Notice2026-09533
Biomarker Incubator: Urinary Kidney Safety Biomarkers; Request for Information
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Published
May 13, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA or Agency) is announcing a request for information regarding a regulatory science initiative. The aims of the initiative are to advance biomarker validation through the compilation of data from multiple sources and through a specific pilot project focused on aggregating data for biomarkers of drug-induced kidney injury. The purpose of this notice is to inform the public of the aims of this initiative, to encourage human data submission and sharing, and to identify opportunities to enhance interactions between relevant stakeholders and FDA. The Agency intends to use the information submitted to inform future activities related to data sharing, biomarker development, and broader translation of biomarkers of drug-induced kidney injury.
Full Text
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<title>Federal Register, Volume 91 Issue 92 (Wednesday, May 13, 2026)</title>
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[Federal Register Volume 91, Number 92 (Wednesday, May 13, 2026)]
[Notices]
[Pages 27056-27060]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-09533]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-N-0005]
Biomarker Incubator: Urinary Kidney Safety Biomarkers; Request
for Information
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for information.
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SUMMARY: The Center for Drug Evaluation and Research (CDER) of the Food
and Drug Administration (FDA or Agency) is announcing a request for
information regarding a regulatory science initiative. The aims of the
initiative are to advance biomarker validation through the compilation
of data from multiple sources and through a specific pilot project
focused on aggregating data for biomarkers of drug-induced kidney
injury. The purpose of this notice is to inform the public of the aims
of this initiative, to encourage human data submission and sharing, and
to identify opportunities to enhance interactions between relevant
stakeholders and FDA. The Agency
[[Page 27057]]
intends to use the information submitted to inform future activities
related to data sharing, biomarker development, and broader translation
of biomarkers of drug-induced kidney injury.
DATES: Either electronic or written comments on the notice must be
submitted by July 13, 2026.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of July 13, 2026. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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-2026-N-0005 for ``Biomarker Incubator: Urinary Kidney Safety
Biomarkers; Request for Information.'' Received comments filed in a
timely manner (see ADDRESSES) will be placed in the docket and, except
for those submitted as ``Confidential Submissions,'' will be publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Yvonne Knight, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 2142, Silver Spring, MD 20993, 301-796-
2133, <a href="/cdn-cgi/l/email-protection#025b746d6c6c672c496c6b656a76426466632c6a6a712c656d74"><span class="__cf_email__" data-cfemail="d58ca3babbbbb0fb9ebbbcb2bda195b3b1b4fbbdbda6fbb2baa3">[email protected]</span></a>, with the subject line ``Kidney
Biomarker for CDER.''
SUPPLEMENTARY INFORMATION:
I. Background
CDER in partnership with the Quantitative Medicine Center of
Excellence is undertaking a regulatory science initiative to aggregate
biomarker data from multiple sources (e.g., clinical trials from
multiple drug development programs) for the purpose of validating
biomarkers for use in drug development. This notice seeks to: (1)
inform the public of this initiative, herein referred to as the
``Biomarker Incubator''; (2) request voluntary submission of human data
to support the goals of the pilot phase of the Biomarker Incubator
initiative; and (3) obtain input on the scope and direction of the
Biomarker Incubator initiative.
The 21st Century Cures Act established a formal pathway for
biomarker qualification, codified under section 507 of the Federal
Food, Drug, and Cosmetic Act, through which FDA may qualify a biomarker
for a specific context of use in drug development following a
structured evidentiary review process. The qualification process often
relies on assembly of data from academic or industry-sponsored studies,
typically through consortia. Biomarker data are commonly generated
within individual drug development programs for various purposes, such
as to evaluate pharmacodynamic responses and safety in early phase
trials or to complement assessments of efficacy in later phase trials.
