Document ID: FDA-2017-D-6617-0012
Agency: fda
Document Type: Notice
Title: Developing Targeted Therapies in Low-Frequency Molecular Subsets of a
Disease; Guidance for Industry; Availability
Posted Date: 2018-10-16T04:00Z

[Federal Register Volume 83, Number 200 (Tuesday, October 16, 2018)]
[Notices]
[Pages 52222-52223]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-22437]

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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; 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 final guidance for industry entitled ``Developing 
Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.'' 
This final guidance incorporates public comments to the draft guidance 
published in the Federal Register of December 18, 2017.
    The pharmacological effect of a targeted therapy is often related 
to a particular molecular alteration, and many diseases are caused by a 
range of different molecular alterations (some of which may be rare). 
Therefore, a targeted therapy may have differential effects among 
patients with the same disease who have different molecular 
alterations. The purpose of this guidance is to describe 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: The announcement of the guidance is published in the Federal 
Register on October 16, 2018.

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-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.gpo.gov/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 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 (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 that 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: 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 guidance for industry 
entitled ``Developing Targeted Therapies in

[[Page 52223]]

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 molecular subsets 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 
influenced or caused by a range of different molecular alterations, 
some of which may be rare, that impact a common target protein or 
pathway involved in the disease pathogenesis. This heterogeneity in the 
molecular etiology of a given disease can result in differential 
effects of a targeted therapy among patients with the same disease but 
who have different molecular alterations. Therefore, the type and 
quantity of evidence that is needed to demonstrate efficacy across 
molecular subsets within a disease needs to be clearly specified.
    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 to the study population
 Benefit-risk determination and therapeutic product labeling
 Refining the indicated population after the initial approval

    This final guidance incorporates public comments to the draft 
guidance published in December of 2017 and includes minimal revisions 
for clarity.
    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 ``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 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: October 10, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-22437 Filed 10-15-18; 8:45 am]
 BILLING CODE 4164-01-P