Agency Information Collection Activities; Submission for OMB Review; Comment Request

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N-0424]

Agency Information Collection Activities; Submission for OMB

Review; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the

proposed collection of information listed below has been submitted to

the Office of Management and Budget (OMB) for review and clearance

under the Paperwork Reduction Act of 1995 (the PRA).

DATES: Submit written comments on the collection of information by July

9, 1998.

ADDRESSES: Submit written comments on the collection of information to

Office of Information and Regulatory Affairs, OMB, New Executive Office

Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attention:

Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information

Resources Management (HFA-250), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-827-1482.

SUPPLEMENTARY INFORMATION: In compliance with section 3507 of the PRA

(44 U.S.C. 3507), FDA has submitted the following proposed collection

of information to OMB for review and clearance.

Transmittal of Advertisements and Promotional Labeling for Drugs

and Biologics for Human Use (Form FDA 2253)

Under Sec. 314.81(b)(3)(i) (21 CFR 314.81(b)(3)(i)), sponsors of

approved applications for marketed prescription drugs and antibiotic

drugs for human use are required to submit specimens of promotional

labeling and advertisements at the time of initial dissemination of the

labeling and at the time of initial publication of the advertisements.

Each submission is required to be accompanied by a completed

transmittal Form FDA 2253 (Transmittal of Advertisements and

Promotional Labeling for Drugs for Human Use). Statutory authority for

the collection of this information is provided by sections 505(a), (b),

(j), and (k), 507(g), and 701(a) of the Federal Food, Drug, and

Cosmetic Act (the act) (21 U.S.C. 355(a), (b), (j), and (k), 357 (g),

and 371(a)).

Similarly, under Sec. 601.12(f)(4) (21 CFR 601.12(f)(4)) (62 FR

39890, July 24, 1997; effective October 7, 1997), manufacturers of

licensed biological products are required to submit specimens of

advertising and promotional labeling to FDA in accordance with

Sec. 314.81(b)(3)(i). Statutory authority for the collection of this

information is provided by section 351 of the Public Health Service Act

(42 U.S.C. 262), which gives FDA the responsibility to prescribe

standards designed to ensure the safety, purity, potency, and

effectiveness of biological products. In furtherance of this

responsibility, FDA regulates advertising and labeling for biological

products. Currently, specimens of advertising and promotional labeling

are submitted to FDA with Form FDA 2567, a two-part transmittal form

that is also used to transmit other forms of labeling (e.g., circulars,

package labels, and container labels) for FDA review when a firm is

requesting premarket approval of a product or proposing changes to

product carton or container labeling.

FDA is revising Form FDA 2253 to enable it to be used to transmit

specimens of promotional labeling and advertisements for biological

products as well as for prescription drugs and antibiotics. The

proposed revised form has the following major changes:

1. The revised, harmonized form will be used by sponsors of

approved applications for marketed prescription drugs and antibiotic

drugs regulated by the Center for Drug Evaluation and Research (CDER)

who must submit specimens of advertisements and promotional labeling to

the agency, and may be used by manufacturers of licensed biological

products regulated by the Center for Biologics Evaluation and Research

(CBER) who submit draft and/or final copies of promotional labeling and

advertisements to the agency. Revising and harmonizing Form FDA 2253

will eliminate the need for sponsors to use two different forms to

transmit similar materials for submission to the agency; however,

manufacturers of biological products may continue to use Form FDA 2567

to transmit advertisements and promotional labeling if they wish. The

other uses of Form FDA 2567 will remain unchanged.

2. The revised, harmonized form updates the information about the

types

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of promotional materials and the codes that are used to clarify the

type of advertisement or labeling submitted; clarifies the intended

audience for the advertisements or promotional labeling (e.g.,

consumers, professionals, news services); and helps ensure that the

submission is complete.

