Notice2026-19563
Improving Patient Access to Deceased Donor Islet Cells and Cell Products; Request for Information
Primary source
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Published
September 24, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug AdministrationHealth Resources and Services Administration
Abstract
The Department of Health and Human Services (HHS) is opening a public docket to solicit input, supporting data, and comments to assist HHS as it considers how best to regulate deceased donor islet cells and/or deceased donor islet cell products for the treatment of Type 1 diabetes (T1D). The purpose of this information is to allow HHS agencies to better understand how best to regulate these therapies, including whether and how regulation could differ between isolated and otherwise unmodified deceased donor islet cells and deceased donor islet cell products. In this request for information, HHS will specify the type where appropriate or will refer to both types under the umbrella term of islet therapies. HHS seeks information on whether sufficient publicly available information exists to establish standards for how to transplant deceased donor islet cells and/or develop deceased donor islet cell products, as well as whether other publicly available data exist to support their safe and effective use. Additionally, HHS seeks input on the possibility of defining unmodified deceased donor islet cells as organs, which would allow the procurement, allocation, and transplantation of these cells to be performed in accordance with applicable Organ Procurement and Transplantation Network (OPTN) policy and regulated by HRSA. Doing so would require OPTN establishing appropriate standards for safety, effectiveness, quality and consistency of islet cell processing and isolation, and surveillance and policies regarding the training and experience of transplant surgeons and transplant physicians in designated pancreatic islet cell transplant programs.
Full Text
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<title>Federal Register, Volume 91 Issue 184 (Thursday, September 24, 2026)</title>
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[Federal Register Volume 91, Number 184 (Thursday, September 24, 2026)]
[Notices]
[Pages 60632-60637]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-19563]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Health Resources and Services Administration
[Docket No. FDA-2026-N-10738]
Improving Patient Access to Deceased Donor Islet Cells and Cell
Products; Request for Information
AGENCY: Food and Drug Administration, Health Resources and Services
Administration, Department of Health and Human Services.
ACTION: Notice; request for information.
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SUMMARY: The Department of Health and Human Services (HHS) is opening a
public docket to solicit input, supporting data, and comments to assist
HHS as it considers how best to regulate deceased donor islet cells
and/or deceased donor islet cell products for the treatment of Type 1
diabetes (T1D). The purpose of this information is to allow HHS
agencies to better understand how best to regulate these therapies,
including whether and how regulation could differ between isolated and
otherwise unmodified deceased donor islet cells and deceased donor
islet cell products. In this request for information, HHS will specify
the type where appropriate or will refer to both types under the
umbrella term of islet therapies. HHS seeks information on whether
sufficient publicly available information exists to establish standards
for how to transplant deceased donor islet cells and/or develop
deceased donor islet cell products, as well as whether other publicly
available data exist to support their safe and effective
[[Page 60633]]
use. Additionally, HHS seeks input on the possibility of defining
unmodified deceased donor islet cells as organs, which would allow the
procurement, allocation, and transplantation of these cells to be
performed in accordance with applicable Organ Procurement and
Transplantation Network (OPTN) policy and regulated by HRSA. Doing so
would require OPTN establishing appropriate standards for safety,
effectiveness, quality and consistency of islet cell processing and
isolation, and surveillance and policies regarding the training and
experience of transplant surgeons and transplant physicians in
designated pancreatic islet cell transplant programs.
DATES: Either electronic or written comments on the notice must be
submitted by November 9, 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 November 9, 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-10738 for ``Improving Patient Access to Deceased Donor Islet
Cells and Cell Products; Request for Information.'' Received comments,
those filed in a timely manner (see ADDRESSES), will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
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: Phillip Kurs, Center for Biologics
Evaluation and Research, Food and Drug Administration, 240-402-7911;
Fraser Byrne, Health Resources and Services Administration, 240-472-
0297, or <a href="/cdn-cgi/l/email-protection#226a71606d6363624a5051430c454d54"><span class="__cf_email__" data-cfemail="cd859e8f828c8c8da5bfbeace3aaa2bb">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
T1D, a chronic autoimmune disease where a patient's immune system
destroys insulin-producing beta cells in the pancreas, remains a
significant public health problem affecting millions of people globally
with over 2 million individuals impacted in the United States. The Food
and Drug Administration (FDA) has made significant progress in
advancing treatments for T1D, moving beyond traditional insulin
replacement. Islet therapies offer a viable option for eligible
patients with T1D who meet strict criteria. To date, FDA has licensed
one deceased donor islet cell product, Lantidra, which is an allogeneic
pancreatic islet cellular therapy used in conjunction with concomitant
immunosuppression, indicated for the treatment of adults with T1D who
are unable to approach target hemoglobin A1c (HbA1c) because of current
repeated episodes of severe hypoglycemia despite intensive diabetes
management and education.
