[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR202.1]

[Page 72-81]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                                SERVICES
 
PART 202--PRESCRIPTION DRUG ADVERTISING--Table of Contents
 
Sec. 202.1  Prescription-drug advertisements.

    (a)(1) The ingredient information required by section 502(n) of the 
Federal Food, Drug, and Cosmetic Act shall appear together, without any 
intervening

[[Page 73]]

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 feature inert or inactive 
ingredients in a manner that creates an impression of value greater than 
their true functional role in the formulation.
    (5) The advertisement shall not designate a drug or ingredient by a 
proprietary name that, because of similarity in spelling or 
pronunciation, may be confused with the proprietary name or the 
established name of a different drug or ingredient.
    (b)(1) If an advertisement for 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 such proprietary name or 
designation each time it is featured in the advertisement for the drug; 
but, except as provided below in this subparagraph, the established name 
need not be used with the proprietary name or designation in the running 
text of the advertisement. On any page of an advertisement in which the 
proprietary name or designation is not featured but is used in the 
running text, the established name shall be used at least once in the 
running text in association with such proprietary name or designation 
and in the same type size used in the running text: Provided, however, 
That if the proprietary name or designation is used in the running text 
in larger size type, the established name shall be used at least once in 
association with, and in type at least half as large as the type used 
for, the most prominent presentation of the proprietary name or 
designation in such running text. If any advertisement includes a column 
with running text containing detailed information as to composition, 
prescribing, side effects, or contraindications and the proprietary name 
or designation is used in such column but is not featured above or below 
the column, the established name shall be used at least once in such 
column of running text in association with such proprietary name or 
designation and in the same type size used in such column of running 
text: Provided, however, That if the proprietary name or designation is 
used in such column of running text in larger size type, the established 
name shall be used at least once in association with, and in type at 
least half as large as the type used for, the most prominent 
presentation of the proprietary name or designation in such column of 
running text. Where the established name is required to accompany or to 
be used in association with the 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, by brackets surrounding the established name, or by other suitable 
means.
    (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, 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 mixture and there is no established

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name corresponding to such proprietary name or designation, the 
quantitative ingredient information required in the advertisement by 
section 502(n) 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.
    (d)(1) If the advertisement employs one proprietary name or 
designation to refer to a combination of active ingredients present in 
more than one preparation (the individual preparations differing from 
each other as to quantities of active ingredients and/or the form of the 
finished preparation) and there is no established name corresponding to 
such proprietary name or designation, a listing showing the established 
names of the active ingredients shall be placed in direct conjunction 
with the most prominent display of such proprietary name or designation. 
The prominence of this listing of active ingredients shall bear a 
reasonable relationship to the prominence 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'', preceding the listing of active ingredients.
    (2) The advertisement shall prominently 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 direct conjunction 
with such display. If other dosage forms are listed in the 
advertisement, the quantitative ingredient 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) True statement of information in brief summary relating to side 
effects, contraindications, and effectiveness:
    (1) When required. All advertisements for any prescription drug 
(``prescription drug'' as used in this section means drugs defined in 
section 503(b)(1) of the act and Sec. 201.105, applicable to drugs for 
use by man and veterinary drugs, respectively), except advertisements 
described in paragraph (e)(2) of this section, shall present a true 
statement of information in brief summary relating to side effects, 
contraindications (when used in this section ``side effects, 
contraindications'' include side effects, warnings, precautions, and 
contraindications and include any such information under such headings 
as cautions, special considerations, important notes, etc.) and 
effectiveness. Advertisements broadcast through media such as radio, 
television, or telephone communications systems shall include 
information relating to the major side effects and contraindications of 
the advertised drugs in the audio or audio and visual parts of the 
presentation and unless adequate provision is made for dissemination of 
the approved or permitted package labeling in connection with the 
broadcast presentation shall contain a brief summary of all necessary 
information related to side effects and contraindications.
    (2) Exempt advertisements. The following advertisements are exempt 
from the requirements of paragraph (e)(1) of this section under the 
conditions specified:
    (i) Reminder advertisements. Reminder advertisements are those which 
call attention to the name of the drug product but do not include 
indications or dosage recommendations for use of the drug product. These 
reminder advertisements shall contain only the proprietary name of the 
drug product, if any; the established name of the drug product, if any; 
the established name of each active ingredient in the drug product; and, 
optionally, information relating to quantitative ingredient statements, 
dosage form, quantity of package contents, price, the name and address 
of the manufacturer, packer, or distributor or other written, printed, 
or graphic matter containing no representation or suggestion relating to 
the advertised drug product. If the Commissioner finds that there is 
evidence of significant incidence of fatalities or serious injury 
associated with the use of a particular prescription drug, he may 
withdraw this exemption by so notifying the manufacturer, packer, or 
distributor of the drug by letter. Reminder advertisements, other than 
those solely intended to convey

