appear thereon in the foreign language. (3) If the labeling contains any representation in a foreign language, all words, statements, and other information required by or under authority of the act to appear on the label or labeling shall appear on the labeling in the foreign language.

(Sec. 502, 52 Stat. 1050, as amended; 21 U.S.C. 352) [20 F.R. 9531, Dec. 20, 1955, as amended at 28 F.R. 5719, June 12, 19631 $ 1.104 Drugs; statement of ingredients. (a) The ingredient information required by section 502(e) of the Federal Food, Drug, and Cosmetic Act shall appear together, without any intervening written, printed, or graphic matter, except the proprietary names of ingredients, which may be included with the listing of established names, and such statements as "Warning-May be habit forming" that are specifically required for certain ingredients by the act or regulations in this chapter.

(b) The term "ingredient" applies to any substance in the drug, whether added to the formulation as a single substance or in admixture with other substances. (c) The labeling of a drug may be misleading by reason (among other reasons) of:

(1) The order in which the names of the ingredients present in the drug appear in the labeling, or the relative prominence otherwise given such names. (2) Failure to reveal the proportion of, or other fact with respect to, an ingredient present in such drug, when such proportion or other fact is material In the light of the representation that such ingredient is present in such drug. (3) The employment of a fanciful proprietary name for a drug or ingredient in such a manner as to imply that the drug or ingredient has some unique effectiveness or composition when, in fact, the drug or ingredient is a common substance, the limitations of which are readily recognized when the drug or ingredient is listed by its established name.

(4) The featuring in the labeling of nert or inactive ingredients in a manner That creates an impression of value greater than their true functional role n the formulation.

(5) Designation of a drug or ingredient by a proprietary name that, because f similarity in spelling or pronunciaion, may be confused with the proprieary name or the established name of a lifferent drug or ingredient.

(d) (1) If the drug is in tablet or capsule form or other unit dosage form, any statement of the quantity of an ingredient contained therein shall express the quantity of such ingredient in each such unit. If the drug is not in unit dosage form, any statement of the quantity of an ingredient contained therein shall express the amount of such ingredient in a specified unit of weight or measure of the drug, or the percentage of such ingredient in such drug. Such statements shall be in terms that are informative to licensed practitioners, in the case of a prescription drug, and to the layman, in the case of a nonprescription drug.

(2) A statement of the percentage of an ingredient in a drug shall, if the term "percent" is used without qualification, mean percent weight-in-weight, if the ingredient and the drug are both solids, or if the ingredient is a liquid and the drug is a solid; percent weight in volume at 68° F. (20° C.), if the ingredient is a solid and the drug is a liquid; and percent volume in volume at 68° F. (20° C.), if both the ingredient and the drug are liquids, except that alcohol shall be stated in terms of percent volume of absolute alcohol at 60° F. (15.56° C.).

(e) A derivative or preparation of a substance named in section 502(e) of the act is an article derived or prepared from such substance by any method, including actual or theoretical chemical action.

(f) If an ingredient is a derivative or preparation of a substance specifically named in section 502(e) of the act and the established name of such ingredient does not indicate that it is a derivative or preparation of the parent substance named in section 502(e) of the act, the labeling shall, in conjunction with the listing of the established name of such ingredient, declare that such article is a derivative or preparation of such parent substance.

(g) (1) If the label or labeling of a prescription drug bears a proprietary name or designation for the drug or any ingredient thereof, the established name, if such there be, corresponding to such proprietary name or designation, shall accompany each appearance of such proprietary name or designation. The established name shall be placed in direct conjunction with the proprietary name or designation, and the relationship between the proprietary name or designation and the established name shall be made clear by use of a phrase such as

"brand of," preceding the established name, or by brackets surrounding the established name.

(2) The established name shall be printed in letters that are at least half as large as the letters comprising the proprietary name or designation with which it is joined, and the established name shall have a prominence commensurate with the prominence with which such proprietary name or designation appears, taking into account all pertinent factors, including typography, layout, contrast, features.

and other printing

(h) (1) In the case of a prescription drug containing two or more active ingredients, if the label bears a proprietary name or designation for such mixture and there is no established name corresponding to such proprietary name or designation, the quantitative ingredient information required on the label by section 502(e) of the act shall be placed in direct conjunction with the most prominent display of the proprietary name or designation. The prominence of the quantitative ingredient information shall bear a reasonable relationship to the prominence of the proprietary name.

(2) If the drug is packaged in a container too small to bear the quantitative ingredient information on the main display panel, the quantitative ingredient information required by section 502(e) of the act may appear elsewhere on the label, even though the proprietary name or designation appears on the main display panel of the label; but side- or backpanel placement shall in this case be so arranged and printed as to provide size and prominence of display reasonably related to the size and prominence of the front-panel display.

