a New Drug," Form FD-1571 set forth in § 130.3 of this chapter, must be submitted to cover clinical investigations designed to obtain evidence that such preparations are effective for such uses.

(d) Regulatory proceedings may be initiated with respect to drug preparations shipped within the jurisdiction of the act that are contrary to provisions of this statement after 30 days from the date of publication of this statement in the FEDERAL REGISTER.

(Secs. 502 (a), (f), 505, 52 Stat. 1050, 1051, 1052, as amended; 21 U.S.C. 352 (a), (f), 355) [32 F.R. 4350, Mar. 22, 1967]

§ 3.54 Epinephrine injection 1:1000 in 10-milliliter containers for emergency treatment of anaphylactoid shock in cattle, horses, sheep, and swine.

(a) Anaphylactoid reactions in cattle, horses, sheep, and swine occur occasionally from the injection of antibiotics, bacterins, and vaccines. Adequate directions for use of these antibiotics, bacterins, and vaccines can generally be written for use by the laity and thus are available to livestock producers. Epinephrine injection is effective for the treatment of anaphylactoid reactions in animals and would be of value in saving lives of animals if it were readily available at the time of administration of the causative agents. In connection with this problem the Food and Drug Administration has obtained the views of the Advisory Committee on Veterinary Medicine, and other experts, and has concluded that adequate directions for overthe-counter sale of epinephrine injection 1:1000 can be prepared.

(b) In view of the above, the Commissioner of Food and Drugs has concluded that it is in the public interest to make epinephrine injection 1: 1000 available for sale without a prescription provided that it is packaged in vials not exceeding 10 milliliters and its label bears, in addition to other required information, the following statements in a prominent and conspicuous manner: "For emergency use only in treating anaphylactoid shock. Usual Dosage: Cattle, horses, sheep, and swine-1 cubic centimeter per 100 pounds of body weight. Inject subcutaneously."

(c) The labeling must also bear a description of the symptoms of anaphylactoid shock including glassy eyes, increased salivation, grinding of the teeth, rapid breathing, muscular tremors, staggering gait, and collapse with death fol

lowing. These symptoms may appear shortly after injection of a bacterin, vaccine, or antibiotic.

[31 F.R. 11383, Aug. 27, 1966]

§ 3.55

Antibiotics used in veterinary medicine and for nonmedical purposes; required data.

(a) An ad hoc committee, Committee on the Veterinary Medical and Nonmedical Uses of Antibiotics, was formed by the Food and Drug Administration to study, and advise the Commissioner on, the uses of antibiotics in veterinary medicine and for various nonmedical purposes as such uses may affect the enforcement of the Federal Food, Drug, and Cosmetic Act with respect to the safety and effectiveness of such substances. A copy of the report may be obtained from the Food and Drug Administration, Office of Education and Information, Washington, D.C. 20204.

(b) On the basis of the report of the Committee and other information, sponsors of drugs containing any antibiotic intended for use in food-producing animals shall submit data for determining whether or not such antibiotics and their metabolites are present as residues in edible tissues, milk, and eggs from treated animals; however, in the case of a drug for which such data have already been submitted and for which a regulation has been promulgated under section 409 of the act, only such data as has been accumulated since the issuance of the regulation need be submitted.

(c) The required data shall be submitted within 180 days of the date of publication of this section in the FEDERAL REGISTER; except that in the case of data on intramammary infusion preparations, the data shall be submitted within 60 days of such publication. Data demonstrating the absence in milk of residues of intramammary infusion preparations when used as directed in their labeling are needed within the 60-day period because of the importance of milk in the human diet.

(d) Regulatory proceedings including revocation of prior sanctions, or actions to suspend or amend new drug or antibiotic approvals granted prior to passage of the Food Additives Amendment of 1958 (72 Stat. 1784), may be initiated with regard to the continued marketing of any antibiotic preparation on which the required information is not submitted within the period of time prescribed by paragraph (c) of this section.

(e) Questions relating to the acceptability of proposed research protocols and assay methods for determining the amount of antibiotic residues in food should be directed to the Director of The Bureau of Veterinary Medicine, Food and Drug Administration, Washington, D.C. 20204.

(Secs. 409, 505, 507, 52 Stat. 1052, as amended, 59 Stat. 463, as amended, 72 Stat. 1785; 21 U.S.C. 348, 355, 357) [31 F.R. 11141, Aug. 23,

1966] § 3.56

Labeling of articles intended for lay use in the repairing and/or refitting of dentures.

