[Code of Federal Regulations] [Title 21, Volume 1] [Revised as of April 1, 2002] From the U.S. Government Printing Office via GPO Access [CITE: 21CFR2.125] [Page 19-21] TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES PART 2--GENERAL ADMINISTRATIVE RULINGS AND DECISIONS--Table of Contents Subpart G--Provisions Applicable to Specific Products Subject to the Federal Food, Drug, and Cosmetic Act Sec. 2.125 Use of chlorofluorocarbon propellants in self-pressurized containers. (a) As used in this section: (1) Chlorofluorocarbon means any fully halogenated chlorofluoroalkane. (2) Propellant means a liquefied or compressed gas that is used in whole or in part to expel from the same self-pressurized container or from a separate container a liquid or solid material different from the propellant, but the term does not include the use of a chlorofluorocarbon as an aerating agent for foamed or sprayed food products. (b) Chlorofluorocarbons are widely used in products subject to the Federal Food, Drug, and Cosmetic Act, with the principal use being as propellants in self-pressurized containers. Information recently developed indicates that chlorofluorocarbons may reduce the amount of ozone in the stratosphere and thus increase the amount of ultraviolet radiation reaching the earth. An increase in ultraviolet radiation may increase the incidence of skin cancer, change the climate, and produce other effects of unknown magnitude on humans, animals, and plants. Chlorofluorocarbons may also affect the climate by increasing infrared absorption in the atmosphere. (c) Except as provided in paragraph (e) of this section, any food, drug, device, or cosmetic in a self-pressurized container that contains a chlorofluorocarbon propellant is adulterated and/or misbranded in violation of the act, and any drug product in a self-pressurized container that contains a chlorofluorocarbon propellant is a new drug or a new animal drug. (d) The use of a chlorofluorocarbon as a propellant in a self- pressurized container of a drug product will not result in the drug product being adulterated and/or misbranded provided a new drug [[Page 20]] application, a new animal drug application, or in the case of a certifiable antibiotic an antibiotic application for the drug product has been approved, a petition has been filed as provided by paragraph (f) of this section, and paragraph (e) of this section has been amended to specify the use as essential. (e) The adulteration and misbranding provisions of paragraph (c) of this section shall not apply to the following essential uses of chlorofluorocarbons: (1) Metered-dose steriod human drugs for nasal inhalation, (2) Metered-dose steriod human drugs for oral inhalation, (3) Metered-dose adrenergic bronchodilator human drugs for oral inhalation, (4) Contraceptive vaginal foams for human use, and (5) Metered-dose ergotamine tartrate drug products administered by oral inhalation for use in humans. (6) Intrarectal hydrocortisone acetate for human use. (7) Polymyxin B sulfate-bacitracin zinc-neomycin sulfate soluble antibiotic powder without excipients, for topical use on humans. (8) Anesthetic drugs for topical use on accessible mucous membranes of humans where a cannula is used for application. (9) Metered-dose nitroglycerin human drugs administered to the oral cavity. (10) Metered-dose cromolyn sodium human drugs administered by oral inhalation. (11) Metered-dose ipratropium bromide for oral inhalation. (12) Metered-dose atropine sulfate aerosol human drugs administered by oral inhalation. (13) Metered-dose nedocromil sodium human drugs administered by oral inhalation. (14) Metered-dosed ipratropium bromide and albuterol sulfate, in combination, administered by oral inhalation for human use. (15) Sterile aerosol talc administered intrapleurally by thoracoscopy for human use. (f) Any person may file a petition in accordance with part 10 of this chapter to amend paragraph (e) of this section to specify a use of chlorofluorocarbons in a product as not being subject to the adulteration and misbranding provisions in paragraph (c) of this section. The petition must be supported by an adequate showing that: (1) There are no technically feasible alternatives to the use of a chlorofluorocarbon in the product, (2) The product provides a substantial health benefit, environmental benefit, or other public benefit that would not be obtainable without the use of the chlorofluorocarbon, and (3) The use does not involve a significant release of chlorofluorocarbons into the atmosphere or that the release is warranted in view of the consequence if the use were not permitted. (g) Any holder of an approved new drug application or new animal drug application for a drug product containing a chlorofluorocarbon in a self-pressurized container, except those drug products listed in paragraph (e) of