drug in cases of hepatitis and hypersensitivity reactions. In view of the potentially serious effects found to be associated with preparations of this drug intended for use by man, the Commissioner of Food and Drugs will regard such preparations as misbranded within the meaning of section 502(f) (1) and (2) of the Federal Food, Drug, and Cosmetic Act, unless the label and labeling on or within the package from which the drug is to be dispensed, and any other labeling furnishing or purporting to furnish information for use of the drug, bear a conspicuous warning statement to the following effect: "Warning: Agranulocytosis and hepatitis have been associated with the use of phenindione. Patients should be instructed to report promptly prodromal symptoms such as marked fatigue, chill, fever, and sore throat. Periodic blood studies and liver function tests should be performed. of the drug should be discontinued if leukopenia occurs or if evidence of hypersensitivity, such as dermatitis or fever, appears." Use (b) Regulatory action may be initiated with respect to preparations of phenindione intended for use by man found within the jurisdiction of the act on or after November 25, 1961, unless such preparations are labeled in accordance with paragraph (a) of this section. (Secs. 502(f), 52 Stat. 1051, 21 U.S.C. 352(f)) [26 F.R. 9041, Sept. 26, 1961; 26 F.R. 9131, Sept. 28, 1961] There is a current interest in the utilization of newly developed sources of radiation for the sterilization of drugs. Prior to the marketing of a drug sterilized by such means, it is necessary in the interest of protecting the public health to establish by adequate investigations that the irradiation treatment does not cause the drug to become unsafe or otherwise unsuitable for use. Accordingly, all drug products, including injections, ophthalmic solutions, surgical sutures, and surgical dressings sterilized by means of irradiation are regarded as new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act. An effective new-drug application pursuant to section 505 of the act is therefore a prerequisite to interstate shipment of such articles, except as provide 505 (i). (Secs. 201, 505, 52 Stat. 1040 1052, as amended; 21 U.S.C. F.R. 9554, Dec. 20, 1955] § 3.48 Cobalt preparations use by man. The present state of scie edge concerning the use o as hemopoietic agents is li the mechanism of their known and the possible d fects of prolonged admini not been fully determined. effects have been reported ated with such use of col tions, but there is a differer whether the cobalt prepa causative agents in these view of the limitations of state of scientific knowled cobalt and in the intere health protection, the Fo Administration is adopting policies concerning cobalt intended for use by man. (a) Preparations contain age unit more than 10 r cobalt chloride, or more th grams of cobalt in the form salts are not safe for use the supervision of a practit by law to administer the dr (1) Such preparations s beled with the statemer Federal law prohibits dispe prescription." (2) Such preparations as new drugs within the me tion 201 (p) of the Federa and Cosmetic Act if their la vertising sponsored by or their distributor prescribes, or suggests the administra than 15 milligrams of cobal of any of its salts; for ex than 60 milligrams of co per 24-hour period. (3) The labeling of such should bear adequate inf their use by physicians incl other things, the following (i) A statement that quantities of iron salts sho administered simultaneous administration of cobalt, maximum hemopoietic effe (ii) A forthright disclo toxic and adverse effects r associated with the use of c those effects in which the role of may be controversial. Disclosure of the fact that the ble deleterious effects of prolonged stration of cobalt are not fully Articles containing per dosage more than 2 milligrams but not more 10 milligrams of cobalt chloride, or than 0.5 milligram but not more 2.5 milligrams of cobalt in the form y cobalt salts may be labeled with Late directions for use in the selfcation of simple iron-deficiency a only; but such articles will be Arded as misbranded under the proas of section 502 (f) (1) and/or sec02 (1) (2) and/or section 502 (j), may be regarded as new drugs within meaning of section 201 (p) of the act, all the following conditions are The dosages prescribed, recombed, or suggested in the labeling do exceed 40 milligrams of cobalt chlotor 10 milligrams of cobalt in the of any cobalt salts per 24-hour d When used as directed in the king, the preparations supply not less 100 milligrams of iron (Fe) in the 1 of ferrous sulfate or other assimisalts of iron per 24-hour period. The labeling bears, in juxtaposiwith the directions for use, clear 7g statements, so designated, Exceeding the recommended Administration to children under rears of age unless directed by a tan. -Use for more than 2 months directed by a physician. The policies stated in paragraph this section also apply to any e containing, per dosage unit, not E than 2 milligrams of cobalt chlo1 not more than 0.5 milligram of at in the form of any cobalt salts if erections for its use prescribe, recmend, or suggest the use of more than grams of cobalt chloride or its equivalent per dose, or more than Intagrams of cobalt chloride or its coalt equivalent per 24-hour period. Any cobalt-containing drug ined for use by man and which is reted within the jurisdiction of the contrary to the provisions of this ment after 60 days from the date publication in the FEDERAL REGISTER may be