Islet cells and islet cell products, like Lantidra, may be
developed from whole pancreata, procured from multiple deceased organ
donors, and are not transplanted as whole pancreata. The National Organ
Transplant Act, 42 U.S.C. 274 and its implementing regulations at 42
CFR 121 authorize the Health Resources and Services Administration
(HRSA) and the OPTN to oversee organ donations, procurements, and
transplants.
The OPTN is charged with developing organ allocation policies and
managing the organ matching system and waiting list. Organs are a
scarce national resource where demand far outpaces supply--there are
currently over 100,000 people on the waiting list for an organ
transplant. Patients needing a pancreas transplant are added to this
national waitlist and charged a registration fee when added to the
list. These patient registration fees support most of the annual costs
of operating the OPTN. HRSA, as the federal agency overseeing the OPTN,
also provides oversight of OPTN member
[[Page 60634]]
organizations (including transplant hospitals and organ procurement
organizations) to ensure patient safety for donors and transplant
recipients, equitable organ allocation, and compliance with OPTN
policies.
Lantidra is licensed by FDA as a biological product under section
351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262). FDA's
regulation of Lantidra includes ensuring the safety and effectiveness
of Lantidra. FDA oversight covers the full manufacturing process for an
islet cell product, including multiple critical steps that can affect
product safety, purity, potency, viability, and sterility. This
oversight extends to manufacturers, processing facilities, quality
systems, product sponsors, and clinical administration of cellular
therapies prior to marketing and continuing throughout the lifecycle of
the product.
The Centers for Medicare & Medicaid Services (CMS) and the National
Institutes of Health (NIH) also have a limited role regarding
pancreatic islet cell transplantation. Section 733 of the Medicare
Prescription Drug, Improvement, and Modernization Act of 2003 (Pub. L.
108-173, 117 Stat. 2066, 2352) mandates that CMS cover the costs of the
transplantation of pancreatic islet cells, but only in the context of
an NIH-sponsored clinical trial. CMS also plays a role in its
regulation of Organ Procurement Organizations (OPO). Specifically, the
Pancreatic Islet Cell Transplantation Act of 2004 (Pub. L. 108-362, 118
Stat. 1703) requires that pancreata procured for use in islet cell
transplantation or islet cell transplantation research be counted in
performance metrics for OPO certification purposes.
II. Regulation of Deceased Donor Islet Cells and Cell Products
HHS is considering how to best regulate unmodified deceased donor
islet cells and cell products to ensure patients' access while ensuring
safety and effectiveness. To assist us in doing so, HHS seeks public
input regarding how best to regulate these islet therapies. For
example, we are seeking input to better understand whether sufficient
publicly available information exists to establish standards for
regulation of deceased donor islet cell products, which could
streamline sponsor development and FDA evaluation of Biologics License
Applications (BLAs) for such products, and specifically whether
publicly available data exist to support their safe and effective use.
Additionally, we are seeking input on the possibility of defining
deceased donor islet cells as organs, which would allow the
procurement, allocation, and transplantation of these cells to be
regulated via HRSA's oversight of the OPTN rather than by the FDA
pursuant to a BLA. Doing so would require OPTN establishing appropriate
standards for safety, effectiveness, manufacturing quality and
consistency, communicable disease control, and maintaining surveillance
activities.
