[Code of Federal Regulations]

 [Title 21, Volume 1, Parts 1 to 99]

 [Revised as of April 1, 1996]

 From the U.S. Government Printing Office via GPO Access

 [CITE: 21CFR2 ]

 

 [Page 16-22]

 

         TITLE 21--FOOD AND DRUGS

 

 CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

 PART 2--GENERAL ADMINISTRATIVE RULINGS AND DECISIONS

 

       Subpart A--General Provisions

 

 Sec.

 2.5  Imminent hazard to the public health.

 2.10  Examination and investigation samples.

 2.19  Methods of analysis.

 

     Subpart B--Human and Animal Foods

 

 2.25  Grain seed treated with poisonous substances; color identification

           to prevent adulteration of human and animal food.

 2.35  Use of secondhand containers for the shipment or storage of food

           and animal feed.

 

         Subparts C--E  [Reserved]

 

        Subpart F--Caustic Poisons

 

 2.110  Definition of ammonia under Federal Caustic Poison Act.

 

   Subpart G--Provisions Applicable to Specific Products Subject to the

   Federal Food, Drug, and Cosmetic Act

 

 2.125  Use of chlorofluorocarbon propellants in self-pressurized

           containers.

 

     Authority: Secs. 201, 301, 305, 402, 408, 409, 501, 502, 505, 507,

 512, 601, 701, 702, 704 of the Federal Food, Drug, and Cosmetic Act (21

 U.S.C. 321, 331, 335, 342, 346a, 348, 351, 352, 355, 357, 360b, 361,

 371, 372, 374); 15 U.S.C. 402, 409.

 

     Source: 42 FR 15559, Mar. 22, 1977, unless otherwise noted.

 

       Subpart A--General Provisions

 

 Sec. 2.5   Imminent hazard to the public health.

 

     (a) Within the meaning of the Federal Food, Drug, and Cosmetic Act

 an imminent hazard to the public health is considered to exist when the

 evidence is sufficient to show that a product or practice, posing a

 significant threat of danger to health, creates a public health

 situation (1) that should be corrected immediately to prevent injury and

 (2) that should not be permitted to continue while a hearing or other

 formal proceeding is being held. The imminent hazard may be declared at

 any point in the chain of events which may ultimately result in harm to

 the public health. The occurrence of the final anticipated injury is not

 essential to establish that an imminent hazard of such occurrence

 exists.

     (b) In exercising his judgment on whether an imminent hazard exists,

 the Commissioner will consider the number of injuries anticipated and

 the nature, severity, and duration of the anticipated injury.

 

 Sec. 2.10   Examination and investigation samples.

 

     (a)(1) When any officer or employee of the Department collects a

 sample of a food, drug, or cosmetic for analysis under the act, the

 sample shall be designated as an official sample if records or other

 evidence is obtained by him or any other officer or employee of the

 Department indicating that the shipment or other lot of the article from

 which such sample was collected was introduced or delivered for

 introduction into interstate commerce, or was in or was received in

 interstate commerce, or was manufactured within a Territory. Only

 samples so designated by an officer or employee of the Department shall

 be considered to be official samples.

     (2) For the purpose of determining whether or not a sample is

 collected for analysis, the term analysis includes examinations and

 tests.

     (3) The owner of a food, drug, or cosmetic of which an official

 sample is collected is the person who owns the shipment or other lot of

 the article from which the sample is collected.

 

 [[Page 17]]

 

     (b) When an officer or employee of the Department collects an

 official sample of a food, drug, or cosmetic for analysis under the act,

 he shall collect at least twice the quantity estimated by him to be

 sufficient for analysis, unless:

     (1) The amount of the article available and reasonably accessible

 for sampling is less than twice the quantity so estimated, in which case

 he shall collect as much as is available and reasonably accessible.

     (2) The cost of twice the quantity so estimated exceeds $50.

     (3) The sample cannot by diligent use of practicable preservation

 techniques available to the Food and Drug Administration be kept in a

 state in which it could be readily and meaningfully analyzed in the same

 manner and for the same purposes as the Food and Drug Administration's

 analysis.

     (4) The sample is collected from a shipment or other lot which is

 being imported or offered for import into the United States.

     (5) The sample is collected from a person named on the label of the

 article or his agent, and such person is also the owner of the article.

     (6) The sample is collected from the owner of the article, or his

 agent, and such article bears no label or, if it bears a label, no

 person is named thereon.

 

 In addition to the quantity of sample set forth in this paragraph, the

 officer or employee shall, if practicable, collect such further amount

 as he estimates will be sufficient for use as trial exhibits.