FDA may identify a need to characterize a biomarker to inform
regulatory decision-making where qualification activities are not being
considered. As such, FDA staff often undertake research efforts to
assemble human data from different programs to better characterize
biomarker relationships with outcomes and develop endpoints that may be
used to expedite drug development. Examples of disease areas where
these efforts have been undertaken by the Agency include pulmonary
hypertension, schizophrenia, and hepatitis C (Chen et al. 2013; Kalaria
et al. 2021; Kalaria et al. 2020). However, these biomarker
characterization studies are complicated by heterogeneity in data
collection protocols, the possibility that assays used to measure the
biomarker or biomarkers may not be valid, the absence of standardized
submission formats, and a limited volume of data (because such data are
viewed as exploratory and not uniformly submitted to FDA). Therefore,
CDER is seeking to develop infrastructure that
[[Page 27058]]
could help us understand best practices for biomarker data generation,
streamline processes for requesting voluntary data submission, and
create a platform to analyze data. Ultimately, improving CDER's ability
to evaluate novel biomarkers could facilitate the generation of higher
quality biomarker data, expanded use of novel biomarkers, more
consistent interpretation of findings from biomarker studies, and
development of novel endpoints that can support a range of regulatory
and drug development decisions. The initiative outlined in this notice
is intended to complement FDA's existing qualification framework by
strengthening FDA's review of formal qualification submissions and
advancing the use of biomarkers that may not be in the qualification
pipeline.
II. Pilot Project
FDA has focused on advancing the use of biomarkers of drug-induced
kidney injury (DIKI) as a pilot project under this Biomarker Incubator
initiative. In 2018, FDA qualified a panel of biomarkers (including the
six biomarkers listed in this notice) for use in conjunction with
traditional measures to aid in the detection of kidney tubular injury
in phase 1 trials with healthy volunteers when there is an a priori
concern that the drug may cause renal tubular injury in humans. The
qualification submission was based on data submitted jointly by the
Foundation for the National Institutes of Health Biomarkers Consortium
and the Predictive Safety Testing Consortium of the Critical Path
Institute (C-Path).
Following the qualification of the panel of six biomarkers, other
efforts were made to advance biomarker use in drug development. C-Path
created the Biomarker Data Repository (BmDR) in 2019, starting with a
focus on urinary kidney safety biomarkers with intent to expand to
other organ safety biomarkers. The goal of the BmDR is to compile and
provide stakeholders with large, reliable datasets containing masked,
deidentified nonclinical and clinical study data on translational
safety biomarkers. In May 2022, C-Path also convened the
``International 2022 Drug-induced Kidney Injury Biomarker Workshop.''
Participants in this workshop highlighted an unmet need for better
tools to detect DIKI at earlier and reversible stages, which would
protect study participants by reducing clinically significant DIKI.
Further, patient representatives attending the workshop expressed
desire to share their data to support safety and drug development.
As part of CDER's efforts to assess the performance and use of
qualified and exploratory biomarkers of DIKI in drug development, and
to complement the data accumulating through the BmDR, FDA began
aggregating data on urinary kidney safety biomarkers that had
previously been submitted to FDA. The Agency also requested voluntary
submission of data from specific companies that had generated such data
but had not yet submitted those data to FDA. These data were not
expected to be in the BmDR already and were limited in size and scope.
Specific urinary kidney safety biomarkers of interest for the
previously mentioned efforts and the current request include cystatin C
(CysC), osteopontin (OPN), kidney injury molecule-1 (KIM-1), N-acetyl-
[beta]-D-glucosaminidase (NAG), lipocalin-2 (LCN2)/neutrophil
gelatinase-associated lipocalin (NGAL), and apolipoprotein J (APOJ)/
clusterin (CLU). The specific objectives of FDA's pilot project for
urinary kidney safety biomarker data are to: (1) assess data
availability and quality; (2) pool data from a range of clinical trial
participants, drug programs, and phases of development; (3) perform
analyses characterizing intersubject and intrasubject variability,
expected ranges for subpopulations, time-course for changes, use and
quality of different assay methodologies, and the predictive
performance compared to conventional biomarkers; and (4) establish a
process and platform for identifying, requesting, receiving, storing,
and analyzing data to support biomarker use in drug development.
III. Request for Information
This request for information aims to provide an opportunity for
stakeholders--including both commercial drug developers and academic
investigators--to share with FDA deidentified subject-level data on
these biomarkers and experiences and challenges in applying these
biomarkers in drug development.
