82 FR 60021 - Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Draft Guidance for Industry; Availability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)
Food and Drug Administration
Federal Register Volume 82, Issue 241 (December 18, 2017)
| Page Range | 60021-60022 | |
| FR Document | 2017-27156 |
[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] ----------------------------------------------------------------------- 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[Docket No. FDA-2017-D-6617] Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS.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. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.''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 DATES: Submit either electronic or written comments on the draft guidance by February 16, 2018 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.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
![Federal Register / Vol. 82, No. 241 / Monday, December 18, 2017 / Notices 60021
0910–0572. Concerning the immediate DATES: Submit either electronic or • Confidential Submissions—To
container label and outer container or written comments on the draft guidance submit a comment with confidential
package, in the Federal Register of by February 16, 2018 to ensure that the information that you do not wish to be
December 18, 2014 (79 FR 75506), we Agency considers your comment on this made publicly available, submit your
published a proposed rule on the draft guidance before it begins work on comments only as a written/paper
electronic distribution of prescribing the final version of the guidance. submission. You should submit two
information for human prescription ADDRESSES: You may submit comments copies total. One copy will include the
drugs, including biological products. In on any guidance at any time as follows: information you claim to be confidential
Section VII, Paperwork Reduction Act of with a heading or cover note that states
1995, we estimated the burden to design Electronic Submissions ‘‘THIS DOCUMENT CONTAINS
(including revisions), test, and produce Submit electronic comments in the CONFIDENTIAL INFORMATION.’’ The
the label for a drug’s immediate following way: Agency will review this copy, including
container and outer container or • Federal eRulemaking Portal: the claimed confidential information, in
package, as set forth in 21 CFR part 201 https://www.regulations.gov. Follow the its consideration of comments. The
and other sections in subpart A and instructions for submitting comments. second copy, which will have the
subpart B. Comments submitted electronically, claimed confidential information
including attachments, to https:// redacted/blacked out, will be available
III. Electronic Access
www.regulations.gov will be posted to for public viewing and posted on
Persons with access to the internet the docket unchanged. Because your https://www.regulations.gov. Submit
may obtain the draft guidance at either comment will be made public, you are both copies to the Dockets Management
https://www.fda.gov/Drugs/Guidance solely responsible for ensuring that your Staff. If you do not wish your name and
ComplianceRegulatoryInformation/ comment does not include any contact information to be made publicly
Guidances/default.htm, confidential information that you or a available, you can provide this
https;www.fda.gov/ third party may not wish to be posted, information on the cover sheet and not
BiologicsBloodVaccines/Guidance such as medical information, your or in the body of your comments and you
ComplianceRegulatoryInformation/ anyone else’s Social Security number, or must identify this information as
default.htm, or https:// confidential business information, such ‘‘confidential.’’ Any information marked
www.regulations.gov. as a manufacturing process. Please note as ‘‘confidential’’ will not be disclosed
Dated: December 12, 2017. that if you include your name, contact except in accordance with 21 CFR 10.20
Leslie Kux, information, or other information that and other applicable disclosure law. For
identifies you in the body of your more information about FDA’s posting
Associate Commissioner for Policy.
comments, that information will be of comments to public dockets, see 80
[FR Doc. 2017–27133 Filed 12–15–17; 8:45 am]
posted on https://www.regulations.gov. FR 56469, September 18, 2015, or access
BILLING CODE 4164–01–P
• If you want to submit a comment the information at: https://www.gpo.gov/
with confidential information that you fdsys/pkg/FR-2015-09-18/pdf/2015-
do not wish to be made available to the 23389.pdf.
DEPARTMENT OF HEALTH AND
public, submit the comment as a Docket: For access to the docket to
HUMAN SERVICES
written/paper submission and in the read background documents or the
Food and Drug Administration manner detailed (see ‘‘Written/Paper electronic and written/paper comments
Submissions’’ and ‘‘Instructions’’). received, go to https://
www.regulations.gov and insert the
[Docket No. FDA–2017–D–6617] Written/Paper Submissions docket number, found in brackets in the
Developing Targeted Therapies in Low- Submit written/paper submissions as heading of this document, into the
Frequency Molecular Subsets of a follows: ‘‘Search’’ box and follow the prompts
Disease; Draft Guidance for Industry; • Mail/Hand delivery/Courier (for and/or go to the Dockets Management
Availability written/paper submissions): Dockets Staff, 5630 Fishers Lane, Rm. 1061,
Management Staff (HFA–305), Food and Rockville, MD 20852.
