within 180 days following the date of publication of § 3.55 in the FEDERAL REGISTER.

(c) An evaluation of the data now available shows that use of many antibiotic preparations cause residues in edible products of treated animals for varying and, in some cases, for long periods of time following the last administration. Because of the accumulation of new information with regard to the development of resistance of bacteria to antibiotics, the ability of bacteria to transfer this resistance, and the development of sensitivity to antibiotics in humans, unauthorized and unsafe residues of antibiotics cannot be permitted in food obtained from treated animals.

(d) Based on evaluation of information available, including the conclusions of the aforementioned ad hoc Committee, the Commissioner concludes that antibiotic preparations intended for use in food-producing animals, other than topical and ophthalmic preparations, are not generally recognized among qualified experts as having been shown to be safe for their intended use(s) within the meaning of section 201 (s) of the Federal Food, Drug, and Cosmetic Act.

(e) Therefore, all exemptions from the provisions of section 409 of the act for use of antibiotics in food-producing animals based on sanctions or approvals granted prior to enactment of the Food Additives Amendment of 1958 (Public Law 85-929; 72 Stat. 1784) will be revoked and the uses which are concluded to be safe will be covered by food additive regulations. On those products for which there are inadequate residue data, actions will be initiated to amend or revoke antibiotic regulations under the provisions of section 507 of the act, or to withdraw approval of new-drug applications under the provisions of section 505 of the act. Antibiotic preparations, other than those for topical and ophthalmic application in food-producing animals, which are not covered by food additive regulations will be subject to regulatory action within 180 days after publication of the forthcoming revocation order.

(f) Because of the variation in the period of time that antibiotic residues may remain in edible products from treated animals, all injectable, intramammary infusion, intrauterine, and

oral preparations (except certifiable antibiotics), including medicated premixes intended for use in food-producing animals, are deemed to be new drugs as well as food additives. An Antibiotic Form 6 (see § 146.13 of this chapter) will be required for all medicated premixes containing certifiable antibiotics.

(Sec. 409, 505, 507, 52 Stat. 1052, as amended, 59 Stat. 463, as amended, 72 Stat. 1785 et seq., as amended; 21 U.S.C. 348, 355, 357) [33 F.R. 5616, Apr. 11, 1968]

The Secretary of Health, Education, and Welfare will refrain from recommending criminal, injunction, or seizure proceedings on charges that a food repackaged in a retail establishment was misbranded, while held for sale, because it did not comply with the following provisions of the Federal Food, Drug, and Cosmetic Act, if the conditions herein specified are met:

(a) Section 403 (e) (1) (requiring a statement on the label of the name and place of business of the manufacturer, packer, or distributor);

(b) Section 403 (g) (2) (requiring the label of a food which purports to be or is represented as one for which a definition and standard of identity has been prescribed to bear the name of the food specified in the definition and standard and, insofar as may be required by the regulation establishing the standard the common names of the optional ingredients present in the food), if the food was displayed to the purchaser with its interstate labeling clearly in view, or with a counter card, sign, or other appropriate device bearing prominently and conspicuously the information required by these provisions; or

(c) Section 403 (i) (1) (requiring the label to bear the common or usual name of the food), if the food was displayed to the purchaser with its interstate labeling clearly in view, or with a counter card, sign, or other appropriate device bearing prominently and conspicuously the common or usual name of the food, or if the common or usual name of the food is clearly revealed by its appearance.

[20 F.R. 9548, Dec. 20, 1955]

§ 3.27

Status of fluoridated water and foods prepared with fluoridated water under the Federal Food, Drug, and Cosmetic Act.

(a) The program for fluoridation of public water supplies recommended by the Department of Health, Education, and Welfare, through the Public Health Service, contemplates the controlled addition of fluorine at a level optimum for the prevention of dental caries.

(b) Public water supplies do not ordinarily come under the provisions of the Federal Food, Drug, and Cosmetic Act. Nevertheless, a substantial number of inquiries have been received concerning the status of such water under the provisions of the act and the status, in interstate commerce, of commercially prepared foods in which fluoridated water has been used.

(c) The Department of Health, Education, and Welfare will regard water supplies containing fluorine, within the limitations recommended by the Public Health Service, as not actionable under the Federal Food, Drug, and Cosmetic Act. Similarly, commercially prepared foods within the jurisdiction of the act, in which a fluoridated water supply has been used in the processing operation, will not be regarded as actionable under the Federal law because of the flourine content of the water so used, unless the process involves a significant concentration of fluorine from the water. In the latter instance the facts with respect to the particular case will be controlling. [20 F.R. 9548, Dec. 20, 1955]

§3.28 Ophthalmic solutions and dis

pensers.