made the subject of regulatory proceedings under the act. (Secs. 201, 502, 52 Stat. 1041, as amended, 1050, as amended; 21 U.S.C. 321, 352) [21 F.R. 8395, Nov. 2, 1956, as amended at 21 F.R. 10274, Dec. 21, 1956] § 3.49 Pessaries for intracervical and intrauterine use. (a) Because of the limited evidence previously available concerning the hazards attending the use of intracervical and intrauterine pessaries, the shipment of such devices within the jurisdiction of the Federal Food, Drug, and Cosmetic Act, with labeling limiting them to sale only on prescription, has not been subjected to regulatory proceedings. A recent survey shows that it is now the consensus of medical opinion among experts qualified by scientific training and experience to evaluate the safety of such devices that stem-type and wing-type intracervical and intrauterine pessaries are too dangerous for use under any form of labeling and serve no useful purpose. This opinion is particularly applicable to pessaries offered or intended for contraceptive use. These views do not apply to those pessaries, made with hollow tubes, intended solely for use when necessary to maintain drainage from the uterine cavity. (b) On the basis of this consensus of expert opinion and the supporting evidence of many known injuries, the Food and Drug Administration concludes that stem-type and wing-type intracervical and intrauterine pessaries are dangerous to health, and regardless of their labeling, may be shown to be misbranded within the meaning of sections 502 (f) (1) and (2) and 502 (j) of the Federal Food, Drug, and Cosmetic Act. It is recommended that distributors of these devices remove them from the interstate market at once. Regulatory action may be instituted in connection with any such devices found within the jurisdiction of the act. [22 F.R. 865, Feb. 12, 1957] § 3.50 Status of salt substitutes under the Federal Food, Drug, and Cosmetic Act. (a) As a result of reported poisonings from salt substitutes containing lithium chloride, under date of March 8, 1949, the Food and Drug Administration announced that it would regard each salt substitute as a new drug within the meaning of section 201 (p) of the Federal Food, Drug, and Cosmetic Act, and that interstate distribution of each salt substitute should be discontinued until a new-drug application had been filed and become effective. Substantial information concerning the safety of many of the ingredients used in salt substitutes has been developed and published since the announcement was made. It is now possible to evaluate the safety of many individual salt substitutes and to determine whether they are new drugs requiring effective applications prior to distribution in interstate commerce. (b) The Food and Drug Administration no longer regards all salt substitutes as new drugs. Upon request, the Administration will express its opinion whether a new-drug application is necessary for any particular product if complete information concerning its composition and proposed labeling is submitted. [22 F.R. 10685, Dec. 25, 1957] § 3.51 Label declaration of D-erythroascorbic acid when it is an ingredient of a fabricated food. (a) The article D-erythroascorbic acid (D-araboascorbic acid, D-erythro-3-ketohexonic acid lactone) has sometimes been designated as D-isoascorbic acid. However, this designation is capable of misleading purchasers of food in which it is used as an ingredient because of the similarity of such designation to the chemical name and the common name of vitamin C, which is ascorbic acid. Ascorbic acid (vitamin C) is capable of preventing the deficiency disease scurvy, but D-isoascorbic acid is ineffective for this purpose. (b) The Joint Committee on Nomenclature of the American Institute of Nutrition and the Society of Biological Chemists has considered this matter, and pursuant to the Committee's recommendation the respective scientific organizations approved a resolution to drop the use of the designation D-isoascorbic acid and to adopt as a common name the name erythorbic acid for Derythroascorbic acid. (c) The compound D-erythroascorbic acid is not specified as an ingredient of any food for which a standard has been established. For foods other than those for which standards have been established, section 403 (i) (2) of the Federal Food, Drug, and Cosmetic Act requires that ingredients be listed on labels by their common or usual names. If the label on a food that contains D-erythro Pyroligneous acid may be insofar as the Federal Food Cosmetic Act is concerned, degree of purity suitable and does not serve to con or inferiority, or to make pear better or of greater v is. If the food is one fo identity standard has been pyroligneous acid should unless it is an ingredient in the definition and stand tity. When used, it should as an artificial flavor by phrase as "pyroligneous a ficial flavor," "pyroligneous ficial smoke flavor," or flavored with pyroligneous should be no representa labeling, either directly or a product flavored with acid has been smoked or has flavor, nor should there b sentation in the labeling of sauce, or similar product co roligneous acid and used flavor other foods that t result in a smoked product a true smoked flavor. (Secs. 402, 403, 52 Stat. 1047, 1 342, 343) [22 F.R. 9594, Nov. § 3.202 Labeling of koshe style foods. The term "kosher" sho only on food products that religious dietary require precise significance of "kosher style" as applied ticular product by the pu been determined. There hood that the use of the te the prospective purchaser the product is "kosher." The Administration recognizes need for sanitizing procedures in ..