(Voice Information) 800-835-4709 or 301-827-1800
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Revised, September 1999
Procedural i
TABLE OF CONTENTS
I.
WHY IS FDA ISSUING THIS GUIDANCE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
II.
HOW DOES A NEW DRUG APPLICATION QUALIFY FOR PEDIATRIC
EXCLUSIVITY? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
A.
New Drug Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
B.
Over-the-Counter Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
C.
Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
III.
WHAT ARE PEDIATRIC STUDIES? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
A.
Definition of a Pediatric Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
B.
Submission of Pediatric Study Protocols to an IND . . . . . . . . . . . . . . . . . . . . . . . 3
C. Studies That May Be Used to Qualify for Pediatric Exclusivity . . . . . . . . . . . . . . 4
IV.
WHAT IS AN FDA WRITTEN REQUEST FOR PEDIATRIC STUDIES? . . . . . . . . . . 4
A.
Description of FDA's Written Request . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
B.
Studies Requested by FDA in the Written Request . . . . . . . . . . . . . . . . . . . . . . . . 6
C.
Issuance of FDA's Written Request . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
V. HOW DO I OBTAIN A WRITTEN REQUEST? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
A. Proposed Pediatric Study Requests From Interested Persons . . . . . . . . . . . . . . . . 8
B. FDA Prioritization and Processing of Proposed Pediatric Study Requests . . . . . . 8
C.
Changes to the List of Approved Drugs for Which Additional Pediatric Information
May Produce Health Benefits in the Pediatric Population . . . . . . . . . . . . . . . . . . . 9
VI.
WHAT IS THE CONTENT OF A WRITTEN AGREEMENT FOR THE CONDUCT OF
PEDIATRIC STUDIES? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 0
VII.
WHAT ARE COMMONLY ACCEPTED SCIENTIFIC PRINCIPLES AND
PROTOCOLS? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
VIII. HOW DO I FILE MY REPORTS OF STUDIES WITH FDA? . . . . . . . . . . . . . . . . . . . 11
IX.
WHAT CONSTITUTES ACCEPTANCE OF MY REPORTS OF STUDIES? . . . . . . . 12
A.
Definition of Acceptance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
B. Notification of Acceptance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
X.
IF MY STUDY QUALIFIES FOR PEDIATRIC EXCLUSIVITY, TO WHAT WILL THE
PERIOD OF PEDIATRIC EXCLUSIVITY ATTACH? . . . . . . . . . . . . . . . . . . . . . . . . . 13
A. Pediatric Exclusivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 ii
B. A Second 6-Month Period of Pediatric Exclusivity . . . . . . . . . . . . . . . . . . . . . . . 14
C. Later-filed Applications Containing the Same Active Moiety . . . . . . . . . . . . . . . 15
XI. WHERE DOES FDA PUBLISH INFO ABOUT PEDIATRIC EXCLUSIVITY?. . . . . . 15
A.
Pediatric Exclusivity Determinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
B. Other Pediatric Exclusivity Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
XII.
HOW WILL FDA TREAT INFORMATION SUBMITTED IN SUPPORT OF A
REQUEST FOR PEDIATRIC EXCLUSIVITY? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
XIII. WILL I QUALIFY FOR PEDIATRIC EXCLUSIVITY IF I COMPLETE PEDIATRIC
STUDIES REQUIRED BY 21 CFR 201.23, 314.55, OR 601.27? . . . . . . . . . . . . . . . . . 16
A. Comparison of Scope of Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
B. Qualifying for Pediatric Exclusivity v. Fulfilling the Requirements of the Rule 17
XIV. WHAT HAPPENS AFTER JANUARY 1, 2002? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
ATTACHMENT A - SECTION 111 OF THE MODERNIZATION ACT . . . . . . . . . . . . . . . . . 19 This guidance has been prepared by the Pediatric Implementation Team in the Center for Drug Evaluation
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and Research (CDER) in consultation with the Center for Biologics Evaluation and Research (CBER) at the Food and
Drug Administration. This guidance document represents the Agencys current thinking on the implementation of
Section 111 of the Modernization Act and pediatric exclusivity. 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, regulations, or both.