Currently, sponsors seeking to market an unmodified deceased donor
islet cell product must submit a biologics license application under
section 351 of the PHS Act. As noted above, we are seeking input to
better understand whether sufficient publicly available information
exists to establish standards for regulation of deceased donor islet
cell products, which could streamline sponsor development and FDA
evaluation of BLAs for such products and whether other publicly
available data exist to support their safe and effective use. This is
not the first time FDA has solicited input from interested parties to
develop alternate approach to streamlining BLA development. For
example, in 1998, FDA solicited clinical outcome data to develop
proposed product standards and establishment and processing controls
for unrelated allogeneic peripheral and placental/umbilical cord blood
hematopoietic stem/progenitor cell products.\1\
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\1\ Request for Proposed Standards for Unrelated Allogeneic
Peripheral and Placental/Umbilical Cord Blood Hematopoietic Stem/
Progenitor Cell Products; Request for Comments (63 FR 2985, January
20, 1998).
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FDA reviewed the aggregate body of the submitted data, along with
the published literature, and determined collectively that the safety
and effectiveness of certain cord blood products had been established.
FDA subsequently issued a guidance \2\ document articulating standards
for those sponsors who wish to rely on the data submitted in the FDA
docket.
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\2\ See FDA's guidance ``BLA for Minimally Manipulated,
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for
Hematopoietic and Immunologic Reconstitution in Patients with
Disorders Affecting the Hematopoietic System,'' available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic</a>.
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III. Request for Public Comments
This request for information provides an opportunity for interested
parties and the public--including sponsors, patients, transplant
centers that may have participated in relevant studies, and other
interested individuals and groups--to provide HHS with input,
supporting data, and comments to assist HHS as it considers how best to
regulate deceased donor islet cell products for the treatment of T1D.
Specifically, HHS is interested in information that would help
establish standards for how to develop and transplant deceased donor
islet cell products and whether other publicly available data exist to
support their safe and effective use, including data around how such
cells and cell products are regulated and made available to patients
outside the United States.
In evaluating potential regulatory approaches regarding the
oversight of deceased donor islet cells and cell products, HHS is also
considering the broader scientific, operational, and public health
implications associated with the following proposed options. These
include potential additional oversight of islet cells by the OPTN under
HRSA's regulatory authority; whether reclassification of deceased donor
islet cells as organs could establish precedent for other donor-derived
cellular products; whether the OPTN framework, which was established to
oversee allocation of vascularized organs, is appropriate for islet
cellular therapies; and the potential effects of any regulatory change
on treatment effectiveness, patient safety, product quality, provider
participation, patient access, program costs, donor willingness, and
Federal oversight responsibilities. HHS seeks information to better
understand these considerations before determining whether any changes
to the current oversight framework are warranted.
IV.A Questions for Consideration Regarding Food and Drug Administration
Regulation
For deceased donor islet cell products that are intended to treat
certain adult T1D patients, HHS is seeking the submission of
information to determine if it would be possible to develop public
standards based on publicly available data, including non-clinical and
clinical data, and whether those data and the public standards would be
sufficient to demonstrate the safety and efficacy of deceased donor
islet cells product for certain subsets of patients with T1D. As part
of this effort, FDA is seeking information to develop a set of
standards to support licensure for deceased donor islet cell products
for the treatment of adults with T1D who are unable to approach target
HbA1c because of repeated episodes of severe hypoglycemia.
We seek input on the questions below. While the questions ask for
information that would help establish standards for how to develop and
[[Page 60635]]
manufacture deceased donor islet cell products and whether other
publicly available data exists to support their safe and effective use,
we welcome any additional comments related to standards for deceased
donor islet cells that may improve our understanding and advance our
public health mission. To help HHS review information efficiently,
please identify the question to which you are responding by its
associated category and number. If you are responding to more than one
question, please identify each question to which you are responding,
and categorize each response by question.
A. General
1. What publicly available data sources/information demonstrate
quality source material for creation of deceased donor islet cellular
products? Elements include, but are not limited to, donor eligibility,
pancreas procurement parameters, organ quality acceptance criteria, and
infectious disease testing. Information might include donor health
status, donor age, donor body mass index for organ quality acceptance
criteria, donor screening and testing records equivalent to the
information required by 21 CFR part 1271, subpart C for donor
eligibility; data on organ procurement procedures, ischemia time (warm/
cold), preservation methods, shipping containers and conditions for
organ procurement parameters; predefined acceptance criteria for organ
or deceased donor islet cell quality: size, fibrosis extent, and
results of all required communicable disease tests using FDA-licensed,
-approved, or -cleared test kits; performed by Clinical Laboratory
Improvement Amendments-certified laboratory for infectious disease
testing.
