81 FR 30310 - Considerations for Use of Histopathology and Its Associated Methodologies To Support Biomarker Qualification; Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 81, Issue 94 (May 16, 2016)
Food and Drug Administration
Federal Register Volume 81, Issue 94 (May 16, 2016)
| Page Range | 30310-30311 | |
| FR Document | 2016-11438 |
[Federal Register Volume 81, Number 94 (Monday, May 16, 2016)] [Notices] [Pages 30310-30311] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2016-11438] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0872] Considerations for Use of Histopathology and Its Associated Methodologies To Support Biomarker Qualification; Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification.'' This guidance is intended to assist submitters of a biomarker for qualification that conduct nonclinical biomarker qualification studies in which histopathology is used as a reference or truth standard. This guidance discusses the processes that we recommend be considered when generating histopathology data to be included in biomarker studies and outlines the scientific standards recommended for histopathology used in nonclinical biomarker characterization and qualification. The recommendations in this guidance are intended for confirmatory studies in nonclinical biomarker qualification that justify the proposed context of use, where scientifically rigorous evaluation of biomarker performance in relation to histopathologic changes is essential. The principles outlined in this guidance are also applicable to exploratory nonclinical biomarker studies. This guidance finalizes the draft guidance ``Use of Histology in Biomarker Qualification Studies,'' issued in December 2011. DATES: Submit either electronic or written comments on Agency guidances at any time. ADDRESSES: You may submit comments as follows: Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: http://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Division of Dockets Management, 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-2011-D-0872 for ``Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification; Guidance for Industry; Availability.'' Received comments will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov. Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. 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. Send one self- addressed adhesive label to assist that office in processing [[Page 30311]] your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. FOR FURTHER INFORMATION CONTACT: Elizabeth Hausner, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4145, Silver Spring, MD 20993-0002, 301- 796-1084. SUPPLEMENTARY INFORMATION: I. Background FDA is announcing the availability of a guidance for industry entitled ``Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification.'' The FDA Critical Path Initiative identified the discovery, characterization, qualification, and use of biomarkers as important for improving the efficiency and success rate of medical product development. Biomarkers have been broadly applied to describe the following: Structural features from the molecular to the anatomic level (e.g., genetic composition, receptor expression patterns, radiographic appearances); Biochemical measurements (e.g., serum levels of electrolytes, cardiac troponins); and Physiologic organ system function tests (e.g., creatinine clearance, pulmonary function tests, cardiac ejection fraction, electrocardiography). The type of study reports to be submitted in support of a biomarker qualification will depend upon the proposed context of use and the ultimate goal of the submission. The proposed context of use dictates the depth, extent, and rigor of the supporting data for the biomarker. If a biomarker becomes qualified, analytically valid measurements of it can be relied upon to have a specific and interpretable meaning (e.g., physiologic, toxicologic, pharmacologic, or clinical) in drug development and regulatory decision-making. Industry can then employ the biomarker for the qualified context of use during premarketing drug development, and FDA reviewers can be confident about its qualified context of use without the need to reconfirm its applicability or utility. Accordingly, data supporting qualification of a nonclinical biomarker should be reliable, repeatable, and of assured integrity. In the Federal Register of December 30, 2011 (76 FR 82306), FDA announced the availability of a draft guidance entitled ``Use of Histology in Biomarker Qualification Studies.'' The Agency received several comments from the pharmaceutical industry and others. We have carefully considered the comments and have made the following changes in response to the comments: (1) Changed the title of the guidance to ``Considerations for Use of Histopathology and Its Associated Methodologies to Support Biomarker Qualification''; (2) clarified the scope of the guidance; (3) added more information concerning data used to support biomarker qualification; (4) confirmed and clarified the rationale for assessment of outcomes without knowledge of group assignments in confirmatory studies; and (5) clarified the distinction between biomarker sensitivity and specificity. In addition we have made editorial changes to improve clarity. This guidance finalizes the draft guidance issued in December 2011. 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 considerations for the use of histopathology and its associated methodologies to support biomarker qualification. 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 This guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information in this guidance were approved under OMB control numbers 0910-0001 for submissions related to 21 CFR 314, and 0910-0014 for submissions related to 21 CFR 312. III. Electronic Access Persons with access to the Internet may obtain the document at either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov. Dated: May 10, 2016. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2016-11438 Filed 5-13-16; 8:45 am] BILLING CODE 4164-01-P
