should ordinarily contain information in substantially the format and order and with the section headings as follows: DESCRIPTION ACTIONS INDICATIONS CONTRAINDICATIONS WARNINGS PRECAUTIONS ADVERSE REACTIONS DOSAGE AND ADMINISTRATION (b) The following sections are optional. If used, they should be placed after the information described above. ANIMAL PHARMACOLOGY AND TOXICOLOGY CLINICAL STUDIES REFERENCES (c) Although ordinarily prescription drug labeling should employ the format, order, and section headings described above, in the case of some drugs special warnings may be required to appear conspicuously in the beginning of the labeling for special attention by physicians for the safety of patients. In the case of a drug for which there is no information applicable to a section heading described in paragraph (a) of this section, such heading and section may be omitted. (Secs. 503, 503, 52 Stat. 1050-52, as amended; 21 U.S.C. 352, 353) [35 F.R. 2656, Feb. 6, 1970] § 3.76 Contract facilities (including consulting laboratories) utilized as extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory, warehouse, or establishment in which prescription drugs are manufactured, processed, packed, or held. (b) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products utilize extramural independent contract facilities, such as testing laboratories, contract packers or labelers, and custom grinders, and regards extramural facilities as an extension of the manufacturer's own facility. (c) The Food and Drug Administration reserves the right to disclose to the pharmaceutical manufacturer, or to the applicant of a new drug application (NDA) or to the sponsor of a Notice of Claimed Exemption for Investigational New Drug (IND), any information ob tained during the inspection of an extramural facility having a specific bearing on the compliance of the manufacturer's, applicant's, or sponsor's product with the Federal Food, Drug, and Cosmetic Act. The Food and Drug Administration's position is that by the acceptance of such contract work, the extramural facility authorizes such disclosures. (d) The Food and Drug Administration does not consider results of validation studies of analytical and assay methods and control procedures to be trade secrets that may be withheld from the drug manufacturer by the contracted extramural facility. (Secs. 501, 505, 704(a), 52 Stat. 1049-50, as amended, 1052-53, as amended, 67 Stat. 477, as amended, 76 Stat. 792; 21 U.S.C. 351, 355, 374(a)) [35 F.R. 7696, May 19, 1970] § 3.77 The use of methadone in the maintenance treatment of narcotic addicts. (a) The Food and Drug Administration and the Bureau of Narcotics and Dangerous Drugs recognize that the investigational use of methadone requiring the prolonged maintenance of narcotic dependence as part of a total treatment effort has shown promise in the management and rehabilitation of selected narcotic addicts. It is also recognized that a number of dangers and possible abuses may arise from such efforts if professional services and controls are inadequately applied. It is further felt that additional research is urgently needed so that data may be accumulated which will permit sound determinations of safety, efficacy, and necessary procedural safeguards. (b) Therefore, the Commissioner of Food and Drugs and the Director of the Bureau of Narcotics and Dangerous Drugs agree that interested professionals, municipalities, and organizations should be allowed to conduct further research in this area within a framework of adequate controls designed to protect the individual patients and the community. To facilitate this purpose, the Food and Drug Administration and the Bureau of Narcotics and Dangerous Drugs have jointly agreed upon acceptable criteria and guidelines which are set forth in proposed § 130.44 of this chapter. In addition such other provisions of the Federal Narcotic laws and regulations as are applicable must also be observed. (Sec. 505, 52 Stat. 1052-53, as amended; 21 U.S.C. 355) [35 F.R. 9000, June 11, 1970] § 3.78 Combinations of nutritive and nonnutritive sweeteners in canned fruits. Due to the ban on the use of cyclamates in foods by the order published in the FEDERAL REGISTER of October 21, 1969 (34 F.R. 17063), canners are seeking to provide palatable, calorie reduced, canned fruits sweetened by a combination of nutritive and nonnutritive sweeteners, including saccharin or its salts. The Commissioner has received inquiry as to the application of the Federal Food, Drug, and Cosmetic Act to canned fruits containing combinations of nutritive and nonnutritive sweeteners pending the establishment of standards of identity. Established identity standards in Part 27 of this chapter for artificially sweetened canned fruits do not permit the use of a combination of nutritive and nonnutritive sweeteners. The Commissioner concludes that pending amendment of the standards for artificially sweetened canned fruits to permit use of nutritive and nonnutritive sweeteners, the Food and Drug Administration will not recommend regulatory action against canned fruits