(i) A drug packaged in a container too small or otherwise unable to accommodate a label with sufficient space to bear the information required for compliance with section 502(e) (1) (A) (ii) and (B) of the act shall be exempt from compliance with those clauses: Provided, That: (1) The label bears:

(i) The proprietary name of the drug; (ii) The established name, if such there be, of the drug;

(iii) An identifying lot or control number; and

(iv) The name of the manufacturer, packer, or distributor of the drug; and

(2) All the information required to appear on the label by the act and the regulations in this chapter appears on

(a) (1) The ingredient information required by section 502 (n) of the Federal Food, Drug, and Cosmetic Act shall appear together, without any intervening written, printed, or graphic matter, except the proprietary names of ingredients, which may be included with the listing of established names.

(2) The order of listing of ingredients in the advertisement shall be the same as the order of listing of ingredients on the label of the product, and the information presented in the advertisement concerning the quantity of each such ingredient shall be the same as the corresponding information on the label of the product.

(3) The advertisement shall not employ a fanciful proprietary name for the drug or any ingredient in such a manner as to imply that the drug or ingredient has some unique effectiveness or composition, when, in fact, the drug or ingredient is a common substance, the limitations of which are readily recognized when the drug or ingredient is listed by its established name.

(4) The advertisement shall not fea ture inert or inactive ingredients in a manner that creates an impression o value greater than their true functiona role in the formulation.

(5) The advertisement shall not desig nate a drug or ingredient by a proprie tary name that, because of similarity i spelling or pronunciation, may be con fused with the proprietary name or th established name of a different drug o ingredient.

(b) (1) If an advertisement for a pre scription drug bears a proprietary nam or designation for the drug or any in gredient thereof, the established nam if such there be, corresponding to suc proprietary name or designation, sha accompany each appearance of suc proprietary name or designation. established name shall be placed in d rect conjunction with the proprietar name or designation, and the relation ship between the proprietary name designation and the established nam

Th

shall be made clear by use of a phrase such as “brand of," preceding the established name, or by brackets surrounding the established name.

(2) The established name shall be printed in letters that are at least half as large as the letters comprising the proprietary name or designation with which it is joined, and the established name shall have a prominence commensurate with the prominence with which such proprietary name or designation appears, taking into account all pertient factors, including typography, lay›ut, contrast, and other printing features.

(c) In the case of a prescription drug containing two or more active ingredients, if the advertisement bears a proprietary name or designation for such nixture and there is no established name corresponding to such proprietary name or designation, the quantitative ingredient information required in the adverisement by section 502 (n) of the act hall be placed in direct conjunction with the most prominent display of the proprietary name or designation. The prominence of the quantitative ingredint information shall bear a reasonable elationship to the prominence of the proprietary name.

(d) (1) If the advertisement employs ›ne proprietary name or designation to efer to a combination of active ingredints present in more than one preparaion (the individual preparations differng from each other as to quantities of active ingredients and/or the form of the inished preparation) and there is no established name corresponding to such proprietary name or designation, a listng showing the established names of the active ingredients shall be placed in diect conjunction with the most promient display of such proprietary name or designation. The prominence of this isting of active ingredients shall bear reasonable relationship to the promience of the proprietary name and the relationship between such proprietary name or designation, and the listing of active ingredients shall be made clear by use of such phrase as "brand of," preeding the listing of active ingredients. (2) The advertisement shall promiently display the name of at least one specific dosage form and shall have the quantitative ingredient information required by section 502(n) of the act in firect conjunction with such display. If ther dosage forms are listed in the adertisement, the quantitative ingredi

ent information for such dosage forms shall appear in direct conjunction and in equal prominence with the most prominent listing of the names of such dosage forms.

(e) A brief summary relating to side effects, contraindications, and effectiveness shall be presented in any prescription-drug advertisement that provides any information regarding indications or dosage recommendations. This summary shall fairly show the effectiveness of the drug in the conditions for which it is recommended in the advertisement, together with a showing of those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and any other use or uses for which the dosage form advertised is commonly prescribed. A fair balance shall be made in presenting the information on effectiveness and that on side effects and contraindications; such fair balance shall be achieved even if small size of the advertisement limits the total amount of information presented.

(f) An advertisement for a prescription drug covered by an approved newdrug application shall not recommend nor suggest any use that is not in the labeling accepted in the approved newdrug application. The advertisement shall present information from the approved new-drug application labeling concerning those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and any other use or uses for which the dosage form advertised is commonly prescribed.

(g) An advertisement for a prescription drug subject to certification shall not recommend nor suggest any use that is not in the labeling covered by the certification or covered by the applicable certification regulations or regulations providing for exemption from certification. The advertisement shall present information from such labeling covered by the certification, or the applicable certification regulations or regulations providing for exemption from certification, concerning those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and any other use or uses for which the dosage form advertised is commonly prescribed.

(h) In the case of a prescription drug not subject to the new-drug provisions

or the certification provisions, an advertisement may recommend use of the drug only for those purposes for which the article is generally recognized as safe and effective by medical experts or for those purposes for which the article is generally recognized as safe by medical experts and for which there exists substantial evidence, consisting of adequate and well-controlled investigations, including clinical investigations, by medical experts, on the basis of which it can fairly and responsibly be concluded that the drug is effective for such purposes. The advertisement shall present information concerning those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and for any other use or uses for which the dosage form advertised is commonly prescribed.

