Federal Register / Vol. 66, No. 98 / Monday, May 21, 2001 / Notices 27983

appendices for each of the copies,

should be delivered to Cynthia M. Polit

(address above). The application receipt

date is July 5, 2001. If the receipt date

falls on a weekend, or if the date falls

on a holiday, the date of submission

will be extended to the following

workday. No supplemental or

addendum material will be accepted

after the receipt date.

The outside of the mailing package

and item 2 of the application face page

should be labeled ‘‘Response to RFA–

FDA–ORA–01–Project I’’ or ‘‘RFA–

FDA–ORA–01–Project II.’’ Submit only

one project application (an original and

two copies) per package.

VII. Method of Application

A. Submission Instructions

Each application must be submitted

under separate cover. Do NOT submit

more than one application (with copies)

per envelope. Applications will be

accepted during working hours, 8 a.m.

to 4:30 p.m., Monday through Friday, on

or before the established receipt date.

Applications will be considered

received on time if sent or mailed on or

before the receipt date as evidenced by

a legible U.S. Postal Service dated

postmark or a legible date receipt from

a commercial carrier, unless they arrive

too late for orderly processing. Private

metered postmarks shall not be

acceptable as proof of timely mailing.

Applications not received on time will

not be considered for review and will be

returned to the applicant. Applicants

should note that the U.S. Postal Service

does not uniformly provide dated

postmarks. Before relying on this

method, applicants should check with

their local post office.

Do not send applications to the Center

for Scientific Research, National

Institutes of Health (NIH). Any

application that is sent to NIH, that is

then forwarded to FDA and not received

in time for orderly processing, will be

deemed unresponsive and returned to

the applicant. Instructions for

completing the application are included

in form PHS–5161–1. FDA is unable to

receive applications via Internet.

B. Format for Application

Submission of the application must be

on grant application form PHS 5161–1

(revised 7/00). All instructions for the

enclosed Standard Form 424 (SF–424)

should be followed using the

nonconstruction application pages.

The face page of the application

should indicate ‘‘RFA–FDA–ORA–01–

Project I,’’ or ‘‘RFA–FDA–ORA–01–

Project II.’’

Data included in the application, if

restricted with the legend specified

below, may be entitled to confidential

treatment as trade secret or confidential

commercial information within the

meaning of the Freedom of Information

Act (FOIA) (5 U.S.C. 552(b)(4)) and

FDA’s implementing regulations (21

CFR 20.61).

Information collection requirements

requested on PHS Form 5161–1 were

approved and issued under Office of

Management and Budget Circular A–

102.

C. Legend

Unless disclosure is required by FOIA

as amended (5 U.S.C. 552), as

determined by the freedom of

information officials of DHHS or by a

court, data contained in the portions of

this application which have been

specifically identified by page number,

paragraph, etc., by the applicant as

containing restricted and/or proprietary

information shall not be used or

disclosed except for evaluation

purposes.

Dated: May 15, 2001.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 01–12626 Filed 5–18–01; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 01N–0103]

Issues Associated With the

Intersection of 180-Day Generic Drug

Exclusivity and Pediatric Exclusivity;

Request for Comments

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice; request for comments.

SUMMARY: The Food and Drug

Administration (FDA) is establishing the

public docket identified in brackets in

the heading of this document to receive

comments related to the interpretation

of provisions of the Federal Food, Drug,

and Cosmetic Act (the act) and

regulations governing the intersection of

180-day generic drug exclusivity and

pediatric exclusivity. To date, there has

not been a situation where pediatric

exclusivity and 180-day generic

exclusivity have actually overlapped.

However, FDA has received a large

number of inquiries about its

interpretation of these provisions and,

therefore, is establishing this docket to

give the public an opportunity to

comment on these issues.

DATES: Submit written or electronic

comments by June 20, 2001.

ADDRESSES: Submit electronic

comments to http://www.fda.gov/

ohrms/dockets/default.htm. Submit

written comments to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 5630 Fishers

Lane, rm. 1061, Rockville, MD 20852.

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.

FOR FURTHER INFORMATION CONTACT: Rose

Cunningham, Center for Drug

Evaluation and Research (HFD–6), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

5468, FAX 301–594–5493.

SUPPLEMENTARY INFORMATION:

I. Background

Recently FDA has been asked to

evaluate the intersection of 180-day

generic drug exclusivity and pediatric

exclusivity, specifically with respect to

whether the exclusivity periods should

run concurrently or consecutively. FDA

has received written correspondence

and telephone inquiries from

pharmaceutical firms, organizations,

individuals, and members of Congress

concerning FDA’s interpretation of these

provisions. FDA is seeking broader

public comment on the intersection of

these two statutory provisions.

The 180-day generic drug exclusivity

provision was created by the 1984 Drug

Price Competition and Patent Term

Restoration Act (also known as the

Hatch-Waxman Amendments), enacted

on September 24, 1984. This provision,

contained in section 505(j)(5)(B)(iv) of

the act (21 U.S.C. 355(j)(5)(B)(iv)),

provides an incentive for generic drug

applicants to challenge innovator patent

claims and thereby speed the entry of

generic competition onto the market.