3. Currently, when more than one prescription drug product is

promoted in the promotional labeling or in an advertisement, sponsors

submit specimens of the promotional labeling or advertisement to the

approved application for each product promoted in the promotional

labeling or advertisement. The revised form, provides for sponsors to

submit specimens of multi-product promotional labeling and

advertisements to only two files; to the approved product application

most frequently promoted, and to a company name file. This multi-

product submission should cross-reference the other approved

applications. The agency anticipates that the proposed revised form and

revised submission will save sponsors time and money by eliminating the

need for making multiple submissions and for maintaining dual

inventories of both forms and multiple processing capabilities.

Under Executive Order 12866, FDA published a notice in the Federal

Register of October 24, 1997 (62 FR 55408 through 55409), that

announced an opportunity for public comment on a proposed revision of

Form FDA 2253. Based on the five responses to FDA's proposal to

streamline the submission of promotional labeling and advertisements

via Form FDA 2253, none of the respondents objected to the agency

revising the form, and two respondents had very favorable comments

regarding the initiative to revise the form and streamline the

submission process for multiple product submissions.

One respondent stated that it was unclear whose burden had been

measured for the estimate and stated that information about methodology

and assumptions was insufficient for it to comment. The agency noted in

the October 24, 1997, notice that its estimate was based on contacts

with industry representatives. The agency's estimate of 2 hours per

response, including time for reviewing instructions, searching existing

data sources, gathering and maintaining the data needed, and completing

and reviewing the collection of information, was obtained from an

informal survey of current respondents who were asked how long it took

them to prepare and submit data and materials intended to accompany

Form FDA 2253. The comment did not provide an alternative estimate for

the proposed burden hours. The agency's estimate, thus, will remain the

same. No other comment provided an alternative estimate.

Several respondents commented on the physical layout of the form

and suggested that some parts of the form be made larger or smaller.

The agency agrees with some of these suggestions and will modify the

layout of the form. In the section of the form that describes various

submitted promotional items, some respondents suggested different

descriptions for types of promotional materials (such as replace the

proposed term ``profession journal ad'' with ``profession print

advertisements''), and suggested combining various similar types of

materials with the addition and deletion of specific promotional items.

The agency agrees that the consolidation of material types will make

the form easier to understand and plans to make these modifications.

Two respondents questioned whether it was necessary to identify the

submission preparer, and whether it was necessary for the ``responsible

official'' to actually sign the form. The agency agrees that it is not

necessary to know who prepared the submission, because agency inquiries

will be directed to the ``responsible official'' (contact person)

either by telephone or by written correspondence. The agency considers

that it would be helpful to have the ``responsible official'' sign the

form to assure that the actual submission was seen or reviewed by the

contact person.

One respondent commented on whether the revised Form FDA 2253

should accompany draft promotional materials intended for CBER for

promoting a biologic. The respondent suggested that the revised form

created an artificial distinction between drugs and biologics by

requiring that draft biologic promotional materials submitted for

voluntary preclearance continue to be accompanied by a form (now Form

FDA 2253 in place of Form FDA 2567) because CDER does not use a form to

accompany draft promotional materials. Thus, the respondent considered

use of the form to be unnecessary for voluntary submissions.

CBER notes that some sponsors have submitted proposed promotional

materials to CBER for comment without the Form FDA 2567, and that this

has been, and continues to be, an acceptable method of submitting draft

promotional materials. However, from past experience, CBER considers

that the use of the Form FDA 2567 to accompany draft promotional

materials makes tracking and followup of the materials more efficient

and more timely. For example, the form provides a quick and efficient

way of providing comments to sponsors without the need for a formal

letter which would require more time. CBER also wants to emphasize that

the option of using Form FDA 2253 or 2567 to accompany draft

promotional materials to CBER does in no way mandate or obligate drug

sponsors to use a form when submitting proposed promotional materials

to CDER for comment.

