83_FR_52422 83 FR 52222 - Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Guidance for Industry; Availability

83 FR 52222 - Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 200 (October 16, 2018)

Page Range52222-52223
FR Document2018-22437

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 This final guidance incorporates public comments to the draft guidance published in the Federal Register of December 18, 2017.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.

Federal Register, Volume 83 Issue 200 (Tuesday, October 16, 2018) 
[Federal Register Volume 83, Number 200 (Tuesday, October 16, 2018)]
[Notices]
[Pages 52222-52223]
From the Federal Register Online  [www.thefederalregister.org]
[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This final guidance incorporates public comments to the draft guidance 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.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 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

52222 Federal Register / Vol. 83, No. 200 / Tuesday, October 16, 2018 / Notices Desk Officer for the Administration for solely responsible for ensuring that your contact information to be made publicly Children and Families. comment does not include any available, you can provide this confidential information that you or a information on the cover sheet and not Robert A. Sargis, third party may not wish to be posted, in the body of your comments and you Reports Clearance Officer. such as medical information, your or must identify this information as [FR Doc. 2018–22461 Filed 10–15–18; 8:45 am] anyone else’s Social Security number, or ‘‘confidential.’’ Any information marked BILLING CODE P confidential business information, such as ‘‘confidential’’ will not be disclosed as a manufacturing process. Please note except in accordance with 21 CFR 10.20 that if you include your name, contact and other applicable disclosure law. For DEPARTMENT OF HEALTH AND information, or other information that more information about FDA’s posting HUMAN SERVICES identifies you in the body of your of comments to public dockets, see 80 comments, that information will be FR 56469, September 18, 2015, or access Food and Drug Administration posted on https://www.regulations.gov. the information at: https://www.gpo.gov/ [Docket No. FDA–2017–D–6617] • If you want to submit a comment fdsys/pkg/FR-2015-09-18/pdf/2015- with confidential information that you 23389.pdf. Developing Targeted Therapies in Low- do not wish to be made available to the Docket: For access to the docket to Frequency Molecular Subsets of a public, submit the comment as a read background documents or the Disease; Guidance for Industry; written/paper submission and in the electronic and written/paper comments Availability manner detailed (see ‘‘Written/Paper received, go to https:// Submissions’’ and ‘‘Instructions’’). www.regulations.gov and insert the AGENCY: Food and Drug Administration, HHS. Written/Paper Submissions docket number, found in brackets in the ACTION: Notice of availability. heading of this document, into the Submit written/paper submissions as ‘‘Search’’ box and follow the prompts follows: and/or go to the Dockets Management SUMMARY: The Food and Drug • Mail/Hand delivery/Courier (for Administration (FDA or Agency) is Staff, 5630 Fishers Lane, Rm. 1061, written/paper submissions): Dockets announcing the availability of a final Rockville, MD 20852. Management Staff (HFA–305), Food and guidance for industry entitled You may submit comments on any Drug Administration, 5630 Fishers ‘‘Developing Targeted Therapies in guidance at any time (see 21 CFR Lane, Rm. 1061, Rockville, MD 20852. Low-Frequency Molecular Subsets of a 10.115(g)(5)). • For written/paper comments Disease.’’ This final guidance Submit written requests for single submitted to the Dockets Management incorporates public comments to the copies of this guidance to the Division Staff, FDA will post your comment, as draft guidance published in the Federal of Drug Information, Center for Drug well as any attachments, except for Register of December 18, 2017. Evaluation and Research, Food and information submitted, marked and The pharmacological effect of a Drug Administration, 10001 New identified, as confidential, if submitted targeted therapy is often related to a Hampshire Ave., Hillandale Building, as detailed in ‘‘Instructions.’’ particular molecular alteration, and Instructions: All submissions received 4th Floor, Silver Spring, MD 20993– many diseases are caused by a range of must include the Docket No. FDA– 0002; or the Office of Communication, different molecular alterations (some of 2017–D–6617 for ‘‘Developing Targeted Outreach, and Development, Center for which may be rare). Therefore, a Therapies in Low-Frequency Molecular Biologics Evaluation and Research targeted therapy may have differential Subsets of a Disease.’’ Received (CBER), Food and Drug Administration, effects among patients with the same comments will be placed in the docket 10903 New Hampshire Ave., Bldg. 71, disease who have different molecular and, except for those submitted as Rm. 3128, Silver Spring, MD 20993– alterations. The purpose of this ‘‘Confidential Submissions,’’ publicly 0002. Send one self-addressed adhesive guidance is to describe general viewable at https://www.regulations.gov label to assist that office in processing approaches to evaluating the benefits or at the Dockets Management Staff your requests. The guidance may also be and risks of targeted therapeutics within between 9 a.m. and 4 p.m., Monday obtained by mail by calling CBER at 1– a clinically defined disease where some through Friday. 800–835–4709 or 240–402–8010. See molecular alterations may occur at low • Confidential Submissions—To the SUPPLEMENTARY INFORMATION section frequencies. submit a comment with confidential for electronic access to the guidance DATES: The announcement of the information that you do not wish to be document. guidance is published in the Federal made publicly available, submit your FOR FURTHER INFORMATION CONTACT: Register on October 16, 2018. comments only as a written/paper Michael Pacanowski, Center for Drug ADDRESSES: You may submit either submission. You should submit two Evaluation and Research, Food and electronic or written comments on copies total. One copy will include the Drug Administration, 10903 New Agency guidances at any time as information you claim to be confidential Hampshire Ave., Bldg. 71, Rm. 7301, follows: with a heading or cover note that states Silver Spring, MD 20993–0002, 301– ‘‘THIS DOCUMENT CONTAINS 796–3919; or Stephen Ripley, Center for Electronic Submissions CONFIDENTIAL INFORMATION.’’ The Biologics Evaluation and Research, Submit electronic comments in the Agency will review this copy, including Food and Drug Administration, 10903 following way: the claimed confidential information, in New Hampshire Ave., Bldg. 71, Rm. • Federal eRulemaking Portal: its consideration of comments. The 7301, Silver Spring, MD 20993–0002, amozie on DSK3GDR082PROD with NOTICES1 https://www.regulations.gov. Follow the second copy, which will have the 240–402–7911. instructions for submitting comments. claimed confidential information SUPPLEMENTARY INFORMATION: Comments submitted electronically, redacted/blacked out, will be available including attachments, to https:// for public viewing and posted on I. Background www.regulations.gov will be posted to https://www.regulations.gov. Submit FDA is announcing the availability of the docket unchanged. Because your both copies to the Dockets Management a guidance for industry entitled comment will be made public, you are Staff. If you do not wish your name and ‘‘Developing Targeted Therapies in VerDate Sep<11>2014 18:44 Oct 15, 2018 Jkt 247001 PO 00000 Frm 00035 Fmt 4703 Sfmt 4703 E:\FR\FM\16OCN1.SGM 16OCN1