2. What publicly available data sources/information demonstrate
control of the manufacturing? Elements might include summary of control
strategy, process validation data and facility and Current Good
Manufacturing Practice (CGMP) compliance.
3. What publicly available data sources/information demonstrate
product quality and potency? Elements include characterization, release
tests, validated potency assays and lot-to-lot consistency data, and
other quality parameters.
4. What publicly available nonclinical toxicology data supports use
of existing immunosuppressive regimens?
a. Reproductive, developmental, and carcinogenic risk studies:
Should these studies be waived for sponsors using conventional
allogeneic islet products manufactured by methods frequently reported
in the scientific literature for these endpoints, as considered by
FDA.\3\
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\3\ See FDA's guidance ``Considerations for Allogeneic
Pancreatic Islet Cell Products,'' available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products</a>, Section III.F, p. 6.
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b. Novel route-of-administration safety data: Should animal model
safety studies for the delivery route be waived where sponsors propose
the standard percutaneous transhepatic portal vein delivery route?
5. What impact, if any, could reclassification of deceased donor
islet cells as ``organs'' have on the existing regulatory framework for
biological products regulated by FDA? What factors distinguish deceased
donor islet cells from other biological products that justifies
different regulatory treatment?
B. Data Sources
6. What types of information and data would be necessary to show
that publicly available real-world evidence (RWE) is relevant to
deceased donor allogeneic islet transplantation for the noted
indication:
a. FDA welcomes data and information on the volume and duration of
international clinical trial data.
b. Established and consistent clinical endpoints. Should FDA
continue to apply the same primary endpoint in evaluating RWE that FDA
considered in the 2009 Islet Guidance--composite HbA1c <=6.5% and
elimination of severe hypoglycemia to facilitate direct comparison with
endpoint routinely applied in Collaborative Islet Transplant Registry
(CITR) and international registries? \4\
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\4\ See FDA's guidance ``Considerations for Allogeneic
Pancreatic Islet Cell Products,'' available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products</a>, Section IV.D.1, p. 9.
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c. Well-defined patient population with robust natural history as
control: Should FDA apply criteria such as persistent, life-threatening
hypoglycemia, poor glycemic control despite intensive insulin
management and education, or hypoglycemia unawareness, as enrollment
criteria?
d. Should FDA consider a robust external control, consistent with
the `historical control arm' design FDA's 2009 Islet Guidance referred
to as sufficient for clinical trials? \5\
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\5\ See FDA's guidance ``Considerations for Allogeneic
Pancreatic Islet Cell Products,'' Section IV.A, p. 6, available at
<a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-allogeneic-pancreatic-islet-cell-products</a>.
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e. Are there additional reasons to support or limit RWE-supported
deceased donor islet cell transplantation for the noted indication?
7. What real-world data (RWD) sources would be acceptable? Could
available registries such as CITR, UK Transplant Registry/National
Health Service Blood and Transplant (NHSBT), Edmonton Protocol cohort
(University of Alberta), published peer-reviewed literature, or data
generated from a sponsor-held U.S. investigational new drug (IND) be
considered as data sources? What are the limitations and advantages of
each category?
8. What are the criteria to determine the RWD fitness? Should
criteria such as: data completeness, endpoint consistency,
manufacturing comparability, confounding and bias, and generalizability
to U.S. patients be included? What are their limitations and
advantages?
C. Manufacturing Data
9. How should Product Standards Derivation be addressed? Should
FDA, based on RWE review, establish product standards (potency
specifications, viability thresholds, etc.),\6\ that individual
sponsors must demonstrate their product meets? \7\
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\6\ FDA has successfully applied this approach for cord blood
products.