![30310 Federal Register / Vol. 81, No. 94 / Monday, May 16, 2016 / Notices
October 1, 2012, with the understanding nonclinical biomarker qualification that 2011–D–0872 for ‘‘Considerations for
that the data set would expand in future justify the proposed context of use, Use of Histopathology and Its
rulemaking years with the adoption of where scientifically rigorous evaluation Associated Methodologies to Support
additional quality measures. Relevant of biomarker performance in relation to Biomarker Qualification; Guidance for
data elements contained in other well- histopathologic changes is essential. Industry; Availability.’’ Received
known and clinically established data The principles outlined in this guidance comments will be placed in the docket
sets, including but not limited to the are also applicable to exploratory and, except for those submitted as
Minimum Data Set 3.0 (MDS 3.0) and nonclinical biomarker studies. This ‘‘Confidential Submissions,’’ publicly
CARE, were incorporated into the LTCH guidance finalizes the draft guidance viewable at http://www.regulations.gov
CARE Data Set V1.01, V2.00 and V2.01. ‘‘Use of Histology in Biomarker or at the Division of Dockets
LTCH CARE Data Set V3.00 will be Qualification Studies,’’ issued in Management between 9 a.m. and 4 p.m.,
implemented April 1, 2016. Form December 2011. Monday through Friday.
Number: CMS–10409 (OMB control DATES: Submit either electronic or
• Confidential Submissions—To
number: 0938–1163); Frequency: written comments on Agency guidances submit a comment with confidential
Occasionally; Affected Public: Private at any time. information that you do not wish to be
Sector: Business or other for-profit and made publicly available, submit your
ADDRESSES: You may submit comments comments only as a written/paper
not-for-profit institutions; Number of
Respondents: 424; Total Annual as follows: submission. You should submit two
Responses: 405,344; Total Annual Electronic Submissions copies total. One copy will include the
Hours: 328,346. (For policy questions information you claim to be confidential
Submit electronic comments in the with a heading or cover note that states
regarding this collection contact Staci
following way: ‘‘THIS DOCUMENT CONTAINS
Payne at 410–786–2838.)
• Federal eRulemaking Portal: http:// CONFIDENTIAL INFORMATION.’’ The
Dated: May 11, 2016. www.regulations.gov. Follow the Agency will review this copy, including
William N. Parham, III, instructions for submitting comments. the claimed confidential information, in
Director, Paperwork Reduction Staff, Office Comments submitted electronically, its consideration of comments. The
of Strategic Operations and Regulatory including attachments, to http://
Affairs. second copy, which will have the
www.regulations.gov will be posted to claimed confidential information
[FR Doc. 2016–11500 Filed 5–13–16; 8:45 am] the docket unchanged. Because your redacted/blacked out, will be available
BILLING CODE 4120–01–P comment will be made public, you are for public viewing and posted on http://
solely responsible for ensuring that your www.regulations.gov. Submit both
comment does not include any copies to the Division of Dockets
DEPARTMENT OF HEALTH AND confidential information that you or a
HUMAN SERVICES Management. If you do not wish your
third party may not wish to be posted, name and contact information to be
such as medical information, your or made publicly available, you can
Food and Drug Administration
anyone else’s Social Security number, or provide this information on the cover
[Docket No. FDA–2011–D–0872] confidential business information, such sheet and not in the body of your
as a manufacturing process. Please note comments and you must identify this
Considerations for Use of that if you include your name, contact
Histopathology and Its Associated information as ‘‘confidential.’’ Any
information, or other information that information marked as ‘‘confidential’’
Methodologies To Support Biomarker identifies you in the body of your
Qualification; Guidance for Industry; will not be disclosed except in
comments, that information will be accordance with 21 CFR 10.20 and other
Availability posted on http://www.regulations.gov. applicable disclosure law. For more
AGENCY: Food and Drug Administration, • If you want to submit a comment information about FDA’s posting of
HHS. with confidential information that you comments to public dockets, see 80 FR
ACTION: Notice of availability. do not wish to be made available to the 56469, September 18, 2015, or access
public, submit the comment as a the information at: http://www.fda.gov/
SUMMARY: The Food and Drug written/paper submission and in the regulatoryinformation/dockets/
Administration (FDA) is announcing the manner detailed (see ‘‘Written/Paper default.htm.
