[Federal Register Volume 66, Number 103 (Tuesday, May 29, 2001)]
[Notices]
[Pages 29147-29148]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-13304]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-0084]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; Guidance for Industry on Special Protocol 
Assessment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995 (PRA).

DATES: Submit written comments on the collection of information by June 
28, 2001.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information 
Resources Management (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1482.

SUPPLEMENTARY INFORMATION:

I. Background

    In compliance with 44 U.S.C. 3507, FDA has submitted the following 
proposed collection of information to OMB for review and clearance.

Guidance for Industry on Special Protocol Assessment

    FDA is issuing a guidance on agency procedures to evaluate issues 
related to the adequacy of certain proposed studies. The guidance 
describes procedures for sponsors to request special protocol 
assessment and for the agency to act on such requests. The guidance 
provides information on how the agency will interpret and apply 
provisions of the Food and Drug Administration Modernization Act of 
1997 and the specific Prescription Drug User Fee Act of 1992 (PDUFA) 
goals for special protocol assessment associated with the development 
and review of PDUFA products.
    The guidance describes two collections of information: (1) The 
submission of a notice of intent to request special protocol assessment 
of a carcinogenicity protocol, and (2) the submission of a request for 
special protocol assessment.

II. Notification for a Carcinogenicity Protocol

    As described in the guidance, a sponsor interested in agency 
assessment of a carcinogenicity protocol should notify the appropriate 
division in FDA's Center for Drug Evaluation and Research (CDER) or 
Center for Biologics Evaluation and Research (CBER) of an intent to 
request special protocol assessment at least 30 days prior to 
submitting the request. With such notification, the sponsor should 
submit relevant background information so that the agency may review 
reference material related to carcinogenicity protocol design prior to 
receiving the carcinogenicity protocol. The agency is currently 
drafting a separate guidance describing the type of information that 
would be appropriate to submit before requesting carcinogenicity 
protocol assessment.

III. Request for Special Protocol Assessment

    In the guidance, CDER and CBER ask that a request for special 
protocol assessment be submitted as an amendment to the investigational 
new drug application (IND) for the underlying product and that it be 
submitted to the agency in triplicate with Form FDA 1571 attached. The 
agency also suggests that the sponsor submit the cover letter to a 
request for special protocol assessment via facsimile to the 
appropriate division in CDER or CBER. Agency regulations (21 CFR 
312.23(d)) state that information provided to the agency as part of an 
IND is to be submitted in triplicate and with the appropriate cover 
form, Form FDA 1571. An IND is submitted to FDA under existing 
regulations in part 312 (21 CFR part 312), which specifies the 
information that manufacturers must submit so that FDA may properly 
evaluate the safety and effectiveness of investigational drugs and 
biological products. The information collection requirements resulting 
from the preparation and submission of an IND under part 312 have been 
estimated by FDA and the reporting and recordkeeping burden has been 
approved by OMB until September 30, 2002, under the OMB control number 
0910-0014. In the Federal Register of May 6, 1999 (64 FR 24402), FDA 
published a notice requesting comments on the burden estimates for the 
information collection requirements in part 312. The notice also 
requested an extension of OMB approval for this information collection.
    FDA suggests that the cover letter to the request for special 
protocol assessment be submitted via facsimile to the appropriate 
division in CDER or CBER to enable agency staff to prepare for the 
arrival of the protocol for assessment. The agency recommends that a 
request for special protocol assessment be submitted as an amendment to 
an IND for two reasons: (1) To ensure that each request is kept in the 
administrative file with the entire IND, and (2) 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 evaluation of the protocol and to ensure that appropriate steps 
will be taken in a timely manner.
    CDER and CBER have determined and the guidance recommends that the 
following information should be submitted to the appropriate Center 
with each request for special protocol assessment so that the Center 
may quickly and efficiently respond to the request:
    <bullet>  Questions to the agency concerning specific issues 
regarding the protocol; and
    <bullet>  All data, assumptions, and information needed to permit 
an adequate evaluation of the protocol, including: (1) The role of the 
study in the overall development of the drug; (2) information 
supporting the proposed trial, including power calculations, the choice 
of study endpoints, and other critical design features; (3) regulatory 
outcomes that could be supported by the results of the study; (4) final 
labeling that could be supported by the results of the study; and (5) 
for stability protocol, product characterization and relevant 
manufacturing data.