(a) The American Dental Association and leading dental authorities have advised the Food and Drug Administration of their concern regarding the safety of denture reliners, repair kits, pads, cushions, and other articles marketed and labeled for lay use in the repairing, refitting, or cushioning of ill-fitting, broken, or irritating dentures. It is the opinion of dental authorities and the Food and Drug Administration that to properly repair and properly refit dentures a person must have professional knowledge and specialized technical skill. Layman cannot be expected to maintain the original vertical dimension of occlusion and the centric relation essential in the proper repairing or refitting of dentures. The continued wearing of improperly repaired or refitted dentures may cause acceleration of bone resorption, soft tissue hyperplasia, and other irreparable damage to the oral cavity. Such articles designed for lay use should be limited to emergency or temporary situations pending the services of a licensed dentist.

(b) The Food and Drug Administration therefore regards such articles as unsafe and misbranded under the Federal Food, Drug, and Cosmetic Act, unless the labeling:

(1) (i) Limits directions for use for denture repair kits to emergency repairing pending unavoidable delay in obtaining professional reconstruction of the denture;

(ii) Limits directions for use for denture reliners, pads, and cushions to temporary refitting pending unavoidable delay in obtaining professional reconstruction of the denture;

(2) Contains in a conspicuous manner the word "emergency" preceding and modifying each indication-for-use statement for denture repair kits and the

word "temporary" preceding and modifying each indication-for-use statement for reliners, pads, and cushions; and

(3) Includes a conspicuous warning statement to the effect:

(i) For denture repair kits: "Warning-For emergency repairs only. Longterm use of home-repaired dentures may cause faster bone loss, continuing irritation, sores, and tumors. This kit for emergency use only. See Dentist Without Delay."

(ii) For denture reliners, pads, and cushions: "Warning-For temporary use only. Long-term use of this product may lead to faster bone loss, continuing irritation, sores, and tumors. For Use Only Until a Dentist Can Be Seen."

(c) Adequate directions for use require full information of the temporary and emergency use recommended in order for the layman to understand the limitations of usefulness, the reasons therefor, and the importance of adhering to the warnings. Accordingly, the labeling should contain substantially the following information:

(1) For denture repair kits: Special training and tools are needed to repair dentures to fit properly. Home-repaired dentures may cause irritation to the gums and discomfort and tiredness while eating. Long-term use may lead to more troubles, even permanent changes in bones, teeth, and gums, which may make it impossible to wear dentures in the future. For these reasons, dentures repaired with this kit should be used only in an emergency until a dentist can be seen. Dentures that don't fit properly cause irritation and injury to the gums and faster bone loss, which is permanent. Dentures that don't fit properly cause gum changes that may require surgery for correction. Continuing irritation and injury may lead to cancer in the mouth. You must see your dentist as soon as possible.

(2) For denture reliners, pads, and cushions: Use of these preparations or devices may temporarily decrease the discomfort; however, their use will not make the denture fit properly. Special training and tools are needed to repair a denture to fit properly. Dentures that do not fit properly cause irritation and injury to the gums and faster bone loss, which is permanent and may require a a completely new denture. Changes in the gums caused by dentures that do not fit properly may require surgery for correction. Continuing irritation and injury

may lead to cancer in the mouth. You must see your dentist as soon as possible.

(3) If the denture relining or repairing material forms a permanent bond with the denture, a warning statement to the following effect should be included: "This reliner becomes fixed to the denture and a completely new denture may be required because of its use."

(d) Labeling claims exaggerating the usefulness or the safety of the material or failing to disclose all facts relevant to the claims of usefulness will be regarded as false and misleading under sections 201(n) and 502(a) of the Federal Food, Drug, and Cosmetic Act.

(e) Regulatory action may be initiated with respect to any article found within the jurisdiction of the act contrary to the provisions of this policy statement after 90 days following the date of publication of this section in the FEDERAL REGISTER.

[34 F.R. 14168, Sept. 9, 1969]

§ 3.57

Stocks of packages and labels not complying with section 4 of the Fair Packaging and Labeling Act.

(a) Implementation of the Fair Packaging and Labeling Act (Public Law 89755) will require changes in the labels of many foods, drugs, devices, and cosmetics now on the market. The law does not contemplate a disruption of legitimate business practices nor destruction of all stocks of labels and packages rendered not-in-compliance by the effective dates of the regulations promulgated pursuant to that Act. Section 6 of the Fair Packaging and Labeling Act provides that "no regulation adopted under this Act shall preclude the continued use of returnable or reusable glass containers for beverages in inventory or with the trade as of the effective date of this Act, nor shall any regulation under this Act preclude the orderly disposal of packages in inventory or with the trade as of the effective date of such regulation." Section 13 provides that the promulgating authority may by regulation postpone the effective date of the Fair Packaging and Labeling Act for an additional 12month period for classes or types of consumer commodities.