availability of a guidance for industry Submissions’’ and ‘‘Instructions’’). Docket: For access to the docket to
entitled ‘‘Considerations for Use of read background documents or the
Histopathology and Its Associated Written/Paper Submissions
electronic and written/paper comments
Methodologies to Support Biomarker Submit written/paper submissions as received, go to http://
Qualification.’’ This guidance is follows: www.regulations.gov and insert the
intended to assist submitters of a • Mail/Hand delivery/Courier (for docket number, found in brackets in the
biomarker for qualification that conduct written/paper submissions): Division of heading of this document, into the
nonclinical biomarker qualification Dockets Management (HFA–305), Food ‘‘Search’’ box and follow the prompts
studies in which histopathology is used and Drug Administration, 5630 Fishers and/or go to the Division of Dockets
as a reference or truth standard. This Lane, Rm. 1061, Rockville, MD 20852. Management, 5630 Fishers Lane, Rm.
guidance discusses the processes that • For written/paper comments 1061, Rockville, MD 20852.
we recommend be considered when submitted to the Division of Dockets Submit written requests for single
asabaliauskas on DSK3SPTVN1PROD with NOTICES
generating histopathology data to be Management, FDA will post your copies of this guidance to the Division
included in biomarker studies and comment, as well as any attachments, of Drug Information, Center for Drug
outlines the scientific standards except for information submitted, Evaluation and Research, Food and
recommended for histopathology used marked and identified, as confidential, Drug Administration, 10001 New
in nonclinical biomarker if submitted as detailed in Hampshire Ave., Hillandale Building,
characterization and qualification. The ‘‘Instructions.’’ 4th Floor, Silver Spring, MD 20993–
recommendations in this guidance are Instructions: All submissions received 0002. Send one self-addressed adhesive
intended for confirmatory studies in must include the Docket No. FDA– label to assist that office in processing
VerDate Sep<11>2014 18:48 May 13, 2016 Jkt 238001 PO 00000 Frm 00074 Fmt 4703 Sfmt 4703 E:\FR\FM\16MYN1.SGM 16MYN1](https://thefederalregister.org/doc/81_FR_30404/page/1.svg)
![Federal Register / Vol. 81, No. 94 / Monday, May 16, 2016 / Notices 30311
your requests. See the SUPPLEMENTARY received several comments from the DEPARTMENT OF HEALTH AND
INFORMATION section for electronic pharmaceutical industry and others. We HUMAN SERVICES
access to the guidance document. have carefully considered the comments
FOR FURTHER INFORMATION CONTACT: and have made the following changes in Food and Drug Administration
Elizabeth Hausner, Center for Drug response to the comments: (1) Changed [Docket No. FDA–2011–D–0514]
Evaluation and Research, Food and the title of the guidance to
Drug Administration, 10903 New ‘‘Considerations for Use of Postmarket Surveillance Under Section
Hampshire Ave., Bldg. 22, Rm. 4145, Histopathology and Its Associated 522 of the Federal Food, Drug, and
Silver Spring, MD 20993–0002, 301– Methodologies to Support Biomarker Cosmetic Act; Guidance for Industry
796–1084. Qualification’’; (2) clarified the scope of and Food and Drug Administration
SUPPLEMENTARY INFORMATION: the guidance; (3) added more Staff; Availability
I. Background information concerning data used to AGENCY: Food and Drug Administration,
support biomarker qualification; (4) HHS.
FDA is announcing the availability of confirmed and clarified the rationale for ACTION: Notice of availability.
a guidance for industry entitled assessment of outcomes without
‘‘Considerations for Use of knowledge of group assignments in SUMMARY: The Food and Drug
Histopathology and Its Associated confirmatory studies; and (5) clarified Administration (FDA or Agency) is
Methodologies to Support Biomarker the distinction between biomarker announcing the availability of the
Qualification.’’ The FDA Critical Path guidance entitled ‘‘Postmarket
sensitivity and specificity. In addition
Initiative identified the discovery, Surveillance Under Section 522 of the
we have made editorial changes to
characterization, qualification, and use Federal Food, Drug, and Cosmetic Act.’’
of biomarkers as important for improve clarity. This guidance finalizes
This guidance is intended to assist
improving the efficiency and success the draft guidance issued in December
manufacturers of devices subject to
rate of medical product development. 2011. section 522 postmarket surveillance
Biomarkers have been broadly applied This guidance is being issued orders by providing an overview of the
to describe the following: consistent with FDA’s good guidance Federal Food, Drug, and Cosmetic Act
• Structural features from the practices regulation (21 CFR 10.115). (the FD&C Act), information on how to
molecular to the anatomic level (e.g., The guidance represents the current fulfill section 522 obligations, and
genetic composition, receptor thinking of FDA on considerations for recommendations on the format,
expression patterns, radiographic the use of histopathology and its content, and review of postmarket
appearances); associated methodologies to support surveillance plan submissions.