(a) Investigations by pharmaceutical manufacturers, physicians, and the Food and Drug Administration have revealed that liquid preparations for ophthalmic use contaminated with viable microorganisms have been responsible for serious eye injuries and, in some cases, loss of vision. The Administration has conducted a survey and has found that it is the consensus of informed medical opinion that such preparations should be sterile. It is evident that liquid preparations offered or intended for ophthalmic use, including cosmetic-type preparations for cleansing the eyes and contact-lens solutions, purport to be of

such purity and quality as to be suitable for safe use in the eye. The Administration concludes that such preparations fall below their professed standard of purity or quality and may be unsafe for use if they are not sterile. Accordingly, such liquid preparations offered or intended for ophthalmic use that are not sterile may be regarded as adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act and, further, may be misbranded within the meaning of section 502(j) of the act.

(b) Liquid ophthalmic preparations packed in multiple-dose containers should:

(1) Contain one or more suitable and harmless substances that will inhibit the growth of micro-organisms; or

(2) Be so packaged as to volume and type of container and so labeled as to duration of use and with such necessary warnings as to afford adequate protection and minimize the hazard of injury resulting from contamination during use.

(c) Eye cups, eye droppers, and other dispensers intended for ophthalmic use should be sterile, and may be regarded as falling below their professed standard of purity or quality if they are not sterile. They should be so packaged as to maintain sterility until the package is opened and be so labeled, on or within the retail package, as to afford adequate directions and necessary warnings to minimize the hazard of injury resulting from contamination during use.

[29 F.R. 12458, Sept. 1, 1964]

§ 3.29 Chlorcyclizine, cyclizine, meclizine; warnings; labeling require

ments.

(a) The Food and Drug Administration, pursuant to its responsibility for the safety and effectiveness of drugs, has conducted active investigations of reports of available animal data which reveal that chlorcyclizine hydrochloride, cyclizine hydrochloride and lactate, and meclizine hydrochloride exert a teratogenic response in animals such as the rat, mouse, rabbit, pig, and dog. While clinical studies to date are inconclusive, scientific experts are of the opinion that

these drugs may possess a potential for adverse effects on the human fetus. Investigations have led to the conclusion that there exists sufficient evidence of teratogenicity in animals administered these drugs to justify warnings against their use in pregnancy except on advice of a physician. An Ad Hoc Advisory Committee on the Teratogenic Effect of Certain Drugs, comprised of scientists in various branches of medicine concerned with the problem, has submitted its findings and conclusions to the Commissioner of Food and Drugs and has recommended that all over-the-counter preparations containing chlorcyclizine, cyclizine, or meclizine or their salts bear a warning.

(b) On the basis of studies made by the Food and Drug Administration and on the recommendations of the Advisory Committee, the Commissioner of Food and Drugs has concluded that it is necessary for the protection of users that the label and labeling of all over-the-counter preparations containing chlorcyclizine, cyclizine, or meclizine or their salts bear a statement to the following effect: "Warning-Not for use by women who are pregnant or who may possibly become pregnant, unless directed by a physician, since this drug may have the potentiality of injuring the unborn child."

(c) The marketing of oral and parenteral drugs containing chlorcyclizine, cyclizine, or meclizine or their salts may be continued provided that all the following conditions are met:

(1) Within 30 days from the date of publication of this statement in the FEDERAL REGISTER.

(i) The label and applicable labeling of drugs containing chlorcyclizine, cyclizine, or meclizine or their salts at acceptable levels for over-the-counter distribution, shall prominently and conspicuously display the statement: "Warning-Not for use by women who are pregnant or who may possibly become pregnant, unless directed by a physician, since this drug may have the potentiality of injuring the unborn child."