\7\ See FDA's guidance ``BLA for Minimally Manipulated,
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for
Hematopoietic and Immunologic Reconstitution in Patients with
Disorders Affecting the Hematopoietic System,'' Section II.D, pp. 6-
7, available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic</a>.
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D. Clinical Data
10. Should manufacturers or health care facilities be required to
submit postmarketing data? Should the following be incorporated:
a. Clinical outcome data collection: Manufacturers required to
collect and report product-related clinical outcomes from transplant
centers (e.g., graft failure, delayed engraftment, infusion reactions,
infection transmission).\8\
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\8\ See FDA's guidance ``BLA for Minimally Manipulated,
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for
Hematopoietic and Immunologic Reconstitution in Patients with
Disorders Affecting the Hematopoietic System,'' Section VIII.A, p.
45, available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic</a>.
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b. Adverse experience reporting: Mandatory reporting of serious and
unexpected adverse experiences of the type currently required by 21 CFR
600.80, including toxicity associated
[[Page 60636]]
with islet infusion and immunosuppressive regimens.\9\
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\9\ See FDA's guidance ``BLA for Minimally Manipulated,
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for
Hematopoietic and Immunologic Reconstitution in Patients with
Disorders Affecting the Hematopoietic System,'' Section VIII.C, p.
46, available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic</a>.
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c. Biological product deviation reporting: Required reporting of
deviations from CGMP, applicable regulations, or established
specifications that may affect safety, purity, or potency of a
distributed product, within 45 calendar days of acquiring information
reasonably suggesting that a reportable event has occurred, as is
currently submitted on Form FDA 3486 as required by 21 CFR 600.14.\10\
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\10\ See FDA's guidance ``BLA for Minimally Manipulated,
Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for
Hematopoietic and Immunologic Reconstitution in Patients with
Disorders Affecting the Hematopoietic System,'' Section VIII.D, p.
46, available at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic">https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bla-minimally-manipulated-unrelated-allogeneic-placentalumbilical-cord-blood-intended-hematopoietic</a>.
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d. Annual product quality review: Annual review of production and
control records to evaluate product quality and determination of the
need for changes in specifications or manufacturing controls.\11\
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\11\ 21 CFR 211.180(e).
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e. Postmarketing Registry contribution: Should manufacturers
contribute standardized outcome data to CITR or a designated FDA
registry supporting ongoing RWE generation for the U.S. patient
population.
11. List additional data sources to address clinical risks
associated with deceased donor islet cell transplantation. Risks
include but are not limited to bleeding, blood clots, allograft
rejection, immunosuppression related risks, graft function loss, and
long-term burden of lifelong immunosuppression on patients who receive
these transplants.
12. What information on product quality and manufacturing is needed
to allow HHS to evaluate available effectiveness data regarding donor
islet therapies? For example, some RWE is generated under international
regulatory frameworks that treat unmodified deceased donor islets as
tissue/organ products rather than biological products. Clinical
outcomes data (efficacy and safety endpoints) from these international
cohorts could be relevant and informative. However, manufacturing
quality data from these cohorts may not be directly translatable to
current standards for biological products because they were generated
under tissue/organ frameworks rather than CGMP-equivalent manufacturing
oversight. What standards and supporting data would explicitly
distinguish between the use of international RWE for clinical outcomes
support (high fitness) versus manufacturing quality support (limited
fitness; must be supplemented by the sponsor's own CGMP data)?
13. What is the current data regarding long-term graft durability
beyond 5 years, and how does it weigh against the risk of long-term
immunosuppression use?
14. Please discuss the comparability of international RWE. How
generalizable are the experiences of international cohorts to the U.S.
T1D population? Are there differences in disease management practices,
HbA1c targets, hypoglycemia thresholds and other factors that could
significantly impact the interpretability and applicability of
international RWE to the US T1D population?
IV.B Questions for Consideration Regarding HHS Oversight Framework
The OPTN framework, overseen by HRSA, is built on creating policy
and equity for allocating scarce, life-saving resources to the many
patients in dire medical need for a new organ. HRSA's existing
authorizing statute \12\ and regulations \13\ define the organs that
the OPTN is responsible for, including the pancreas. Reclassifying
deceased donor islet cells as ``organs'' would be a departure for this
established oversight framework.