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price information including, but not limited to, those subject to the 
requirements of Sec. 200.200 of this chapter, are not permitted for a 
prescription drug product whose labeling contains a boxed warning 
relating to a serious hazard associated with the use of the drug 
product. Reminder advertisements which are intended to provide consumers 
with information concerning the price charged for a prescription for a 
drug product are exempt from the requirements of this section if they 
meet all of the conditions contained in Sec. 200.200 of this chapter. 
Reminder advertisements, other than those subject to the requirements of 
Sec. 200.200 of this chapter, are not permitted for a drug for which an 
announcement has been published pursuant to a review on the labeling 
claims for the drug by the National Academy of Sciences/National 
Research Council (NAS/NRC), Drug Efficacy Study Group, and for which no 
claim has been evaluated as higher than ``possibly effective.'' If the 
Commissioner finds the circumstances are such that a reminder 
advertisement may be misleading to prescribers of drugs subject to NAS/
NRC evaluation, such advertisements will not be allowed and the 
manufacturer, packer, or distributor will be notified either in the 
publication of the conclusions on the effectiveness of the drug or by 
letter.
    (ii) Advertisements of bulk-sale drugs. Advertisements of bulk-sale 
drugs that promote sale of the drug in bulk packages in accordance with 
the practice of the trade solely to be processed, manufactured, labeled, 
or repackaged in substantial quantities and that contain no claims for 
the therapeutic safety or effectiveness of the drug.
    (iii) Advertisements of prescription-compounding drugs. 
Advertisements of prescription-compounding drugs that promote sale of a 
drug for use as a prescription chemical or other compound for use by 
registered pharmacists in compounding prescriptions if the drug 
otherwise complies with the conditions for the labeling exemption 
contained in Sec. 201.120 and the advertisement contains no claims for 
the therapeutic safety or effectiveness of the drug.
    (3) Scope of information to be included; applicability to the entire 
advertisement. (i) The requirement of a true statement of information 
relating to side effects, contraindications, and effectiveness applies 
to the entire advertisement. Untrue or misleading information in any 
part of the advertisement will not be corrected by the inclusion in 
another distinct part of the advertisement of a brief statement 
containing true information relating to side effects, contraindications, 
and effectiveness of the drug. If any part or theme of the advertisement 
would make the advertisement false or misleading by reason of the 
omission of appropriate qualification or pertinent information, that 
part or theme shall include the appropriate qualification or pertinent 
information, which may be concise if it is supplemented by a prominent 
reference on each page to the presence and location elsewhere in the 
advertisement of a more complete discussion of such qualification or 
information.
    (ii) The information relating to effectiveness is not required to 
include information relating to all purposes for which the drug is 
intended but may optionally be limited to a true statement of the 
effectiveness of the drug for the selected purpose(s) for which the drug 
is recommended or suggested in the advertisement. The information 
relating to effectiveness shall include specific indications for use of 
the drug for purposes claimed in the advertisement; for example, when an 
advertisement contains a broad claim that a drug is an antibacterial 
agent, the advertisement shall name a type or types of infections and 
microorganisms for which the drug is effective clinically as 
specifically as required, approved, or permitted in the drug package 
labeling.
    (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

