UNITED STATES FOOD & DRUG ADMINISTRATION
Special Protocol Assessments
OMB Control No. 0910-0470 – Revision
SUPPORTING STATEMENT – Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA, the agency, us or we)
efforts in implementing provisions of the FDA Modernization Act of 1992, and certain
provisions of the Prescription Drug User Fee Authorization Act (PDUFA) under the FDA
Reauthorization Act of 2017 (FDARA). The guidance document entitled, “Special Protocol
Assessment: Guidance for Industry” describes agency procedures and general policies our
Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and
Research (CBER) will follow for special protocol assessment (SPA). SPA is a process in which
product application sponsors may ask to meet with FDA to reach agreement on the design and
size of certain clinical trials, clinical studies, or animal studies (i.e., a Request for SPA (hereafter
Request); see section III., Eligible Protocols and General Information) to determine if they
adequately address scientific and regulatory requirements for a study that could support
marketing approval. While regulations in 21 CFR 312, 314, and 601 cover various drug and
biological drug application submission types (information collection associated with these
regulations are approved under OMB control nos. 0910-0014, 0910-0001, and 0910-0338,
respectively), this information collection communicates content, format, and submission
information relating specifically to SPA.
A. 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 within CDER or 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.
B. 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.
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 (§ 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.
We have revised the guidance document to reflect updated commitment goals established by
FDARA. The revised guidance clarifies information we recommend respondents submit to
FDA, including questions concerning specific issues regarding the protocol. In addition, we
recommend that respondents provide 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 a stability protocol, product characterization
and relevant manufacturing data. The guidance was developed and issued in accordance with
our Good Guidance Practice regulations in 21 CFR part 10.115 which provide for public
comment at any time.
2. Purpose and Use of the Information Collection
The information respondents submit allows FDA to evaluate drug study protocols 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 a stability protocol,
product characterization and relevant manufacturing data.
3. Use of Improved Information Technology and Burden Reductions
Information is submitted electronically as required under FDA regulations governing the
submission of Investigational New Drug (IND) applications (21 CFR 312); Applications to
Market a New Drug (NDA) (21 CFR 314); and Biologics Licensing Applications (BLA) (21
CFR 601). To assist respondents in this regard we have developed the guidance document
“Providing Regulatory Submissions in Electronic Format--General Considerations” available at
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection.
5. Impact on Small Businesses or Other Small Entities
The information collection does not impose undue burden on small entities. At the same time,
we provide assistance to all respondents through agency resources on our website at
www.fda.gov and through agency staff available in CBER and CDER.
6. Consequences of Collecting the Information Less Frequently
As explained above, the guidance sets forth procedures adopted by CDER and CBER to evaluate
issues related to the adequacy (e.g., design, conduct, analysis) 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 information collection schedule is driven by respondents to
the information collection.
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5
There are no special circumstances for this collection of information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
In accordance with 5 CFR 1320.8(d), we published a 60-day notice for public comment in the
Federal Register of January 3, 2020, 2019 (85 FR 320). Although one comment was received, it
was not responsive to the information collection topics solicited in the notice and not addressed
9. Explanation of Any Payment or Gift to Respondents
No payments or gifts are provided to respondents to the information collection.
10. Assurance of Confidentiality Provided to Respondents
Confidentiality of the information submitted under this guidance is protected under 21 CFR
312.130 and under 21 CFR part 20. The unauthorized use or disclosure of trade secrets required
in applications is specifically prohibited under section 310(j) of the FD&C Act.
11. Justification for Sensitive Questions
The information collection contains no questions of a sensitive nature.
12. Estimates of Annualized Burden Hours And Costs
12a. Annualized Hour Burden Estimate:
Table 1.--Estimated Annual Reporting Burden1
Requests for Special Protocol
There are no capital costs or operating and maintenance costs associated with this collection of information.
Burden Estimate: Table 1 provides an estimate of the annual reporting burden for
notifications for a carcinogenicity protocol and requests for a special protocol assessment.
Notification for a Carcinogenicity Protocol: Based on the number of notifications for
carcinogenicity protocols and the number of carcinogenicity protocols currently submitted to
CDER and CBER, CDER estimates that it will receive approximately 188 notifications of an
intent to request special protocol assessment of a carcinogenicity protocol per year from
approximately 105 sponsors. CBER estimates that it will receive approximately one notification
of an intent to request special protocol assessment of a carcinogenicity protocol per year from
approximately one sponsor. The hours per response, which is the estimated number of hours that
a sponsor would spend preparing the notification and background information to be submitted in
accordance with the guidance, is estimated to be approximately 8 hours.
Requests for Special Protocol Assessment: Based on the number of requests for special
protocol assessment currently submitted to CDER and CBER, CDER estimates that it will
receive approximately 108 requests for special protocol assessment per year from approximately
105 sponsors. CBER estimates that it will receive approximately eight requests from
approximately eight sponsors. 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 our experience with these submissions, we estimate approximately 15 hours on
average would be needed per response. The information collection reflects an adjustment in
burden by 608 hours. We attribute this adjustment to an increase in the number of submissions
we received over the last few years.
12b. Annualized Cost Burden Estimate
We use an average industry wage rate of $85 per hour (averaged from wages for upper
management, middle management, and clerical support, plus overhead and personnel benefits)
for preparing and submitting the information requested under the guidance. Using the averaged
wage rate of $85 per hour, and multiplied times the total hour burden estimated above (3,250),
the total cost burden to respondents is approximately $276,250.
13. Estimates of Other Total Annual Costs Burden to Respondents and/or
We do not anticipate any other costs, including capital costs or operating and maintenance costs,
resulting from the information collection in this guidance.
14. Estimates of Annualized Cost to the Federal Government
Costs to the Federal Government are absorbed under existing resource and user fee allocations.
15. Explanation for Program Changes or Adjustments
The information collection reflects adjustments. The overall number of requests has decreased
while notifications for carcinogenicity protocols has increased. This results in 32 additional
annual responses, but 472 less hours.
16. Plans for Tabulation and Publication and Project Time Schedule
The agency has no such plans.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of the OMB Expiration Date is appropriate.
18. Exception to the Certification for Paperwork Reduction Act Submission
There are no exceptions to the certification.
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