Federal Register / Vol. 65, No. 208 / Thursday, October 26, 2000 / Notices 64225

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D–1537]

Draft Guidance for Industry on

Referencing Discontinued Labeling for

Listed Drugs in Abbreviated New Drug

Applications; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a draft guidance for

industry entitled ‘‘Referencing

Discontinued Labeling for Listed Drugs

in Abbreviated New Drug

Applications.’’ This document is

intended to provide guidance to

applicants on referencing discontinued

labeling for listed drugs in abbreviated

new drug applications (ANDA’s)

submitted for approval under the

Federal Food, Drug, and Cosmetic Act

(the act). This issue has only recently

arisen and is not addressed directly in

the agency’s regulations governing the

approvals of ANDA’s.

DATES: Submit written comments on the

draft guidance by January 24, 2001.

General comments on agency guidance

documents are welcome at any time.

ADDRESSES: Copies of this draft

guidance for industry are available on

the Internet at http://www.fda.gov/cder/

guidance/index.htm. Submit written

requests for single copies of this draft

guidance to the Drug Information

Branch (HFD–210), Center for Drug

Evaluation and Research, Food and

Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857. Send one

self-addressed adhesive label to assist

that office in processing your requests.

Submit written comments on the draft

guidance to the Dockets Management

Branch (HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Cecelia M. Parise, Center for Drug

Evaluation and Research (HFD–600),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–5845.

SUPPLEMENTARY INFORMATION: The Drug

Price Competition and Patent Term

Restoration Act of 1984 (the HatchWaxman amendments) established the

generic drug approval program used

today to ensure that lower price generic

drugs are made available to the public

promptly upon the expiration of patent

and exclusivity protections covering the

innovator products. The generic drug

approval process generally depends on

the ANDA applicant establishing that

the generic drug is the same as an

approved innovator product (the listed

drug) with respect to active ingredients,

dosage form, strength, route of

administration, conditions of use, and

labeling.

During the period when an innovator

drug is being marketed, it may undergo

a number of changes that are approved

through supplements to new drug

applications (NDA’s). Such changes can

include the addition of new indications,

changes to the product formulation, and

labeling changes. In the past, when

ANDA’s have been submitted, they have

referenced only the innovator drug

product labeling as it appeared at the

time of ANDA submission. However,

recently a question has been raised as to

whether, in certain circumstances, an

ANDA can refer to discontinued

labeling for the listed drug. The issue of

referencing discontinued labeling arises

when the sponsor of the listed drug

product has obtained exclusivity or

patent protection for a new part of

product labeling and has removed a part

of the previous labeling, unprotected by

exclusivity or patents, for reasons other

than safety or effectiveness. When the

holder of the listed drug obtains

approval and market protection for a

change to the drug and removes the

corresponding unprotected information

from the current labeling, there remains

no current labeling for the ANDA

applicant to reference. This raises the

question of whether applicants will be

barred from obtaining approval for any

ANDA referencing that listed drug until

the protection for the particular aspect

of the labeling expires, because relevant

labeling is either protected or has been

removed from the currently marketed

product.

FDA has developed an approach to

this situation that ensures that labeling

removed from a drug product for

reasons of safety or effectiveness cannot

be referenced in an ANDA, while at the

same time permitting approval of

generic drugs that reference

discontinued labeling for safe and

effective innovator products. This

approach ensures that safe and effective

generic drug products are made

available to the public as promptly as

possible when relevant market

protections have expired.

An ANDA will be permitted to

reference discontinued labeling for a

listed drug when: (1) The holder of the

NDA for the innovator drug has

obtained approval for a change in the

drug labeling; (2) the change has

received either a patent listed in

‘‘Approved Drug Products with

Therapeutic Equivalence Evaluations’’

(the Orange Book) or market exclusivity

under the act; (3) the NDA sponsor has

removed or revised the labeling

describing the corresponding

unprotected aspects of the drug; (4) the

change to the drug product is not one

for which a suitability petition may be

filed (21 CFR 314.93); (5) the sponsor

wishing to reference the discontinued

labeling has submitted a petition

requesting that the agency determine

whether the previous labeling was

withdrawn for reasons of safety or

effectiveness, or the agency on its own

initiative, begins the process of

determining the reasons for the

withdrawal of the previous labeling; (6)

the agency has determined that the

previous innovator labeling was not

withdrawn for reasons of safety or

effectiveness; and (7) the agency has

determined that omission of the

protected information will not render

the drug product less safe or effective

than the currently marketed innovator

product.

The draft guidance identifies the

provisions of the act and FDA

regulations relevant to this issue, and

provides a detailed description of the

process an ANDA applicant should

follow to refer to discontinued labeling

for a listed drug. It also describes the

actions FDA will take to determine

whether the use of such labeling is

acceptable because the labeling was not

withdrawn from the market for reasons

of safety or effectiveness.

This draft guidance is being issued

consistent with FDA’s good guidance

practices (65 FR 56468, September 19,

2000). The draft guidance represents the

agency’s current thinking on referencing

discontinued labeling for listed drugs in

ANDA’s. 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 statutes

and regulations.