A. Description of Respondents

    A sponsor, applicant, or manufacturer of a drug or biologic product 
regulated by the agency under the Federal Food, Drug, and Cosmetic Act 
(the act) or section 351 of the Public Health Service Act who requests 
special protocol assessment.

[[Page 29148]]

B. Burden Estimate

    Table 1 of this document provides an estimate of the annual 
reporting burden for requests for special protocol assessment. The 
procedures for requesting special protocol assessment that are set 
forth in the guidance have not been previously described by the agency, 
although the PDUFA goals and the requirements of section 505(b)(4)(B) 
of the act (21 U.S.C. 355 (b)(4)(B)) have been in effect since October 
and November 1998, respectively, as follows:
1. Notification for a Carcinogenicity Protocol
    Based on data collected from the review divisions and offices 
within CDER and CBER, including the number of carcinogenicity protocols 
submitted for review in the first half of fiscal year (FY) 1999 and the 
number of INDs for new molecular entities that were received by the 
agency per year over the last 5 years, CDER and CBER anticipate that 
approximately 30 respondents will notify the agency of an intent to 
request special protocol assessment of a carcinogenicity protocol. The 
agency further estimates that the total annual responses, i.e., the 
total number of notifications that will be sent to CDER and CBER, will 
be 60, based on data collected from the offices within CDER and CBER. 
Therefore, the agency estimates that there will be approximately two 
responses per respondent. The hours per response, which is the 
estimated number of hours that a respondent would spend preparing the 
notification and background information to be submitted in accordance 
with the guidance, is estimated to be approximately 8 hours. While FDA 
has not finalized the separate guidance describing background 
information that should be submitted with notification of a 
carcinogenicity protocol for assessment, the agency anticipates that it 
will take respondents approximately 8 hours to gather and copy articles 
and study reports that are relevant to the carcinogenicity protocol. 
Therefore, the agency estimates that respondents will spend 480 hours 
per year notifying the agency of an intent to request special protocol 
assessment of a carcinogenicity protocol.
2. Requests for Special Protocol Assessment
    Based on data collected from the review divisions and offices 
within CDER and CBER, including the number of requests for special 
protocol assessment in the first half of FY 1999, the number of INDs 
for new molecular entities that were received by the agency per year 
over the past 5 years, the number of sponsors who have submitted 
protocols for agency review in the past and in the first half of FY 
1999, and the number of end-of-phase 2/prephase 3 meetings that occur 
between respondents and the agency per year, FDA anticipates that 70 
respondents will request special protocol assessment per year. The 
total annual responses are the total number of requests for special 
protocol assessment that are submitted to CDER and CBER in 1 year. 
Based on data collected from the review divisions and offices within 
CDER and CBER, FDA estimates that it will receive approximately 180 
requests for special protocol assessment per year. Therefore, the 
agency estimates that there will be approximately 2.57 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 special protocol assessment, including the time it 
takes to gather and copy questions to be posed to the agency regarding 
the protocol and data, assumptions, and information needed to permit an 
adequate evaluation of the protocol. Based on estimates provided by the 
regulated industry and on the agency's experience in requesting similar 
information, FDA estimates approximately 15 hours on average would be 
needed per response.
    Therefore, FDA estimates that 2,700 hours will be spent per year by 
respondents requesting special protocol assessment. Overall, FDA 
anticipates that respondents will spend 3,180 hours per year to 
participate in the programs described in the guidance.
    In the Federal Register of February 9, 2000 (65 FR 6377), the 
agency requested comments on the proposed collections of information. 
Eight comments were received, however they were related to the Protocol 
Assessment and not to the collection of information.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden\1\
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                                                Number of
    Notification and         Number of        Responses per     Total Annual       Hours per       Total Hours
        Requests            Respondents        Respondent         Responses        Response
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Notification for         30                2.0                 60              8                 480
 Carcinogencity
 Protocols
Requests for Special     70                2.57                180             15                2,700
 Protocol Assessment
                                                                                                ----------------
Total                                                                                            3,180
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: May 18, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-13304 Filed 5-25-01; 8:45 am]
BILLING CODE 4160-01-S