# Presentation: 372841

## Allocation of Pancreata for Whole Organ and Islet Transplantation

- James Burdick, M.D.
- Director
- Health Resources and Services Administration
- Division of Transplantation
- BRMAC Meeting October 10, 2003

## National Organ Transplant Act (NOTA) of 1984 

- Created Organ Procurement and Transplantation Network (OPTN)
- Prohibited purchase of transplantable organs (Section 301)

**Notes:**
As a reminder...

## Section 1138 of theSocial Security Act

- A hospital that performs organ transplants must be a member and abide by the rules of the OPTN

**Notes:**
Section 1138 of the Social Security Act requires that a transplant center must be a member and abide by the rules of the OPTN.

## Transplant Programs

- 246  kidney
- 124 liver
- 139 pancreas
- 37 pancreas islet cell
- 44 intestine
- 139 heart
- 73 heart/lung
- 70 lung

**Notes:**
There are 254 OPTN-member transplant centers in the U.S.  These are the transplant programs represented by those 254 transplant centers.

## Islet Program Membership

- Currently, there are no OPTN membership criteria for islet programs
- The OPTN Kidney-Pancreas Transplantation Committee has developed criteria
- Public comment period closed October 4, 2003 for most recent proposal on islet program membership
- Proposed criteria will be submitted to the OPTN Board of Directors for final approval in November

**Notes:**
(The next Board of Directors meeting is scheduled for November 20-21.)

## Proposed Islet Program Membership Criteria

- Must be located in a hospital at a center approved to perform whole pancreas transplants
- Must provide data on patients transplanted
- Must report the disposition of the islets (transplanted, discarded, other use)
- Must have a qualified surgeon, physician, and radiologist
- Must have access to ancillary personnel

**Notes:**
This is a summary of the proposed islet program membership criteria.  Of significance is the requirement that an islet program must be located at a transplant center that also performs whole pancreas transplants.  This requirement attempts to address the concern that patients may not be informed about the option of whole organ transplantation if the transplant center does not offer that option.  Also, the requirement attempts to ensure that there is appropriate expertise to handle complications of the procedure and to manage immunosuppression.
There is an exceptions pathway for an islet program not located at a center with a whole pancreas program.  The exceptions pathway requires documentation of affiliation with a whole pancreas transplant program and an interview.  The islet center still must be in a hospital

## OPTN Policy 3.2 Waiting List

- All patients who are potential recipients of deceased organ transplants must be listed on the computer Waiting List
- OPTN Members shall not provide organs to non-member transplant centers

**Notes:**
All transplant candidates must be listed on the national waiting list.  This includes candidates for islet transplants.

Non-OPTN members should not receive organs for clinical transplantation.

## Waiting List Size

- Candidates waiting as of September 19, 2003:
- 1445 pancreas
- 2418 kidney/pancreas
- 164 islet

**Notes:**
As of September 19, there were 164 candidates waiting for islet transplants.
(NOTE: candidates are only counted once; there is no duplication in the other counts)

## Allocation of Pancreata for Islet Transplantation

- Current OPTN allocation algorithm for pancreata gives priority for whole organ transplantation
- OPTN has approved requests for variances giving higher priority for allocation of pancreata for use in islet transplantation locally
- Approved variances generally limit the number of pancreata diverted for use in islet transplantation

## Variances Under Final Rule

- Experimental policies that test methods of improving allocation
- Accompanied by a research design
- Include plans for data collection and analysis
- Time limited
- Subject to same approval process as standard policies

**Notes:**
The OPTN Final Rule defines variances as experimental policies designed to test methods of improving allocation.

## Current Pancreas Allocation Algorithm

- Candidates ranked by length of time on the waiting list
- Current algorithm gives highest priority to:
- 0-mismatch and highly sensitized candidates
- Isolated and combined whole pancreas transplantation
- Efforts are made to place the pancreas locally, regionally, then nationally for whole pancreas transplantation before offering it for clinical islet transplantation
- If a pancreas still is not accepted, it is offered for research use (not clinical research)

**Notes:**
Note that a pancreas allocated for research use is not intended for use in clinical transplantation.

## Proposed Pancreas Allocation Algorithm

- Donor age  50 years _AND_ BMI  30 kg/m2
- Local isolated or combined whole pancreas, or combined solid organ-islet; then
- Regional then national isolated or combined whole pancreas; then
- Local, regional, then national islet; then
- Research

**Notes:**
The OPTN Kidney-Pancreas Transplantation kidney has proposed modifying the allocation algorithm to improve availability of pancreata for use in islet transplantation.  The proposed algorithm is based on data that pancreata from older donors and donors with high BMI may have better islet yields.  Also, older and high BMI donor pancreata are sometimes difficult to place for whole organ transplantation.
This is a somewhat simplified summary of the algorithm.  Highest priority for zero mismatches would be preserved.