[[Page 76]]

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 Secs. 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 Secs. 201.100 or 201.105.
    (4) Substance of information to be included in brief summary. (i)(a) 
An advertisement for a prescription drug covered by a new-drug 
application approved pursuant to section 505 of the act after October 
10, 1962 or section 512 of the act after August 1, 1969, or any approved 
supplement thereto, shall not recommend or suggest any use that is not 
in the labeling accepted in such approved new-drug application or 
supplement. The advertisement shall present information from labeling 
required, approved, or permitted in a new-drug application relating to 
each specific side effect and contraindication in such labeling that 
relates to the uses of the advertised drug dosage form(s) or shall 
otherwise conform to the provisions of paragraph (e)(3)(iii) of this 
section.
    (b) If a prescription drug was covered by a new-drug application or 
a supplement thereto that became effective prior to October 10, 1962, an 
advertisement may recommend or suggest:
    (1) Uses contained in the labeling accepted in such new-drug 
application and any effective, approved, or permitted supplement 
thereto.
    (2) Additional uses contained in labeling in commercial use on 
October 9, 1962, to the extent that such uses did not cause the drug to 
be an unapproved ``new drug'' as ``new drug'' was defined in section 
201(p) of the act as then in force, and to the extent that such uses 
would be permitted were the drug subject to paragraph (e)(4)(iii) of 
this section.
    (3) Additional uses contained in labeling in current commercial use 
to the extent that such uses do not cause the drug to be an unapproved 
``new drug'' as defined in section 201(p) of the act as amended or a 
``new animal drug'' as defined in section 201(v) of the act as amended.

The advertisement shall present information from labeling required, 
approved, or permitted in a new-drug application relating to each 
specific side effect and contraindication in such labeling that relates 
to the uses of the advertised drug dosage form(s) or shall otherwise 
conform to the provisions of paragraph (e)(3)(iii) of this section.
    (ii) In the case of an advertisement for a prescription drug other 
than a drug the labeling of which causes it to be an unapproved ``new 
drug'' and other than drugs covered by paragraph (e)(4)(i) of this 
section, an advertisement may recommend and suggest the drug only for 
those uses contained in the labeling thereof:
    (a) For which the drug is generally recognized as safe and effective 
among experts qualified by scientific training and experience to 
evaluate the safety and effectiveness of such drugs; or
    (b) For which there exists substantial evidence of safety and 
effectiveness, consisting of adequate and well-controlled 
investigations, including clinical investigations (as used in this 
section ``clinical investigations,'' ``clinical experience,'' and 
``clinical significance'' mean in the case of drugs intended for 
administration to man, investigations, experience, or significance in 
humans, and in the case of drugs intended for administration to other 
animals, investigations, experience, or significance in the specie or 
species for which the drug is advertised), by experts qualified by 
scientific training and experience to evaluate the safety and 
effectiveness of the drug involved, on the basis of which it can fairly 
and responsibly be concluded by such experts that the drug is safe and 
effective for such uses; or
    (c) For which there exists substantial clinical experience (as used 
in this section this means substantial clinical experience adequately 
documented in medical literature or by other data (to

[[Page 77]]

be supplied to the Food and Drug Administration, if requested)), on the 
basis of which it can fairly and responsibly be concluded by qualified 
experts that the drug is safe and effective for such uses; or
    (d) For which safety is supported under any of the preceding clauses 
in paragraphs (e)(4)(iii) (a), (b), and (c) of this section and 
effectiveness is supported under any other of such clauses.

