[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This guidance finalizes the draft guidance issued May 30, 2012.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