[Federal Register Volume 64, Number 53 (Friday, March 19, 1999)]
[Notices]
[Pages 13587-13589]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-6749]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 99D-0297]


Draft Guidance for Industry on Formal Dispute Resolution; Appeals 
Above the Division Level; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Formal Dispute 
Resolution: Appeals Above the Division Level.'' This draft guidance is 
intended to provide guidance for industry on procedures that will be 
adopted by the Center for Drug Evaluation and Research (CDER) and the 
Center for Biologics Evaluation and Research (CBER) for resolving 
scientific and procedural disputes that cannot be resolved at the 
division level.

DATES: Written comments on the draft guidance document may be submitted 
by May 18, 1999. General comments on agency guidance documents are 
welcome at any time. Submit written comments on the information 
collection provisions by April 19, 1999.

ADDRESSES: Copies of this draft guidance for industry are available on 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 requests for 
single copies of the draft guidance to the Drug Information Branch 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, or Office of 
Communication, Training, and Manufacturers Assistance (HFM-40), Center 
for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, 
MD 20852-1448, 301-827-3844, or FAX 888-CBERFAX or 301-827-3844. Send 
two self-addressed adhesive labels to assist the office in processing 
your request. Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Requests and comments should be identified with 
the docket number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT:
    Patricia L. DeSantis, Center for Drug Evaluation and Research (HFD-
2), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-594-5400, or
    Rebecca A. Devine, Center for Biologics Evaluation and Research 
(HFM-10), Food and Drug Administration, 1401 Rockville Pike, Rockville, 
MD 20852-1448, 301-827-0373.

SUPPLEMENTARY INFORMATION:

I. Description of the Guidance

     FDA is announcing the availability of a draft guidance for 
industry entitled ``Formal Dispute Resolution: Appeals Above the 
Division Level.'' The draft guidance is intended to provide guidance 
for industry on procedures that will be adopted by CDER and CBER for 
resolving scientific and procedural disputes that cannot be resolved at 
the division level. This draft guidance describes procedures for 
formally appealing such disputes to the office or center level and for 
submitting information to assist agency officials in resolving the 
issue(s) presented.
     FDA regulations Sec. 10.75 (21 CFR 10.75) provide a mechanism for 
any interested person to obtain formal review of any agency decision by 
raising the matter with the supervisor of the employee who made the 
decision. If the issue is not resolved at the primary supervisory 
level, the interested person may request that the matter be reviewed at 
the next higher supervisory level. This process may continue through 
the agency's entire supervisory chain of command, through the centers 
to the Deputy Commissioner for Operations and then to the Commissioner. 
CDER and CBER regulations for dispute resolution during the 
investigational new drug (IND) process (Sec. 312.48 (21 CFR 312.48)) 
and the new drug application (NDA)/abbreviated new drug application 
(ANDA) process (Sec. 314.103 (21 CFR 314.103)) establish similar 
procedures for the resolution of scientific and procedural matters at 
the division level and subsequent formal review of decisions through 
center management.
     On November 21, 1997, President Clinton signed into law the Food 
and Drug Administration Modernization Act of 1997 (the Modernization 
Act) (Pub. L. 105-115). Section 404 of the Modernization Act creates 
new section 562 of the Federal Food, Drug, and Cosmetic Act (the act) 
(21 U.S.C. 360bbb-1). Section 562 of the act provides that if, 
regarding an obligation concerning drugs or devices under the act or 
section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 
262), there is a scientific dispute between the agency and a sponsor, 
applicant, or manufacturer, and no specific provision of the act or 
regulation provides a right of review of the matter in controversy, FDA 
shall, by regulation, establish a procedure under which such sponsor, 
applicant, or manufacturer may request a review of the controversy, 
including review by an advisory committee. Section 562 of the act 
further provides that such review of the controversy shall take place 
in a timely manner. In the Federal Register of November 18, 1998 (63 FR 
63978), FDA amended Sec. 10.75 to explicitly state that a sponsor, 
applicant, or manufacturer of a drug or device may request review of a 
scientific controversy by an appropriate advisory committee. In the 
preamble to the final rule, FDA stated that implementation of this 
provision would be undertaken by the individual FDA centers and would 
be described in guidance documents.
     The Prescription Drug User Fee Act of 1992 (PDUFA) (Pub. L. 102-
571) was reauthorized in November 1997 (PDUFA 2) as part of the 
Modernization Act. In conjunction with PDUFA 2, FDA agreed to specific 
performance goals (PDUFA goals) for activities associated with the 
development and review of products in human drug applications as 
defined in section 735(1) of the act (21 U.S.C. 379g(1)) (PDUFA 
products). The PDUFA goals are summarized in ``PDUFA Reauthorization 
Performance Goals and Procedures,'' an enclosure to a letter dated 
November 12, 1997, from the Secretary of Health and Human Services, 
Donna E. Shalala, to Senator James M. Jeffords. The PDUFA goals for 
major dispute resolution describe specific timeframes for CDER and CBER 
response to formally appealed decisions regarding scientific or 
procedural matters concerning PDUFA products.
     The policies and procedures described in this draft guidance 
document will implement agency

