[Federal Register Volume 86, Number 125 (Friday, July 2, 2021)]
[Notices]
[Pages 35305-35307]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-14194]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-D-0938]


Evaluating Cancer Drugs in Patients With Central Nervous System 
Metastases; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

[[Page 35306]]


ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance entitled ``Evaluating Cancer Drugs 
in Patients with Central Nervous System Metastases; Guidance for 
Industry.'' The guidance document provides recommendations regarding 
the design of clinical trials of drugs and biological products 
regulated by the Center for Drug Evaluation and Research (CDER) and the 
Center for Biologics Evaluation and Research (CBER) that are intended 
to support product labeling describing the antitumor activity in 
patients with central nervous system (CNS) metastases from solid tumors 
originating outside the CNS. The guidance includes study design 
recommendations regarding the patient population, available therapy, 
prior therapies, assessment of CNS disease, study endpoints, and 
leptomeningeal disease. The guidance announced in this notice finalizes 
the draft guidance of the same title dated August 2020.

DATES: The announcement of the guidance is published in the Federal 
Register on July 2, 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-2020-D-0938 for ``Evaluating Cancer Drugs in Patients with Central 
Nervous System Metastases.'' 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 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 the guidance to the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), 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 the office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Shanthi Marur, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2369, Silver Spring, MD 20993-0002, 240-
402-6373; or Stephen Ripley, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a document entitled 
``Evaluating Cancer Drugs in Patients with Central Nervous System 
Metastases.'' This guidance provides recommendations for sponsors 
designing clinical trials of drugs and biological products regulated by 
CDER and CBER that are intended to support product labeling describing 
the antitumor activity in patients with CNS metastases from solid 
tumors originating outside the CNS. Specifically, the guidance includes 
recommendations regarding the patient population, available therapy, 
prior therapies, assessment of CNS disease, study endpoints, and 
leptomeningeal disease. The guidance describes that CNS metastases 
should be evaluated in the context of the entire disease burden and 
discusses how treatment effects may be described in drug labeling. The 
recommendations pertain to clinical trials for systemic anticancer 
drugs where patients with CNS metastases are included in the study 
population. These recommendations are also applicable to

[[Page 35307]]

trials conducted exclusively in patients with CNS metastases.
    CNS metastases are associated with significant morbidity and 
mortality and development of therapeutic products for patients with CNS 
metastases is needed. FDA has participated in efforts to facilitate 
drug development for patients with CNS metastases, including a March 
2019 ``Workshop on Product Development for CNS Metastases.'' 
Stakeholders at this meeting stated there is a need for further FDA 
guidance on specific topics, including identifying optimal study 
endpoints. Study design challenges for CNS metastases include 
uncertainty regarding optimal endpoints, lack of standardized response 
assessments, understanding how CNS metastases are evaluated in the 
context of the entire burden of metastatic disease to characterize a 
drug's potential benefit (e.g., timing of CNS radiographic assessments 
relative to other sites of metastases), and interpreting radiographic 
response in the setting of recent radiation therapy or surgery. This 
guidance is intended to provide recommendations on these study design 
challenges.
    In the Federal Register of August 27, 2020 (85 FR 53007), FDA 
announced the availability of the draft guidance ``Evaluating Cancer 
Drugs in Patients with Central Nervous System Metastases'' dated August 
2020. FDA received several comments on the draft guidance and those 
comments were considered as the guidance was finalized. A summary of 
changes includes: Clarification on the number of stratification factors 
the protocol should specify in order to minimize bias, confirmation of 
the version of Response Evaluation Criteria in Solid Tumours (RECIST) 
that should be referred to when evaluating CNS disease, clarification 
that both CNS and systematic duration of response should be captured 
and the addition of a 6-month timepoint, and the addition of 
progression-free survival in patients with brain metastasis as another 
measurement to be reported when CNS is a common metastatic site. In 
addition, editorial changes were made to improve clarity. The guidance 
announced in this notice finalizes the draft guidance dated August 27, 
2020.
    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 ``Evaluating Cancer Drugs in Patients with 
Central Nervous System Metastases.'' 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 part 314 
have been approved under OMB control number 0910-0001; the collections 
of information in 21 CFR part 601 have been approved under 0910-0338; 
and the collections of information in 21 CFR 201.56 and 201.57 have 
been approved under OMB control number 0910-0572.

III. Electronic Access

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

    Dated: June 28, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-14194 Filed 7-1-21; 8:45 am]
BILLING CODE 4164-01-P