Federal Register / Vol. 83, No. 200 / Tuesday, October 16, 2018 / Notices 52223 Low-Frequency Molecular Subsets of a applicable statutes and regulations. This • Federal eRulemaking Portal: Disease.’’ This guidance is intended to guidance is not subject to Executive https://www.regulations.gov. Follow the assist sponsors in designing drug Order 12866. instructions for submitting comments. development programs to generate the Comments submitted electronically, II. Electronic Access evidence needed to demonstrate efficacy including attachments, to https:// of a targeted therapy across molecular Persons with access to the internet www.regulations.gov will be posted to subsets within a disease where some may obtain the guidance at either the docket unchanged. Because your molecular alterations may occur at low https://www.fda.gov/Drugs/Guidance comment will be made public, you are frequencies. ComplianceRegulatoryInformation/ solely responsible for ensuring that your In recent years, advances in our Guidances/default.htm, https:// comment does not include any understanding of the molecular www.fda.gov/BiologicsBloodVaccines/ confidential information that you or a pathology of many diseases have led to GuidanceComplianceRegulatory third party may not wish to be posted, the development of targeted therapies. Information/Guidances/default.htm, or such as medical information, your or Although variability in drug response https://www.regulations.gov. anyone else’s Social Security number, or has long been recognized in drug Dated: October 10, 2018. confidential business information, such development, targeted therapies present Leslie Kux, as a manufacturing process. Please note new challenges in addressing the Associate Commissioner for Policy. that if you include your name, contact heterogeneity in drug response because [FR Doc. 2018–22437 Filed 10–15–18; 8:45 am] information, or other information that the pharmacological effect of a targeted identifies you in the body of your BILLING CODE 4164–01–P therapy is often related to a particular comments, that information will be molecular alteration (e.g., a mutation, posted on https://www.regulations.gov. gene fusion, epigenetic change, etc.). DEPARTMENT OF HEALTH AND • If you want to submit a comment Many clinically defined diseases are HUMAN SERVICES with confidential information that you influenced or caused by a range of do not wish to be made available to the different molecular alterations, some of Food and Drug Administration public, submit the comment as a which may be rare, that impact a written/paper submission and in the [Docket No. FDA–2018–D–3268] manner detailed (see ‘‘Written/Paper common target protein or pathway involved in the disease pathogenesis. Rare Diseases: Early Drug Submissions’’ and ‘‘Instructions’’). This heterogeneity in the molecular Development and the Role of Pre- Written/Paper Submissions etiology of a given disease can result in Investigational New Drug Application differential effects of a targeted therapy Submit written/paper submissions as Meetings; Draft Guidance for Industry; follows: among patients with the same disease Availability • Mail/Hand delivery/Courier (for but who have different molecular AGENCY: Food and Drug Administration, written/paper submissions): Dockets alterations. Therefore, the type and HHS. Management Staff (HFA–305), Food and quantity of evidence that is needed to ACTION: Notice of availability. Drug Administration, 5630 Fishers demonstrate efficacy across molecular Lane, Rm. 1061, Rockville, MD 20852. subsets within a disease needs to be SUMMARY: The Food and Drug • For written/paper comments clearly specified. Administration (FDA or Agency) is submitted to the Dockets Management This guidance addresses the following announcing the availability of a draft Staff, FDA will post your comment, as important topics in evaluating the guidance for industry entitled ‘‘Rare well as any attachments, except for benefits and risks of targeted Diseases: Early Drug Development and information submitted, marked and therapeutics within a disease where the Role of Pre-Investigational New identified, as confidential, if submitted some molecular alterations may occur at Drug Application Meetings.’’ The as detailed in ‘‘Instructions.’’ low frequencies: purpose of this draft guidance is to Instructions: All submissions received • Identification of patients for inclusion assist sponsors of drug and biological must include the Docket No. FDA– in clinical trials products for the treatment of rare 2018–D–3268 for ‘‘Rare Diseases: Early • Interpretation of study results and diseases in planning and conducting Drug Development and the Role of Pre- generalizability of findings to the more efficient and productive pre- Investigational New Drug Application study population investigational new drug application Meetings; Draft Guidance for Industry.’’ • Benefit-risk determination and (pre-IND) meetings. Drug development Received comments will be placed in therapeutic product labeling for rare diseases has many challenges the docket and, except for those • Refining the indicated population related to the nature of these diseases. submitted as ‘‘Confidential after the initial approval This draft guidance is intended to Submissions,’’ publicly viewable at This final guidance incorporates advance and facilitate the development https://www.regulations.gov or at the public comments to the draft guidance of drugs and biological products for the Dockets Management Staff between 9 published in December of 2017 and treatment of rare diseases. a.m. and 4 p.m., Monday through includes minimal revisions for clarity. DATES: Submit either electronic or Friday. This guidance is being issued written comments on the draft guidance • Confidential Submissions—To consistent with FDA’s good guidance by December 17, 2018 to ensure that the submit a comment with confidential practices regulation (21 CFR 10.115). Agency considers your comment on this information that you do not wish to be The guidance represents the current draft guidance before it begins work on made publicly available, submit your amozie on DSK3GDR082PROD with NOTICES1 thinking of FDA on ‘‘Developing the final version of the guidance. comments only as a written/paper Targeted Therapies in Low-Frequency ADDRESSES: You may submit comments submission. You should submit two Molecular Subsets of a Disease.’’ It does on any guidance at any time as follows: copies total. One copy will include the not establish any rights for any person information you claim to be confidential and is not binding on FDA or the public. Electronic Submissions with a heading or cover note that states You can use an alternative approach if Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS it satisfies the requirements of the following way: CONFIDENTIAL INFORMATION.’’ The VerDate Sep<11>2014 18:44 Oct 15, 2018 Jkt 247001 PO 00000 Frm 00036 Fmt 4703 Sfmt 4703 E:\FR\FM\16OCN1.SGM 16OCN1


Document Created: 2018-10-15 23:42:01
Document Modified: 2018-10-15 23:42:01
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice of availability.
DatesThe announcement of the guidance is published in the Federal Register on October 16, 2018.
ContactMichael 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.
FR Citation83 FR 52222 
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