3750 Federal Register / Vol. 63, No. 16 / Monday, January 26, 1998 / Notices

The potential environmental impact

of this action is being reviewed. To

encourage public participation

consistent with regulations promulgated

under the National Environmental

Policy Act (40 CFR 1501.4(b)), the

agency is placing the environmental

assessment submitted with the petition

that is the subject of this notice on

public display at the Dockets

Management Branch (address above) for

public review and comment. Interested

persons may, on or before February 25,

1998, submit to the Dockets

Management Branch (address above)

written comments. Two copies of any

comments are to be submitted, except

that individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

above between 9 a.m. and 4 p.m.,

Monday through Friday. FDA will also

place on public display any

amendments to, or comments on, the

petitioner’s environmental assessment

without further announcement in the

Federal Register. If, based on its review,

the agency finds that an environmental

impact statement is not required and

this petition results in a regulation, the

notice of availability of the agency’s

finding of no significant impact and the

evidence supporting that finding will be

published with the regulation in the

Federal Register in accordance with 21

CFR 25.40(c).

Dated: January 7, 1998.

Laura M. Tarantino,

Acting Director, Office of Premarket

Approval, Center for Food Safety and Applied

Nutrition.

[FR Doc. 98–1663 Filed 1–23–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0528]

Draft ‘‘Guidance for Industry: Efficacy

Studies to Support Marketing of Fibrin

Sealant Products Manufactured for

Commercial Use’’

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft document entitled

‘‘Guidance for Industry: Efficacy Studies

to Support Marketing of Fibrin Sealant

Products Manufactured for Commercial

Use.’’ After reviewing recent experience

with fibrin sealant products in clinical

studies conducted under Investigational

New Drug (IND) regulations, the agency

is proposing to accept applications for

licensure of fibrin sealant products

based on evidence from pivotal studies

in which the primary endpoint is

hemostasis effectiveness. As in the past,

other endpoints such as wound healing

or tissue sealing may serve as primary

endpoints for pivotal studies, depending

on the nature of the indications sought.

This draft document will provide

guidance to manufacturers of fibrin

sealant products for the design of

clinical trials intended to support

licensure.

DATES: Written comments may be

submitted at any time, however,

comments should be submitted by April

27, 1998, to ensure their adequate

consideration in preparation of the final

document.

ADDRESSES: Submit written requests for

single copies of the draft guidance

document ‘‘Guidance for Industry:

Efficacy Studies to Support Marketing of

Fibrin Sealant Products Manufactured

for Commercial Use’’ to the Office of

Communication, Training, and

Manufacturers Assistance (HFM–40),

Center for Biologics Evaluation and

Research (CBER), Food and Drug

Administration, 1401 Rockville Pike,

Rockville, MD 20852–1448. Send one

self-addressed adhesive label to assist

that office in processing your requests.

The draft guidance document may also

be obtained by mail by calling the CBER

Voice Information System at 1–800–

835–4709 or 301–827–1800, or by fax by

calling the FAX Information System at

1–888–CBER–FAX or 301–827–3844.

Submit written comments on the draft

guidance document to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857.

FOR FURTHER INFORMATION CONTACT:

Paula S. McKeever, Center for Biologics

Evaluation and Research (HFM–17),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–827–6210.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of

a draft document entitled ‘‘Efficacy

Studies to Support Marketing of Fibrin

Sealant Products Manufactured for

Commercial Use.’’ This draft guidance

document represents the agency’s

current thinking with regard to

information on the efficacy studies to

support marketing of licensure of fibrin

sealant products manufactured for

commercial use. It does not create or

confer any rights for or on any person

and does not operate to bind FDA or the

public. An alternative approach may be

used if such approach satisfies the

requirements of the applicable statute,

regulations, or both. As with other

guidance documents, FDA does not

intend this draft document to be allinclusive and cautions that not all

information may be applicable to all

situations. The draft guidance document

is intended to provide information and

does not set forth requirements.

II. Comments

This draft document is being

distributed for comment purposes only,

and is not intended for implementation

as general guidance at this time.

