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

a large number of drug preparations containing thyroid or thyrogenic substances in combination with central nervous system stimulants, with or without one or more additional drug substances such as barbiturates or laxatives, are being marketed for or as adjuncts to the treatment, control, or management of obesity in humans. The Commissioner of Food and Drugs finds that the administration of such combinations for said purposes is without medical rationale except possibly in those relatively uncommon instances where the condition is directly related to hypothyroidism and there exists a concurrent need for appetite control (in such instances the safety and effectiveness of such combinations are not generally recognized). In particular, the Commissioner of Food and Drugs inds that neither the consensus of informed medical opinion nor clinical experience justifies any representation that such combinations are safe and effective in connection with the treatment, control, or management of obesity in patients having normal thyroid funesion.

b) Combinations of thyroid or other shrogenic drugs with central nervous system stimulants with or without other drug substances when offered for or as adjuncts to the treatment, control, or management of obesity not related to hypothyroidism are regarded as misbranded. Such combinations when offered for obesity in humans directly attributable to established hypothyroidism are regarded as new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act. (Secs. 201(p), 502, 52 Stat, 1041-42, 1060, as amended; 21 U.S.C. 331p), 362) [33 FE. 2017, 3pr. 11, 1968]

$3.04 Stramonium preparations labeled

with directions for use in self-medication regarded as misbranded. (a) Stramonium products for inhalation have been offered for use in the therapy of the acute attacks of bronchial asthma for many years although their reliability and effectiveness are questionable. Recently, a significantly increased number of reports have come to the actendon of the Food and Drug Adminis tracion showing that such products have been subject to abuse and misuse on a fairly large scale, mostly by young people, through oral ingestion for the purpose of producing hallucinations. Reports of such use have been received from physicians and police and other

law enforcement authorities. Reports have also appeared in the public press and in medical journals.

(b) Labeling these products with a warning that they are not for oral ingestion has not been effective in protecting the public. Misuse of stramonium preparations can cause serious toxic effects including toxic delirium, visual disturbances, fever, and coma. A number of serious reactions have already occurred from the oral ingestion of such products.

(c) On the basis of this information, the Commissioner of Food and Drugs has concluded that such articles have a potentiality for harmful effect through misuse and are not safe for use except under the supervision of a physiciar.. In the interest of public health protection, therefore, the Food and Drug Administration adopts the following policy:

(1) Preparations containing stramonium supplied from the leaves, seeds, or any other part of the plant in the form of a powder, pipe mixture, cigarette, or any other form, with or without admixture of other ingredients, will be regarded as misbranded if they are labeled with directions for use in self-medication.

(2) The Food and Drug Administration will, on request, furnish comment on proposed labeling limiting any such preparation to prescription sale.

(d) The labeling or dispensing of stramonium preparations contrary to this statement after 60 days following the date of its publication in the FEDERAL REGISTER may be made the subject of regulatory proceedings.

Secs. 5023), 2), 503 b; 52 Stat. 1050-51, 1062, as amended; 2 U.S.C. 352 (a), (f), 353 ) 33 FR. 2040, Aug. 14, 1968] $3.65 Status of foods and drugs con

taining calamus, as the root, oil, or extract.

(a) Oil of calamus has been used in the past as a favoring agent in fabricated feeds. It is not an authorized food additive. Calamus, as the root, oil, or extract, has been used in drug preparations as a carminative and as a topical counterirritant A recent 3-year rat-feeding study of an al of calamus, identified as the Jammu variety of the oil, conducted by the Food and Drug Administration found the Jammu varety to be a carcinogen. The indings of the study were confirmed by the Interdepartmental Technicsi Panel on Carcinogens.

b) Chronie feeding studies are not available on other varieties of the oil of calamus Chal evidence is offered to

demonstrate that the carcinogenic capability of Jammu oil of calamus is absent in the other varieties of calamus, it is the policy of the Food and Drug Administration to refuse to promulgate any regulation prescribing the use of calamus, as the root, oil, or extract, in food. In addition, drug preparations containing any form of calamus are not generally recognized by qualified experts as safe and effective for any condition of use and are regarded as new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act.

(c) Any food or drug within the jurisdiction of the Federal Food, Drug, and Cosmetic Act containing any form of calamus shall be regarded, therefore, as in violation of the Act and subject to regulatory proceedings.

(Secs. 402 (a), 406, 409, 502 (a), (f), 505, 52 Stat. 1046, as amended, 1049-53, as amended, 72 Stat. 1785-89, as amended; 21 U.S.C. 342(a), 346, 348, 352 (a), (f), 355) [33 F.R. 6967, May 9, 1968]

§3.67 Isoproterenol inhalation preparations (pressurized aerosols, nebulizers, powders) for human use; warnings.

(a) Accumulating reports have been received by the Food and Drug Administration and have appeared in the medical literature of severe paradoxical bronchoconstriction associated with repeated, excessive use of isoproterenol inhalation preparations in the treatment of bronchial asthma and other chronic bronchopulmonary disorders. The cause of this paradoxical reaction is unknown; it has been observed, however, that patients have not responded completely to other forms of therapy until use of the isoproterenol inhalation preparation was discontinued. In addition, sudden unexpected deaths have been associated with the excessive use of isoproterenol inhalation preparations. The mechanism of these deaths and their relationship, if any, to the cases of severe paradoxical bronchospasm are not clear. Cardiac arrest was noted in several of these cases of sudden death.