The advertisement shall present information relating to each specific 
side effect and contraindication that is required, approved, or 
permitted in the package labeling by Secs. 201.100 or 201.105 of this 
chapter of the drug dosage form(s) or shall otherwise conform to the 
provisions of paragraph (e)(3)(iii) of this section.
    (5) ``True statement'' of information. An advertisement does not 
satisfy the requirement that it present a ``true statement'' of 
information in brief summary relating to side effects, 
contraindications, and effectiveness if:
    (i) It is false or misleading with respect to side effects, 
contraindications, or effectiveness; or
    (ii) It fails to present a fair balance between information relating 
to side effects and contraindications and information relating to 
effectiveness of the drug in that the information relating to 
effectiveness is presented in greater scope, depth, or detail than is 
required by section 502(n) of the act and this information is not fairly 
balanced by a presentation of a summary of true information relating to 
side effects and contraindications of the drug; Provided, however, That 
no advertisement shall be considered to be in violation of this section 
if the presentation of true information relating to side effects and 
contraindications is comparable in depth and detail with the claims for 
effectiveness or safety.
    (iii) It fails to reveal facts material in the light of its 
representations or material with respect to consequences that may result 
from the use of the drug as recommended or suggested in the 
advertisement.
    (6) Advertisements that are false, lacking in fair balance, or 
otherwise misleading. An advertisement for a prescription drug is false, 
lacking in fair balance, or otherwise misleading, or otherwise violative 
of section 502(n) of the act, among other reasons, if it:
    (i) Contains a representation or suggestion, not approved or 
permitted for use in the labeling, that a drug is better, more 
effective, useful in a broader range of conditions or patients (as used 
in this section patients means humans and in the case of veterinary 
drugs, other animals), safer, has fewer, or less incidence of, or less 
serious side effects or contraindications than has been demonstrated by 
substantial evidence or substantial clinical experience (as described in 
paragraphs (e)(4)(ii) (b) and (c) of this section) whether or not such 
representations are made by comparison with other drugs or treatments, 
and whether or not such a representation or suggestion is made directly 
or through use of published or unpublished literature, quotations, or 
other references.
    (ii) Contains a drug comparison that represents or suggests that a 
drug is safer or more effective than another drug in some particular 
when it has not been demonstrated to be safer or more effective in such 
particular by substantial evidence or substantial clinical experience.
    (iii) Contains favorable information or opinions about a drug 
previously regarded as valid but which have been rendered invalid by 
contrary and more credible recent information, or contains literature 
references or quotations that are significantly more favorable to the 
drug than has been demonstrated by substantial evidence or substantial 
clinical experience.
    (iv) Contains a representation or suggestion that a drug is safer 
than it has been demonstrated to be by substantial evidence or 
substantial clinical experience, by selective presentation of 
information from published articles or other references that report no 
side effects or minimal side effects with the drug or otherwise selects 
information from any source in a way that makes a drug appear to be 
safer than has been demonstrated.
    (v) Presents information from a study in a way that implies that the 
study represents larger or more general experience with the drug than it 
actually does.

[[Page 78]]