sweetened in part with saccharin and in part with sugar, sorbitol, mannitol, and other nutritive sweeteners, provided that: (a) The product is so formulated that its caloric value is at least 50 percent less than the same product formulated with heavy syrup; except that if a canned fruit cannot be so formulated as to result in a 50 percent caloric reduction, all pertinent data may be submitted to the Food and Drug Administration for a decision on a product basis. In no case will a product be permitted unless its caloric value has been reduced by at least 25 percent when compared to the same product canned in heavy syrup. (b) The name of the product is “(name of fruit) in water sweetened with saccharrin and (name of nutritive sweetener)." (c) If the product is to be marketed under a name heretofore used on a product represented to have a few calories per serving, the name shall be modified by the word "new" for at least 1 year following the time such product is introduced in a given market. (d) The label bears in a prominent place on the principal display panel or on an adjacent panel: (1) A statement of the percentage of saccharin or saccharin salt used and the statement "Contains_-_-__mg. saccharin (or saccharin salt), a nonnutritive sweetener, per serving." (2) A statement of the carbohydrate content per serving. (3) A statement of the caloric content per serving. (4) A statement of the carbohydrates and calories contained in a serving of this product as compared to the carbohydrates and calories contained in the product prepared in extra heavy syrup. (e) The label bears in a prominent place on the principal display panel, in addition to the name of the food, the statements "Contains sugar" or "Contains (common or usual name of nutritive sweetener used)" and "Not for use by diabetics without advice of a physician" to avoid injury through inadvertent use by diabetics in the belief that the product does not contain carbohydrates. For the purposes of this section, a serving shall be stated in terms of a household unit, which is normally considered to be one-half cup. For the purposes of paragraphs (a) and (d) of this section, the caloric values for "extra heavy syrup" and "heavy syrup" shall be that given in USDA Handbook Number 8. The policy set forth in this section will remain in effect not longer than 1 year after the date this section is published in the FEDERAL REGISTER unless extended for good reason. (Secs. 201 (s), 401, 403, 409, 52 Stat. 1046-48, as amended, 72 Stat. 1784-88, as amended; 21 U.S.C. 321(s), 341, 343, 348) [35 F.R. 11621, July 21, 1970] § 3.80 Red blood cells frozen. (human) (a) Containers and solutions used as essential elements of a processing procedure for manufacturing red blood cells (human) -frozen, a biologic subject to regulation by the Division of Biologics Standards, National Institutes of Health, as authorized under the Public Health Service Act of July 1, 1944 (58 Stat. 682, as amended; 42 U.S.C. 201 et seq.), will be reviewed by the Division of Biologics Standards to determine that the safety, purity, and potency of the final product submitted for license is not adversely affected by the use of such containers and solutions. When used for this purpose, such containers and solutions will not require Food and Drug Administration approval prior to their review and licensing by the Division of Biologics Standards. (b) Such solutions and containers used for drug purposes other than manufacturing red blood cells (human) — frozen and other biologics subject to regulation by the Division of Biologics Standards will be subject to regulation by the Food and Drug Administration under provisions of the Federal Food, Drug, and Cosmetic Act. (Secs. 502, 503, 505, 52 Stat. 1050-53, as amended, 21 U.S.C. 352, 353, 355) [35 F.R. 12890, Aug. 14, 1970] § 3.82 Quantity of contents declaration on open basket type carriers for soft drinks. (a) In full recognition that open basket type carriers used in the soft drink industry are not ordinarily considered to be "packages" within the meaning of section 10(b) of the Fair Packaging and Labeling Act, manufacturers may cause them to become packages by appropriate labeling, particularly with respect to the quantity of contents declaration, and thereby make them subject to § 1.8b (s) of this chapter. The effective date of § 1.8b (s) is February 12, 1971. (b) To facilitate the orderly disposal of such open basket type carriers in inventory, which bear quantity of contents declarations that do not conform to § 1.8b (s), and to provide sufficient time for the necessary revisions, the Commissioner extends the time during which such revisions must be completed to December 31, 1972. (Secs. 4, 5(a), 6(a), 80 Stat. 1297-1300; 15 U.S.C. 1453-55) [35 F.R. 16317, Oct. 17, 1970] Subpart B-Informal Statements of General Policy or Interpretation FOODS §3.201 Declaration of pyroligneous acid in food. Pyroligneous acid may be used in foods insofar as the Federal Food, Drug, and Cosmetic Act is concerned, if it is of a degree of purity suitable for food use and does not serve to