(b) In the orders published in the FEDERAL REGISTER of July 21, 1967, and September 20, 1967, it is stated that the effective date of that initial order covering food labels under the Fair Packaging and Labeling Act shall be December 31,

1967, for all new food packages, new label designs, and labels being reordered, and shall be July 1, 1968, for all food packages and labels being introduced into interstate commerce. Extensions for stocks of packages and labels beyond July 1, 1968, will be considered on an individual case basis and are grantable for good cause shown. Good cause would necessarily include a showing that:

(1) The stocks are in compliance with the present terms of the Federal Food, Drug, and Cosmetic Act and the regulations thereunder;

(2) Due diligence was expended in devising and obtaining labels and packages in compliance with the new regulations insofar as the facilities of the label and package manufacturers permit; and

(3) The stocks did not result from a deliberate attempt to overstock.

(c) The criteria set forth in paragraph (b) (1), (2), and (3) of this section will be equally applicable to stocks of packages and labels of drugs, devices, and cosmetics when the order of January 11, 1968 (33 F.R. 404), amending Part 1 of this chapter with respect to these items, becomes effective.

(d) Extension requests showing good cause, along with pertinent labels, packages, etc., shall be submitted in duplicate and shall consist of the following:

(1) A statement of the total number (not quantity) of labels or packages for which the extension is requested.

(2) Approximate dates revisions will be completed.

(3) The number of labels or packages which have been revised to comply with the Fair Packaging and Labeling Act.

(4) The number of labels or packages scheduled for revision by July 1, 1968.

(5) A duplicate set of representative product labels or packages for which extension is requested. The number to be submitted should be determined as follows:

(i) Ten products or less: Submit all. (ii) More than 10 products: Submit sufficient labels, but not less than 10, to be fully representative.

This procedure is not to be construed as label preclearance. Extension requests need not be submitted for products that are the subject of pending petitions for exemption pursuant to § 1.1a of this chapter.

(Secs. 4, 6, 80 Stat. 1297, 1299, 1300, 15 U.S.C. 1453, 1455) [33 F.R. 3426, Feb. 28, 1968]

§ 3.58 Animal feeds contaminated with Salmonella micro-organisms.

(a) Investigations by the Food and Drug Administration, the Communicable Disease Center of the U.S. Public Health Service, the Animal Health Division of the Agricultural Research Service, U.S. Department of Agriculture, and by various State public health agencies have revealed that processed fish meal, poultry meal, meat meal, tankage, and other animal byproducts intended for use in animal feed may be contaminated with Salmonella bacteria, an organism pathogenic to man and animals. Contamina

tion of these products may occur through inadequate heat treatment of the product during its processing or through recontamination of the heat-treated product during a time of improper storage or handling subsequent to processing.

(b) Articles used in food for animals are included within the definition of "food" in section 201(f) of the Federal Food, Drug, and Cosmetic Act. Further, Salmonella contamination of such animal feeds having the potentiality for producing infection and disease in animals must be regarded as an adulterant within the meaning of section 402(a) of the act. Therefore, the Food and Drug Administration will regard as adulterated within the meaning of section 402(a) of the act shipments of the following when intended for animal feed and encountered in interstate commerce and found upon examination to be contaminated with Salmonella micro-organisms: Bone meal, blood meal, crab meal, feather meal, fish meal, fish solubles, meat scraps, poultry meat meal, tankage, or other similar animal byproducts, or blended mixtures of these.

(Secs. 402(a), 52 Stat. 1046, as amended, 21 U.S.C. 342(a)) [32 FR. 4058, Mar. 15, 1967]

§ 3.59 Use of poultry litter as animal feed.

(a) Poultry rations used today generally contain drugs including antibiotic drugs used individually or in combination. The levels of drug use vary from very small quantities of antibiotic drugs for growth promotion to relatively large quantities of drugs for treatment of diseases. Consequently, poultry litter can be expected to contain drugs and antibiotic drugs or their metabolites. It is not practical to determine, or feasible to estimate, the nature and levels of the drugs and their metabolites in litter.

Therefore, it is not possible to conclude that poultry litter is safe as a feed or as a component of feed for animals, nor is it possible to conclude that there will be no drug residues in the tissues and byproducts of animals fed poultry litter.

(b) Disease organisms may be transmitted from poultry to other animals through the use of poultry litter as animal feed. There are several diseases affecting poultry that can also affect cattle, hogs, and sheep as well as man. Thus such transmission of disease organisms from poultry to other animals and possibly to man constitutes a hazard to animals and to the public health.