AGENCY: Food and Drug Administration, Drug Administration, 5630 Fishers You may submit comments on any
HHS. Lane, Rm. 1061, Rockville, MD 20852. guidance at any time (see 21 CFR
ACTION: Notice of availability. • For written/paper comments 10.115(g)(5)).
submitted to the Dockets Management Submit written requests for single
SUMMARY: The Food and Drug Staff, FDA will post your comment, as copies of the draft guidance to the
Administration (FDA or Agency) is well as any attachments, except for Division of Drug Information, Center for
announcing the availability of a draft information submitted, marked and Drug Evaluation and Research, Food
guidance for industry entitled identified, as confidential, if submitted and Drug Administration, 10001 New
‘‘Developing Targeted Therapies in as detailed in ‘‘Instructions.’’ Hampshire Ave., Hillandale Building,
Low-Frequency Molecular Subsets of a Instructions: All submissions received 4th Floor, Silver Spring, MD 20993–
Disease.’’ The purpose of this guidance must include the Docket No. FDA– 0002; or the Office of Communication,
is to describe the FDA’s current 2017–D–6617 for ‘‘Developing Targeted Outreach, and Development, Center for
recommendations on how to group Therapies in Low-Frequency Molecular Biologics Evaluation and Research,
patients with different molecular Subsets of a Disease.’’ Received Food and Drug Administration, 10903
daltland on DSKBBV9HB2PROD with NOTICES
alterations for eligibility in clinical comments will be placed in the docket New Hampshire Ave., Bldg. 71, Rm.
trials; and general approaches to and, except for those submitted as 3128, Silver Spring, MD 20993–0002.
evaluating the benefits and risks of ‘‘Confidential Submissions,’’ publicly Send one self-addressed adhesive label
targeted therapeutics within a clinically viewable at https://www.regulations.gov to assist that office in processing your
defined disease where some molecular or at the Dockets Management Staff requests. See the SUPPLEMENTARY
alterations may occur at low between 9 a.m. and 4 p.m., Monday INFORMATION section for electronic
frequencies. through Friday. access to the draft guidance document.
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![60022 Federal Register / Vol. 82, No. 241 / Monday, December 18, 2017 / Notices
FOR FURTHER INFORMATION CONTACT: • Benefit-risk determination and Therapeutic Products.’’ This draft
Michael Pacanowski, Center for Drug therapeutic product labeling guidance is intended to assist sponsors
Evaluation and Research, Food and • Refining the indicated population of clinical investigations of therapeutic
Drug Administration, 10903 New after the initial approval products that also include
Hampshire Ave., Bldg. 71, Rm. 7301, In addition to comments on the investigational in vitro diagnostics
Silver Spring, MD 20993–0002, 301– general content of the draft guidance, (IVDs) and institutional review boards
796–3919; or Stephen Ripley, Center for FDA requests input on whether the (IRBs) that review such investigations in
Biologics Evaluation and Research, principles described for grouping complying with the Investigational
Food and Drug Administration, 10903 molecular subsets for clinical trial Device Exemption (IDE) regulation. This
New Hampshire Ave., Bldg. 71, Rm. enrollment should be limited to diseases draft guidance is also intended to assist
7301, Silver Spring, MD 20993–0002, with low-frequency molecular FDA staff participating in the review of
240–402–7911. alterations or whether they could be these investigations. This draft guidance
SUPPLEMENTARY INFORMATION: broadly applicable to all targeted is not final nor is it in effect at this time.
therapies. DATES: Submit either electronic or
I. Background This draft guidance is being issued written comments on the draft guidance
FDA is announcing the availability of consistent with FDA’s good guidance by March 19, 2018 to ensure that the
a draft guidance for industry entitled practices regulation (21 CFR 10.115). Agency considers your comment on this
‘‘Developing Targeted Therapies in The draft guidance, when finalized, will draft guidance before it begins work on
Low-Frequency Molecular Subsets of a represent the current thinking of FDA the final version of the guidance.