Pancreata from younger, low BMI donors would be preferentially allocated for whole pancreas transplantation. 

## Proposed Pancreas Allocation Algorithm (Cont.)

- Donor age > 50 years _OR_ BMI > 30 kg/m2
- Local isolated or combined whole pancreas, or combined solid organ-islet; then
- Local, regional, then national islet; then
- Regional then national isolated or combined whole pancreas; then
- Research

**Notes:**
Pancreata from older or high BMI donors would receive higher priority for islet transplantation.
Majority of Kidney-Pancreas Committee felt very strongly that a pancreas always should be offered for whole organ transplantation before offered for islet transplantation, since islet transplantation is experimental.

## Issues/Concerns

- Non-OPTN member institutions doing islet transplants
- FDA IND does not take into account that non-OPTN member institutions can not receive pancreata for clinical transplantation
- Pancreata allocated for research being used for clinical islet transplantation

**Notes:**
FDA does not require OPTN membership for islet IND, and apparently some institutions that are not OPTN members have INDs in effect.
It has come to the OPTN’s attention that some institutions have received pancreata allocated for research, isolated the islets, and transplanted those islets into patients not on the OPTN Waiting List.

## OPTN Response

- Proposal by the Kidney-Pancreas Committee
- All pancreata for clinical islet transplantation must be allocated through the OPTN/UNOS allocation system
- Pancreata initially allocated for research cannot be used for clinical transplantation unless re-allocated through the system

**Notes:**
To address this concern, the OPTN Kidney-Pancreas Committee has The islet product would re-enter the allocation system if the pancreas was not initially allocated for use in islet transplantation.
The recipient of the islet product would have to be on the OPTN Waiting List.

## Issues/Concerns (Cont.)

- Allocation of pancreas for islets
- Pancreas is allocated to a specific patient on waiting list, _not_ an institution
- Allocation based on need, equitable access
- Any difference in cost/reimbursement for licensed product vs IND product?

**Notes:**
Is it possible to ensure that access to islet products is equitable, and not limited to those who can pay for the product if it costs more than the product under IND?

## Issues/Concerns (Cont.)

- Islets as a licensed/commercial product
- May shift procurement focus towards ideal islet donors
- May shift a center’s listing focus
- Dual regulation (HRSA & FDA)
- NOTA section 301 implications?

**Notes:**
Is there a danger that procurement efforts will shift from a focus on whole pancreas transplantation to islet transplantation—older, high BMI donors?
Will require dual regulation--HRSA regulates the allocation while FDA regulates the safety and efficacy.

Are there any NOTA section 301 implications (transfer for valuable  consideration), particularly if HRSA regards islet as organs or subparts for the purpose of allocation?  Needs further exploration.

## Issues/Concerns (Cont.)

- Whole pancreas transplantation is a proven therapy—how does islet transplantation compare
- Patients adequately informed about both options (whole pancreas vs. islet transplant)
- Transplant program expertise
- Surgical management of complications of islet transplant procedure
- Management of immunosuppression

**Notes:**
FDA licensure does not require comparison of efficacy of whole pancreas transplantation vs. islet transplantation.
Again, the proposed islet program membership criteria attempt to address the concerns about informing patients about their options and ensuring availability of appropriate expertise.

On-site qualified transplant physician and surgeon 
Available operating and recovery room resources

evidence of collaborative involvement with specialists
immediate access to clinical support services and capacity to monitor treatment with immunosuppressive drugs, and 
available psychiatric and social support services for candidates, recipients and families

## Contact Information

- James Burdick, M.D.
- (301) 443-7577
- _[jburdick@HRSA.gov](mailto:jburdick@HRSA.gov)_
- DoT Website [www.hrsa.gov/osp/dot]
- OPTN Final Rule
- OPTN Website [www.optn.org]
- SRTR Website [www.ustransplant.org]