• Biochemical measurements (e.g., biomarker qualification. It does not DATES: Submit either electronic or
serum levels of electrolytes, cardiac establish any rights for any person and written comments on this guidance at
troponins); and is not binding on FDA or the public. any time. General comments on Agency
• Physiologic organ system function You can use an alternative approach if guidance documents are welcome at any
tests (e.g., creatinine clearance, it satisfies the requirements of the time.
pulmonary function tests, cardiac ADDRESSES: You may submit comments
applicable statutes and regulations.
ejection fraction, electrocardiography). as follows:
The type of study reports to be II. Paperwork Reduction Act of 1995
submitted in support of a biomarker Electronic Submissions
qualification will depend upon the This guidance contains information Submit electronic comments in the
proposed context of use and the collection provisions that are subject to following way:
ultimate goal of the submission. The review by the Office of Management and • Federal eRulemaking Portal: http://
proposed context of use dictates the Budget (OMB) under the Paperwork www.regulations.gov. Follow the
depth, extent, and rigor of the Reduction Act of 1995 (44 U.S.C. 3501– instructions for submitting comments.
supporting data for the biomarker. If a 3520). The collections of information in Comments submitted electronically,
biomarker becomes qualified, this guidance were approved under including attachments, to http://
analytically valid measurements of it OMB control numbers 0910–0001 for www.regulations.gov will be posted to
can be relied upon to have a specific submissions related to 21 CFR 314, and the docket unchanged. Because your
and interpretable meaning (e.g., 0910–0014 for submissions related to 21 comment will be made public, you are
physiologic, toxicologic, pharmacologic, CFR 312. solely responsible for ensuring that your
or clinical) in drug development and comment does not include any
regulatory decision-making. Industry III. Electronic Access confidential information that you or a
can then employ the biomarker for the third party may not wish to be posted,
Persons with access to the Internet
qualified context of use during such as medical information, your or
may obtain the document at either
premarketing drug development, and anyone else’s Social Security number, or
FDA reviewers can be confident about http://www.fda.gov/Drugs/Guidance
confidential business information, such
its qualified context of use without the ComplianceRegulatoryInformation/
as a manufacturing process. Please note
need to reconfirm its applicability or Guidances/default.htm or http:// that if you include your name, contact
utility. Accordingly, data supporting www.regulations.gov. information, or other information that
asabaliauskas on DSK3SPTVN1PROD with NOTICES
qualification of a nonclinical biomarker Dated: May 10, 2016. identifies you in the body of your
should be reliable, repeatable, and of Leslie Kux, comments, that information will be
assured integrity. Associate Commissioner for Policy. posted on http://www.regulations.gov.
In the Federal Register of December • If you want to submit a comment
[FR Doc. 2016–11438 Filed 5–13–16; 8:45 am]
30, 2011 (76 FR 82306), FDA announced with confidential information that you
the availability of a draft guidance BILLING CODE 4164–01–P do not wish to be made available to the
entitled ‘‘Use of Histology in Biomarker public, submit the comment as a
Qualification Studies.’’ The Agency written/paper submission and in the
VerDate Sep<11>2014 18:48 May 13, 2016 Jkt 238001 PO 00000 Frm 00075 Fmt 4703 Sfmt 4703 E:\FR\FM\16MYN1.SGM 16MYN1](https://thefederalregister.org/doc/81_FR_30404/page/2.svg)
Document Created: 2016-05-14 01:16:49
Document Modified: 2016-05-14 01:16:49
| 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 Agency guidances at any time. | |
| Contact | Elizabeth Hausner, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4145, Silver Spring, MD 20993-0002, 301- 796-1084. | |
| FR Citation | 81 FR 30310 |
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