conceal damage or inferiority, or to make the food appear better or of greater value than it is. If the food is one for which an identity standard has been promulgated, pyroligneous acid should not be used unless it is an ingredient provided for in the definition and standard of identity. When used, it should be declared as an artificial flavor by some such phrase as "pyroligneous acid, an artificial flavor," "pyroligneous acid, an artificial smoke flavor," or "artificially flavored with pyroligneous acid." There should be no representation in the labeling, either directly or implied, that a product flavored with pyroligneous acid has been smoked or has a true smoke flavor, nor should there be any representation in the labeling of a seasoning, sauce, or similar product containing pyroligneous acid and used to season or flavor other foods that their use will result in a smoked product or one having a true smoked flavor. (Secs. 402, 403, 52 Stat. 1047, 1048; 21 U. S. C. 342, 343) [22 F.R. 9594, Nov. 30, 1957] § 3.202 Labeling of kosher and kosherstyle foods. The term "kosher" should be used only on food products that meet certain religious dietary requirements. The precise significance of the phrase "kosher style" as applied to any particular product by the public has not been determined. There is a likelihood that the use of the term may cause the prospective purchaser to think that the product is "kosher." Accordingly, the Food and Drug Administration believes that use of the phrase should be discouraged on products that do not meet the religious dietary requirements. (Sec. 402, 52 Stat. 1046; 21 U.S.C. 342) [22 F.R. 9594, Nov. 30, 1957] § 3.203 Use of chemical sanitizing agents in food-manufacturing establishments. (a) The Administration recognizes the need for sanitizing procedures in food-manufacturing plants; it recognizes that chemical sanitizing agents aid in the maintenance of plant cleanliness; and it recognizes that a number of sanitizing agents that are poisonous or deleterious may properly be employed so that they are effective and do not leave residues in food. (b) The Food and Drug Administration does not object to the use of effective chemical sanitizing agents on food han dling equipment in establishments subject to its jurisdiction provided precautions are taken to prevent adulteration of food that comes in contact with the treated equipment. (Sec. 402, 52 Stat. 1046; 21 U.S.C. 342) [23 F.R. 3774, May 30, 1958] § 3.206 Whipped cream products containing flavoring or sweetening. The unqualified name "whipped cream" should not be applied to any product other than one made by whipping the cream that complies with the standards of identity for whipping cream (§§ 18.510, 18.511, and 18.515 of this chapter). If flavoring and/or sweetening is added, the resulting product is a flavored and/or sweetened whipped cream, and should be so identified. (Secs. 401, 403, 52 Stat. 1047, 1048; 21 U. S. C. 341, 348) [22 FR. 9594, Nov. 30, 1957] DRUGS § 3.501 Mailing of important information about drugs. Manufacturers and distributors of drugs and the Food and Drug Administration occasionally are required to mail important information about drugs to physicians and others responsible for patient care. In the public interest, such mail should be distinctive in appearance so that it will be promptly recognized and read. The Food and Drug Administration will make such mailings in accordance with the specifications set forth in this section. Manufacturers and distributors of drugs are asked to make such mailings as prescribed by this section and not to use the distinctive envelopes for ordinary mail. (a) Use first class mail and No. 10 white envelopes. (b) The name and address of the agency or the drug manufacturer or distributor is to appear in the upper left corner of the envelope. (c) The following statements are to appear in the far left third of the envelope front, in the type and size indicated, centered in a rectangular space approximately 3 inches wide and 24 inches high with an approximately 8inch-wide border in the color indicated: (1) When the information concerns a significant hazard to health, the statement: IMPORTANT DRUG WARNING The statement shall be in three lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Drug" and "Warning" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be red. (2) When the information concerns important changes in drug package labeling, the statement: IMPORTANT PRESCRIBING INFORMATION The statement shall be in three lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Prescribing" and "Information" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be blue. (3) When the information concerns a correction of prescription drug advertising or labeling, the statement: IMPORTANT CORRECTION OF DRUG INFORMATION The statement shall be in four lines, all capitals, and centered. "Important" shall be in 36 point Gothic Bold type. "Correction," "Of Drug," and "Information" shall be in 36 point Gothic Condensed type. The rectangle's border and the statement therein shall be brown. (Sec. 705 (b), 52 