-manufacturing plants; it recogthat chemical sanitizing agents aid ghe maintenance of plant cleanliness; L& recognizes that a number of sani- agents that are poisonous or de cus may properly be employed so they are effective and do not leave Les in food. : The Food and Drug Administradoes not object to the use of effective cal sanitizing agents on food hanequipment in establishments et to its jurisdiction provided preons are taken to prevent adulteraf food that comes in contact with treated equipment. 42 52 Stat. 1046; 21 U.S.C. 342) [23 4 Net weight statement on foods The Food and Drug Administrahas been requested to comment on try proposals to omit the net weight ment on foods such as bananas, and fish fillets that are prepackin cellophane or similar films and stitute therefor statements or inons on the label that the article is weighed and marked at time of ree. The articles that are the subif these proposals would be food in ged form under the Federal Food, and Cosmetic Act. Sections 2 and 405 of the act contain aupermitting reasonable variations the required label statement of the -y of contents under certain conarising in good packing practices; pons for small packages and open zers of fresh fruits and fresh vegand exemptions for food which accordance with the practice of the te to be processed, labeled, or reacted at establishments other than where originally processed or ed. However, there is no authority he statute for exemptions such as requested in this instance. Thereany such food shipped in domestic 59 interstate commerce or imported into the United States shall bear, among other mandatory statements on the label, an accurate statement of the net contents, whether or not it is intended that such package be weighed and marked at the time of retail sale. However, under the pertinent regulations, if preferred, a minimum net weight statement may be used, rather than an average net weight statement, if all units are in excess of the minimum quantity stated and if the variations above the stated minimum are not unreasonably large. (b) This statement cancels that contained in Trade Correspondence Letter No. 258 (TC-258), issued April 25, 1940, with reference to a similar situation involving the labeling of individually wrapped frozen fish with a statement of net contents. (Secs. 403 (e) (2), 701(a); 52 Stat. 1047, 1055; 21 U.S.C. 343 (e) (2), 371(a)) [27 F.R. 11943, Dec. 4, 1962] § 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, 343) [22 F.R. 9594, Nov. 30, 1957] § 3.501 DRUGS Disposition of outdated drugs. When certification becomes invalid because the expiration date is passed, such articles should not be disposed of for drug use either through commercial or charitable channels unless the articles have been assayed to establish potency and recertified. (Secs. 506, 507, 55 Stat. 851, 59 Stat. 463, as amended; 21 U.S.C. 356, 357) [22 F.R. 9594, Nov. 30, 1957] § 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] § 3.504 Prescription legend on drugs intended for export. The legend "Caution: Federal law prohibits dispensing without prescription" might be inappropriate on drugs exported from the United States, since their sale may or may not be restricted under the laws of the country of destination. The Food and Drug Administration would not object to a slight modification of the wording to read, "Caution: Federal (U.S.A.) law prohibits dispensing without prescription," by a manufacturer who wishes to market a drug under the same label both in domestic and foreign commerce. (Secs. 503, 801, 52 Stat. 1052, 1058; 21 U. S. C. 353, 381) [22 F.R. 9594, Nov. 30, 1957, as amended at 28 F.R. 5719, June 12, 1963] CROSS-REFERENCE: For the Spanish-language version of the required labeling statement, see § 1.108 of this chapter. § 3.505 Estradiol labeling. The article presently recognized in The National Formulary under the heading "Estradiol" and which is said to be “17cis-beta estradiol" 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 know Estradiol)." (Secs. 201, 502, 52 Stat. 1040, 10 321, 352) [22 F.R. 9594, Nov. § 3.506 Use of octadecylar lines of food and dr ments. (a) Octadecylamine is poisonous and deleterious therefore, it may not be used lines of steam that may be into food products unless it lished that it is required in tion of the food and a established for the amount safe for such use. (b) The Food and Drug tion will not object to octadecylamine in steam li steam may be used for aut gical instruments and g octadecylamine in the stear than 2.4 parts per million. (Secs. 406, 502, 52 Stat. 1049, 1 346, 352) [22 F.R. 9594, Nov. § 3.507 Location of expir drug labeling. Drugs which require a date should show the ex on the immediate containe immediate container is pa individual carton, the ex should also be placed on When single-dose containe in individual cartons, the ex may properly appear on th (Secs. 505, 506, 507, 52 Stat. 10. 55 Stat. 851, 59 Stat. 463, 61 S 409; 21 U. S. C. 355, 356, 357) July 16, 1958] § 3.508 Significance of co on drug labeling. The lot number on the la should be capable of yield plete manufacturing histor age. An incorrect lot nu regarded as causing the misbranded. (Sec. 502, 52 Stat. 1050; 21 U F. R. 5379, July 16, 1958] § 3.509 Labeling of drug containing salicylates. (a) The label of any ora ration intended for sale wit tion and which contains ingredient (including asp mide, other salicylates a tions) must bear a conspic statement such as: "Warn |