A. Voluntary Data Submission
If data use agreements allow and data owners are willing, FDA is
requesting that data owners submit any shareable human data that have
not already been or are not in the process of being submitted to FDA or
C-Path's BmDR. This submission can be accomplished under an existing
Investigational New Drug (IND) application, with a cover letter
indicating any data use restrictions, or under a new pre-IND (for
submissions that are not associated with an existing IND or need to be
isolated and deidentified from an existing IND). Additionally, data
owners may submit a response to this information request, including a
desired approach to facilitate voluntary submission of exploratory
data.
FDA emphasizes the importance of storing and sharing data using the
most updated terminology standards as outlined in the final guidance
for industry Providing Regulatory Submissions in Electronic Format--
Standardized Study Data (June 2021). Adherence to data standards may
improve data quality and reliability. The Agency requests that datasets
be submitted in Clinical Data Interchange Standards Consortium (CDISC)
format and contain deidentified subject-level data that includes
clinical and demographic information, pharmacokinetic data, and urinary
kidney safety biomarker data. Any dataset submitted should follow the
format of one record per subject per parameter per treatment group per
time point (if applicable). An example of a data structure that would
be acceptable is provided in Table 1. The study protocol or a protocol
synopsis, and NCT number, if available, should be included to aid in
data interpretation. A description of the assay for each biomarker
should also be submitted along with any available analytical validation
reports that support the reliability, accuracy, and precision of assays
used to measure the various urinary kidney safety biomarkers. The assay
description should include the analytical method (e.g., ELISA),
manufacturer, controls, lower limit of quantitation, within- and
between-run precision, assay linearity, and percent recovery.
Table 1--Data Structure Example
[Requested Data File Formats: .csv, .xlsx, .xpt, or .xml]
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Variable name Description Format Comment
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STUDYID............ Study ID........ Char.......
USUBJID............ Unique subject Char.......
ID.
[[Page 27059]]
TRTP............... Planned Char.......
treatment.
TRTA............... Actual treatment Char.......
SEX................ Sex............. Char....... M or F.
AGE................ Age at baseline. Num........ Years.
RACE............... Race............ Char.......
ETHNIC............. Ethnicity....... Char....... The ethnicity of the
subject. Submitters
should refer to the
guidance for
industry Collection
of Race and
Ethnicity Data in
Clinical Trials
(2016) regarding
the collection of
ethnicity.
COUNTRY............ Country......... Char....... Country of the
investigational
site in which the
subject
participated in the
trial.
ARM................ Description of Char....... Name of the arm to
planned arm. which the subject
was assigned. If
the subject was not
assigned to an arm,
ARM is null, and
ARMNRS is
populated. With the
exception of
studies that use
multistage arm
assignments, the
name provided must
be a value of ARM
in the Trial Arms
Dataset.
ARMNRS............. Reason ARM is Char....... A coded reason that
Null. Arm variables and/
or actual Arm
variables are null.
Examples: ``SCREEN
FAILURE``, ``NOT
ASSIGNED``,
``ASSIGNED, NOT
TREATED``,
``UNPLANNED
TREATMENT``. It is
assumed that if the
Arm and actual Arm
variables are null,
the same reason
applies to both Arm
and actual Arm.
HGT................ Baseline height. Num........ cm.
WGT................ Baseline weight. Num........ kg.
BMI................ Body mass index. Num........ kg/m2.
EGFR............... Baseline eGFR... Num........ ml/min per 1.73 m2.
CMAX............... Cmax............ Num........ ng/ml, if collected
for a drug.
TMAX............... Tmax............ Num........ H, if collected for
a drug.
AUCLAST............ AUC 0-last...... Num........ ng*h/ml, if
collected for a
drug.
AUCINF............. AUC 0-INF....... Num........ ng*h/ml, if
collected for a
drug.
ATP................ Analysis time Char....... e.g., Baseline, day
point. 1, (add time points
per schedule of
assessments).
LBNAM.............. Vender name..... Char....... The name or
identifier of the
laboratory/machine
that performed the
test.
PARAMCD............ Parameter code.. Char....... From CDISC SDTM
standards--2024:
KIM1: Kidney injury
molecule 1.
LCN2: Lipocalin-2,
also known as NGAL/
neutrophil
gelatinase-
associated
lipocalin.
NAGASE: N-acetyl-
beta-D-
glucosaminidase.
APOJ:
Apolipoprotein
J, also known as
CLU/clusterin.