This benefit is available to the first

abbreviated new drug application

(ANDA) received that is a substantially

complete application that contains a

‘‘paragraph IV’’ certification. This type

of certification states the ANDA

applicant’s belief that a patent listed for

the innovator drug is invalid or

unenforceable or that the ANDA

product seeking approval will not

infringe a listed patent. Under the terms

of the statute, 180-day generic drug

exclusivity is triggered by and begins to

run from either: (1) A court decision

finding the challenged patent invalid,

unenforceable, or not infringed; or (2)

the date of first commercial marketing of

the ANDA drug product, whichever is

earlier. During the 180-day generic drug

exclusivity period, FDA is prohibited

27984 Federal Register / Vol. 66, No. 98 / Monday, May 21, 2001 / Notices

from approving a subsequently filed

ANDA containing a paragraph IV

certification.

Pediatric exclusivity was created by

the passage of the Food and Drug

Administration Modernization Act,

enacted on November 21, 1997. This

provision, contained in section 505A of

the act, provides an incentive for

innovator companies to perform and

submit to the agency pediatric studies

that may produce health benefits in the

pediatric population. This benefit is

available to a new drug application

holder for the submission of pediatric

studies in response to a written request

issued by the agency. Pediatric

exclusivity extends for 6 months

existing patent and/or exclusivity

protection on the innovator drug and

begins to run on the date the existing

patent and/or exclusivity protection on

the innovator drug would otherwise

expire. ANDAs referencing the

innovator drug may not be approved

during the pediatric exclusivity period.

FDA seeks public comment on

whether pediatric exclusivity runs

concurrently or consecutively with 180-

day generic drug exclusivity when a

favorable court decision in a paragraph

IV patent challenge lawsuit is issued

less than 180 days before the beginning

of or during the pediatric exclusivity

period.

II. Request for Comments

Interested persons may submit to the

Dockets Management Branch (address

above) written comments by June 20,

2001. 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 Dockets Management Branch

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

through Friday.

Dated: May 14, 2001.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 01–12615 Filed 5–15–01; 4:12 pm]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 01N–0197]

Clinical Development Programs for

Drugs, Biological Products, and

Devices for the Treatment of

Ankylosing Spondylitis (AS) and

Related Disorders; Request for

Assistance

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is requesting

assistance in developing guidance for

industry on issues related to drugs,

biological products, and devices for the

treatment of AS and related disorders.

Once finalized, the guidance would aid

sponsors and others interested in

developing new agents to treat AS and

related disorders.

Before the agency can develop such

guidance, a critical appraisal of certain

fundamentals of the science related to

AS is needed. FDA is interested

specifically in identifying a party, or

parties, willing to take the lead in

coordinating this critical appraisal.

DATES: Submit written comments on

this notice by July 20, 2001.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Mary Jane Walling, Center for Drug

Evaluation and Research (HFD–105),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–2268.

SUPPLEMENTARY INFORMATION: Because of

the positive response to the agency’s

guidance on rheumatoid arthritis, the

agency has recognized the need for more

information on the development of

drugs, biological products, and devices

for the treatment of AS and related

disorders. FDA intends to put the

information received in response to this

notice in a public docket so that

interested parties can learn of each other

and coordinate these activities.

Specifically, the agency is interested

in identifying an interested group or

consortium of interested groups from

academia, industry, practitioners, and

patients and their representatives

willing to take the lead in a critical

appraisal of certain fundamentals of the

science related to AS. Initially, the

parties may want to organize a public

meeting to discuss relevant questions (a

number of which are noted below). The

agency hopes this meeting will lead to

conceptual advances now not present

and their expression in a series of

concept papers. Subsequent workshops

would then be able to fully discuss

these concept papers, soliciting

feedback from all quarters including

regulators from the United States and

elsewhere. Emphasis should be on

debating the rationale for various

approaches to key issues. The agency

welcomes other suggestions of activities

that could be undertaken as part of this

guidance development effort.

To provide a starting point for

discussion, the agency has developed a

list of some key concepts that the

interested parties may want to consider

at the meeting:

1. Scope: Should the guidance discuss

AS alone, or a broader

spondyloarthropathy rubric? What

about the clinical subgroups and

pediatric expressions of the disorder(s)?

2. Claims: What type of claims

structure is optimal to encompass the

types of clinical benefit a therapeutic

product might have on patients with

AS? What type of evidence would be

needed to support each proposed claim?

3. Measures of disease activity: Are

currently available instruments for

measuring disease activity adequate or

are new measures required? Which

disease activity should be measured in

clinical trials in AS, and on what basis:

(1) A consensus approach, which aims

for agreement (clinicians, patients, and

others) based on a blend of an observerdriven approach and performance

characteristics; (2) a decision based on

the comparative statistical

characteristics of each measurement

using concepts such as random

measurement error; or (3) a fully datadriven approach where each

measurement is tested in a standard

venue to assess its predictive capacity.

4. Overall trial design: Are

longitudinal comparison of means

optimal? Because longer trials inevitably

have substantial dropouts, would a

survival analysis be more appropriate?

5. Intrinsic trial design: Which

measures should be included in the

primary analysis of the clinical trial to

assess whether the therapeutic product

is associated with a clinical benefit? Do

all measures need equal-weight in the

primary analysis? Can they be unequally

weighted? Is the use of composites

justified? Are outcomes of secondary

endpoints essential for determining the

success of the trial?

Interested persons should submit to

the Dockets Management Branch

(address above) comments and