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\12\ 42 U.S.C. 274b(d)(2).
\13\ 42 CFR 121.2.
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1. Existing shared oversight. The current framework divides
responsibilities between FDA oversight of manufacturing and biological
product regulation and HRSA's oversight of the OPTN and its policies
governing organ donation, procurement, and transplantation. Are there
modifications to the existing shared oversight framework that could
improve patient access to unmodified deceased donor islet cells and
cell products without an alteration of FDA's and HRSA's current
regulatory responsibilities? If so, please describe.
2. Evidence of access barriers. Stakeholders have expressed concern
that the current regulatory structure, with most pancreatic islet cell
transplants conducted under an IND, may have unintentionally limited
the ability of providers to regularly or consistently perform islet
cell therapies or infusions. Please provide RWD or documented delays in
providing this care as clinically indicated for patients who would
benefit from this therapy. Please provide quantitative data or
documented evidence demonstrating that FDA regulatory requirements,
rather than manufacturing capacity, reimbursement, clinical
infrastructure, donor availability, or other factors, are the primary
cause of limited patient access.
3. Alternative approaches. Please provide publicly available
examples of alternative approaches to regulating deceased donor islet
cells for transplant (e.g., legal oversight frameworks implemented by
other regulatory authorities).
4. Implementation. What operational changes may be necessary to
implement reclassification of deceased donor islet cell products as
organs under the OPTN framework? Please identify any policy changes
that would be required and discuss any implementation challenges.
5. Precedential effects. If deceased donor islet cells were
classified as organs for purposes of Federal oversight, what precedent
could this establish for other donor-derived cellular products or
future cell-based therapies? What factors should HHS consider in
determining whether pancreatic islet cells are distinguishable from
processed donor-derived cellular products?
6. Suitability of the OPTN framework. The OPTN framework was
established primarily to oversee allocation of vascularized organs and
transplant programs. What aspects of that framework are well suited--or
not well suited--for oversight of processed cellular therapy products
such as deceased donor islet cell products? Please identify any
additional policies, expertise, or infrastructure that would be
necessary.
7. Manufacturing and product quality oversight. FDA currently
oversees manufacturing processes, quality systems, product release
testing, potency, sterility, and other controls applicable to
biological products. If regulatory oversight were transferred to HRSA,
via its oversight of the OPTN, how should the full range of oversight
functions across the products' life cycle be executed? Are there
aspects of the current FDA framework that should continue at FDA,
versus moving to HRSA via its oversight of the OPTN, regardless of the
regulatory classification?
8. Patient safety. What patient safety risks should HHS consider
when evaluating whether post-marketing oversight of deceased donor
islet cell products should remain within the FDA biological product
regulatory framework
[[Page 60637]]
or be wholly incorporated into the OPTN framework? Please address
issues including communicable disease transmission, manufacturing
variability, sterility, product potency, traceability, and post-market
surveillance.
9. Provider implications. If deceased donor islet cell products
were reclassified as ``organs'', would OPTN membership need to expand
to include new types of providers (e.g., endocrinologists) to perform
these treatments? Or would the existing pool of providers at OPTN
member institutions perform these treatments if islet cells are
classified as ``organs''?
a. What are the potential provider implications?
b. What are the potential system costs and implications for each
approach?
10. Patient access. If deceased donor islet cell products were
reclassified as organs, what effect could that have on:
a. the number and geographic distribution of treatment centers;
b. patient travel requirements;
c. provider participation;
d. waiting times;
e. patient costs;
f. insurance coverage and
g. donor willingness to participate in organ donation?
11. Operational and financial impact on OPTN. The OPTN is funded
primarily through organ transplant patient registration fees. What
operational, administrative, or financial impacts would
reclassification have on the OPTN, its member organizations, and
patients waiting for an organ transplant? Please comment on potential
effects on policy development, Board of Directors and committee
workload, information technology systems, membership requirements,
patient registration processes, and overall program costs.
Robert F. Kennedy, Jr.,
Secretary, Department of Health and Human Services.
[FR Doc. 2026-19563 Filed 9-23-26; 8:45 am]
BILLING CODE 4150-28-P
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