(b) On the basis of the above information and after discussion with and concurrence of the Respiratory and Anesthetic Drugs Advisory Committee for Food and Drug Administration, the Commissioner of Food and Drugs conIcludes that in order for the labeling of such drugs to bear adequate information for their safe use, as required by § 1.106

(b) of this chapter, such labeling must include the following:

Warning: Occasional patients have been reported to develop severe paradoxical airway resistance with repeated, excessive use of isoproterenol inhalation preparations. The cause of this refractory state is unknown. It is advisable that in such instances the use of this preparation be discontinued immediately and alternative therapy instituted, since in the reported cases the patients did not respond to other forms of therapy until the drug was withdrawn.

Deaths have been reported following excessive use of isoproterenol inhalation preparations and the exact cause is unknown. Cardiac arrest was noted in several instances.

(c) (1) The Commissioner also conIcludes that in view of the manner in which these preparations are self-administered for relief of attacks of bronchial asthma and other chronic bronchopulmonary disorders, it is necessary for the protection of users that warning information to patients be included as a part of the label and as part of any instructions to patients included in the package dispensed to the patient as follows:

Warning: Do not exceed the dose prescribed by your physician. If difficulty in breathing persists, contact your physician immediately.

(2) The warning on the label may be accomplished (i) by including it on the immediate container label with a statement directed to pharmacists not to remove the label or (ii) by including in the package a printed warning with instructions to pharmacists to place the warning on the container prior to dispensing. (d) The marketing of isoproterenol inhalation preparations may be continued if all the following conditions are met:

(1) Within 30 days following the date of publication of this section in the FEDERAL REGISTER:

(i) The label and labeling of such preparations shipped within the jurisdiction of the act are in accordance with paragraphs (b) and (c) of this section.

(ii) The holder of an approved newdrug application for such preparation submits a supplement to his new-drug application to provide for appropriate labeling changes as described in paragraphs (b) and (c) of this section.

(2) Within 90 days following the date of publication of this section in the FEDERAL REGISTER, the manufacturer, packer, or distributor of any drug containing isoproterenol intended for inhalation for which a new-drug approval is not in

effect submits a new-drug application containing satisfactory information of the kinds required by items 4, 5, 6, 7, 8, and 9 of the new-drug application form (form FD-356H set forth in § 130.4(c) (2) of this chapter), including appropriate labeling as described in paragraphs (b) and (c) of this section.

(3) The applicant submits additional information required for the approval of the application as may be specified in a written communication from the Food and Drug Administration.

(e) After 270 days following expiration of said 90 days, regulatory proceedings based on section 505(a) of the Federal Food, Drug, and Cosmetic Act may be initiated with regard to any such drug shipped within the jurisdiction of the act for which an approved new-drug application is not in effect.

(Secs. 502 (f), (j), 505, 52 Stat. 1051-53, as amended; 21 U.S.C. 352 (f), (1), 355) [33 F.R. 8812, June 18, 1968]

§ 3.68 Medicated feeds; approval of new-drug applications.

(a) The Food and Drug Administration cannot approve an initial new-drug application for a drug that is to be added to animal feed until a food additive regulation providing for the safe use of the new-drug substance as a food additive has been promulgated by publication in the FEDERAL REGISTER in accordance with section 409 of the Federal Food, Drug, and Cosmetic Act.

(b) In the past the Food and Drug Administration has received many medicated feed new-drug applications from feed manufacturers prior to the promulgation of the required food additive regulation, and these applications could not or cannot be reviewed until such promulgation. Frequently when such applications were finally reviewed after issuance of the food additive regulation, they were found to contain information and labeling not in conformance with such regulation. This resulted in considerable unnecessary work on the part of the applicants and the Food and Drug Administration.

(c) Accordingly, effective on date of publication of this section in the FEDERAL REGISTER, the following is the policy of the Food and Drug Administration regarding the processing of medicated feed new-drug applications:

(1) Only those applications for a new drug for which a food additive regulation has been established in Subpart C of Part

121 of this chapter will be accepted and reviewed.

(2) Applications for new drugs for which no such regulation has been established will be returned to the applicant without review or comment.

(Secs. 409, 505, 52 Stat. 1052-53, as amended, 72 Stat. 1785-88, as amended; 21 U.S.C. 348, 355) [33 F.R. 9609, July 2, 1968]

§ 3.69

Artificially red-dyed yellow varieties of sweetpotatoes.

(a) It has been the practice of some growers, packers, and distributors of yellow varieties of sweetpotatoes to artificially color the skins of such potatoes with a red dye. Surveys made by the Food and Drug Administration and letters received by the Administration from consumers reveal that this practice can deceive those persons who prefer the naturally red varieties of sweetpotatoes. Also, representatives of the red sweetpotato industry have alleged that some consumers refuse to purchase any red sweetpotatoes since they cannot distinguish between the naturally red ones and those artificially colored with red dye.