    (vi) Contains references to literature or studies that misrepresent 
the effectiveness of a drug by failure to disclose that claimed results 
may be due to concomitant therapy, or by failure to disclose the 
credible information available concerning the extent to which claimed 
results may be due to placebo effect (information concerning placebo 
effect is not required unless the advertisement promotes the drug for 
use by man).
    (vii) Contains favorable data or conclusions from nonclinical 
studies of a drug, such as in laboratory animals or in vitro, in a way 
that suggests they have clinical significance when in fact no such 
clinical significance has been demonstrated.
    (viii) Uses a statement by a recognized authority that is apparently 
favorable about a drug but fails to refer to concurrent or more recent 
unfavorable data or statements from the same authority on the same 
subject or subjects.
    (ix) Uses a quote or paraphrase out of context to convey a false or 
misleading idea.
    (x) Uses literature, quotations, or references that purport to 
support an advertising claim but in fact do not support the claim or 
have relevance to the claim.
    (xi) Uses literature, quotations, or references for the purpose of 
recommending or suggesting conditions of drug use that are not approved 
or permitted in the drug package labeling.
    (xii) Offers a combination of drugs for the treatment of patients 
suffering from a condition amenable to treatment by any of the 
components rather than limiting the indications for use to patients for 
whom concomitant therapy as provided by the fixed combination drug is 
indicated, unless such condition is included in the uses permitted under 
paragraph (e)(4) of this section.
    (xiii) Uses a study on normal individuals without disclosing that 
the subjects were normal, unless the drug is intended for use on normal 
individuals.
    (xiv) Uses ``statistics'' on numbers of patients, or counts of 
favorable results or side effects, derived from pooling data from 
various insignificant or dissimilar studies in a way that suggests 
either that such ``statistics'' are valid if they are not or that they 
are derived from large or significant studies supporting favorable 
conclusions when such is not the case.
    (xv) Uses erroneously a statistical finding of ``no significant 
difference'' to claim clinical equivalence or to deny or conceal the 
potential existence of a real clinical difference.
    (xvi) Uses statements or representations that a drug differs from or 
does not contain a named drug or category of drugs, or that it has a 
greater potency per unit of weight, in a way that suggests falsely or 
misleadingly or without substantial evidence or substantial clinical 
experience that the advertised drug is safer or more effective than such 
other drug or drugs.
    (xvii) Uses data favorable to a drug derived from patients treated 
with dosages different from those recommended in approved or permitted 
labeling if the drug advertised is subject to section 505 of the act, 
or, in the case of other drugs, if the dosages employed were different 
from those recommended in the labeling and generally recognized as safe 
and effective. This provision is not intended to prevent citation of 
reports of studies that include some patients treated with dosages 
different from those authorized, if the results in such patients are not 
used.
    (xviii) Uses headline, subheadline, or pictorial or other graphic 
matter in a way that is misleading.
    (xix) Represents or suggests that drug dosages properly recommended 
for use in the treatment of certain classes of patients or disease 
conditions are safe and effective for the treatment of other classes of 
patients or disease conditions when such is not the case.
    (xx) Presents required information relating to side effects or 
contraindications by means of a general term for a group in place of 
disclosing each specific side effect and contraindication (for example 
employs the term blood dyscrasias instead of ``leukopenia,'' 
``agranulocytosis,'' ``neutropenia,'' etc.) unless the use of such 
general term conforms to the provisions of paragraph (e)(3)(iii) of this 
section.

Provided, however, That any provision of this paragraph shall be waived 
with respect to a specified advertisement as set forth in a written 
communication

[[Page 79]]

