§201.100. Prescription drugs for human use. — Inbound Citations

(b) This exemption from §§ 201.100 and 202.1 of this chapter is applicable to all prescription drug reminder labeling and reminder advertisements solely intended to provide consumers with information regarding the price charged for prescriptions including price lists, catalogs, and other promotional material, whether mailed, posted in a pharmacy, placed in a newspaper, or aired on radio or television.

(f) A prescription drug intended for both human and veterinary use shall comply with paragraphs (e) and (f) of this section and § 201.100.

A drug subject to § 201.100 or § 201.105, shall be exempt from section 502(f)(1) of the act if shipped or sold to, or in the possession of, persons regularly and lawfully engaged in instruction in pharmacy, chemistry, or medicine not involving clinical use, or engaged in law enforcement, or in research not involving clinical use, or in chemical analysis, or physical testing, and is to be used only for such instruction, law enforcement, research, analysis, or testing.

(b) The exemptions conferred by §§ 201.117, 201.119, 201.120, 201.122, and 201.125 shall continue until the drugs are used for the purposes for which they are exempted, or until they are relabeled to comply with section 502(f)(1) of the act. If, however, the drug is converted, compounded, or manufactured into a dosage form limited to prescription dispensing, no exemption shall thereafter apply to the article unless the dosage form is labeled as required by section 503(b) and §§ 201.100 or 201.105.

(b) Manufacturers have heretofore taken advantage of § 201.100 permitting omission of directions for use when the label bears the prescription legend. Section 201.100(c) requires that the labeling of the drug, which may include brochures readily available to licensed practitioners, bear information as to the use of the drug by practitioners licensed by law to administer it. Obviously, information adequate for the use of an inert glandular preparation is not available to practitioners licensed by law.

(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 concludes that in order for the labeling of such drugs to bear adequate information for their safe use, as required by § 201.100, such labeling must include the following:

(ii) The labeling on or within the package from which the drug is to be dispensed bears adequate information for its use by practitioners in accord with the “full disclosure” labeling requirements of § 201.100 of this chapter, including the following warning statement:

(iii) The information relating to side effects and contraindications shall disclose each specific side effect and contraindication (which include side effects, warnings, precautions, and contraindications and include any such information under such headings as cautions, special considerations, important notes, etc.; see paragraph (e)(1) of this section) contained in required, approved, or permitted labeling for the advertised drug dosage form(s): Provided, however,

(a) The side effects and contraindications disclosed may be limited to those pertinent to the indications for which the drug is recommended or suggested in the advertisement to the extent that such limited disclosure has previously been approved or permitted in drug labeling conforming to the provisions of §§ 201.100 or 201.105; and

(b) The use of a single term for a group of side effects and contraindications (for example, “blood dyscrasias” for disclosure of “leukopenia,” “agranulocytosis,” and “neutropenia”) is permitted only to the extent that the use of such a single term in place of disclosure of each specific side effect and contraindication has been previously approved or permitted in drug labeling conforming to the provisions of §§ 201.100 or 201.105.

(f) A radioactive drug prepared, packaged, distributed, and primarily intended for use in accordance with the requirements of this section shall be exempt from section 502(f)(1) of the act and §§ 201.5 and 201.100 of this chapter if the packaging, label, and labeling are in compliance with Federal, State, and local law regarding radioactive materials and if the label of the immediate container and shielded container, if any, either separate from or as part of any label and labeling required for radioactive materials by the Nuclear Regulatory Commission or by State or local radiological health authorities bear the following:

(1) The statement “Rx only”;

(2) The statement “To be administered in compliance with the requirements of Federal regulations regarding radioactive drugs for research use (21 CFR 361.1)”;

(3) The established name of the drug, if any;

(4) The established name and quantity of each active ingredient;

(5) The name and half-life of the radionuclide, total quantity of radioactivity in the drug product's immediate container, and amount of radioactivity per unit volume or unit mass at a designated referenced time;

(6) The route of administration, if it is for the other than oral use;

(7) The net quantity of contents;

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

(9) The name and address of the manufacturer, packer, or distributor;

(10) The expiration date, if any;

(11) If the drug is intended for parenteral use, a statement as to whether the contents are sterile;

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

(i) Trace amounts of harmless substances added solely for individual product identification need not be named.