GUIDANCE FOR INDUSTRY
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Qualifying for Pediatric Exclusivity
Under Section 505A of the
Federal Food, Drug, and Cosmetic Act
I.
WHY IS FDA ISSUING THIS GUIDANCE?
Section 111 of Title I of the Food and Drug Administration Modernization Act of 1997 (the
Modernization Act), signed into law by President Clinton on November 21, 1997, created section
505A of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 355a). Section 505A
permits certain applications to obtain an additional six months of exclusivity if, in accordance with the
requirements of the statute, the sponsor submits requested information relating to the use of the active
moiety in the pediatric population. The text of section 505A is reproduced at Attachment A. The
Food and Drug Administration (FDA) plans to issue regulations through notice and comment
rulemaking to further implement the pediatric exclusivity provisions of the Modernization Act. The
Agency is publishing this updated guidance to assist industry in interpreting section 505A in the interim.
This guidance supersedes the guidance for industry on Qualifying for Pediatric Exclusivity Under
Section 505A of the Federal Food, Drug, and Cosmetic Act that FDA issued in June 1998. FDA
will continue to update the guidance as appropriate. This guidance will remain in effect until superseded
by regulations or new guidance.
This guidance describes how studies may qualify for pediatric exclusivity under section 505A. Topics
covered include (1) whether studies for certain drugs will be requested under section 505A(a) or (c),
(2) the definition of pediatric studies, (3) the content and format of an FDA request for pediatric
studies, (4) how an applicant can obtain an FDA Written Request, (5) the content of a written
agreement for the conduct of pediatric studies, (6) the definition of commonly accepted scientific
principles, (7) the filing of reports of studies, (8) acceptance of studies by FDA, (9) scope and nature of
pediatric exclusivity, (10) publication of exclusivity information, (11) treatment of information submitted
in support of a request for pediatric exclusivity, (12) how pediatric studies required under FDA
regulations may qualify for pediatric exclusivity, and (13) what happens after January 1, 2002, the Consult individual sections of this guidance for additional information on each step.
2
Applications submitted under section 505(b)(1) include full new drug applications (NDAs) and 505(b)(2)
3
applications. A 505(b)(2) application is an NDA submitted under section 505(b)(1) of the Act for which one or more
of the investigations relied upon for approval of the application were not conducted by or for the applicant and for
which the applicant has not obtained a right of reference or use from the person by or for whom the investigations
were conducted.
If a drug is not currently approved for a specific indication, a Written Request to study the use of the drug
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for that indication would issue under section 505A(a) of the Act, which addresses pediatric studies of unapproved
drugs. A drug eligible to receive a Written Request under section 505A(a) would not be included on the list because
it would not be an approved drug for purposes of the list.
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sunset date for the pediatric exclusivity provisions of the Modernization Act.
II.
HOW DOES A NEW DRUG APPLICATION QUALIFY FOR PEDIATRIC
EXCLUSIVITY?
2
A.
New Drug Applications
In general, a 505(b)(1) (21 U.S.C. 355(b)(1)) application will qualify for pediatric exclusivity if all of
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the following have occurred:
1.
The Agency issued a Written Request for pediatric studies:
a.
before the approval of a new drug application (NDA) submitted under section
505(b)(1) (section 505A(a)), or
b.
for an active moiety approved for adults and/or part of the pediatric population for an
approved indication that occurs in the pediatric population and appears on the List of
Approved Drugs for Which Additional Pediatric Information May Produce Health
Benefits in the Pediatric Population (the List) (section 505A(c)). Refer to Docket
98N-0056 for the current list of approved priority and nonpriority drugs.
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2.
The sponsor submitted reports of the requested studies to the NDA after the Agency made the
Written Request.
3.
The sponsor submitted studies that responded completely to the Written Request (section
505A(d)(2) and (3)).
4.
The sponsor submitted reports of the studies in accordance with a written agreement (section
505A(d)(1) and (2)) or, if there was no written agreement, in accordance with commonly