24314 Federal Register / Vol. 61, No. 94 / Tuesday, May 14, 1996 / Notices

Biologic, or Antibiotic Drug for Human

Use, for use in accordance with part 601

(21 CFR part 601), by applicants for

licenses for specified biotechnology and

specified synthetic biological products.

In the final rule, ‘‘Elimination of

Establishment License Application for

Specified Biotechnology and Specified

Synthetic Biological Products,’’

published elsewhere in this issue of the

Federal Register, FDA is amending

§ 601.2 (a) and adding new § 601.2 (c) to

create a licensing scheme for specified

biotechnology and specified synthetic

biological products. The final rule

requires an applicant seeking marketing

approval for specified biotechnology

and specified synthetic biological

products to submit a single biologics

license application to CBER. FDA Form

3439 has received interim approval from

OMB for use by applicants subject to the

above-referenced final rule.

In the November 1995 report entitled,

‘‘Reinventing the Regulation of Drugs

Made from Biotechnology’’ report, the

President and Vice-President

announced a series of regulatory reform

initiatives, including FDA’s intention to

use a single harmonized application

form for all licensed biological products

and all drug products. The harmonized

form will be made available for public

comment and submitted to OMB for

review and approval. FDA also intends

to develop guidance to assist applicants

in completing the harmonized

application. Once it is approved for use

by OMB, the harmonized form will

supersede FDA Form 3439. Until that

time, applicants for licenses for

specified biotechnology and specified

synthetic biological products may use

the interim FDA Form 3439.

Under the Paperwork Reduction Act

of 1995 (Pub. L. 104–13), all forms

requesting a collection of information

on identical items from 10 or more

public respondents must be approved

by OMB and must display a valid OMB

control number and expiration date.

FDA Form 3439 was approved under

OMB control number 0910–0316. The

expiration date for the form is December

31, 1997.

Dated: May 9, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96–12145 Filed 5–10–96; 10:13 am]

BILLING CODE 4160–01–F

[Docket No. 95N–0227]

Direct-to-Consumer Promotion

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice; request for comments.

SUMMARY: The Food and Drug

Administration (FDA) is publishing a

notice making clear that the agency does

not require preclearance of prescription

product promotion (advertising and

promotional labeling) of human or

animal drugs, biologics, or restricted

medical devices directed toward

consumers. FDA is also requesting

comments on its intent to consider

certain FDA-approved patient labeling

as adequate to fulfill the brief summary

requirement in consumer-directed

advertisements. Finally, FDA is

soliciting comments concerning several

issues related to consumer-directed

promotion of prescription biologics,

human and animal drugs, and restricted

medical devices to help guide policy

decisions.

DATES: Written comments by August 12,

1996.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Nancy M. Ostrove, Division of Drug

Marketing, Advertising and

Communications (HFD–40), Center for

Drug Evaluation and Research, Food

and Drug Administration, 5600 Fishers

Lane, rm. 17–B04, Rockville, MD 20857,

301–827–2828, or via Internet at

Ostrove@cder.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

Under the Federal Food, Drug, and

Cosmetic Act (act) and the Public Health

Service Act, the Food and Drug

Administration (FDA) has responsibility

for regulating the labeling and

advertising of prescription drugs

(animal and human), biologics, and

restricted medical devices. Labeling and

advertising must follow certain

requirements, as defined by the Act and

implementing regulations.

Under section 502(n)of the act (21

U.S.C. 352(n)), an advertisement for a

prescription drug must contain, in

addition to the product’s established

name and quantitative composition,

‘‘such other information in brief

summary relating to side effects,

contraindications, and effectiveness * *

*.’’ This requirement is further defined

in prescription drug advertising

regulations at § 202.1(e) (21 CFR

202.1(e)). Under section 502(r) of the act

(21 U.S.C. 352(r)), an advertisement for

a restricted medical device must

contain, in addition to the established

name, ‘‘a brief statement of the intended

uses of the device and relevant

warnings, precautions, side effects, and

contraindications * * *.’’

The act and FDA’s advertising

regulations do not distinguish between

targeted audiences. FDA recognizes,

however, that there are differences

between the information needs of health

care professionals and consumers

resulting from differences in medical

and pharmaceutical expertise, and

differences in roles as potential

recipients of medications or prescribers

of medications, that may affect their

perceptions, comprehension, and

interpretation of promotional claims. In

light of these differences, FDA is

continuing to evaluate its policies and

regulations.