Interested persons may submit to the

Dockets Management Branch (address

above) written comments on the draft

guidance. 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 draft

guidance and received comments are

available for public examination in the

Dockets Management Branch between 9

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

Friday.

64226 Federal Register / Vol. 65, No. 208 / Thursday, October 26, 2000 / Notices

Dated: October 13, 2000.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 00–27452 Filed 10–25–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D–0282]

Revised Guidance for Industry on

Submitting and Reviewing Complete

Responses to Clinical Holds;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a revised guidance for

industry entitled ‘‘Submitting and

Reviewing Complete Responses to

Clinical Holds.’’ This guidance

describes how to submit a complete

response if an investigational new drug

(IND) application is placed on clinical

hold. The revised guidance reflects

amendments to FDA’s clinical hold

regulations, includes the definition of a

commercial IND, and discusses the

agency’s policy on resolving clinical

trial issues that are not related to the

imposition of a clinical hold.

DATES: Comments on agency guidance

documents are welcome at any time.

ADDRESSES: Copies of this guidance for

industry are available on the Internet at

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

index.htm; or http://www.fda.gov/cber/

guidelines.htm. Submit written

comments on this guidance to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

5630 Fishers Lane, rm. 1061, Rockville,

MD 20852. Comments are to be

identified with the docket number

found in brackets in the heading of this

document.

FOR FURTHER INFORMATION CONTACT:

Linda S. Carter (HFD–101), Center for

Drug Evaluation and Research, Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

6578; or Robert A. Yetter (HFM–10),

Center for Biologics Evaluation and

Research, Food and Drug

Administration, 1401 Rockville Pike,

Rockville, MD 20852–1448, 301–827–

0373.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of a revised

guidance for industry entitled

‘‘Submitting and Reviewing Complete

Responses to Clinical Holds.’’ Section

117 of the Food and Drug

Administration Modernization Act of

1997 (Modernization Act), signed into

law by President Clinton on November

21, 1997, provides that a written request

that a clinical hold be removed shall

receive a decision in writing, specifying

the reasons for that decision, within 30

days after receipt of such request.

Section 117(3)(c) of the Modernization

Act is codified in the Federal Food,

Drug, and Cosmetic Act at section

505(i)(3)(c) (21 U.S.C. 355(i)(3)(c)). In

addition, the agency committed to user

fee performance goals incorporating the

same response time. In the Federal

Register of December 14, 1998 (63 FR

68676), FDA amended its clinical hold

regulations in § 312.42(e) (21 CFR

312.42(e)) to include this 30-day

response requirement. This guidance

describes how sponsors should submit

responses to clinical holds so that they

may be identified as complete responses

and the agency can track the time to

response.

In the Federal Register of May 14,

1998 (63 FR 26809), FDA published a

notice announcing the availability of the

original guidance and soliciting

comments. Two comments on the

guidance were submitted to the docket.

After considering the comments, FDA is

issuing a revised guidance.

The revised guidance: (1) Reflects

amendments to FDA’s clinical hold

regulations, stating that FDA will

respond in writing within 30-calendar

days of receipt of a sponsor’s request to

release a clinical hold and complete

response to the issue(s) that led to the

clinical hold (§ 312.42(e)); (2) includes

the definition of a commercial IND and

clarifies that the Prescription Drug User

Fee Act goals apply only to commercial

IND’s, although the 30-calendar day

response applies to all IND clinical hold

complete responses; and (3) states that

clinical trial issues that are not related

to the imposition of a clinical hold may

be discussed in the letter placing the

trial on clinical hold, but will be clearly

marked as nonhold issues and that a

sponsor’s response to such nonhold

issues should be addressed in a separate

amendment to the IND.

The collection of information

contained in the revised guidance has

been approved by the Office of

Management and Budget under OMB

control number 0910–0445.

This revised guidance document

supersedes the original guidance. This

Level 1 guidance document is being

issued consistent with FDA’s good

guidance practices (65 FR 56468,

September 19, 2000). The revised

guidance represents the agency’s current

thinking on the submission of responses

to clinical holds. 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

and regulations.

Interested persons may submit to the

Dockets Management Branch (address

above) written comments on the

guidance at any time. 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

and received comments are available for

public examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

Dated: October 13, 2000.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 00–27453 Filed 10–25–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Health Care Financing Administration

[Document Identifier: HCFA–304 and 304a]

Agency Information Collection

Activities: Proposed Collection;

Comment Request

AGENCY: Health Care Financing

Administration, HHS.

In compliance with the requirement

of section 3506(c)(2)(A) of the

Paperwork Reduction Act of 1995, the

Health Care Financing Administration

(HCFA), Department of Health and

Human Services, is publishing the

following summary of proposed

collections for public comment.

Interested persons are invited to send

comments regarding this burden

estimate or any other aspect of this

collection of information, including any

of the following subjects: (1) The

necessity and utility of the proposed

information collection for the proper

performance of the agency’s functions;

(2) the accuracy of the estimated

burden; (3) ways to enhance the quality,

utility, and clarity of the information to

be collected; and (4) the use of

automated collection techniques or

other forms of information technology to

minimize the information collection

burden.

Type of Information Collection

Request: Extension of a currently

approved collection; Title of

Information Collection: Reconciliation