this section, shall submit to the Food and Drug Administration on or before October 1, 1978, either a supplemental application providing for a revised formulation complying with the requirements of Sec. 314.70 or Sec. 514.8 of this chapter or a letter requesting that a new drug application or a new animal drug application for the drug product containing chlorofluorocarbon be withdrawn and that the right to a hearing on the withdrawal of the application is waived. (h)(1) Each manufacturer of a drug product listed in paragraph (e) of this section that is not covered by an approved new drug application shall submit a new drug application in accord with Sec. 314.50 of this chapter on or before June 15, 1978. (2) An abbreviated new drug application conforming to Sec. 314.94 of this chapter is acceptable in lieu of a full new drug application for any product included in the classes of products in paragraph (e) of this section if the product is one that is described under Sec. 314.92 of this chapter. A finding has been made that an abbreviated new drug application may be submitted for the following products included in the classes of products listed in paragraph (e) of this section: (i) Ergotamine tartrate supplied in a metered-dose aerosol form suitable for oral inhalation for the treatment of [[Page 21]] migraine headaches. Each measured dose must deliver a dose of the active ingredient equivalent to that contained in the product that has been the subject of a separate finding that an abbreviated new drug application is suitable. (ii) Isoproterenol hydrochloride supplied in a metered-dose aerosol form suitable for oral inhalation for use as an adrenergic bronchodilator. Each measured dose must deliver a dose of the active ingredient equivalent to that contained in the products that have been the subject of a separate finding that an abbreviated new drug application is suitable. (iii) Epinephrine, epinephrine bitartrate, or epinephrine hydrochloride (racemic) in a metered-dose aerosol form suitable for oral inhalation for use as an adrenergic bronchodilator. Each measured dose must deliver a dose of the active ingredient equivalent to that specified in an OTC proposed or final monograph issued under the provisions of 21 CFR part 330. (iv) Nonoxynol 9 in an aerosol foam suitable for vaginal administration as a contraceptive foam. The aerosol foam must contain 8 to 12.5 percent of nonoxynol 9. (i) Any sponsor of an ``Investigational New Drug Application'' (IND) or ``Notice of Claimed Exemption for a New Animal Drug'' (INAD) for a drug product containing a chlorofluorocarbon shall: (1) Amend the IND or INAD on or before December 15, 1978, to revise the formulation removing the chlorofluorocarbon. (2) Submit the information required under paragraph (f) of this section to amend paragraph (e) of this section to show that the use of chlorofluorocarbon is essential, or (3) Submit the information required under paragraph (j) of this section requesting that studies with the drug product containing a chlorofluorocarbon propellant be allowed to be performed. (j) Any sponsor of an IND or INAD who wishes to initiate or continue a study beyond December 15, 1978 on a drug product containing a chlorofluorocarbon shall submit a petition in accordance with part 10 of this chapter requesting that studies be permitted to collect the data to show that the use of the chlorofluorocarbon is an essential use. The petitions must be supported by the following: (1) A description of the drug product, (2) An explanation why a chlorofluorocarbon propellant is used in the product rather than another propellant or another dosage form of the product, and (3) The benefit that the investigational product is believed to have and that the sponsor hopes to demonstrate by the studies. (k) The Commissioner will initiate action to withdraw approval of an application or terminate an IND or INAD notice in accordance with the applicable provisions of section 505 of the act and parts 312 and 314 of this chapter, or section 512 of the act and parts 511 and 514 of this chapter upon failure of a holder of an approved new drug application or approved new animal drug application or sponsor of an IND or INAD notice to comply with the applicable provisions of this section. (l) Food, drug, device, or cosmetic products manufactured or packaged on or after December 15, 1978, and finished products initially introduced into interstate commerce on or after April 15, 1979, shall comply with this regulation. [43 FR 11316, Mar. 17, 1978, as amended at 44 FR 3961, Jan. 19, 1979; 44 FR 30334, May 26, 1979; 45 FR 22902, April 4, 1980; 51 FR 4591, Feb. 6, 1986; 52 FR 15717, Apr. 30, 1987; 54 FR 9034, Mar. 3, 1989; 55 FR 39267, Sept. 26, 1990; 57 FR 17980, Apr. 28, 1992; 58 FR 6088, Jan. 26, 1993; 61 FR 15700, Apr. 9, 1996; 61 FR 25392, May 21, 1996]