from the Food and Drug Administration on a petition for such a waiver 
from a person who would be adversely affected by the enforcement of such 
provision on the basis of a showing that the advertisement is not false, 
lacking in fair balance, or otherwise misleading, or otherwise violative 
of section 502(n) of the act. A petition for such a waiver shall set 
forth clearly and concisely the petitioner's interest in the 
advertisement, the specific provision of this paragraph from which a 
waiver is sought, a complete copy of the advertisement, and a showing 
that the advertisement is not false, lacking in fair balance, or 
otherwise misleading, or otherwise violative of section 502(n) of the 
act.
    (7) Advertisements that may be false, lacking in fair balance, or 
otherwise misleading. An advertisement may be false, lacking in fair 
balance, or otherwise misleading or otherwise violative of section 
502(n) of the act if it:
    (i) Contains favorable information or conclusions from a study that 
is inadequate in design, scope, or conduct to furnish significant 
support for such information or conclusions.
    (ii) Uses the concept of ``statistical significance'' to support a 
claim that has not been demonstrated to have clinical significance or 
validity, or fails to reveal the range of variations around the quoted 
average results.
    (iii) Uses statistical analyses and techniques on a retrospective 
basis to discover and cite findings not soundly supported by the study, 
or to suggest scientific validity and rigor for data from studies the 
design or protocol of which are not amenable to formal statistical 
evaluations.
    (iv) Uses tables or graphs to distort or misrepresent the 
relationships, trends, differences, or changes among the variables or 
products studied; for example, by failing to label abscissa and ordinate 
so that the graph creates a misleading impression.
    (v) Uses reports or statements represented to be statistical 
analyses, interpretations, or evaluations that are inconsistent with or 
violate the established principles of statistical theory, methodology, 
applied practice, and inference, or that are derived from clinical 
studies the design, data, or conduct of which substantially invalidate 
the application of statistical analyses, interpretations, or 
evaluations.
    (vi) Contains claims concerning the mechanism or site of drug action 
that are not generally regarded as established by scientific evidence by 
experts qualified by scientific training and experience without 
disclosing that the claims are not established and the limitations of 
the supporting evidence.
    (vii) Fails to provide sufficient emphasis for the information 
relating to side effects and contraindications, when such information is 
contained in a distinct part of an advertisement, because of repetition 
or other emphasis in that part of the advertisement of claims for 
effectiveness or safety of the drug.
    (viii) Fails to present information relating to side effects and 
contraindications with a prominence and readability reasonably 
comparable with the presentation of information relating to 
effectiveness of the drug, taking into account all implementing factors 
such as typography, layout, contrast, headlines, paragraphing, white 
space, and any other techniques apt to achieve emphasis.
    (ix) Fails to provide adequate emphasis (for example, by the use of 
color scheme, borders, headlines, or copy that extends across the 
gutter) for the fact that two facing pages are part of the same 
advertisement when one page contains information relating to side 
effects and contraindications.
    (x) In an advertisement promoting use of the drug in a selected 
class of patients (for example, geriatric patients or depressed 
patients), fails to present with adequate emphasis the significant side 
effects and contraindications or the significant dosage considerations, 
when dosage recommendations are included in an advertisement, especially 
applicable to that selected class of patients.
    (xi) Fails to present on a page facing another page (or on another 
full page) of an advertisement on more than one page, information 
relating to side effects and contraindications when such information is 
in a distinct part of the advertisement.

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    (xii) Fails to include on each page or spread of an advertisement 
the information relating to side effects and contraindications or a 
prominent reference to its presence and location when it is presented as 
a distinct part of an advertisement.
    (xiii) Contains information from published or unpublished reports or 
opinions falsely or misleadingly represented or suggested to be 
authentic or authoritative.
    (f)-(i) [Reserved]
    (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.

If the Commissioner finds that the program presented is not being 
followed, he will notify the sponsor that prior approval of all 
advertisements for the particular drug will be required. Nothing in this 
paragraph is to be construed as limiting the Commissioner's or the 
Secretary's rights, as authorized by law, to issue publicity, to suspend 
any new-drug application, to decertify any antibiotic, or to recommend 
any regulatory action.
    (2) Within a reasonable time after information concerning the 
possibility that a drug may cause fatalities or serious damage has been 
widely publicized in medical literature, the Food and Drug 
Administration shall notify the sponsor of the drug by mail that prior 
approval of advertisements for the drug is no longer necessary.
    (3) Dissemination of an advertisement not in compliance with this 
paragraph shall be deemed to be an act that causes the drug to be 
misbranded under section 502(n) of the act.
    (4) Any advertisement may be submitted to the Food and Drug 
Administration prior to publication for comment. If the advertiser is 
notified that the submitted advertisement is not in violation and, at 
some subsequent time, the Food and Drug Administration changes its 
opinion, the advertiser will be so notified and will be given a 
reasonable time for correction before any regulatory action is taken 
under this section. Notification to the advertiser that a proposed 
advertisement is or is not considered to be in violation shall be in 
written form.
    (5) The sponsor shall have an opportunity for a regulatory hearing 
before the Food and Drug Administration pursuant to part 16 of this 
chapter with respect to any determination that prior approval is 
required for advertisements concerning a particular prescription drug, 
or that a particular advertisement is not approvable.
    (k) An advertisement issued or caused to be issued by the 
manufacturer, packer, or distributor of the drug promoted by the 
advertisement and which is not in compliance with section 502(n) of the 
act and the applicable regulations thereunder shall cause stocks of such 
drug in possession of the person responsible for issuing or causing the 
issuance of the advertisement, and stocks of the drug distributed by 
such person and still in the channels of commerce, to be misbranded 
under section 502(n) of the act.
    (l)(1) Advertisements subject to section 502(n) of the act include 
advertisements in published journals, magazines, other periodicals, and 
newspapers, and advertisements broadcast through media such as radio, 
television, and telephone communication systems.
    (2) Brochures, booklets, mailing pieces, detailing pieces, file 
cards, bulletins, calendars, price lists, catalogs, house organs, 
letters, motion picture films, film strips, lantern slides, sound