(ii) If the drug is intended for parenteral use, the quantity or proportion of all inactive ingredients, except that ingredients added to adjust pH or to make the drug isotonic may be declared by name and a statement of their effect; if the vehicle is water for injection, it need not be named. 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, the information required by paragraphs (f) (1) and (12) of this section may be placed on the shielded container only.

(C) The same qualitative and/or quantitative ingredient information as required under § 201.100(b) for drug labels or §§ 610.60 and 610.61 of this chapter for biological product labels;

(iii) The same qualitative and/or quantitative ingredient information as required under § 201.100(b) for labels;

(d) Any labeling, as defined in section 201(m) of the act, whether or not it is on or within a package from which the drug is to be dispensed, distributed by or on behalf of the manufacturer, packer, or distributor of the drug, that furnishes or purports to furnish information for use or which prescribes, recommends, or suggests a dosage for the use of the drug (other than dose information required by paragraph (b)(2) of this section and § 201.100(b)(2)) contains:

(1) Adequate information for such use, including indications, effects, dosages, routes, methods, and frequency and duration of administration, and any relevant warnings, hazards, contraindications, side effects, and precautions, and including information relevant to compliance with the new animal drug provisions of the act, under which veterinarians licensed by law to administer the drug can use the drug safely and for the purposes for which it is intended, including all conditions for which it is advertised or represented; and if the article is subject to section 512 or 572 of the act, the parts of the labeling providing such information are the same in language and emphasis as labeling approved, permitted, or indexed under the provisions of section 512 or 572, and any other parts of the labeling are consistent with and not contrary to such approved, permitted, or indexed labeling; and

(2) The same information concerning the ingredients of the drug as appears on the label and labeling on or within the package from which the drug is to be dispensed;

Section 201.100(b)(2) 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.

(b) Manufacturers have heretofore taken advantage of § 201.100 permitting omission of directions for use when the label bears the prescription legend. Section 201.100(c) requires that the labeling of the drug, which may include brochures readily available to licensed practitioners, bear information as to the use of the drug by practitioners licensed by law to administer it. Obviously, information adequate for the use of an inert glandular preparation is not available to practitioners licensed by law.

(b) Therefore, amyl nitrite inhalant will be regarded as misbranded unless the labeling on or within the package from which the drug is to be dispensed bears adequate information for its safe and effective use by physicians, in accordance with § 201.100(c) of this chapter, and its label bears the statement “Rx only.”

(1) Because of their potential for harmful effect, drugs containing hexachlorophene, other than as a preservative as described below, are not considered to have been shown to be safe and effective, are regarded as new drugs requiring approved new drug applications, and would be misbranded for over-the-counter distribution. In the interest of public health protection, hexachlorophene containing drugs will be regarded as misbranded and subject to regulatory proceedings unless the label bears the statement “Rx only,” and the labeling on or within the package from which the drug is to be dispensed bears adequate information for its safe and effective use by practitioners, in accord with § 201.100(c) of this chapter.

(c) Therefore, after publication in the Federal Register of a Drug Efficacy Study Implementation notice on a prescription drug, unless exempted or otherwise provided for in the notice, all package labeling (other than the immediate container or carton label, unless such labeling contains information required by § 201.100(c)(1) in lieu of a package insert), promotional labeling, and advertisements shall include, as part of the information for practitioners under which the drug can be safely and effectively used, an appropriate qualification of all claims evaluated as other than “effective” by a panel of the National Academy of Sciences—National Research Council, Drug Efficacy Study Group, if such claims continue to be included in either the labeling or advertisements. However, this qualifying information will be required in advertisements only if promotional material is included therein for claims evaluated as less than “effective” or if such claims are included in the indications section of the portion of the advertisement containing the information required in brief summary by § 202.1(e)(1) of this chapter. When, however, the Food and Drug Administration classification of such claim is “effective” (for example, on the basis of revision of the language of the claim or submission or existence of adequate data), such qualification is not necessary. When the Food and Drug Administration classification of the claim, as stated in the implementation notice, differs from that of the Academy but is other than “effective,” the qualifying statement shall refer to this classification in lieu of the Academy's classification.