(b) The Food and Drug Administration concludes, therefore, that yellow varieties of sweetpotatoes artificially colored with a red dye are adulterated within the meaning of section 402(b) of the Federal Food, Drug, and Cosmetic Act.

(c) The Food and Drug Administration will consider appropriate regulatory action regarding such adulterated sweetpotatoes shipped in interstate commerce if the act of adulterating the potatoes occurs after 90 days following the date of publication of this statement of policy in the FEDERAL REGISTER.

(Secs. 402(b), 52 Stat. 1046-47; 21 U.S.C. 342 (b)) [33 F.R. 9166, June 21, 1968]

§ 3.70 Labeling for food fish of the species Reinhardtius hippoglossoides. (a) (1) Reinhardtius hippoglossoides is a species of Pleuronectidae right-eye flounders. Although smaller in size it resembles the Atlantic halibut (Hippoglossus hippoglossus) and Pacific halibut (Hippoglossus stenolepis) more closely than it does any of the other species of the Pleuronectidae which are commonly designated by names which include the word "flounder," "sole," or "turbot." Its resemblance to halibut is reflected in its scientific name (hippoglossoides means "halibut like") and in the common names by which it is known.

In Canada and England it is called "Greenland halibut." In Norway, West Germany, Russia, France, and Spain it is known by names which in translation mean "black halibut." It is also known as "lesser halibut," "blue halibut," or "mock halibut."

(2) The difference in morphological characteristics between Reinhardtius hippoglossoides and the true halibut or the species commonly sold as flounder or sole are of less concern to American consumers than the differences in characteristics and food values of the flesh. The flesh of Reinhardtius hippoglossoides contains significantly less protein than that of halibut or turbot, but about the same as flounder or sole. It contains much more fat and provides significantly more calories per 100 grams than halibut, turbot, flounder, or sole. The higher oil content causes the flesh to develop rancidity more quickly. The flesh is not as firm and requires more care in cooking than that of the other flatfishes.

(3) The commercial marketing of "Greenland halibut" in the United States began in 1964. Between 1964 and 1967 the catch by Newfoundland fishermen increased from about 31⁄2 million pounds live weight to over 30 million pounds. Of the live weight, 30 to 35 percent can be "recovered" as fillets or blocks. There is no domestic production of Reinhardtius hippoglossoides.

(4) Halibut and flounder have a long history of marketing in the United States. The 1967 records show that U.S. halibut production was about 55.8 million pounds valued at $13.2 million to the fishermen. The 1967 flounder catch was about 155 million pounds valued at $17.4 million to the fishermen.

(5) There is no domestic production of true turbot. Imports in 1968 are estimated at over 400,000 pounds, valued at $1.50 to $1.60 per pound (total value over $600,000). Most of this is marketed to restaurants, but there have been limited sales direct to consumers through retail outlets.

(6) The claim is made that the marketing of "Greenland halibut" has had an adverse impact on sales and prices of the true halibut. Four States have enacted laws prohibiting the labeling or offering for sale of any food fish product designated as halibut, with or without additional descriptive words, unless it is the product of Hippoglossus hippoglossus or Hippoglossus stenolepis.

(7) In upholding the constitutionality of the Oregon law, a three-judge Federal court found that "Although the term 'Greenland Halibut' is accepted in the scientific community to describe Reinhardtius hippoglossoides, it is not a commonly understood name among the general public," and that because the consumer is not aware of the differences between "halibut" and "Greenland halibut" the labeling and sale of Reinhardtius hippoglossoides as "Greenland halibut" is deceptive. The decision of the lower court was affirmed on November 12, 1968, by the U.S. Supreme Court.

(8) Essentially the same differences exist between Reinhardtius hippoglossoides and the fish now commercially marketed in the United States as flounder, sole, or turbot. Producers and distributors of these fish have testified that marketing Reinhardtius hippoglossoides by names which include the words "flounder" or "turbot" will have an adverse impact on sales and prices of the fish they produce and distribute.

(9) Unfortunately, no name has been suggested that will fully inform consumers of the characteristics of Reinhardtius hippoglossoides. Unless importation and distribution of this fish is to be halted, producers and packers must be permitted to label their products with some name, even though it is not fully informative and even though it may have some adverse impact on sales and prices for some other species.

(10) From the information submitted to the Food and Drug Administration by all segments of the fishing industry, it appears that the name "Greenland turbot," while not fully informative:

(i) Is likely to mislead the smallest segment of U.S. consumers, since fewer of them are well acquainted with the characteristics of the delicacy, Psetta maxima;

(ii) Is likely to have less adverse impact on prices and sales, since the restaurant owners who purchase most of the imported Psetta maxima will not be deceived by the name "Greenland turbot";

(iii) Has some history of scientific and lay use, including use in official government statistical reports in the United States from 1911 to the present and in Canada from 1931 to the present; and

(iv) Is reported as an optional name for "Greenland halibut" in annual statistical reports ("FAO Yearbook of Fishery Statistics") of the Food and