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recordings, exhibits, literature, and reprints and similar pieces of 
printed, audio, or visual matter descriptive of a drug and references 
published (for example, the ``Physicians Desk Reference'') for use by 
medical practitioners, pharmacists, or nurses, containing drug 
information supplied by the manufacturer, packer, or distributor of the 
drug and which are disseminated by or on behalf of its manufacturer, 
packer, or distributor are hereby determined to be labeling as defined 
in section 201(m) of the act.

[40 FR 14016, Mar. 27, 1975, as amended at 40 FR 58799, Dec. 18, 1975; 
41 FR 48266, Nov. 2, 1976; 42 FR 15674, Mar. 22, 1977; 60 FR 38480, July 
27, 1995; 64 FR 400, Jan. 5, 1999]

    Effective Date Note: At 44 FR 37467, June 26, 1979, Sec. 202.1(e)(6) 
(ii) and (vii) were revised. At 44 FR 74817, Dec. 18, 1979, paragraphs 
(e)(6) (ii) and (vii) were stayed indefinitely. At 64 FR 400, Jan. 5, 
1999, these paragraphs were amended. For the convenience of the user, 
paragraphs (e)(6) (ii) and (vii), published at 44 FR 37467, are set 
forth below:

Sec. 202.1  Prescription-drug advertisements.

                                * * * * *

    (e) * * *
    (6) * * *
    (ii) Represents or suggests that a prescription drug is safer or 
more effective than another drug in some particular when the difference 
has not been demonstrated by substantial evidence. An advertisement for 
a prescription drug may not, either directly or by implication, e.g., by 
use of comparative test data or reference to published reports, 
represent that the drug is safer or more effective than another drug, 
nor may an advertisement contain a quantitative statement of safety or 
effectiveness (a) unless the representation has been approved as part of 
the labeling in a new drug application or biologic license, or (b) if 
the drug is not a new drug or biologic, unless the representation of 
safety or effectiveness is supported by substantial evidence derived 
from adequate and well-controlled studies as defined in 
Sec. 314.111(a)(5)(ii) of this chapter, or unless the requirement for 
adequate and well-controlled studies is waived as provided in 
Sec. 314.111(a)(5)(ii) of this chapter.

                                * * * * *

    (vii) Suggests, on the basis of favorable data or conclusions from 
nonclinical studies of a prescription drug, such as studies in 
laboratory animals or in vitro, that the studies have clinical 
significance, if clinical significance has not been demonstrated. Data 
that demonstrate activity or effectiveness for a prescription drug in 
animal or in vitro tests and have not been shown by adequate and well-
controlled clinical studies to pertain to clinical use may be used in 
advertising except that (a), in the case of anti-infective drugs, in 
vitro data may be included in the advertisement, if data are immediately 
preceded by the statement ``The following in vitro data are available 
but their clinical significance is unknown'' and (b), in the case of 
other drug classes, in vitro and animal data that have not been shown to 
pertain to clinical use by adequate and well-controlled clinical studies 
as defined in Sec. 314.111(a)(5)(ii) of this chapter may not be used 
unless the requirement for adequate and well-controlled studies is 
waived as provided in Sec. 314.111(a)(5)(ii) of this chapter.

                                * * * * *