Appendix B

APPENDIX B

[Code of Federal Regulations]

[Title 21, Volume 4]

[Revised as of April 1, 2010]

From the U.S. Government Printing Office via GPO Access

[CITE: 21CFR202.1]

[Page 98-106]

TITLE 21--FOOD AND DRUGS

CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN

SERVICES (CONTINUED)

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 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

[[Page 99]]

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 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,

[[Page 100]]

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 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.

[[Page 101]]

(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 Sec. Sec. 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 Sec. Sec. 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 a prescription drug covered by a new animal drug

application approved pursuant to section 512 of the act after August 1,

1969, or any approved supplement thereto, or for a prescription drug

listed in the index pursuant to section 572 of the act, or any granted

modification thereto, shall not recommend or suggest any use that is not

in the labeling accepted in such approved new-drug application or

supplement, new animal drug application or supplement, or new animal

drug index listing or modification. The advertisement shall present

information from labeling required, approved, permitted, or granted in a

new-drug or new animal drug application or new animal drug index listing

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,

[[Page 102]]

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 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 Sec. Sec. 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

[[Page 103]]

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.

(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.

[[Page 104]]

(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 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

[[Page 105]]

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.

(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

[[Page 106]]

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

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; 72 FR 69119, Dec. 6, 2007]

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: