[Federal Register Volume 79, Number 194 (Tuesday, October 7, 2014)]
[Notices]
[Pages 60476-60477]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-23845]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0432]


Pathological Complete Response in Neoadjuvant Treatment of High-
Risk Early-Stage Breast Cancer: Use as an Endpoint To Support 
Accelerated Approval; Guidance for Industry; 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 guidance for industry entitled ``Pathological 
Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage 
Breast Cancer: Use as an Endpoint to Support Accelerated Approval.'' 
This guidance is intended to assist applicants in designing trials to 
support marketing approval of drugs to treat breast cancer in the 
neoadjuvant (preoperative) setting using pathological complete response 
(pCR) as a surrogate endpoint that could support approval under the 
accelerated approval regulations. Despite advances in systemic therapy 
of early-stage breast cancer over the past few decades, there remains a 
significant unmet medical need for certain high-risk or poor prognosis 
populations of early-stage breast cancer patients. This guidance is 
intended to encourage industry innovation and expedite the development 
of breakthrough therapies to treat high-risk early-stage breast cancer. 
This guidance finalizes the draft guidance issued May 30, 2012.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Tatiana Prowell, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2112, Silver Spring, MD 20993-0002, 301-
796-2330.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Pathological Complete Response in Neoadjuvant Treatment of 
High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support 
Accelerated Approval.'' Under the accelerated approval regulations (21 
CFR part 314, subpart H, and 21 CFR part 601, subpart E), FDA may grant 
marketing approval for a new drug on the basis of adequate and well-
controlled trials establishing

[[Page 60477]]

that the drug has an effect on a surrogate endpoint that is reasonably 
likely to predict clinical benefit (e.g., in early-stage breast cancer, 
an improvement in disease-free or overall survival), provided that the 
applicant conducts additional trials or collects additional data after 
approval to verify and describe the predicted clinical benefit. This 
guidance is intended to assist applicants in designing trials to 
support marketing approval of drugs to treat breast cancer in the 
neoadjuvant (preoperative) setting using pCR as a surrogate endpoint 
that could support approval under the accelerated approval regulations. 
The guidance provides acceptable definitions of pCR for regulatory 
purposes. The guidance also describes appropriate patient populations 
for inclusion in neoadjuvant trials conducted with regulatory intent. 
Finally, the guidance outlines critical design features of trials for 
both accelerated approval and confirmation of clinical benefit to 
support regular approval.
    FDA recognizes that despite advances in adjuvant systemic therapy 
of breast cancer over the past few decades, there remains a significant 
unmet medical need for certain high-risk or poor prognosis populations 
of early-stage breast cancer patients. Developing highly effective new 
drugs for these populations is an FDA priority. In providing guidance 
on the use of pCR as a surrogate endpoint that could support 
accelerated approval in the neoadjuvant setting, FDA hopes to encourage 
industry innovation and expedite the development and widespread 
availability of highly effective novel therapies to treat high-risk 
early-stage breast cancer.
    This guidance finalizes the draft guidance issued May 30, 2012 (77 
FR 31858). The current version clarifies appropriate trial designs and 
development strategies to support accelerated approval in the 
neoadjuvant setting, defines acceptable endpoints for accelerated 
approval and confirmation of clinical benefit, standardizes the 
approach to postoperative systemic therapy, includes guidelines for 
evaluation of the axillary lymph nodes, and provides detailed 
recommendations for pathology standard operating procedures.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on use of pCR as an endpoint to support 
accelerated approval of drug and biological products to treat high-risk 
early-stage breast cancer patient populations. 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 and regulations.

II. The Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively. The collections of information for special protocol 
assessments have been approved under OMB control number 0910-0470.

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: October 1, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-23845 Filed 10-6-14; 8:45 am]
BILLING CODE 4164-01-P