In the Federal Register of August 16,

1995 (60 FR 42581), FDA announced a

part 15 (21 CFR part 15) hearing to be

held on October 18 and 19, 1995. In that

document, the agency solicited oral

testimony and written responses to a

series of questions concerning direct-toconsumer (DTC) promotion of

prescription drugs. At the hearing, the

agency heard testimony from

representatives of consumer and patient

groups, advertising associations, and

foreign governments, as well as from

individual academicians, attorneys,

marketers, and pharmaceutical

manufacturers. The agency accepted

written comments until December 29,

1995. FDA is currently evaluating the

testimony, comments, and issues raised

by both the public hearing and citizen

petitions submitted prior to the hearing.

While this evaluation proceeds, FDA

is providing clarification of two of its

policies and soliciting additional

information to help in the development

of overall policy. FDA views these

efforts as part of a comprehensive

process designed to encourage

meaningful communication to

consumers about prescription drugs,

biologics, and restricted medical

devices, while continuing to help

ensure that consumers are adequately

protected from false, misleading or

otherwise violative promotion.

II. Preclearance

One issue raised in oral testimony,

written comments, and citizen petitions

was an objection to the perceived

requirement for manufacturers to obtain

prior clearance from the agency for all

prescription drug and biological DTC

promotion. There is, in fact, no such

requirement. Given public and

congressional concern since the early

1980’s about prescription drug DTC

promotion, together with the

inexperience of the pharmaceutical

industry in producing DTC advertising,

FDA had informally requested

manufacturers to submit, on a voluntary

basis, proposed DTC promotional
Federal Register / Vol. 61, No. 94 / Tuesday, May 14, 1996 / Notices 24315

1This does not apply to submissions required in

a premarket notification submission or premarket

approval application (PMA) under 21 CFR 807.87(e)

and 814.20(b)(10) or submissions required in

connection with accelerated approval under 21 CFR

314.550 and 601.45.

labeling and advertising for review and

comment prior to use. See § 202.1(j)(4),

which provides that ‘‘any advertisement

may be submitted to the Food and Drug

Administration prior to publication for

comment.’’

FDA wishes to clarify that it has never

required preclearance of consumerdirected prescription drug promotion, or

advertising for restricted devices. Under

sections 502(n) and 502(r) of the act,

FDA may require prior approval of

prescription drug and medical device

advertisements only in ‘‘extraordinary

circumstances.’’ (See, e.g., § 202.1(j)(1)—

prior approval will be required when a

sponsor or FDA receives information,

not widely publicized in medical

literature, that a drug may cause

fatalities or serious injuries, and despite

notification from FDA, the sponsor fails

to publicize adequately such

information.)

FDA believes that industry’s desire for

agency guidance on proposed DTC

promotion and applicable regulatory

requirements, and the cost of

developing corrective materials or

campaigns explains the high rate of

submission of DTC promotional

materials for prior review and comment.

However, it appears that the agency’s

request that manufacturers voluntarily

obtain advice on proposed DTC

materials has been misinterpreted as a

requirement. FDA reiterates that it does

not now require, nor has it ever

required, manufacturers to submit DTC

promotional labeling and advertising for

preclearance. 1

III. Patient Labeling in Fulfillment of

the ‘‘Brief Summary’’ Requirement

FDA recognizes that many consumers

do not have the technical background to

understand fully the information

typically included in prescription drug

and biological advertisements to fulfill

the ‘‘brief summary’’ requirement. To

meet the ‘‘brief summary’’ requirement,

sponsors typically reprint, in small type,

whole sections of the professional

labeling, which is generally written in

terms that are not easily understood by

the average consumer.

Some prescription drugs and

biological products have FDA-approved

labeling, in addition to that written for

health professionals, that contains

information intended to be

understandable to patients. This patient

labeling contains information that

comprehensively, although not

exhaustively, describes the safety and

efficacy of the product. Although it is

less comprehensive than professional

labeling, patient labeling is intended to

provide patients prescribed the

medication with information that will

help them use their medication

effectively and safely. It should also,

therefore, provide potential users with

appropriately written product

information they may want to consider.