(ii) The package labeling and other labeling providing professional use in

formation concerning prescription drugs containing chlorcyclizine, cyclizine, or meclizine or their salts and not contraindicated for use in pregnancy because of some other ingredient, shall bear, in accordance with § 1.106(b)1 of this chapter, a section under "Adverse Reactions" headed "Use in Pregnancy," as follows:

The following information should be taken into account in determining whether the potential benefits of [chlorcyclizine, cyclizine, meclizine, or their salts] outweigh the risks of their use in women of childbearing age and particularly during pregnancy. A review of available animal data reveals that this drug exerts a teratogenic response in the [rat, mouse, rabbit, pig, dog]. While available clinical data are inconclusive, scientific experts are of the opinion that this drug may possess a potential for adverse effects on the human fetus. Consequently, consideration should be given to initial use of a nonphenothiazine agent that is not suspected of having a teratogenic potential. In any case, the dosage and duration of treatment should be kept to minimum.

This statement shall be followed with an appropriate summary of the pertinent animal studies and adverse clinical experiences, with adequate references to the scientific literature. Also, the labeling shall contain, in juxtaposition with any representation for use in the treatment of nausea and vomiting in pregnancy, the following statement: for the pre

The effectiveness of vention and treatment of nausea and vomiting of pregnancy has not been established, and the decision to use should be based on the seriousness of the situation, remembering that while this drug has been used clinically for a decade, there are yet no controlled studies to demonstrate its usefulness in an objective fashion. In most cases, nausea and vomiting of pregnancy may be unpleasant but do not present a serious threat to the health of the patient or to the progress of her pregnancy. In view of the desirability of keeping the administration of all drugs to a minimum during pregnancy, management by physiologic means such as proper nutrition and by psychologic support is preferable to antiemetic therapy.

(2) Within 30 days from the date of publication of this statement of policy in the FEDERAL REGISTER, the applicant

1 Section 1.105 will require that prescription drug advertising contain this warning.

under an approved new-drug application for a drug containing chlorcyclizine, cyclizine, or meclizine or their salts shall submit a supplement to his new-drug application, providing for appropriate labeling changes as described in subparagraph (1) (i) or (ii) of this paragraph.

(3) Within 90 days from the date of publication of this statement of policy in the FEDERAL REGISTER, the manufacturer, packer, or distributor of any drug containing chlorcyclizine, cyclizine, or meclizine or their salts for which a new-drug approval is not in effect shall submit a new-drug application containing satisfactory information of the kinds required in the new-drug application form contained in § 130.4 (c) of this chapter, including appropriate labeling as described in subparagraph (1) (i) or (ii) of this paragraph.

(d) In view of the fact that no substantial evidence has been offered for the effectiveness of chlorcyclizine, cyclizine, and meclizine or their salts in the prevention and treatment of nausea and vomiting of pregnancy, but mindful of the fact that some practicing physicians believe that these drugs exert a beneficial effect upon this condition, the Food and Drug Administration will permit a modified claim in indications for this use for a period not exceeding 2 years. However, this modified indication for use of these drugs in the prevention and treatment of nausea and vomiting of pregnancy will be deleted from the labeling unless substantial evidence is offered before the expiration of this period of time. The Food and Drug Administration will also continue to follow the large-scale surveys of clinical experience and any reports of adverse reaction that may be due to the use of these drugs under the revised labeling.

[30 F.R. 13628, Oct. 27, 1965; 30 F.R. 14047, Nov. 6, 1965]

§ 3.30 Ipecac syrup; warnings and directions for use for over-the-counter sale.

(a) It is estimated that each year about 500,000 accidental poisonings occur in the United States and result in approximately 1,500 deaths, of which over 400 are children. In the emergency treatment of these poisonings, ipecac syrup is considered the emetic of choice.

The immediate availability of this drug for use in such situations is critical, since rapid treatment may be the difference between life and death. The restriction of this drug to prescription sale limits its availability in emergencies. On the other hand, it is the consensus of informed medical opinion that ipecac syrup should be used only under medical supervision in the emergency treatment of poisonings. In view of these facts, the question of whether ipecac syrup labeled as an emergency treatment for use in poisonings should be available over the counter has been controversial.

(b) In connection with its study of this problem, the Food and Drug Administration has obtained the views of medical authorities. It is the unanimous recommendation of the American Academy of Pediatrics, the American Association of Poison Control Centers, the American Medical Association, and the Medical Advisory Board of the Food and Drug Administration that ipecac syrup in 1 fluid ounce containers be permitted to be sold without prescription so that it will be readily available in the household for emergency treatment of poisonings, under medical supervision, and that the drug be appropriately packaged and labeled for this purpose.