     (c) After the Food and Drug Administration has completed such

 analysis of an official sample of a food, drug, or cosmetic as it

 determines, in the course of analysis and interpretation of analytical

 results, to be adequate to establish the respects, if any, in which the

 article is adulterated or misbranded within the meaning of the act, or

 otherwise subject to the prohibitions of the act, and has reserved an

 amount of the article it estimates to be adequate for use as exhibits in

 the trial of any case that may arise under the act based on the sample,

 a part of the sample, if any remains available, shall be provided for

 analysis, upon written request, by any person named on the label of the

 article, or the owner thereof, or the attorney or agent of such person

 or owner, except when:

     (1) After collection, the sample or remaining part thereof has

 become decomposed or otherwise unfit for analysis, or

     (2) The request is not made within a reasonable time before the

 trial of any case under the act, based on the sample to which such

 person or owner is a party. The person, owner, attorney, or agent who

 requests the part of sample shall specify the amount desired. A request

 from an owner shall be accompanied by a showing of ownership, and a

 request from an attorney or agent by a showing of authority from such

 person or owner to receive the part of sample. When two or more requests

 for parts of the same sample are received the requests shall be complied

 with in the order in which they were received so long as any part of the

 sample remains available therefor.

     (d) When an official sample of food, drug, or cosmetic is the basis

 of a notice given under section 305 of the act, or of a case under the

 act, and the person to whom the notice was given, or any person who is a

 party to the case, has no right under paragraph (c) of this section to a

 part of the sample, such person or his attorney or agent may obtain a

 part of the sample upon request accompanied by a written waiver of right

 under such paragraph (c) from each person named on the label of the

 article and owner thereof, who has not exercised his right under such

 paragraph (c). The operation of this paragraph shall be subject to the

 exceptions, terms, and conditions prescribed in paragraph (c) of this

 section.

     (e) The Food and Drug Administration is authorized to destroy:

     (1) Any official sample when it determines that no analysis of such

 sample will be made;

     (2) Any official sample or part thereof when it determines that no

 notice under section 305 of the act, and no case under the act, is or

 will be based on such sample;

     (3) Any official sample or part thereof when the sample was the

 basis of a notice under section 305 of the act, and when, after

 opportunity for

 

 [[Page 18]]

 

 presentation of views following such notice, it determines that no other

 such notice, and no case under the act, is or will be based on such

 sample;

     (4) Any official sample or part thereof when the sample was the

 basis of a case under the act which has gone to final judgment, and when

 it determines that no other such case is or will be based on such

 sample;

     (5) Any official sample or part thereof if the article is

 perishable;

     (6) Any official sample or part thereof when, after collection, such

 sample or part has become decomposed or otherwise unfit for analysis;

     (7) That part of any official sample which is in excess of three

 times the quantity it estimates to be sufficient for analysis.

 

 Sec. 2.19   Methods of analysis.

 

     Where the method of analysis is not prescribed in a regulation, it

 is the policy of the Food and Drug Administration in its enforcement

 programs to utilize the methods of analysis of the Association of

 Official Analytical Chemists (AOAC) as published in the latest edition

 (13th Ed., 1980) of their publication ``Official Methods of Analysis of

 the Association of Official Analytical Chemists,'' and the supplements

 thereto (``Changes in Methods'' as published in the March issues of the

 ``Journal of the Association of Official Analytical Chemists''), which

 are incorporated by reference, when available and applicable. Copies are

 available from the Association of Official Analytical Chemists, 2200

 Wilson Blvd., Suite 400, Arlington, VA 22201-3301, or available for

 inspection at the Office of the Federal Register, 800 North Capitol

 Street NW., suite 700, Washington, DC. In the absence of an AOAC method,

 the Commissioner will furnish a copy of the particular method, or a

 reference to the published method, that the Food and Drug Administration

 will use in its enforcement program. Other methods may be used for

 quality control, specifications, contracts, surveys, and similar

 nonregulatory functions, but it is expected that they will be calibrated

 in terms of the method which the Food and Drug Administration uses in

 its enforcement program. Use of an AOAC method does not relieve the

 practioner of the responsibility to demonstrate that he can perform the

 method properly through the use of positive and negative controls and

 recovery and reproducibility studies.

 

 [42 FR 15559, Mar. 22, 1977, as amended at 47 FR 946, Jan. 8, 1982; 54

 FR 9034, Mar. 3, 1989]

 

     Subpart B--Human and Animal Foods

 

 Sec. 2.25   Grain seed treated with poisonous substances; color

           identification to prevent adulteration of human and animal

           food.