FDA believes that such FDA-approved

patient labeling generally meets the

brief summary requirements, and,

because it is written for patients, is a

more appropriate vehicle for

communicating risk information to

consumers than the technically-written

brief summary. FDA is requesting

comment on its intention to consider

the reprinting of certain FDA-approved

patient labeling as adequate to fulfill the

brief summary requirement in

consumer-directed advertisements for

prescription drug and biological

products. The following products offer

prototypical examples of such

comprehensive patient labeling: Oral

contraceptives, estrogenic products,

Cardura, Fosamax, Glucophage,

Hytrin, Proscar, Seldane, and

Ticlid.

Not all FDA-approved patient

labeling, however, generally meets the

brief summary requirements. Some

approved patient labeling primarily is

intended to give instructions for use

(e.g., directions on how to use

medications delivered via inhalation,

nasal spray, patch, or injection). Other

patient labeling focuses primarily on a

single warning (e.g., Accutane , the

class auxiliary warning labels on

angiotensin-converting-enzyme (ACE)

inhibitors and isoproterenol inhalers).

In both of these instances, the patient

labeling has a narrow focus that is not

intended to offer comprehensive risk

information to patients. Because of this

narrow focus, such patient labeling

would not generally meet the brief

summary requirements and would not

be considered acceptable consumer brief

summaries.

FDA also notes that many

manufacturers have voluntarily

produced informational brochures and

other product-specific materials for

patients that are disseminated through

various outlets. These materials are

typically submitted to the agency either

for prior review and comment, or

through the postmarketing review

process specified in 21 CFR

314.81(b)(3)(i). Such materials that have

not been through the formal labeling

review process should not be

considered automatically acceptable as

a consumer brief summary. Instead, they

may be used as brief summaries only if

they fulfill all of the applicable

requirements in § 202.1(e).

IV. Requests for Comments on Other

Issues

Many complex public health issues

are raised by DTC promotion. In the

August 16, 1995, Federal Register

document, FDA solicited broad public

comment on the major issues

concerning DTC promotion and whether

the agency’s current regulatory

approach should be modified. Some of

these issues were specifically addressed

in testimony and written comments.

These raised additional questions, about

which FDA is now soliciting public

comment.

1. Currently, § 202.1(e) states that the

brief summary shall include information

relating to side effects, warnings,

precautions, contraindications, and

other risk information. In print

advertising, this requirement is

generally fulfilled by including the riskrelated sections of the approved labeling

in, or adjacent to, the advertisement. For

advertisements broadcast through media

such as radio, television, and telephone

communications systems, § 202.1(e)(1)

provides that the advertisement ‘‘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.’’

In addition, section 502(r) of the act

requires that advertisements for

restricted devices contain a brief

statement of the intended uses of the

device and relevant warnings,

precautions, side effects, and

contraindications.

Much testimony, petitions, and

comments questioned the usefulness,

for consumers, of the existing ‘‘brief

summary’’ of risk information that

results from application of these

requirements. Many comments

contended that, for consumer

advertising, a shorter, more focused

presentation of user-friendly

information could meet the statutory

requirement and also provide

appropriate risk-related information.

Some comments suggested that a

consumer brief summary should include

‘‘information relating to the major side

effects and contraindications’’ of the

product, as currently required in

prescription drug and biological product
24316 Federal Register / Vol. 61, No. 94 / Tuesday, May 14, 1996 / Notices

broadcast advertising. (This information

has colloquially been referred to as the

‘‘major statement.’’)

If FDA required or permitted more

limited risk information in place of the

current brief summary, what specific

information should be included? What

criteria should be used by

manufacturers and the agency to

identify the ‘‘major’’ risk information for

any particular product? FDA is also

interested in empirical research that

specifically addresses the issues of how

much and what kind of risk information

can and should be communicated in

DTC advertising of prescription drug

and biological products.

2. Some comments suggested that risk

information could be communicated to

consumers through standardized general

disclosures. This kind of disclosure

would not reference particular

characteristics of a product. Instead,

such statements would reference one or

more general risks, such as the fact that

all prescription drug and biological

products have side effects; that they are

only available from a physician or other

prescribing health care professional;

that they have significant benefits, but

may have significant risks; that patients

should discuss product risks with a

physician, etc.

Such disclosures, however, are

susceptible to habituation or ‘‘wearout,’’ which results in the viewer

quickly learning to ignore the message,

thus lowering its effectiveness. In

addition, such messages may not be

perceived as risk messages at all, but

instead interpreted as reassurances. If

the latter is the case, these messages

would not fulfill the purpose of the brief

summary requirement, which helps

ensure that advertising conveys a

balanced impression about the product’s

benefits and risks.