Stat. 1058; 21 U.S.C. 375 (b)) [32 F.R. 7127, May 11, 1967, as amended at 33 F.R. 12139, Aug. 28, 1968] § 3.502 Use of term "infant" in drug labeling. The regulations affecting special dietary foods (§ 125.1(d) of this chapter) define an infant as a child not more than 12 months old. Apart from this, the Food and Drug Administration has not established any definition of the term "infant." Some question has arisen whether, for the purposes of drug labeling, an infant means a child up to 1 year of age or a child up to 2 years of age. Until the term is more precisely defined by legislation or formal regulation, where the exact meaning of the term is significant, manufacturers should qualify any reference to "infant" to indicate whether it refers to a child who is not more than 1 year of age, or a child not more than 2 years of age. (Sec. 502, 52 Stat. 1051; 21 U.S.C. 352) [22 F.R. 9594, Nov. 30, 1957] § 3.503 Magnesium sulfate heptahydrate; label declaration on drug products. Magnesium sulfate heptahydrate should be listed on the label of a drug product as epsom salt, which is its common or usual name. (Sec. 502, 52 Stat. 1051; 21 U.S.C. 352) [22 F.R. 9594, Nov. 30, 1957] §3.505 Estradiol labeling. The article presently recognized in The National Formulary under the heading "Estradiol" and which is said to be "17cis-beta estrodiol" is the same substance formerly recognized in the United States Pharmacopeia under the designation "Alpha Estradiol." The substance should no longer be referred to in drug labeling as "Alpha Estradiol." The Food and Drug Administration would not object to label references to the article as simply "Estradiol"; nor would it object if the label of a preparation containing this substance referred to the presence of "Estradiol (formerly known as Alpha Estradiol)." (Secs. 201, 502, 52 Stat. 1040, 1051; 21 U. S. C. 321, 352) [22 F.R. 9594, Nov. 30, 1957] § 3.506 Use of octadecylamine in steam lines of drug establishments. The Food and Drug Administration will not object to the use of octadecylamine in steam lines where the steam may be used for autoclaving surgical instruments and gauze if the octadecylamine in the steam is not more than 2.4 parts per million. (Sec. 502, 52 Stat. 1051; 21 U.S.C. 352) [34 F.R. 8704, June 3, 1969] § 3.507 Location of expiration date in drug labeling. Drugs which require an expiration date should show the expiration date on the immediate container. When the immediate container is packaged in an individual carton, the expiration date should also be placed on the carton. When single-dose containers are packed in individual cartons, the expiration date may properly appear on the carton only. (Secs. 505, 506, 507, 52 Stat. 1052, as amended, 55 Stat. 851, 59 Stat. 463, 61 Stat. 12, 63 Stat. 409; 21 U. S. C. 355, 356, 357) [23 F. R. 5379, July 16, 1958] § 3.508 Significance of control numbers on drug labeling. The lot number on the label of a drug should be capable of yielding the com plete manufacturing history of the package. An incorrect lot number may be regarded as causing the article to be misbranded. (Sec. 502, 52 Stat. 1050; 21 U. S. C. 352) [23 F. R. 5379, July 16, 1958] § 3.509 Labeling of drug preparations containing salicylates. (a) The label of any oral drug preparation intended for sale without prescription and which contains any salicylate ingredient (including aspirin, salicylamide, other salicylates, and combinations) must bear a conspicuous warning statement in heavy block type on clearly contrasting background, such as: "Warning-Keep this and all medicines out of children's reach. In case of accidental overdose, contact a physician immediately," or "Warning-Keep out of the reach of children," except that if the article is an aspirin preparation, it shall bear the first of these warning statements. Such a warning statement is required for compliance with section 502(f) (2) of the Federal Food, Drug, and Cosmetic Act and is intended to guard against accidental poisonings. Safety closures that prevent access to the drug by young children are also recommended to guard against accidental poisonings. (b) Effervescent preparations and preparations containing para-aminosalicylate as the only salicylate ingredient are exempted from this labeling requirement. (c) Aspirin tablets sold as such and containing no other active ingredients, except tablets which cannot be readily subdivided into a child's dose because of their coating or size, should always bear dosage directions for each age group down to 3 years of age, with a statement such as "For children under 3 years of age, consult your physician." It is rec ommended that: (1) Aspirin tablets especially made for pediatric use be produced only in 14-grain size to reduce the hazard of errors in dosage; (2) By June 1, 1967, manufacturers and distributors of 14-grain size aspirin tablets discontinue the distribution of such tablets in retail containers containing more than 36 tablets, to reduce the hazard of accidental poisoning; (3) The flavoring of 5-grain aspirin tablets or other "adult aspirin tablets" be discontinued; and |