[Federal Register Volume 86, Number 150 (Monday, August 9, 2021)]
[Notices]
[Pages 43551-43552]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-16929]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3931]


Nonmetastatic Castration-Resistant Prostate Cancer: 
Considerations for Metastasis-Free Survival Endpoint in Clinical 
Trials; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled 
``Nonmetastatic Castration-Resistant Prostate Cancer: Considerations 
for Metastasis-Free Survival Endpoint in Clinical Trials.'' Recent 
approvals of several drug products for patients with nonmetastatic 
castration-resistant prostate cancer have been supported by randomized 
clinical trials demonstrating improvements in metastasis-free survival. 
This guidance intends to inform potential future applicants regarding 
the Agency's expectations for collection, analysis, and reporting of 
data pertaining to metastasis-free survival. This guidance finalizes 
the draft guidance of the same title issued on November 14, 2018.

DATES: The announcement of the guidance is published in the Federal 
Register on August 9, 2021.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-D-3931 for ``Nonmetastatic Castration-Resistant Prostate 
Cancer: Considerations for Metastasis-Free Survival Endpoint in 
Clinical Trials.'' Received comments will be placed in the docket and, 
except for those submitted as ``Confidential Submissions,'' publicly 
viewable at https://www.regulations.gov or at the Dockets Management 
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper

[[Page 43552]]

submission. You should submit two copies total. One copy will include 
the information you claim to be confidential with a heading or cover 
note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' 
The Agency will review this copy, including the claimed confidential 
information, in its consideration of comments. The second copy, which 
will have the claimed confidential information redacted/blacked out, 
will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management 
Staff. If you do not wish your name and contact information to be made 
publicly available, you can provide this information on the cover sheet 
and not in the body of your comments and you must identify this 
information as ``confidential.'' Any information marked as 
``confidential'' will not be disclosed except in accordance with 21 CFR 
10.20 and other applicable disclosure law. For more information about 
FDA's posting of comments to public dockets, see 80 FR 56469, September 
18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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; or the Office of 
Communication, Outreach, and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, 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.

FOR FURTHER INFORMATION CONTACT: Julia Beaver, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2100, Silver Spring, MD 20993-0002, 240-
402-0489; or Stephen Ripley, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
71, Rm 7268, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Nonmetastatic Castration-Resistant Prostate Cancer: 
Considerations for Metastasis-Free Survival Endpoint in Clinical 
Trials.'' Nonmetastatic castration-resistant prostate cancer (nmCRPC) 
is defined by rising prostate-specific antigen (PSA) despite castrate 
levels of testosterone and no radiographic evidence of distant 
metastatic disease. Despite earlier detection of localized prostate 
cancer and advances in surgical and radiation techniques, many patients 
will continue to have rising PSA after local therapy (e.g., surgery, 
radiation) for recurrent disease and subsequent androgen deprivation 
therapy. Patients with nmCRPC can have a prolonged disease course 
following the detection of a rising PSA until documentation of distant 
metastases or death. Such a prolonged assessment period (in which 
patients may receive multiple therapies) with low death rates may make 
the use of overall survival impractical as a primary endpoint to 
support approval of products in this disease setting.
    These issues were discussed at an Oncologic Drugs Advisory 
Committee meeting in 2011, during which the committee acknowledged that 
endpoints that can be measured earlier in the course of disease, such 
as metastasis-free survival, defined as the time from randomization to 
distant radiographic disease or death, would be useful in assessing the 
treatment effect of products in patients with nmCRPC. Additionally, the 
Oncologic Drugs Advisory Committee noted that the transition from 
nmCRPC to radiographically detectable metastatic disease (e.g., bone 
disease or visceral disease) is a clinically relevant event that can be 
associated with morbidity and the need for additional medical 
interventions. Conversely, local progression events may be treated with 
local therapies, may never progress to distant disease, and may not 
lead to systemic morbidity. Thus, a large treatment effect on 
metastasis-free survival with an acceptable safety profile could 
demonstrate clinical benefit and support product approval.
    This guidance finalizes the draft guidance of the same title issued 
on November 14, 2018, (83 FR 56857). Changes from the draft to the 
final include clarifying edits and expanding upon certain 
recommendations in the draft guidance.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``Nonmetastatic Castration-Resistant 
Prostate Cancer: Considerations for Metastasis-Free Survival Endpoint 
in Clinical Trials.'' It does not establish any rights for any person 
and is not binding on FDA or the public. You can use an alternative 
approach if it satisfies the requirements of the applicable statutes 
and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 312 have been approved under OMB control 
number 0910-0014. The collections of information in 21 CFR parts 50 and 
56 (Protection of Human Subjects and Institutional Review Boards) have 
been approved under OMB control number 0910-0130.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, or 
https://www.regulations.gov.

    Dated: August 2, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-16929 Filed 8-6-21; 8:45 am]
BILLING CODE 4164-01-P