Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices 27093

1See U.S. Congress, Senate Committee on Labor

and Human Resources, ‘‘Food and Drug

Administration Modernization Act of 1997,’’ S.

Rept. 105–43 on S. 830, pp. 41–42, 105th Cong., 1st

sess., 1 July 1997; and House Committee on

Commerce, ‘‘Prescription Drug User Fee

Authorization and Drug Regulation Act of 1997,’’ H.

Rept. 105–310 on H.R. 1411, pp. 63–64, 105th

Cong., 1st sess., 7 October 1997.

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857. Comments are to

be identified with the docket number

found in brackets in the heading of this

document. After the comment period,

comments may be submitted to one of

the centers at the addresses below.

FOR FURTHER INFORMATION CONTACT:

Joseph P. Griffin, Center for Drug

Evaluation and Research (HFD–7),

Food and Drug Administration,

5600 Fishers Lane, Rockville, MD

20857, 301–594–2041, or

Robert A. Yetter, Center for Biologics

Evaluation and Research (HFM–10),

Food and Drug Administration,

1401 Rockville Pike, Rockville, MD

20852–1448, 301–827–0373.

SUPPLEMENTARY INFORMATION: Section

403(a) of the Modernization Act requires

that FDA publish in the Federal

Register standards for the ‘‘prompt

review of supplemental applications

submitted for approved articles * * *.’’

The legislative history indicates that

this provision was directed at certain

types of efficacy supplements, i.e.,

supplemental applications proposing to

add a new use of an approved drug to

the product labeling.1 Section 403(b)(3)

of the Modernization Act requires that

FDA provide guidance to define

supplemental applications that are

eligible for priority review. This

guidance document fulfills both

Modernization Act requirements.

Section 101 of the Modernization Act

reauthorized for an additional 5 years,

with certain technical changes, the user

fee program described in the

Prescription Drug User Fee Act of 1992.

Section 101 of the Modernization Act

directed that the user fees authorized by

the amendments in that subtitle be

dedicated toward expediting the drug

development process and the review of

human drug applications as set forth in

the performance goals identified in

letters from the Secretary of Health and

Human Services to the chairman of the

Committee on Commerce of the House

of Representatives and the chairman of

the Committee on Labor and Human

Resources of the Senate, as set forth in

the Congressional Record. The

referenced performance goals include

standards for the review of efficacy

supplements and distinguish between

priority and standard supplements. The

guidance also defines ‘‘priority’’ for

purposes of applying the performance

goals.

The guidance document is being

issued as a Level 1 guidance consistent

with FDA’s good guidance practices (62

FR 8961, February 27, 1997). It is being

implemented without prior public

comment because the guidance is

needed to implement the Modernization

Act. However, the agency wishes to

solicit comment from the public and is

providing a 90-day comment period and

establishing a docket for the receipt of

comments.

This guidance document represents

the agency’s current thinking on the

standards for the prompt review of

efficacy supplements. 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.

Interested persons may, at any time,

submit written comments on the

guidance document to the Dockets

Management Branch (address above).

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. The guidance document and

received comments are available for

public examination in the office above

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

through Friday.

Dated: May 8, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–12900 Filed 5–14–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0100]

Guidance for Industry on Providing

Clinical Evidence of Effectiveness for

Human Drugs and Biological Products;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a guidance for industry

entitled ‘‘Providing Clinical Evidence of

Effectiveness for Human Drug and

Biological Products.’’ The purpose of

this guidance is to clarify what clinical

evidence of effectiveness should be

provided in new drug applications,

biological product license applications,

and supplemental applications for new

uses of drugs and biologics. The

guidance is also intended to fulfill the

requirements of certain provisions of the

Food and Drug Administration

Modernization Act of 1997 (the

Modernization Act).

DATES: General comments on agency

guidance documents are welcome at any

time.

ADDRESSES: An electronic version of this

guidance is available via the Internet at

http://www.fda.gov/cder/guidance/

index.htm and at http://www.fda.gov/

cber/guidelines.htm. Submit written

comments on this guidance to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857. Comments are to

be identified with the docket number

found in brackets in the heading of this

document.

FOR FURTHER INFORMATION CONTACT:

Joseph P. Griffin, Center for Drug

Evaluation and Research (HFD–5), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

5400.

SUPPLEMENTARY INFORMATION: The draft

guidance for industry entitled

‘‘Providing Clinical Evidence of

Effectiveness for Human Drug and

Biological Products’’ (the draft

guidance) was initially developed as

part of an effort to get more information

about valid uses of marketed drugs into

the labeling of these drugs. Uncertainty

on the part of the industry about the

evidentiary requirements for

demonstrating effectiveness for a

supplemental indication was believed to

be an obstacle to sponsors submitting

applications for supplemental

indications. The draft guidance was

intended to clarify the amount and

types of evidence that could be used to

demonstrate effectiveness and thereby

facilitate submission of additional

supplemental applications. In the

Federal Register of March 21, 1997 (62

FR 13650), FDA announced the

availability of the draft guidance. The

notice gave interested persons an

opportunity to submit comments by

May 20, 1997.

