§ 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 heptahy drate; 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 food and drug establish

ments.

(a) Octadecylamine is classed as a poisonous and deleterious substance; therefore, it may not be used in the steam lines of steam that may be incorporated into food products unless it can be established that it is required in the produc

tion of the food and a tolerance is established for the amount that would be safe for such use.

(b) 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.

(Secs. 406, 502, 52 Stat. 1049, 1051; 21 U. S. C. 346, 352) [22 F.R. 9594, Nov. 30, 1957] § 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 complete 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

and

by young children are also recommended to guard against accidental poisonings. (b) Effervescent preparations 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 recommended 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

(4) Labeling giving undue emphasis to the pleasant flavor of flavored aspirin tablets be discontinued.

(d) Salicylate preparations other than aspirin tablets sold as such may, at the option of the distributor, be labeled for use by adults only, if their labeling and advertising clearly offer them for administration to adults only.

(e) (1) It is the obligation of the distributor who labels a salicylate preparation for administration to children to make certain that the article is suitable for such use and labeled with adequate directions for use in the age group for which it is offered, but in no case should such an article bear directions for use in children under 3 years of age. If the directions provide for administration to children as young as 3 years of age, the label should bear the statement, "For children under 3 years of age consult your physician." However, if the directions provide for administration to children only of an age greater than 3 years (for example, the dosage instructions provide for administration of the article to children only down to age 6), the label should bear a statement such as, "For younger children consult your physician."

(2) A statement such as, "For children under 3 years of age consult your physician" or "For younger children consult your physician,” is not required on the label of an article clearly offered for administration to adults only.

(f) If the labeling or advertising of a salicylate preparation offers it for use in arthritis or rheumatism, the label and labeling should clearly state that the beneficial effects claimed are limited to: "For the temporary relief of minor aches and pains of arthritis and rheumatism." The qualifying phrase "for the temporary relief of minor aches and pains" should appear with the same degree of prominence and conspicuousness as the phrase "arthritis and rheumatism." The label and labeling should bear in juxtaposition with such directions for use conspicuous warning statements to the effect: "Caution: If pain persists for more than 10 days, or redness is present, or in conditions affecting children under 12 years of age, consult a physician immediately." The salicylate dosage should not exceed 60 grains in a 24-hour period or 10 grains in a 4-hour period. If the article contains other analgesics, the salicylate dosage should be appropriately reduced.

(g) (1) The label of any drug containing more than 5 percent methyl salicylate (wintergreen oil) should bear a conspicuous warning such as: "Warning: Do not use otherwise than as directed. Keep out of the reach of children to avoid accidental poisoning."

(2) If the preparation is a counterirritant or rubefacient, it should also bear a caution such as, "Caution: Discontinue use if excessive irritation of the skin develops. Avoid getting into the eyes or on mucous membranes." (See also § 3.35.)

(Sec. 502, 52 Stat. 1051; 21 U. S. C. 352) [23 F.R. 5380, July 16, 1958, as amended at 32 F.R. 3440, Mar. 2, 1967]

ately followed in the labeling with a warning statement in prominent type essentially as follows: "Warning-Severe or persistent sore throat or sore throat accompanied by high fever, headache, nausea, and vomiting may be serious. Consult physician promptly. Do not use more than 2 days or administer to children under 3 years of age unless directed by physician."

(Sec. 502, 52 Stat. 1051; 21 U. S. C. 352) [28 F.R. 5380, July 16, 1958, as amended at 27 F.R. 4418, May 9, 1962, 32 F.R. 1172, Feb. 2, 1967]

§ 3.511

Injectable iron preparations for veterinary use.

There has been an increasing interest in the use of injectable iron compounds for the prevention or treatment of irondeficiency anemia in animals. Although some such preparations have been shown to be safe, such articles are regarded as new drugs within the meaning of the Federal Food, Drug, and Cosmetic Act. Accordingly, an effective new-drug application is required prior to the marketing of such preparations within the jurisdiction of the act. In addition to the need for demonstrating the safety of such articles, we are concerned that the labeling of such preparations not only recommends appropriate dosages of iron but also declares the amount (in milligrams) of available iron (Fe) per milliliter of the subject product.

(Secs. 201 (p), 502(f), 505(a), 52 Stat. 1041, 1042, 1051, 1052; 21 U.S.C. 321(p), 355(a)) [24 F.R. 1177, Feb. 17, 1959]

§ 3.512 New-drug status of timed-release dosage forms of drugs.

(a) Many drugs are now being offered in dosage forms that are designed to release the active ingredients over a prolonged period. There is a possibility of unsafe overdosage if such products are improperly made and the active ingredients are released at one time or over too short a time interval. Any such dosage form that contains per dosage unit (for examples, capsule, or tablet), a quantity of active drug ingredients which is not generally recognized as safe for administration as a single dose under the conditions suggested in its labeling, is regarded as a new drug within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act.