Interested persons may submit to the

Dockets Management Branch (address

above) written comments on the draft

guidance document. Written comments

may be submitted at any time, however,

comments should be submitted by April

27, 1998, to ensure adequate

consideration in preparation of the final

document. Two copies of any comment

are to be submitted, except individuals

may submit one copy. Comments and

request for copies should be identified

with the docket number found in the

brackets in the heading of this

document. A copy of the draft guidance

document and received comments are

available for public examination in the

Dockets Management Branch between 9

a.m. and 4 p.m., Monday through

Friday.

III. Electronic Access

Persons with access to the internet

may obtain the draft document using the

World Wide Web (WWW). For WWW

access connect to CBER at ‘‘http://

www.fda.gov/cber/guidelines.htm’’.

Dated: January 13, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

The text of the draft guidance is set

forth below:

BILLING CODE 4160–01–F
Federal Register / Vol. 63, No. 16 / Monday, January 26, 1998 / Notices 3751

BILLING CODE 4160–01–C
3752 Federal Register / Vol. 63, No. 16 / Monday, January 26, 1998 / Notices

1This draft guidance document represents the

FDA’s current thinking on efficacy studies to

support marketing of fibrin sealant products

manufactured for commercial use. It does not create

or confer any rights for or on any person and does

not operate to bind FDA or the public. An

alternative approach may be used if such approach

satisfies the requirements fo the applicable statute,

regulations, or both. For additional copies of this

guidance, contact the Office of Communication,

Training and Manufacturers Assistance, HFM–40,

Center for Biologics Evaluation and Research, Food

and Drug Administration, 1401 Rockville Pike,

Rockville, MD 20852-1448. Send one self-addressed

adhesive label to assist that office in processing

your requests. The document may also be obtained

by mail by calling the CBER Voice Information

System at 1–800–835–4709 or 301–827–1800, or by

fax by calling the FAX Information System at 1–

888–CBER–FAX or 301–827–3844. Persons with

access to the INTERNET may obtain the document

using the World Wide Web (WWW) by connecting

to CBER at ‘‘http//www.fda.gov/cber/

guidelines.htm’’.

Draft-Not for Implementation

Guidance for Industry 1: Efficacy Studies to

Support Marketing of Fibrin Sealant

Products Manufactured for Commercial Use

I. Introduction

This document pertains to commerciallyproduced fibrin sealants composed of

purified, virus-inactivated/removed human

fibrinogen and human or bovine thrombin,

with or without added components such as

virus-inactivated/removed human factor XIII

and/or aprotinin. Such products are currently

available in Europe and Canada as

hemostasis agents. Although manufacturers

and clinicians in the United States have been

actively engaged in the development and

testing of fibrin sealants, no fibrin sealant

product has been licensed in this country.

This document outlines the agency’s current

position with regard to clinical data used to

support licensure of safe and effective

commercially-produced fibrin sealants in the

United States.

II. Background

As early as 1909, surgeons were reporting

the hemostatic properties of fibrin powder

used in the operative field. In the 1940s,

combinations of fibrinogen and thrombin

were first utilized. The development of Cohn

fractionation in the 1940s, and a method for

cryoprecipitation of fibrinogen in the 1960s,

led to the development of fibrin sealants in

the 1970s. However, fibrinogen concentrates

were found to transmit hepatitis and thus all

U.S. licenses for Fibrinogen (Human) were

revoked on December 7, 1977. Since that

time, a number of manufacturers have been

evaluating a new generation of virusinactivated/removed fibrin sealants.

In 1994, the FDA co-sponsored a

conference on the characteristics and clinical

uses of fibrin sealants, held at the Uniformed

Services University of the Health Sciences,

Bethesda, Maryland (summarized in

Transfusion 35:783–790, 1995). A number of

academic investigators presented data from

clinical trials in which fibrin sealants either

reduced blood loss or reduced the time to

achieve hemostasis. However, based on the

available data, FDA representatives were of

the opinion that a direct clinical benefit to

patients treated with fibrin sealant should be

demonstrated in a well-controlled clinical

trial to support product licensure for a

narrow indication.