On November 21, 1997, the President

signed the Modernization Act (Pub. L.

105–115), which addressed both the

standards for providing clinical

evidence of effectiveness and the

evidentiary requirements for

supplemental applications. Section 115

of the Modernization Act amended the

definition of substantial evidence in

section 505(d) of the Federal Food,
27094 Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices

Drug, and Cosmetic Act (the act) (21

U.S.C. 355(d)) to clarify that FDA, at its

discretion, may make exception to the

general requirement that there must be

more than one adequate and wellcontrolled investigation to support an

effectiveness determination. Section 115

of the Modernization Act provides in

relevant part that ‘‘[i]f the [agency]

determines, based on relevant science,

that data from one adequate and wellcontrolled clinical investigation and

confirmatory evidence (obtained prior to

or after such investigation) are sufficient

to establish effectiveness, the [agency]

may consider such data and evidence to

constitute substantial evidence [of

effectiveness].’’

In clarifying the standard for

substantial evidence, Congress

acknowledged the agency’s position that

there have been major advances in the

science and practice of clinical drug

development since the effectiveness

requirement was added to the act in

1962, and confirmed FDA’s

interpretation of the substantial

evidence of effectiveness standard, as

explained in the draft guidance

document.

In addition to the provision on the

evidence standard, the Modernization

Act included section 403, ‘‘Approval of

Supplemental Applications for

Approved Products.’’ Section 403(a) of

the Modernization Act requires FDA to

publish in the Federal Register, within

180 days of enactment, standards for the

prompt review of supplemental

applications for drugs and biological

products. These standards are included

in a guidance document for which a

notice of availability is published

elsewhere in this issue of the Federal

Register.

Section 403(b) of the Modernization

Act requires that FDA, within 180 days

of enactment, issue final guidances to

clarify the requirements for, and

facilitate the submission of data to

support, the approval of supplemental

applications for drugs and biologics.

The guidance issued today fulfills this

statutory requirement as it addresses the

data requirements for both original drug

and biological product applications and

supplements to those applications.

In addition, section 403(b)(1) of the

Modernization Act requires that FDA

provide guidance to ‘‘clarify

circumstances in which published

matter may be the basis for approval of

a supplemental application.’’ Section III

of the guidance describes the

circumstances in which a sponsor may

rely in part, or entirely, on published

reports of studies to support approval of

a supplemental application.

Section 403(b)(2) of the

Modernization Act requires that FDA

provide guidance to ‘‘specify data

requirements that will avoid duplication

of previously submitted data by

recognizing the availability of data

previously submitted in support of an

original application.’’ Section II of the

guidance describes a range of

circumstances in which existing data,

whether or not previously submitted to

an original application, may be used to

support an application for a

supplemental indication, thus

permitting a sponsor to avoid

developing unnecessary additional data.

The agency received 13 submissions

commenting on the draft guidance,

including comments from

pharmaceutical and biological products

companies and their trade associations,

individuals and organizations in

academic medicine and clinical

pharmacology, patient advocacy

organizations, and a consumer. The

response to the draft guidance was

generally favorable. The guidance was

viewed as a significant step forward by

the agency in clarifying and better

articulating its quantitative and

qualitative evidentiary standards for

evidence of effectiveness. Comments

observed that the principles espoused

were scientifically reasonable, practical,

and appropriately flexible. The agency

has considered all of the comments in

making revisions to the guidance

document.

This guidance document is being

issued as a Level 1 guidance consistent

with FDA’s good guidance practices (62

FR 8961, February 27, 1997). It

represents the agency’s current thinking

on clinical evidence of effectiveness for

human drug and biological products. 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.

Submit written requests for single

copies of the guidance for industry

entitled ‘‘Providing Clinical Evidence of

Effectiveness for Human Drug and

Biological Products’’ to the Drug

Information Branch (HFD–210), Center

for Drug Evaluation and Research, Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857; or 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. Please send

one self-addressed adhesive label to

assist the offices in processing your

request. 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 CBER FAX Information

System at 1–888–CBERFAX or 301–

827–3844.

Interested persons may at any time

submit written comments on the

guidance to the Dockets Management

Branch (address above). Requests and

comments should be identified with the

docket number found in brackets in the

heading of this notice. A copy of the

guidance and received comments may

be seen in the office above between 9

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

Friday.

Dated: May 8, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–12901 Filed 5–14–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0214]

Guidance for Industry on

Pharmacokinetics in Patients with

Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a guidance for industry

entitled ‘‘Pharmacokinetics in Patients

with Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling.’’ The guidance is

intended for sponsors planning to

conduct studies to assess the influence

of renal impairment on the

pharmacokinetics of an investigational

drug.

DATES: General comments on agency

guidance documents are welcome at any

time.

ADDRESSES: Copies of this guidance are

available on the Internet at ‘‘http://

www.fda.gov/cder/guidance/

index.htm’’, or ‘‘http://www.fda.gov/

cber/guidelines.htm’’. Submit written

requests for single copies of

‘‘Pharmacokinetics in Patients with

Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling’’ to the Drug

Information Branch (HFD–210), Center

for Drug Evaluation and Research, Food