82 FR 60021 - Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 241 (December 18, 2017)

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.'' The purpose of this guidance is to describe the FDA's current recommendations on how to group patients with different molecular alterations for eligibility in clinical trials; and general approaches to evaluating the benefits and risks of targeted therapeutics within a clinically defined disease where some molecular alterations may occur at low frequencies.

[Federal Register Volume 82, Number 241 (Monday, December 18, 2017)]
[Notices]
[Pages 60021-60022]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-27156]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-6617]


Developing Targeted Therapies in Low-Frequency Molecular Subsets 
of a Disease; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Developing 
Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.'' 
The purpose of this guidance is to describe the FDA's current 
recommendations on how to group patients with different molecular 
alterations for eligibility in clinical trials; and general approaches 
to evaluating the benefits and risks of targeted therapeutics within a 
clinically defined disease where some molecular alterations may occur 
at low frequencies.

DATES: Submit either electronic or written comments on the draft 
guidance by February 16, 2018 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-2017-D-6617 for ``Developing Targeted Therapies in Low-Frequency 
Molecular Subsets of a Disease.'' 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.
     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.thefederalregister.org/fdsys/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.
    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 draft 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 draft guidance document.

[[Page 60022]]


FOR FURTHER INFORMATION CONTACT: Michael Pacanowski, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 301-
796-3919; 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 draft guidance for industry 
entitled ``Developing Targeted Therapies in Low-Frequency Molecular 
Subsets of a Disease.'' This guidance is intended to assist sponsors in 
designing drug development programs to generate the evidence needed to 
demonstrate efficacy of a targeted therapy across subsets of patients 
with different underlying molecular alterations within a disease, where 
some molecular alterations may occur at low frequencies.
    In recent years, advances in our understanding of the molecular 
pathology of many diseases have led to the development of targeted 
therapies. Although variability in drug response has long been 
recognized in drug development, targeted therapies present new 
challenges in addressing the heterogeneity in drug response because the 
pharmacological effect of a targeted therapy is often related to a 
particular molecular alteration (e.g., a mutation, gene fusion, 
epigenetic change, etc.). Many clinically defined diseases are caused 
by a range of different molecular alterations, some of which may occur 
at low frequencies, that impact a common protein or pathway involved in 
the disease pathogenesis. In a population of patients with the same 
clinical disease, the heterogeneity in the molecular etiology may 
result in different responses to a particular therapy. However, certain 
targeted therapies may be effective in multiple groups of patients that 
have different underlying molecular alterations. Therefore, FDA is 
providing guidance on the type and quantity of evidence that can 
demonstrate efficacy across molecular subsets within a disease.
    This guidance addresses the following important topics in 
evaluating the benefits and risks of targeted therapeutics within a 
disease where some molecular alterations may occur at low frequencies:

 Identification of patients for inclusion in clinical trials
 Interpretation of study results and generalizability of 
findings
 Benefit-risk determination and therapeutic product labeling
 Refining the indicated population after the initial approval
    In addition to comments on the general content of the draft 
guidance, FDA requests input on whether the principles described for 
grouping molecular subsets for clinical trial enrollment should be 
limited to diseases with low-frequency molecular alterations or whether 
they could be broadly applicable to all targeted therapies.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Developing 
Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.'' 
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. This 
guidance is not subject to Executive Order 12866.

II. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: December 12, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-27156 Filed 12-15-17; 8:45 am]
 BILLING CODE 4164-01-P