(c) Therefore, the Food and Drug Administration has not sanctioned and does not sanction the use of poultry litter as a feed or as a component of feed for animals. Poultry litter subject to the jurisdiction of the Federal Food, Drug, and Cosmetic Act and offered for use as animal feed may be considered as adulterated within the meaning of section 402(a) (1), (2) (C), and/or (3) of the act. (Secs. 402 (a) (1), (2) (C), and (3), 52 Stat. 1046, as amended 68 Stat. 511, 72 Stat. 1784; 21 U.S.C. 342(a) (1), (2)(C), and (3)) [32 F.R. 12714, Sept. 2, 1967]

§ 3.60

Cosmetics containing bithionol.

(a) Bithionol has been used to some extent as an antibacterial agent in cosmetic preparations such as detergent bars, shampoos, creams, lotions, and bases used to hide blemishes. New evidence of clinical experience and photopatch tests indicate that bithionol is capable of causing photosensitivity in man when used topically and that in some instances the photosensitization may persist for prolonged periods as severe reactions without further contact with sensitizing articles. Also, there is evidence to indicate that bithionol may produce cross-sensitization with other commonly used chemicals such as certain halogenated salicylanilides and hexachlorophene. It is, therefore, the view of the Food and Drug Administration that bithionol is a deleterious substance which may render any cosmetic product that contains it injurious to users. Accordingly, any cosmetic containing bithionol is deemed to be adulterated under section 601(a) of the Federal Food, Drug, and Cosmetic Act.

(b) Regulatory proceedings may be initiated with respect to any cosmetic preparation containing bithionol shipped within the jurisdiction of the act after

30 days from date of publication of this statement in the FEDERAL REGISTER. (Secs. 601(a), 52 Stat. 1054, 21 U.S.C. 361 (a)) [33 F.R. 2935, Feb. 14, 1968]

§ 3.61

Use of secondhand poultry crates as fresh vegetable containers.

(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 that Salmonella organisms are commonly present on dressed poultry and in excreta and fluid exudates from dressed birds.

(b) It is widespread practice among some vegetable growers and packers to employ used poultry crates for shipment of fresh vegetables, including cabbage and celery.

(c) 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.

(d) The Food and Drug Administration, therefore, will regard as 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.

(Sec. 402 (a), 52 Stat. 1046, as amended; 21 U.S.C. 342(a)) [33 F.R. 5617, Apr. 11, 1968] § 3.62 Established names for drugs.

(a) Section 508 of the Federal Food, Drug, and Cosmetic Act (added by the Kefauver-Harris Drug Amendments of 1962; Public Law 87-781) authorizes the Commissioner of Food and Drugs to designate an official name for any drug if he determines that such action is necessary or desirable in the interest of usefulness and simplicity. Section 502(e) of the act (as amended by said Drug Amendments) prescribes that the labeling of a drug must bear its established name, if there is one, to the exclusion of any other nonproprietary name (except the applicable systematic chemical name or the chemical formula) and, if the drug is fabricated from two or more ingredients, the established name of each active ingredient.

(b) The term "established name" is defined in section 502(e) (2) of the act

as (1) an official name designated pursuant to section 508 of the act; (2) if no such official name has been designated for the drug and the drug is an article recognized in an official compendium, then the official title theretof in such compendium; and (3) if neither subparagraphs (1) nor (2) of this section applies, then the common or usual name of the drug.

(c) The Food and Drug Administration recognizes the skill and experience of the U.S. Adopted Names Council (USAN) in deriving names for drugs. The U.S. Adopted Names Council is a private organization sponsored by the American Medical Association, the United States Pharmacopeia, and the American Pharmaceutical Association, and has been engaged in the assignment of names to drugs since January 1964. The Council negotiates with manufacturing firms in the selection of nonproprietary names for drugs.

(d) The Food and Drug Administration cooperates with and is represented on the USAN Council. In addition, the Food and Drug Administration is in agreement with the "Guiding Principles for Coining U.S. Adopted Names for Drugs," published in New Drugs Evaluated by A.M.A. Council on Drugs, 1967 edition, pages 556-561, and in U.S. Adopted Names (USAN), Cumulative List, number 5, 1961-1966, pages 100-105. All applicants for new-drug applications and sponsors for "Notice of Claimed Investigational Exemption for a New Drug" (IND's) are encouraged to contact the USAN Council for assistance in selection of a simple and useful name for a new chemical entity. Approval of a new-drug application providing for the use of a new drug substance or a new antibiotic drug may be delayed if a simple and useful nonproprietary name does not exist for the substance and if one is not proposed in the application that meets the above-cited guidelines. Prior use of a name in the medical literature or otherwise will not commit the Food and Drug Administration to adopting such terminology as official.

(Secs. 502(e), 508, 52 Stat. 1050, as amended, 76 Stat. 789, 790, 21 U.S.C. 352(e), 358) [33 F.R. 4731, Mar. 20, 1968]

§ 3.63 Thyroid-containing drug preparations intended for treatment of obesity in humans.

(a) Investigation by the Food and Drug Administration has revealed that