FDA solicits comments on the

effectiveness of such standardized

general disclosures at transmitting risk

information. FDA is especially

interested in any research that addresses

the issue of the effectiveness of general

risk disclosures of the type described

above.

3. Promotional materials appear in

very different media that each have

distinctive characteristics (e.g., print,

broadcast, telephone communications,

facsimile, Internet). Should FDA require

or permit different disclosures for

consumer-directed promotion of

prescription drug and biological

products that appears in different

media, to reflect the capabilities of these

varying media, or should the disclosure

be the same regardless of medium? For

example, should print media contain

longer and more complete information

than broadcast media because such

information could be made readily

available at minimal cost and because

consumers of print media may be more

willing, able, and/or desirous of

obtaining more complete information?

4. Different products have different

degrees of effectiveness. In some cases,

a product that works for a relatively

small percentage of the appropriate

patient population is approved either

because it is the only available therapy

for a condition; because all other

therapies for the condition also have

only modest benefits; or because it has

relatively few risks. Should FDA require

the communication of the degree of

product effectiveness in DTC

promotion? How could this information

be communicated most effectively?

5. It has been suggested that toll-free

telephone numbers are one way that

product sponsors could make required

information available to audiences. FDA

requests comments and information

from consumers, health professionals,

product sponsors and other interested

individuals regarding: (a) How useful

toll-free numbers are as a mechanism for

obtaining or disseminating information

about medical products, and (b) the

costs to a sponsor of using toll-free

numbers as a means of disseminating

information.

FDA welcomes comments on all of

the issues described above and

especially invites the submission of

relevant empirical research.

Dated: May 8, 1996.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 96–12022 Filed 5–13–96; 8:45 am]

BILLING CODE 4160–01–F

[Docket No. 96E–0043]

Determination of Regulatory Review

Period for Purposes of Patent

Extension; EPIVIRTM

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) has determined

the regulatory review period for

EPIVIRTM and is publishing this notice

of that determination as required by

law. FDA has made the determination

because of the submission of an

application of the Commissioner of

Patents and Trademarks, Department of

Commerce, for the extension of a patent

which claims that human drug product.

ADDRESSES: Written comments and

petitions should be directed to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Brian J. Malkin, Office of Health Affairs

(HFY–20), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–443–1382.

SUPPLEMENTARY INFORMATION: The Drug

Price Competition and Patent Term

Restoration Act of 1984 (Pub. L. 98–417)

and the Generic Animal Drug and Patent

Term Restoration Act (Pub. L. 100–670)

generally provide that a patent may be

extended for a period of up to 5 years

so long as the patented item (human

drug product, animal drug product,

medical device, food additive, or color

additive) was subject to regulatory

review by FDA before the item was

marketed. Under these acts, a product’s

regulatory review period forms the basis

for determining the amount of extension

an applicant may receive.

A regulatory review period consists of

two periods of time: A testing phase and

an approval phase. For human drug

products, the testing phase begins when

the exemption to permit the clinical

investigations of the drug becomes

effective and runs until the approval

phase begins. The approval phase starts

with the initial submission of an

application to market the human drug

product and continues until FDA grants

permission to market the drug product.

Although only a portion of a regulatory

review period may count toward the

actual amount of extension that the

Commissioner of Patents and

Trademarks may award (for example,

half the testing phase must be

subtracted as well as any time that may

have occurred before the patent was

issued), FDA’s determination of the

length of a regulatory review period for

a human drug product will include all

of the testing phase and approval phase

as specified in 35 U.S.C. 156(g)(1)(B).

FDA recently approved for marketing

the human drug product EPIVIRTM

(lamivudine). EPIVIRTM in combination

with Retrovir (zidovudine) is

indicated for the treatment of human

immunodeficiency virus infection when

therapy is warranted based on clinical

and/or immunological evidence of

disease progression. Subsequent to this

approval, the Patent and Trademark

Office received a patent term restoration

application for EPIVIRTM (U.S. Patent

No. 5,047,407) from Glaxo Wellcome,

Inc., and the Patent and Trademark

Office requested FDA’s assistance in

determining this patent’s eligibility for

patent term restoration. In a letter dated

March 1, 1996, FDA advised the Patent

and Trademark Office that this human