(b) The fact that the labeling of this type of drug may claim delayed or prolonged release of all or some of the active ingredients does not affect the new-drug

A new-drug

status of such articles. application is required in any such case to demonstrate that the drug is in fact safe because it is properly made and controlled to release the total dose at a safe rate. It should be noted particularly that such dosage forms are regarded as new drugs even when the total daily dosage recommended in the labeling is generally recognized as safe. For example, a capsule containing 50 milligrams of pyrilamine maleate and 15 milligrams of phenylephrine hydrochloride, offered for sale without prescription, is regarded as a new drug for which the distributor should have an effective new-drug application, even though the directions call for taking no more than two capsules daily. While the daily intake under such directions is within the range regarded as safe for use in self-medication, the single dose is too high for such use unless the release of the drug is sufficiently prolonged. It is obvious that, in filing a newdrug application for such an article, particular attention should be given to data which establish that the active ingredients are released over a period of time, as represented in the labeling. (Sec. 201 (p), 52 Stat. 1042; 21 U.S.C. 321 (p)) [24 F.R. 3756, May 9, 1959]

§ 3.513 Supplying pharmacists with indications and dosage of drugs.

There are presently no regulations under the Federal Food, Drug, and Cosmetic Act that prevent a manufacturer of prescription drugs from sending the pharmacist data he needs on indications and dosage in exercising his important professional function of checking against possible mistakes in a prescription. The Food and Drug Administration believes manufacturers should be encouraged to supply such printed matter to the pharmacist for his professional information. Obviously, such printed matter should not be displayed to prospective purchasers to promote over-the-counter sale of prescription drugs.

(Secs. 502(f) (1), 503(b) (1) (B), 52 Stat. 1051, 52 Stat. 1052, as amended 65 Stat. 648, 649; 21 U.S.C. 352(f) (1), 353(b)(1)(B)) [24 F.R. 4376, May 30, 1959]

§ 3.514 Statement of dosage on prescription drug labels.

Section 1.106 (b) (2) (ii) of this chapter requires that labels for prescription drugs bear a statement of the recommended or usual dosage. Since the dosage for some prescription drugs varies within extremely wide limits, depending

upon the conditions being treated, it may not be possible in all cases to present an informative or useful statement of the recommended or usual dosage in the space available on the label or carton of the package. It is the view of the Food and Drug Administration that when such a situation prevails, compliance with this requirement would be met by a statement such as "See package insert for dosage information," where the detailed information is contained in such insert. However, if an informative, realistic, recommended or usual dosage can readily be set forth on the label, it should appear thereon.

[26 F.R. 12518, Dec. 27, 1961]

§ 3.515 Exemption from certain druglabeling requirements.

(a) Section 1.106(b) (3) of this chapter provides that in the case of certain drugs for which directions, hazards, warnings, and use information are commonly known to practitioners licensed by law, such information may be omitted from the dispensing package. Under this proviso, the Commissioner of Food and Drugs will offer an opinion, upon written request, stating reasonable grounds therefor, on a proposal to omit such information from the dispensing package.

(b) The Commissioner of Food and Drugs has considered submitted material covering a number of drug products and has offered the opinion that the following drugs, when intended for those human uses for which they are now generally employed by the medical profession, should be exempt from the requirements of § 1.106(b)(3) of this chapter, provided that they meet the conditions prescribed in this paragraph. Preparations that are not in dosage unit form (for example, solutions) will be regarded as meeting the conditions with respect to the maximum quantity of drug per dosage unit if they are prepared in a manner that enables accurate and ready administration of a quantity of drug not in excess of the stated maximum per dosage unit:

Aminophylline. For oral use, not in excess of 200 milligrams per dosage unit, with or without not in excess of 33 milligrams of phenobarbital. Atropine methyl nitrate. For oral use, not in excess of 1.0 milligram per dosage unit.

Atropine sulfate. For oral use, not in excess of 0.54 milligram per dosage unit; for injection, not in excess of

0.54 milligram (20-grain) per dosage unit. Barbiturates. For oral use, not in excess of 100 milligrams per dosage unit; for use as suppositories, not in excess of 130 milligrams per suppository.

Chloral hydrate. For oral use, not in excess of 500 milligrams per dosage unit; for use as suppositories, not in excess of 1.0 gram per suppository. Codeine phosphate. For oral use, not in excess of 65 milligrams per dosage unit; for injection, not in excess of 65 milligrams per dosage unit. Codeine sulfate. For oral use, not in excess of 65 milligrams per dosage unit; for injection, not in excess of 65 milligrams per dosage unit. Digitalis. Preparations of whole leaf digitalis including forms such as digitalis tincture. For oral use, containing the equivalent of not more than 1 U.S.P. digitalis unit per dosage unit. Dihydrocodeinone bitartrate. For oral use, not in excess of 10 milligrams per dosage unit.

Dihydromorphinone hydrochloride. For oral use, not in excess of 4 milligrams per dosage unit.