(i) The information concerning side effects and contraindications in an advertisement for a prescription drug shall appear in reasonably close association with the information concerning effectiveness and shall have the same relative degree of prominence as the information concerning effectiveness, taking into account all pertinent factors, including typography, layout, contrast, and other printing features.

(j) (1) No advertisement concerning a particular prescription drug may be disseminated without prior approval by the Food and Drug Administration if:

(i) The sponsor or the Food and Drug Administration has received information that has not been widely publicized in medical literature that the use of the drug may cause fatalities or serious damage;

(ii) The Commissioner (or in his absence the officer acting as Commissioner), after evaluating the reliability of such information, has notified the sponsor that the information must be a part of the advertisements for the drug; and

(iii) The sponsor has failed within a reasonable time as specified in such notification to present to the Food and Drug Administration a program, adequate in light of the nature of the information, for assuring that such information will be publicized promptly and adequately to the medical profession in subsequent advertisements.

(2) Within a reasonable time after information concerning the possibility that a drug may cause fatalities or serious

damage has been widel medical literature, the Administration shall not of the drug by mail that of advertisements for t longer necessary.

(3) Dissemination of a not in compliance with shall be deemed to be an the drug to be misbrande 502(n) of the act.

(4) Any advertisemen mitted to the Food and tration prior to publicatio If the advertiser is no submitted advertisement tion and, at some subsec Food and Drug Administ its opinion, the adverti notified and will be give time for correction before action is taken under this fication to the advertiser advertisement is or is no be in violation shall be in

(k) An advertisement i to be issued by the manuf or distributor of the dru the advertisement and w compliance with section act and the applicable reg under shall cause stocks possession of the person issuing or causing the i advertisement, and stock distributed by such pers the channels of commer branded under section 501

(1) Brochures, mailing ing pieces, file cards, bulle catalogs, house organs, prints, and similar pie matter concerning a drug disseminated by or on beha facturer, packer, or distr ing reference publicatio medical practitioners, p nurses, containing dru supplied by the manufact distributor of the drug, a labeling not subject to se the act but subject to th sure" labeling requiremen or (c), as well as the la ments of § 1.104.

(Sec. 502 (e), (n), 52 Stat U.S.C. 352) [28 F.R. 6376, amended at 28 F.R. 10994, O

NOTE: In § 1.105, the pro graph (h) were stayed at 28 10, 1963.

§1.106 Drugs and devices; directions

for use.

for

use.

directions (a) Adequate "Adequate directions for use" means directions under which the layman can use a drug or device safely and for the purposes for which it is intended. Directions for use may be inadequate because (among other reasons) of omission, in whole or in part, or incorrect specification of:

(1) Statements of all conditions, purposes, or uses for which such drug or device is intended, including conditions, purposes, or uses for which it is prescribed, recommended, or suggested in ts oral, written, printed, or graphic advertising, and conditions, purposes, or uses for which the drug or device is Commonly used; except that such statements shall not refer to conditions, uses, or purposes for which the drug or device can be safely used only under he supervision of a practitioner licensed by law and for which it is advertised olely to such practitioner.

(2) Quantity of dose (including usual quantities for each of the uses for which t is intended and usual quantities for persons of different ages and different physical conditions).

(3) Frequency of administration or pplication.

(4) Duration of administration or aplication.

(5) Time of administration or appliEation (in relation to time of meals, time of onset of symptoms, or other time facors).

(6) Route or method of administraion or application.

(7) Preparation for use (shaking, diution, adjustment of temperature, or ther manipulation or process)..

(b) Exemption for prescription drugs. A drug subject to the requirements of ection 503 (b) (1) of the act shall be xempt from section 502 (f) (1) if all he following conditions are met:

(c) In the possession of a practitioner licensed by law to administer or prescribe such drugs; and

(ii) It is to be dispensed in accordance with section 503(b).

(2) The label of the drug bears:

(i) The statement "Caution: Federal law prohibits dispensing without prescription"; and

(ii) The recommended or usual dosage; and

(iii) The route of administration, if it is not for oral use; and

(iv) The quantity or proportion of each active ingredient, as well as the information required by section 502 (d) and (e); and

(v) If it is for other than oral use, the names of all inactive ingredients, except that:

(a) Flavorings and perfumes may be designated as such without naming their components.

(b) Color additives may be designated as coloring without naming specific color components unless the naming of such components is required by a color additive regulation prescribed in Part 8 of this chapter.

(c) Trace amounts of harmless substances added solely for individual product identification need not be named. If it is intended for administration by parenteral injection, the quantity or proportion of all inactive ingredients, except that ingredients added to adjust the pH or to make the drug isotonic may be declared by name and a statement of their effect; and if the vehicle is water for injection it need not be named.

(vi) An identifying lot or control number from which it is possible to determine the complete manufacturing history of the package of the drug;

Provided, however, That in the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear all such information, but which are packaged within an outer container from which they are removed for dispensing or use, the information required by subdivisions (ii), (iii) and (v) of this subparagraph may be contained in other labeling on or within the package from which it is to be dispensed, and the information referred to in subdivision (i) of this subparagraph may be placed on such outer container only, and the information required by subdivision (vi) of this subparagraph may be on the crimp of the dispensing tube.