Another respondent asked for clarification regarding the biologic

license application (BLA) number referenced in number 3. The respondent

stated that the form provided for the sponsor to identify the BLA

number for biologics, but that the BLA number for the original

application becomes obsolete upon approval. Later supplements are

assigned new BLA numbers, and a sponsor can have multiple submissions

under review at the same time, each with a different number. Therefore,

the respondent requested clarification of which number would be

appropriate to list in number 3. The agency agrees that further

clarification of number 3 is required. We believe the least confusing

and most efficient way to reference the BLA number would be for

sponsors to include the ``most recent reference number'' for an

application concerning a labeling change.

Four of the five respondents requested further explanation

regarding the multiple submissions procedures. The agency will clearly

explain the procedures regarding multiple submissions on the form, and

how to submit multiple drug product promotional materials.

Additionally, one respondent asked whether the ``company named file''

will be releasable under the Freedom of Information Act (FOIA).

Currently, CDER's Division of Drug Marketing, Advertising, and

Communications (DDMAC) maintains two types of files related to

promotional materials. One file contains promotional materials

submitted under the postmarketing requirements of Sec. 314.81. These

promotional materials have been submitted to the agency because they

were already publicly disseminated. The agency would consider this

information releasable under FOIA. The ``company named file'' for

multiple submissions of Form FDA 2253-related materials would be this

type of file. The other types of materials maintained by DDMAC are

related to: (1) Advisory opinions (generally on proposed promotional

materials) which are not

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releasable, and (2) enforcement actions which are releasable.

Three respondents were not clear whether approved product labeling

was still required to accompany promotional materials, and one

respondent proposed an alternative method of submitting labeling. The

agency presently requests that sponsors submit two copies of the

approved product labeling for each referenced drug product. This has

been clarified on the form. Alternative methods of submitting approved

product labeling may be considered at a later time.

Three respondents proposed that the agency provide the revised Form

FDA 2253 in electronic form, and accept some promotional materials via

electronic means. The agency currently provides many forms on the

Internet using the World Wide Web (WWW) at ``http://www.fda.gov/opacom/

morechoices/fdaforms/fdaforms.html'' and intends to add the revised

Form FDA 2253 shortly after it is an approved form. As for the

submission of promotional materials by electronic means, DDMAC is

currently reviewing a pilot project where proposed promotional

materials are submitted for review via CD-ROM and in hard copy. If

successful, DDMAC plans to continue the pilot project and refine the

means of submitting promotional materials by electronic means.

FDA estimates the burden of this collection of information as

follows:

Table 1.--Estimated Annual Reporting Burden1

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Total

Form No. of Total Annual Hours per Estimated

Respondents Responses Response Hours

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FDA 2253 612 12,379 2 24,758

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\1\ There are no capital costs or operating and maintenance costs

associated with this collection of information.

In fiscal year 1995, CDER received 10,879 submissions of

advertising and promotional labeling under Form FDA 2253 from an

estimated 512 manufacturers. In the same period of time, CBER received

1, 034 submissions from 57 manufacturers that could have made use of

revised Form FDA 2253. Prior to October 7, 1997, the submission of

advertising and promotional labeling to CBER using Form FDA 2567 was a

voluntary procedure. Under Sec. 601.12(f)(4) (62 FR 39890),

manufacturers of licensed biological products are required to submit

specimens of advertising and promotional labeling to FDA in accordance

with Sec. 314.81(b)(3)(i), FDA estimates that under the new regulation

CBER will receive over 1,500 submissions from approximately 100

manufacturers that may use the revised Form FDA 2253. Thus, FDA

estimates that there may be 12,379 submissions of advertising and

promotional labeling to FDA under revised Form FDA 2253. Based on

contacts with industry representatives, FDA estimates that 2 hours

would be required for an industry regulatory affairs specialist to fill

out the proposed form, collate the documentation, and send the

submission to CDER or CBER. Manufacturers of biological products may

use the revised Form FDA 2253 or may continue to use Form FDA 2567 for

the submission of advertisements and promotional labeling to CBER.

Dated: June 2, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-15192 Filed 6-8-98; 8:45 am]

BILLING CODE 4160-01-F