting or thumbsucking deterrent.

310.537 Drug products containing active ingredients offered over-the-counter (OTC)

for oral administration for the treatment of fever blisters and cold sores. 310.538 Drug products containing active ingredients offered over-the-counter (OTC) for use for ingrown toenail relief. 310.540 Drug products containing active ingredients offered over-the-counter (OTC) for use as stomach acidifiers. 310.541 Over-the-counter (OTC) drug products containing active ingredients offered for use in the treatment of hypophosphatemia.

310.542 Over-the-counter (OTC) drug products containing active ingredients offered for use in the treatment of hyperphosphatemia.

310.543 Drug products containing active ingredients offered over-the-counter (OTC) for human use in exocrine pancreatic insufficiency. 310.544 Drug products containing active ingredients offered over-the-counter (OTC) for use as a smoking deterrent. 310.545 Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses.

310.546 Drug products containing active ingredients offered over-the-counter (OTC) for the treatment and/or prevention of nocturnal leg muscle cramps.

310.547 Drug products containing quinine offered over-the-counter (OTC) for the treatment and/or prevention of malaria. 310.548 Drug products containing colloidal silver ingredients or silver salts offered over-the-counter (OTC) for the treatment and/or prevention of disease.

AUTHORITY: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262, 263b-263n.

Subpart A-General Provisions

§310.3 Definitions and interpretations. As used in this part:

(a) The term act means the Federal Food, Drug, and Cosmetic Act, as amended (secs. 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

(b) Department means the Department of Health and Human Services.

(c) Secretary means the Secretary of Health and Human Services..

(d) Commissioner means the Commissioner of Food and Drugs.

(e) The term person includes individuals, partnerships, corporations, and

associations.

(f) The definitions and interpretations of terms contained in section 201 of the act shall be applicable to such terms when used in the regulations in this part.

(g) New drug substance means any substance that when used in the manufacture, processing, or packing of a drug, causes that drug to be a new drug, but does not include intermediates used in the synthesis of such substance.

(h) The newness of a drug may arise by reason (among other reasons) of:

(1) The newness for drug use of any substance which composes such drug, in whole or in part, whether it be an active substance or a menstruum, excipient, carrier, coating, or other component.

(2) The newness for a drug use of a combination of two or more substances, none of which is a new drug.

(3) The newness for drug use of the proportion of a substance in a combination, even though such combination containing such substance in other proportion is not a new drug.

(4) The newness of use of such drug in diagnosing, curing, mitigating, treating, or preventing a disease, or to affect a structure or function of the body, even though such drug is not a new drug when used in another disease or to affect another structure or function of the body.

(5) The newness of a dosage, or method or duration of administration or application, or other condition of use prescribed, recommended, or suggested in the labeling of such drug, even though such drug when used in other dosage, or other method or duration of administration or application, or different condition, is not a new drug.

(i) [Reserved]

(j) The term sponsor means the person or agency who assumes responsibility for an investigation of a new drug, including responsibility for compliance with applicable provisions of the act and regulations. The "sponsor" may be an individual, partnership, corporation, or Government agency and may be a manufacturer, scientific institution, or an investigator regularly and lawfully engaged in the investigation of new drugs.

(k) The phrase related drug(s) includes other brands, potencies, dosage forms, salts, and esters of the same drug moiety, including articles prepared or manufactured by other manufacturers: and any other drug containing a com

ponent so related by chemical structure or known pharmacological properties that, in the opinion of experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, it is prudent to assume or ascertain the liability of similar side effects and contraindications.

(1) Special packaging as defined in section 2(4) of the Poison Prevention Packaging Act of 1970 means packaging that is designed or constructed to be significantly difficult for children under 5 years of age to open or obtain a toxic or harmful amount of the substance contained therein within a reasonable time and not difficult for normal adults to use properly, but does not mean packaging which all such children cannot open or obtain a toxic or harmful amount within a reasonable time.

(m) [Reserved]

(n) The term radioactive drug means any substance defined as a drug in section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act which exhibits spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons and includes any nonradioactive reagent kit ornuclide generator which is intended to be used in the preparation of any such substance but does not include drugs such as carbon-containing compounds or potassium-containing salts which contain trace quantities of naturally occurring radionuclides. The term "radioactive drug" includes a "radioactive biological product" as defined in § 600.3(ee) of this chapter..

[39 FR 11680, Mar. 29, 1974, as amended at 39 FR 20484, June 11, 1974; 40 FR 31307, July 25, 1975; 46 FR 8952, Jan. 27, 1981; 50 FR 7492, Feb. 22, 1985]

§310.4 Biologics; products subject to license control.

(a) If a drug has an approved license under section 351 of the Public Health Service Act (42 U.S.C. 262 et seq.) or under the animal virus, serum, and toxin law of March 4, 1913 (21 U.S.C. 151 et seq.), it is not required to have an approved application under section 505 of the act.

(b) To obtain marketing approval for radioactive biological products for human use, as defined in §600.3(ee) of

this chapter, manufacturers must comply with the provisions of 601.2(b) of this chapter.

[64 FR 56448, Oct. 20, 1999]

$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 SciencesNational 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.