Despite FDA’s requests for well-controlled

trials with patient outcomes as endpoints,

many clinicians have been reluctant to

conduct placebo-controlled trials in settings

where they view the standard of care to be

the use of fibrin sealant prepared on site from

commercial bovine thrombin and various

sources of fibrinogen. These clinicians

consider the use of locally-prepared fibrin

sealant to be of such benefit in controlling

bleeding in confined or nearly inaccessible

areas that a placebo-controlled trial would

put the control patients at significant and

unnecessary risk. However, locally-prepared

fibrin sealants are not standardized or

consistent, and the available sources of

fibrinogen are not treated to inactivate or

remove viruses.

III. Guidance

Based on clinical trial experience since

1994, FDA’s Center for Biologics Evaluation

and Research (CBER) proposes to consider,

for licensure of commercially-produced

fibrin sealants, data from pivotal studies in

which the primary endpoint is hemostasis

effectiveness. This review standard is similar

to that used by the Center for Devices and

Radiological Health, in clearing a number of

commercial medical devices on the basis of

clinical studies in which the primary

endpoint was control of hemostasis within a

specific time in a variety of clinical settings.

CBER proposes that time to hemostasis could

also serve as a primary endpoint for pivotal

studies of fibrin sealants.

As in the past, CBER also encourages

manufacturers to conduct well-controlled

clinical trials using a variety of other

endpoints, including blood loss, transfusion

requirements, tissue sealing, and wound

healing. Endpoints for such trials will be

reviewed on a case-by-case basis.

Manufacturers who demonstrate the safety

and efficacy of their fibrin sealant

preparations for specific indications may,

upon FDA licensure, label and promote their

products for these indications. FDA licensure

for a given indication will denote that the

specific formulation of fibrin sealant is safe

and effective for that specific indication.

For fibrin sealant products containing

multiple biologic components, the

contribution of each component may be

demonstrated in a non-clinical setting

appropriate to the indication(s) sought,

although the overall efficacy of multiplecomponent fibrin sealant products should be

demonstrated in clinical trials. Proposals to

utilize in vitro and/or animal studies to

support the inclusion of multiple biologic

components into a fibrin sealant product

should be discussed with CBER.

The following points are proposed for

review of pivotal clinical trials of fibrin

sealant products:

1) Fibrin sealant products should be tested in

settings and under conditions where they

would normally be expected to be used in

clinical practice.

2) Fibrin sealant products may be tested

against a placebo, a cleared hemostatic

device, or other control, as appropriate.

3) Efficacy of fibrin sealant products may be

tested by using either hemostasis endpoints

or other measures of clinical benefit,

depending on the indications sought.

IV. Comments

The agency will review all submitted

comments and consider them in the

preparation of any final guidance document.

Two copies of any comment should be

submitted, except that individuals may

submit one copy. Comments are to be

identified with the docket number found in

brackets in the heading of this document.

Comments received are available for public

examination in the Dockets Management

Branch (address above) between 9 a.m. and

4 p.m., Monday through Friday.

[FR Doc. 98–1664 Filed 1–23–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Health Care Financing Administration

HCFA–2005-NC

RIN 0938–AI39

Medicaid Program; State Allotments

for Payment of Medicare Part B

Premiums for Qualifying Individuals:

Federal Fiscal Year 1998

AGENCY: Health Care Financing

Administration (HCFA), HHS.

ACTION: Notice with Comment Period.

SUMMARY: Section 4732 of the Balanced

Budget Act of 1997 (Public Law 105–33)

amended the Social Security Act to

provide for two additional eligibility

groups of low-income Medicare

beneficiaries for whom Medicaid

payment can be made for Medicare Part

B premiums during the period

beginning January 1998 and ending

December 2002. This notice announces

the Federal fiscal year 1998 State

allotments that are available to pay

Medicare Part B premiums for these two

new eligibility groups and describes the

methodology used to determine each

State’s allotment.

DATES: Effective Date: This is a major

rule under 5 U.S.C. section 804(2). As

indicated in the preamble of this notice,

pursuant to section 5 U.S.C. section

553(b)(B), for good cause we find that

prior notice and comment procedures

are unnecessary and impracticable.

Pursuant to 5 U.S.C. section 808(2), this

notice is effective January 1, 1998, for