[[Page 13588]]

regulations, section 562 of the act, and the PDUFA goals for dispute 
resolution. Unless stated otherwise in the draft guidance, the document 
applies to PDUFA products and non-PDUFA products (e.g., generic drugs).
     This draft Level 1 guidance is being issued consistent with FDA's 
``Good Guidance Practices'' (62 FR 8961, February 27, 1997). It 
represents the agency's current thinking on formal dispute resolution 
in CDER and CBER. 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.

II. Comments

     Interested persons may, on or before May 18, 1999, submit to the 
Dockets Management Branch (address above) written comments on the draft 
guidance document. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Comments should be 
identified with the docket number found in brackets in the heading of 
this document. The draft guidance and received comments may be seen in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

 III. The Paperwork Reduction Act of 1995

     Under the Paperwork Reduction Act (the PRA) (44 U.S.C. 3501-3520), 
Federal agencies must obtain approval from the Office of Management and 
Budget (OMB) for each collection of information they conduct or 
sponsor. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information before 
submitting the collection to OMB for approval. To comply with this 
requirement, FDA is publishing notice of the proposed collection of 
information set forth below.
     With respect to the following collection of information, FDA 
invites comment on: (1) Whether the proposed collection of information 
is necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection on respondents, including through the use of automated 
collection techniques, when appropriate, and other forms of information 
technology.
    Title: Draft Guidance for Industry on Formal Dispute Resolution: 
Appeals Above the Division Level.
    Description: FDA is issuing a draft guidance on the process for 
formally resolving scientific and procedural disputes in CDER and CBER 
that cannot be resolved at the division level. The draft guidance 
describes procedures for formally appealing such disputes to the office 
or center level and for submitting information to assist center 
officials in resolving the issue(s) presented. The draft guidance 
provides information on how the agency will interpret and apply 
provisions of the existing regulations regarding internal agency review 
of decisions (Sec. 10.75) and dispute resolution during the IND process 
(Sec. 312.48) and the NDA/ANDA process (Sec. 314.103). In addition, the 
draft guidance provides information on how the agency will interpret 
and apply the specific PDUFA goals for major dispute resolution 
associated with the development and review of PDUFA products.
     Existing regulations, which appear primarily in parts 10, 312, and 
314 (21 CFR parts 10, 312, and 314), establish procedures for the 
resolution of scientific and procedural disputes between interested 
persons and the agency, CDER, and CBER. All agency decisions on such 
matters are based on information in the administrative file 
(Sec. 10.75(d)). In general, the information in an administrative file 
is collected under existing regulations in parts 312 (OMB Control No. 
0910-0001), 314 (OMB Control No. 0910-0014), and part 601 (21 CFR part 
601) (OMB Control No. 0910-0315), which specify the information that 
manufacturers must submit so that FDA may properly evaluate the safety 
and effectiveness of drugs and biological products. This information is 
usually submitted as part of an IND, NDA, or biologics license 
application (BLA), or as a supplement to an approved application. While 
FDA already possesses in the administrative file the information that 
would form the basis of a decision on a matter in dispute resolution, 
the submission of particular information regarding the request itself 
and the data and information relied on by the requestor in the appeal 
would facilitate timely resolution of the dispute. The draft guidance 
describes the following collection of information not expressly 
specified under existing regulations: The submission of the request for 
dispute resolution as an amendment to the application for the 
underlying product, including the submission of supporting information 
with the request for dispute resolution.
     Agency regulations (Secs. 312.23(11)(d), 314.50, 314.94, and 
601.2) state that information provided to the agency as part of an IND, 
NDA, ANDA, or BLA is to be submitted in triplicate and with an 
appropriate cover form. Form FDA 1571 must accompany submissions under 
IND's and Form FDA 356h must accompany submissions under NDA's, ANDA's, 
and BLA's. Both forms have valid OMB control numbers as follows: FDA 
Form 1571, OMB Control No. 0910-0014, expires December 31, 1999; and 
FDA Form 356h, OMB Control No. 0910-0338, expires April 30, 2000.
     In the draft guidance document, CDER and CBER ask that a request 
for formal dispute resolution be submitted as an amendment to the 
application for the underlying product and that it be submitted to the 
agency in triplicate with the appropriate form attached, either Form 
FDA 1571 or Form FDA 356h. The agency recommends that a request be 
submitted as an amendment in this manner for two reasons: To ensure 
that each request is kept in the administrative file with the entire 
underlying application and to ensure that pertinent information about 
the request is entered into the appropriate tracking databases. Use of 
the information in the agency's tracking databases enables the 
appropriate agency official to monitor progress on the resolution of 
the dispute and to ensure that appropriate steps will be taken in a 
timely manner.
     CDER and CBER have determined and the draft guidance recommends 
that the following information should be submitted to the appropriate 
center with each request for dispute resolution so that the Center may 
quickly and efficiently respond to the request:
     A brief but comprehensive statement of each issue to be 
resolved, including a description of the issue, the nature of the issue 
(i.e., scientific, procedural, or both), possible solutions based on 
information in the administrative file, whether informal dispute 
resolution was sought prior to the formal appeal, whether advisory 
committee review is sought, and the expected outcome;
     A statement identifying the review division/office that 
issued the original decision on the matter and, if applicable, the last 
agency official that attempted to formally resolve the matter;
     A list of documents in the administrative file, or 
additional copies of such documents, that are deemed

