HRSA’s Role in Pancreas and Islet Transplantation

1. HRSA’s Role in Pancreas and Islet Transplantation James Burdick, M.D. Director Health Resources and Services Administration Division of Transplantation BRMAC Meeting October 9, 2003

2. Statutory Authority • National Organ Transplant Act(NOTA) of 1984 (42 U.S.C. § 273, et seq.) • Section 1138 of the Social Security Act (42 U.S.C § 1320b-8(a)(1)(B) )

3. National Organ Transplant Act (NOTA) • Passed in 1984; amended 1988 and 1990 • Created Task Force on Organ Transplantation • Created Organ Procurement and Transplantation Network (OPTN) • Created Scientific Registry of Transplant Recipients (SRTR) • Grants to organ procurement agencies • Prohibited purchase of transplantable organs

4. Organs Covered by NOTA • Kidney, Liver, Heart, Lung, Pancreas • Any other human organ specified by the Secretary

5. NOTA Establishment of the OPTN • NOTA authorized HHS to contract with non-profit entity with expertise in organ procurement and transplantation • United Network for Organ Sharing (UNOS) has been the OPTN contractor since 1986 • Established requirements for organ procurement organization (OPO) participation

6. NOTA Framework for OPTN • Responsibilities of OPTN outlined by NOTA • Select a Board of Directors • Establish a national organ sharing system • Maintain a list of individuals who need organs • Develop a system to match donor organs with individuals in need of transplants • Increase the supply of donated organs • Collect, analyze and publish data

7. Section 1138 of theSocial Security Act • Hospital must have written protocols for the identification of potential donors • A hospital that performs organ transplants must be member and abide by the rules of the OPTN • Hospital must have agreement with assigned OPO [waivers may be approved by CMS] • Requirements for receipt of reimbursement under Medicare for organ procurement costs

8. Structure for HHS Oversight Office of the Secretary Tommy G. Thompson Centers for Medicare and Medicaid Services (CMS) Tom Sculley Other HHS Agencies National Institutes of Health Food & Drug Administration Centers for Disease Control & Prevention Other agencies.. Health Resources and Services Administration Elizabeth Duke * HIV/AIDS Bureau * Bureau of Primary Health Care * Bureau of Health Professions * Maternal & Child Health Bureau * Office of Special Programs - Division of Transplantation

9. Structure for HHS Oversight (Cont.) • Health Resources and Services Administration (HRSA) – Office of Special Programs – Division of Transplantation • OPTN [UNOS] • SRTR [URREA] • National Bone Marrow Donor Registry [NMDP] Contract • Coordination of Organ and Tissue Donor Activities including Secretary’s Initiative

10. Regulatory Framework for HRSA Oversight of OPTN • Organ Procurement and Transplantation Network (OPTN) Final Rule[42 CFR Part 121] – effective March 16, 2000 • OPTN board configuration • OPTN membership requirements • OPTN policies • Designated transplant program requirements • Reviews, evaluation and enforcement • Data collection and reporting • Advisory Committee on Organ Transplantation

11. OPTN Contract UNOS as the OPTN Contractor must: • Maintain organ waitlist and match patients to donor organs 24 hours/day, 365 days/year • Facilitate policy development by the OPTN • Administer the OPTN Board and Committees • Collect, maintain pre- and post-transplant data and data on organ donors • Review and evaluate OPTN member compliance • Maintain website [www.optn.org]

12. OPTN Policy 2.0 MinimumProcurement Standards for an OPO The OPO is responsible for: • Identifying, evaluating and maintaining the donor; • Obtaining consent for the removal of organs; • Verifying pronouncement of death; • Ensuring the approved organ allocation computer program is executed for each donor organ; • Ensuring appropriate preservation and packaging of the organs, proper packaging of donor documentation, and adequacy of tissue typing material.

13. Evaluation of Potential Donors For all potential donors: • CBC • Electrolytes • ABO typing • Chest x-ray

14. Evaluation of Potential Donors (Cont.) • Hepatitis (incl. HBsAg, HBcAb, and Anti-HCV) • VDRL or RPR • FDA licensed Anti-HIV I/II • Anti-HTLV I/II • Anti-CMV • Blood & urine cultures (donor hospitalized 72 hrs) • Donor blood sample for EBV testing provided to transplant program if requested

15. Evaluation of Potential Donors (Cont.) For all potential pancreas donors: • Serum amylase • Serum lipase (if requested) • Glucose

16. Issues in Pancreas Procurement for Islet Transplantation • Under-procurement of pancreata • Limited availability of surgeons with expertise to recover the pancreas in some areas • Placement can be difficult • OPOs do not get credit for recovery of pancreas if discarded • Reimbursement for pancreas allocated for research is lower than for clinical use

17. Disposition of Pancreata Of 18,249 deceased donors recovered 2000-2002: • 4142 (22.7%) recovered/used for whole transplant • 582 (3.2) recovered/used for islet transplant • 243 (1.3%) recovered for whole, used for islets • 248 (1.4%) recovered for whole, used for research • 787 (4.3%) recovered for research • 773 (4.2%) discarded • 11473 (62.9%) not recovered Data Analysis by UNOS

18. Issues in Pancreas Procurement for Islet Transplantation (Cont.) • Islet transplantation may require more than one donor to treat a patient • Pancreas is offered for whole organ transplantation nationally, then for islet transplantation; may be less than ideal (e.g. cold ischemia, donor factors) • Facilitated placement if unable to place after 5 hours or if anticipate retrieval within 1 hour

19. Issues in Pancreas Procurement for Islet Transplantation (Cont.) • Avoid procurement standards that may lead to decreased pancreas utilization or increased cost • Criteria that may exclude reasonable islet donors (limits on donor age or BMI, cold ischemic time) • Standardized preservation method without data to support superiority (OPTN has no requirement for standardized preservation method for any organ)

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

21. 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

22. National Organ Transplant Act (NOTA) of 1984 • Created Organ Procurement and Transplantation Network (OPTN) • Prohibited purchase of transplantable organs (Section 301)

23. Section 1138 of theSocial Security Act • A hospital that performs organ transplants must be a member and abide by the rules of the OPTN

24. Transplant Programs • 246 kidney • 124 liver • 139 pancreas • 37 pancreas islet cell • 44 intestine • 139 heart • 73 heart/lung • 70 lung

25. 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

26. 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

27. 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

28. Waiting List Size Candidates waiting as of September 19, 2003: • 1445 pancreas • 2418 kidney/pancreas • 164 islet

29. 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

30. 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

31. 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)

32. 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

33. 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

34. 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

35. 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

36. 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?

37. 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?

38. 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

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