(3) 5 that are administered orally, nasally, vaginally, or rectally, or for use in the area of the eye, the labeling required by § 201.100(d) of this chapter shall, in addition to the label statement required under paragraph (c)(2) of this section, bear the warning statement “This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.” This warning statement shall appear in the “Precautions” section of the labeling.

(b) 5 that are administered orally, nasally, vaginally, or rectally, or for use in the area of the eye, the labeling required by § 201.100(d) shall bear the warning statement “This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.” This warning statement shall appear in the “Precautions” section of the labeling.

(b) The labeling required by §§ 201.57 and 201.100(d) for prescription drugs for human use containing a sulfite, except epinephrine for injection when intended for use in allergic or other emergency situations, shall bear the warning statement “Contains (insert the name of the sulfite, e.g., sodium metabisulfite), a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.” This statement shall appear in the “Warnings” section of the labeling.

(a) Prescription drug labeling described in § 201.100(d) must meet the following general requirements:

(1) The labeling must contain a summary of the essential scientific information needed for the safe and effective use of the drug.

(2) The labeling must be informative and accurate and neither promotional in tone nor false or misleading in any particular. In accordance with §§ 314.70 and 601.12 of this chapter, the labeling must be updated when new information becomes available that causes the labeling to become inaccurate, false, or misleading.

(3) The labeling must be based whenever possible on data derived from human experience. No implied claims or suggestions of drug use may be made if there is inadequate evidence of safety or a lack of substantial evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the drug in humans must be identified as such and included with human data in the appropriate section of the labeling.

(i) The content of labeling required under § 201.100(d)(3) of this chapter (commonly referred to as the package insert or professional labeling), including all text, tables, and figures, must be submitted to the agency in electronic format as described in paragraph (l)(5) of this section. This requirement is in addition to the requirements of paragraph (e)(2)(ii) of this section that copies of the formatted label and all labeling be submitted. Submissions under this paragraph must be made in accordance with part 11 of this chapter, except for the requirements of § 11.10(a), (c) through (h), and (k), and the corresponding requirements of § 11.30.

(iii) (a) Currently used professional labeling, patient brochures or package inserts (if any), and a representative sample of the package labels.

(b) The content of labeling required under § 201.100(d)(3) of this chapter (i.e., the package insert or professional labeling), including all text, tables, and figures, must be submitted in electronic format. Electronic format submissions must be in a form that FDA can process, review, and archive. FDA will periodically issue guidance on how to provide the electronic submission (e.g., method of transmission, media, file formats, preparation and organization of files). Submissions under this paragraph must be made in accordance with part 11 of this chapter, except for the requirements of § 11.10(a), (c) through (h), and (k), and the corresponding requirements of § 11.30.

(c) A summary of any changes in labeling that have been made since the last report listed by date in the order in which they were implemented, or if no changes, a statement of that fact.

(ii) The content of labeling required under § 201.100(d)(3) of this chapter (commonly referred to as the package insert or professional labeling), including all text, tables, and figures, must be submitted to the agency in electronic format as described in paragraph (d)(1)(iii) of this section. This requirement applies to the content of labeling for the proposed drug product only and is in addition to the requirements of paragraph (a)(8)(ii) of this section that copies of the formatted label and all proposed labeling be submitted. Submissions under this paragraph must be made in accordance with part 11 of this chapter, except for the requirements of § 11.10(a), (c) through (h), and (k), and the corresponding requirements of § 11.30.

(b) The content of labeling required under § 201.100(d)(3) of this chapter (commonly referred to as the package insert or professional labeling), including all text, tables, and figures, must be submitted to the agency in electronic format as described in paragraph (a) of this section. This requirement is in addition to the provisions of §§ 601.2(a) and 601.12(f) that require applicants to submit specimens of the labels, enclosures, and containers, or to submit other final printed labeling. Submissions under this paragraph must be made in accordance with part 11 of this chapter except for the requirements of § 11.10(a), (c) through (h), and (k), and the corresponding requirements of § 11.30.

(4) The labeling may contain a “Product Title” section preceding the “Description” section and containing only the information required by § 201.80(a)(1)(i), (a)(1)(ii), (a)(1)(iii), and (a)(1)(iv) and § 201.100(e). The information required by § 201.80(a)(1)(i) through (a)(1)(iv) must appear in the “Description” section of the labeling, whether or not it also appears in a “Product Title.”