[[Page 13589]]

necessary for resolution of the issue(s); and
     A statement that the previous supervisory level has 
already had the opportunity to review all of the material relied on for 
dispute resolution. The information that the agency suggests submitting 
with a formal request for dispute resolution consists of: (1) 
Statements describing the issue from the perspective of the person with 
a dispute, (2) brief statements describing the history of the matter, 
and (3) documents previously submitted to FDA under an OMB approved 
collection of information (see previous discussion).
     Based on FDA's experience with dispute resolution, the agency 
expects that most persons seeking formal dispute resolution will have 
gathered the materials listed previously when identifying the existence 
of a dispute with the agency. Consequently, FDA anticipates that the 
collection of information attributed solely to the guidance will be 
minimal.
    Description of Respondents: A sponsor, applicant, or manufacturer 
of a drug or biologic product regulated by the agency under the act or 
section 351 of the PHS Act who requests formal resolution of a 
scientific or procedural dispute.
    Burden Estimate: Table 1 of this document provides an estimate of 
the annual reporting burden for requests for dispute resolution. In 
fiscal year (FY) 1998, 39 sponsors and applicants (respondents) 
submitted requests for formal dispute resolution to CDER and 12 
respondents submitted requests for formal dispute resolution to CBER. 
Although the procedures for requesting formal dispute resolution that 
are set forth in the draft guidance document were not in place in FY 
1998, FDA estimates that the number of respondents who would submit 
requests for dispute resolution under the guidance would remain the 
same. The total annual responses are the total number of requests 
submitted to CDER and CBER in 1 year, including requests for dispute 
resolution that a single respondent submits more than one time. In FY 
1998, CDER received approximately 49 requests and CBER received 
approximately 15 requests. The agency estimates that the total annual 
responses will remain the same, averaging to 1.26 responses per 
respondent. The hours per response is the estimated number of hours 
that a respondent would spend preparing the information to be submitted 
with a request for formal dispute resolution in accordance with this 
draft guidance, including the time it takes to gather and copy brief 
statements describing the issue from the perspective of the person with 
the dispute, brief statements describing the history of the matter, and 
supporting information that has already been submitted to the agency. 
Based on experience, FDA estimates that approximately 8 hours on 
average would be needed per response. Therefore, FDA estimates that 512 
hours will be spent per year by respondents requesting formal dispute 
resolution under the guidance.
     FDA invites comments on this analysis of information collection 
burdens.

                                  Table 1.--Estimated Annual Reporting Burden1
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                                                      No. of
   Requests for Formal Dispute        No. of       Responses per   Total Annual      Hours per      Total Hours
           Resolution               Respondents     Respondent       Responses       Response
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CDER                                   39               1.26           49               8             392
CBER                                   12               1.25           15               8             120
Total                                                                                                 512
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

     In compliance with section 3507(d) of the PRA (44 U.S.C. 3507(d)), 
the agency has submitted the information collection provisions of this 
draft guidance to OMB for review. Interested persons are requested to 
send comments on this information collection by April 19, 1999, to the 
Office of Information and Regulatory Affairs, OMB, New Executive Office 
Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: Desk 
Officer for FDA.

    Dated: March 15, 1999.
 William K. Hubbard,
 Acting Deputy Commissioner for Policy.
[FR Doc. 99-6749 Filed 3-18-99; 8:45 am]
BILLING CODE 4160-01-F