Epinephrine injection, 1: 1,000. Erythrityl tetranitrate. For oral use, not in excess of 30 milligrams per dosage unit. Homatropine methylbromide. For oral use, not in excess of 5 milligrams per dosage unit.

Hyoscyamine hydrobromide. For oral use, not in excess of 1 milligram per dosage unit.

Hyoscyamine sulfate. For oral use, not in excess of 1 milligram per dosage unit.

Hyoscyamus tincture. For oral use, not in excess of 2 milliliters per dosage unit.

Mannitol hexanitrate. For oral use, not in excess of 32 milligrams per dosage unit. Methenamine. For oral use, not in excess of 1 gram per dosage unit. Morphine phosphate. For oral use, not in excess of 33 milligrams per dosage unit; for injection, not in excess of 33 milligrams per dosage unit.

Morphine sulfate. For oral use, not in excess of 33 milligrams per dosage unit; for injection, not in excess of 33 milligrams per dosage unit. Nitroglycerin. For oral use, not in excess of 0.65 milligram per dosage unit.

Pentaerythritol tetranitrate.

For oral

use, not in excess of 20 milligrams per dosage unit. Pentaerythritol tetranitrate with phenobarbital. For oral use, not in excess of 20 milligrams of pentaerythritol tetranitrate and 35 milligrams of phenobarbital.

Quinidine sulfate. For oral use, not in excess of 325 milligrams per dosage unit.

Scopolamine methylbromide. For oral use, not in excess of 2.5 milligrams per dosage unit.

Sodium chloride injection.

Sodium nitrite. For oral use, not in excess of 60 milligrams per dosage unit.

Theobromine. For oral use, not in excess of 325 milligrams per dosage unit. Thyroid. For oral use, not in excess of 220 milligrams per dosage unit. Water for injection, sterile.

(c) The Commissioner of Food and Drugs has considered submitted material covering a number of drug products and has offered the opinion that the following drugs, when intended for those veterinary uses for which they are now generally employed by the veterinary medical profession, should be exempt from the requirements of § 1.106 (c) (3) of this chapter, provided that they meet the conditions prescribed in this paragraph. Preparations that are not in dosage unit form (for example, solutions) will be regarded as meeting the conditions with respect to the maximum quantity of drug per dosage unit if they are prepared in a manner that enables accurate and ready administration of a quantity of drug not in excess of the stated maximum per dosage unit:

Atropine sulfate. As an injectable for cattle, goats, horses, pigs, and sheep, not in excess of 15 milligrams per dosage unit; as an injectable for cats and dogs, not in excess of 0.6 milligram per dosage unit.

Barbital sodium. For oral use in cats and dogs, not in excess of 300 milligrams per dosage unit.

Epinephrine injection, 1:1,000. For cats, dogs, cattle, goats, horses, pigs, and sheep.

Morphine sulfate. As an injectable for dogs, not in excess of 15 milligrams per dosage unit.

Pentobarbital sodium. For oral use in cats, and dogs, not in excess of 100 milligrams per dosage unit.

Phenobarbital sodium. For oral use in cats and dogs, not in excess of 100 milligrams per dosage unit. Procaine hydrochloride injection. Containing not in excess of 2 percent procaine hydrochloride, with or without epinephrine up to a concentration of 1:50,000. For use in cats, dogs, cattle, goats, horses, pigs, and sheep. Thyroid. For oral use in dogs, not in excess of 60 milligrams per dosage unit. [26 F.R. 12563, Dec. 28, 1961, as amended at 27 F.R. 5428, June 8, 1962]

§ 3.516

Gelsemium-containing preparations regarded as prescription drugs. It is the consensus of informed medical opinion that the margin of safety between the therapeutic and toxic concentration of gelsemium is narrow and it is difficult to predict the point at which the dose will be toxic. Very small doses may cause toxic symptoms. It is therefore the view of the Food and Drug Administration that gelsemium is not a proper ingredient in any product that is to be sold without prescription. cordingly, any drug containing gelsemium will be regarded as misbranded under section 503(b) (4) of the Federal Food, Drug, and Cosmetic Act if its label fails to bear in a prominent and conspicuous fashion the statement "Caution: Federal law prohibits dispensing without prescription."

[28 F.R. 7673, July 27, 1963]

§ 3.651

COSMETICS

Ac

Shampoo preparations containing egg as one of the ingredients. The present views of the Food and Drug Administration concerning the status of shampoo preparations containing egg as one of the ingredients are as follows:

(a) An article designated as "egg shampoo" should contain one egg (or the equivalent amount of dried whole egg) in that quantity of the article which would be used in one shampooing of the hair.

(b) An article that contains less than one egg per "shampoo" should not be referred to as an "egg shampoo," and the word "egg" should not be used as part of the name of the article. At the present time, the Administration is not raising objection to the marketing of an article containing less than one egg per "shampoo," provided the word "egg" does not appear in the name of the article, the reference to the egg ingredient, such