CYSTATC: Cystatin
C.
OPN: Osteopontin.
CREAT:
Creatinine.
eGFR: Estimated
glomerular
filtration rate.
UACR: Urine
albumin-to-
creatinine
ratio.
UPCR: Urinary
protein-to-
creatinine
ratio.
UNITS.............. Parameter units. Char....... CDISC standards--
2024 (parameter--
urine creatinine
normalized
parameter):
KIM1: ng/mL--ng/mg.
LCN2: ng/mL--ng/mg.
NAGASE: U/mL--U/mg.
APOJ: ng/mL--ng/
mg.
CYSTATC: ng/mL--
ng/mg.
OPN: ng/mL--ng/
mg.
CREAT: mg/mL.
BASE............... Baseline Num........
parameter value.
AVAL............... Parameter value. Num........
AVALU.............. Parameter unit.. Char.......
CHG................ Change from Num........
baseline.
MHSEQ.............. Sequence number. Char....... The medical history
dataset includes
the subject's prior
history at the
start of the trial.
Examples of subject
medical history
information could
include general
medical history,
gynecological
history, and
primary diagnosis.
LBCAT.............. Category for lab Char....... e.g., urinalysis,
test. urine chemistry.
LBSPEC............. Specimen type... Char....... e.g., urine, serum.
LBLLOQ............. Lower limit of Num........ Same units as
quantitation. parameter.
LBULOQ............. Upper limit of Num........ Same units as
quantitation. parameter.
------------------------------------------------------------------------
B. Additional Information
CDER requests that stakeholders comment on the following topics:
1. To improve public health and more optimally inform drug
development, the Agency is interested in derisking the process for data
sharing, overall, and specifically, with regulatory authorities. For
this Biomarker Incubator initiative, efforts to request data
voluntarily have been piloted on a small scale (at the individual IND
level). If there are considerations or barriers that could be addressed
to support future data-sharing efforts, the Agency is interested in
addressing those considerations in future voluntary data requests.
2. FDA seeks to identify and prioritize potential topics related to
voluntary data sharing with interested parties for possible future
inclusion in public workshops. Please comment on specific topics that
may be of value for public
[[Page 27060]]
discussion. Topics can be related to specific data-sharing matters or
specific biomarkers of interest where discussion of translation would
facilitate coordinated research efforts.
3. Please provide input on specific biomarkers that are commonly
collected but not yet accepted as an endpoint and have the potential to
significantly support regulatory decisions related to safety or
efficacy, for which aggregation of data across multiple programs may
advance drug development.
IV. References
The following references are on display at the Dockets Management
Staff (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; these are not
available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a> as these
references are copyright protected. Some may be available at the
website address, if listed. Although FDA verified the website addresses
in this document, please note that websites are subject to change over
time.
Chen J, J Florian, W Carter, RD Fleischer, TS Hammerstrom, PR
Jadhav, W Zeng, J Murray, and D Birnkrant, 2013, Earlier Sustained
Virologic Response End Points for Regulatory Approval and Dose
Selection of Hepatitis C Therapies, Gastroenterology, 144(7):1450-
1455.e2, epub ahead of print March 5, 2013, doi: 10.1053/
j.gastro.2013.02.039.
Kalaria SN, TR Farchione, R Uppoor, M Mehta, Y Wang, and H Zhu,
2021, Extrapolation of Efficacy and Dose Selection in Pediatrics: A
Case Example of Atypical Antipsychotics in Adolescents With
Schizophrenia and Bipolar I Disorder, Journal of Clinical
Pharmacology, 61: S117-S124, doi: 10.1002/jcph.1836.
Kalaria SN, TR Farchione, MV Mathis, M Gopalakrishnan, I Younis, R
Uppoor, M Mehta, Y Wang, and H Zhu, 2020, Assessment of Similarity
in Antipsychotic Exposure-Response Relationships in Clinical Trials
Between Adults and Adolescents With Acute Exacerbation of
Schizophrenia, Journal of Clinical Pharmacology, 60(7): 848-859,
doi: 10.1002/jcph.1580.
(Authority: 21 CFR part 10 and 21 U.S.C. 357.)
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-09533 Filed 5-12-26; 8:45 am]
BILLING CODE 4164-01-P
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