Disease.’’ This guidance is intended to on ‘‘Developing Targeted Therapies in ADDRESSES: You may submit comments
assist sponsors in designing drug Low-Frequency Molecular Subsets of a on any guidance at any time as follows:
development programs to generate the Disease.’’ It does not establish any rights
evidence needed to demonstrate efficacy for any person and is not binding on Electronic Submissions
of a targeted therapy across subsets of FDA or the public. You can use an Submit electronic comments in the
patients with different underlying alternative approach if it satisfies the following way:
molecular alterations within a disease, requirements of the applicable statutes • Federal eRulemaking Portal:
where some molecular alterations may and regulations. This guidance is not https://www.regulations.gov. Follow the
occur at low frequencies. subject to Executive Order 12866. instructions for submitting comments.
In recent years, advances in our Comments submitted electronically,
understanding of the molecular II. Electronic Access
including attachments, to https://
pathology of many diseases have led to Persons with access to the internet www.regulations.gov will be posted to
the development of targeted therapies. may obtain the draft guidance at either the docket unchanged. Because your
Although variability in drug response https://www.fda.gov/Drugs/Guidance comment will be made public, you are
has long been recognized in drug ComplianceRegulatoryInformation/ solely responsible for ensuring that your
development, targeted therapies present Guidances/default.htm, https:// comment does not include any
new challenges in addressing the www.fda.gov/BiologicsBloodVaccines/ confidential information that you or a
heterogeneity in drug response because GuidanceComplianceRegulatory third party may not wish to be posted,
the pharmacological effect of a targeted Information/Guidances/default.htm, or such as medical information, your or
therapy is often related to a particular https://www.regulations.gov. anyone else’s Social Security number, or
molecular alteration (e.g., a mutation, Dated: December 12, 2017. confidential business information, such
gene fusion, epigenetic change, etc.). Leslie Kux, as a manufacturing process. Please note
Many clinically defined diseases are that if you include your name, contact
Associate Commissioner for Policy.
caused by a range of different molecular information, or other information that
[FR Doc. 2017–27156 Filed 12–15–17; 8:45 am]
alterations, some of which may occur at identifies you in the body of your
BILLING CODE 4164–01–P
low frequencies, that impact a common comments, that information will be
protein or pathway involved in the posted on https://www.regulations.gov.
disease pathogenesis. In a population of
DEPARTMENT OF HEALTH AND • If you want to submit a comment
patients with the same clinical disease, with confidential information that you
HUMAN SERVICES
the heterogeneity in the molecular do not wish to be made available to the
etiology may result in different Food and Drug Administration public, submit the comment as a
responses to a particular therapy. written/paper submission and in the
However, certain targeted therapies may [Docket No. FDA–2017–N–6356]
manner detailed (see ‘‘Written/Paper
be effective in multiple groups of Submissions’’ and ‘‘Instructions’’).
patients that have different underlying Investigational In Vitro Diagnostics
molecular alterations. Therefore, FDA is Used in Clinical Investigations of Written/Paper Submissions
providing guidance on the type and Therapeutic Products; Draft Guidance Submit written/paper submissions as
quantity of evidence that can for Industry, Food and Drug follows:
demonstrate efficacy across molecular Administration Staff, Sponsors, and • Mail/Hand delivery/Courier (for
subsets within a disease. Institutional Review Boards; written/paper submissions): Dockets
This guidance addresses the following Availability Management Staff (HFA–305), Food and
important topics in evaluating the AGENCY: Food and Drug Administration, Drug Administration, 5630 Fishers
benefits and risks of targeted HHS. Lane, Rm. 1061, Rockville, MD 20852.
daltland on DSKBBV9HB2PROD with NOTICES
therapeutics within a disease where ACTION: Notice of availability. • For written/paper comments
some molecular alterations may occur at submitted to the Dockets Management
low frequencies: SUMMARY: The Food and Drug Staff, FDA will post your comment, as
• Identification of patients for inclusion Administration (FDA or Agency) is well as any attachments, except for
in clinical trials announcing the availability of the draft information submitted, marked and
• Interpretation of study results and guidance entitled ‘‘Investigational IVDs identified, as confidential, if submitted
generalizability of findings Used in Clinical Investigations of as detailed in ‘‘Instructions.’’
VerDate Sep<11>2014 17:53 Dec 15, 2017 Jkt 244001 PO 00000 Frm 00023 Fmt 4703 Sfmt 4703 E:\FR\FM\18DEN1.SGM 18DEN1](https://thefederalregister.org/doc/82_FR_60262/page/2.svg)
Document Created: 2017-12-15 23:54:46
Document Modified: 2017-12-15 23:54:46
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| 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. | |
| 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. | |
| FR Citation | 82 FR 60021 |
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