(c) In view of the above recommendations, the Commissioner of Food and Drugs has determined that it is in the interest of the public health for ipecac syrup to be available for sale without prescription, provided that it is packaged in a quantity of 1 fluid ounce (30 milliliters), and its label bears, in addition to other required label information, the following, in a prominent and conspicuous manner:

(1) A statement conspicuously boxed and in red letters, to the effect: "For emergency use to cause vomiting in poisoning. Before using, call physician, the Poison Control Center, or hospital emergency room immediately for advice."

(2) A warning to the effect: "Warning-Keep out of reach of children. Do not use in unconscious persons. Ordinarily, this drug should not be used if strychnine, corrosives such as alkalies (lye) and strong acids, or petroleum distillates such as kerosine, gasoline, coal oil, fuel oil, paint thinner, or cleaning fluid have been ingested."

66-041-72———7

(3) Usual dosage: 1 tablespoon (15 milliliters) in persons over 1 year of age. [30 F.R. 13628, Oct. 27, 1965]

§ 3.31 Label declaration of salt in frozen vegetables.

(a) In a number of diseases or disease conditions it is important to restrict the intake of sodium. Sodium occurs in all natural foods, but added salt makes the most important contribution to the total sodium intake in the diet. Most fresh vegetables are of low sodium content and consumers generally regard frozen vegetables as being free of added salt and suitable for use in low-sodium diets. While salt may not be added directly as a seasoning ingredient during the processing of frozen vegetables, the use of salt brine în quality separation of such vegetables as peas and lima beans preparatory to freezing may contribute substantial amounts of salt to the finished article. The failure of the labels of frozen vegetables to declare the presence of salt has been the basis of complaints to the Food and Drug Administration.

(b) Section 403 (1) (2) of the Federal Food, Drug, and Cosmetic Act requires the label of a fabricated food to bear the common or usual name of each ingredient present. The Department of Health, Education, and Welfare regards any frozen vegetable containing salt, added directly or indirectly, as misbranded in violation of section 403 (1) (2) of the Federal Food, Drug, and Cosmetic Act unless its label names salt as an ingredient.

[20 F.R. 9549, Dec. 20, 1955]

§ 3.32

Label declarations of vitamin B1 and folic acid in foods for special dietary uses.

(a) Section 125.3 (a) (2) of this chapter, issued under the authority of section 403 (j) of the Federal Food, Drug, and Cosmetic Act (sec. 403 (j), 52 Stat. 1048; 21 U.S.C. 343 (j)) requires that if a food purports to be or is represented for special dietary use by man by reason, in whole or in part, of a vitamin for which the need in human nutrition has not been established, the label of such food shall bear the statement "The need for in human nutrition has not been established," the blank to be filled in with the name of such vitamin.

(b) Heretofore this Department has considered vitamin B and folic acid as among those vitamins for which the need in human nutrition has not been established. However, recent scientific evidence shows that these vitamins are needed in human nutrition. The Department therefore considers the requirement of § 125.3 (a) (2) quoted in paragraph (a) of this section as no longer applicable to food offered for special dietary use by reason of these vitamins.

(Sec. 403, 52 Stat. 1047, as amended; 21 U.S.C. 343) [20 F.R. 9549, Dec. 20, 1955] § 3.33 Status of foods containing added coumarin.

Manufacturers of coumarin have reported pharmacological investigations showing that it has toxic properties. They have informed the Food and Drug Administration that it will no longer be sold for food use. The Federal Food, Drug, and Cosmetic Act defines food as adulterated if it contains any added poisonous or deleterious substance not required in the production or avoidable in good manufacturing practice. Food containing coumarin added as such or as a constituent of tonka beans or tonka extract will be regarded as adulterated under this provision of the law.

(Secs. 402, 406, 52 Stat. 1046, as amended, 1049, as amended; 21 U.S.C. 342, 346) [20 F.R. 9549, Dec. 20, 1955]

§ 3.34 Labeling of crabmeat.

(a) For many years canned crabmeat has been imported into the United States from Japan. Such imports have consisted primarily of a product designated as "King crabmeat." There have been limited importations of articles designated as "Korean crabmeat" and "Snow crabmeat." Two closely allied species of crab have been packed in Japan for export to the United States under the designation "King crabmeat." These species are Paralithodes camtschatica (tarabagani) and Paralithodes platypus (aburagani). A third species of crab, Paralithodes brevipes, has been labeled either as "King crabmeat" or "Hanasaki crabmeat" when intended for export to the United States. The Food and Drug Administration considers the term "King crabmeat" as an acceptable common name for the product prepared from any one of the three species P. camtschatica,