 

     (a) In recent years there has developed increasing use of poisonous

 treatments on seed for fungicidal and other purposes. Such treated seed,

 if consumed, presents a hazard to humans and livestock. It is not

 unusual for stocks of such treated food seeds to remain on hand after

 the planting season has passed. Despite the cautions required by the

 Federal Seed Act (53 Stat. 1275, as amended 72 Stat. 476, 7 U.S.C. 1551

 et seq.) in the labeling of the treated seed, the Food and Drug

 Administration has encountered many cases where such surplus stocks of

 treated wheat, corn, oats, rye, barley, and sorghum seed had been mixed

 with untreated seed and sent to market for food or feed use. This has

 resulted in livestock injury and in legal actions under the Federal

 Food, Drug, and Cosmetic Act against large quantities of food

 adulterated through such admixture of poisonous treated seeds with good

 food. Criminal cases were brought against some firms and individuals.

 Where the treated seeds are prominently colored, buyers and users or

 processors of agricultural food seed for food purposes are able to

 detect the admixture of the poisonous seed and thus reject the lots; but

 most such buyers, users, and processors do not have the facilities or

 scientific equipment to determine the presence of the poisonous chemical

 at the time crops are delivered, in cases where the treated seeds have

 not been so colored. A suitable color for this use is one that is in

 sufficient contrast to the natural color of the food seed as to make

 admixture of treated, denatured seeds with good food easily apparent,

 and is so applied that it is not readily removed.

 

 [[Page 19]]

 

     (b) On and after December 31, 1964, the Food and Drug Administration

 will regard as adulterated any interstate shipment of the food seeds

 wheat, corn, oats, rye, barley, and sorghum bearing a poisonous

 treatment in excess of a recognized tolerance or treatment for which no

 tolerance or exemption from tolerance is recognized in regulations

 promulgated pursuant to section 408 of the Federal Food, Drug, and

 Cosmetic Act, unless such seeds have been adequately denatured by a

 suitable color to prevent their subsequent inadvertent use as food for

 man or feed for animals.

     (c) Attention is called to the labeling requirements of the Federal

 Hazardous Substances Act, where applicable to denatured seeds in

 packages suitable for household use.

 

 Sec. 2.35   Use of secondhand containers for the shipment or storage of

           food and animal feed.

 

     (a) Investigations by the Food and Drug Administration, the National

 Communicable Disease Center of the U.S. Public Health Service, the

 Consumer and Marketing Service of the U.S. Department of Agriculture,

 and by various State public health agencies have revealed practices

 whereby food and animal feed stored or shipped in secondhand containers

 have been rendered dangerous to health. Such contamination has been the

 result of the original use of these containers for the storage and

 shipment of articles containing or bearing disease organisms or

 poisonous or deleterious substances.

     (b) The Commissioner concludes that such dangerous or potentially

 dangerous practices include, but are not limited to, the following:

     (1) Some vegetable growers and packers employ used poultry crates

 for shipment of fresh vegetables, including cabbage and celery.

 Salmonella organisms are commonly present on dressed poultry and in

 excreta and fluid exudates from dressed birds. Thus wooden crates in

 which dressed poultry has been iced and packed are potential sources of

 Salmonella or other enteropathogenic microorganisms that may contaminate

 fresh vegetables which are frequently consumed without heat treatment.

     (2) Some potato growers and producers of animal feeds use secondhand

 bags for shipment of these articles. Such bags may have originally been

 used for shipping or storing pesticide-treated seed or other articles

 bearing or containing poisonous substances. Thus these secondhand bags

 are potential sources of contamination of the food or animal feed stored

 or shipped therein.

     (c) In a policy statement issued April 11, 1968, the Food and Drug

 Administration declared adulterated within the meaning of section 402(a)

 of the Federal Food, Drug, and Cosmetic Act shipments of vegetables or

 other edible food in used crates or containers that may render the

 contents injurious to health. This policy statement is extended so that

 the Food and Drug Administration will regard as adulterated within the

 meaning of section 402(a) of the act shipments of vegetables, other

 edible food, or animal feed in used crates, bags, or other containers

 that may render the contents injurious to health.

 

         Subparts C--E  [Reserved]

 

        Subpart F--Caustic Poisons

 

 Sec. 2.110   Definition of ammonia under Federal Caustic Poison Act.

 

     For the purpose of determining whether an article containing ammonia

 is subject to the Federal Caustic Poison Act, the ammonia content is to

 be calculated as NH<INF>3.

 

   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

 

 [[Page 20]]

 

 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

 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.

     (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

 

 [[Page 21]]

 

 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 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

 

 [[Page 22]]

 

 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]