CHAPTER I-FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES-Continued (Parts 300 to 499) EDITORIAL NOTE: The Food and Drug Administration published a document at 49 FR 41019, Oct. 19, 1984, establishing July 1, 1987, as a uniform effective date for compliance for regulations affecting the labeling of food products. At 51 FR 34085, Sept. 25, 1986, FDA established January 1, 1989, as a new uniform effective date for compliance. The new uniform effective date will apply only to final FDA food labeling regulations published after July 1, 1986, and before January 1, 1988. At 55 FR 276, Jan. 4, 1990, FDA established January 1, 1993 as a new uniform effective date for compliance. The new uniform effective date will apply only to final FDA food labeling regulations published after January 1, 1990 and before January 1, 1992. 312 314 320 328 Investigational new drug application Applications for FDA approval to market a new Bioavailability and bioequivalence requirements 58 96 179 190 205 329 Habit-forming drugs 206 330 Over-the-counter (OTC) human drugs which are 211 331 Antacid products for over-the-counter (OTC) Topical antimicrobial drug products for over-the- 229 Part Page 336 Antiemetic drug products for over-the-counter 238 338 Nighttime sleep-aid drug products for over-the- 239 340 Stimulant drug products for over-the-counter 241 341 343 344 346 drug products for Cold, cough, allergy, bronchodilator, and anti- Anorectal human use 347 Skin protectant drug products for over-the- 273 348 External analgesic drug products for over-the- Miscellaneous external drug products for over-the- 289 ...... 361 Prescription drugs for human use generally recog- 296 369 Interpretative statements re warnings on drugs 370-499 [Reserved] EDITORIAL NOTE: For nomenclature changes to chapter I see 59 FR 14366, Mar. 28, 1994. 301 Sec. SUBCHAPTER D-DRUGS FOR HUMAN USE 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] EFFECTIVE DATE NOTE: At 64 FR 401, Jan. 5, 1999, §300.50, was amended by removing the words "or antibiotic monograph" from paragraph (b), effective May 20, 1999. 310.201 Exemption for certain drugs limited by new drug applications to prescription sale. 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. 310.516 Progestational drug products; labeling directed to the patient. 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 ingredients 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 ingredients offered over-the-counter (OTC) for use as a nail biting 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 ac tive 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 (OTC) for the over-the-counter treatment and/or prevention of malaria. 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 component 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) Except for radioactive biological products intended for human use, a new drug shall not be deemed to be 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 |