ASTS develops position statements on transplant issues. Transplantation is a rapidly advancing field, and statements are periodically revised.
ASTS Statement on Islet Cell Transplantation Regulations
Drafted by Piotr Witkowski, MD, PhD and approved by the ASTS Executive Committee, December 23, 2020
The issue of declining islet cell transplantation and over regulation emerged from ASTS member Dr. Witkowski.
Definition of the Problem:
Islet allotransplantation in the United States (US) is facing an imminent demise, leaving patients with type 1 diabetes mellitus (T1DM) and severe hypoglycemia without access to a lifesaving therapeutic procedure.
The safety and effectiveness of allo-islet transplantation has been established in NIH-sponsored U.S. clinical trials as well as through the Collaborative Islet Transplantation Registry, U.S. taxpayer-funded research projects, which collectively have analyzed data from more than 2,000 allo-ITx procedures over the past 20 years.
However, despite decades of progress in the field driven by U.S. academic centers, an archaic regulatory framework has stymied U.S. clinical practice. Current Food and Drug Administration (FDA) requirements for allogeneic islets for transplantation do not reflect the clinical or technical state-of-the-art.
- Autologous islets (auto-islets) and allogenic islets (allo-islets) are sourced and processed identically, but are subject to vastly different FDA regulatory requirements:
- Auto-islets, like many tissue- and cellular-based products, are subject to limited requirements aimed at ensuring appropriate collection, storage, processing, and distribution (Section 361 Public Health Service (PHS) Act).
- Allo-islets, in contrast, are subject to much more extensive requirements because they are categorized as biological products (section 351 PHS Act and Federal Food, Drug and Cosmetics Act).
- The distinction between auto- and allo-islets based on criteria established nearly 30 years ago (21 CFR Part 1271) do NOT reflect current standards and clinical practice. As a consequence, there has been significant impact on allo-islet transplantation effectively preventing its therapeutic use in the U.S.
- In the past four years, only 11 patients have undergone allogenic islet transplantation (allo-ITx) in the U.S., all under an investigational protocol. In contrast, in Europe, Canada, Australia, and Japan, islets are NOT regulated as a drug and allo-ITx is a standard-of-care procedure annually benefiting hundreds of patients with type 1 diabetes.
- Allo-islets in the U.S. require premarket approval of a biologics license application (BLA) and extensive post-market compliance obligations. The FDA’s requirements are geared to commercial manufacturers of drug products, and not to clinical transplant centers. Only a commercial (pharma/biotech) company realistically could comply with these requirements.Regulating transplant centers as drug manufacturers and requiring premarket approval for allo-islets effectively precludes clinical transplant centers from offering allo-ITx to patients, and preventing optimal patient care.
- The first commercial entity to obtain FDA approval of a BLA for allo-islets will be eligible for seven years of market exclusivity, further limiting patient access to the therapy. The price for FDA-approved allo-islets produced by a commercial manufacturer foreseeably will be significantly inflated to recover enormous costs associated with preparing a BLA and complying with the manufacturing regulations for commercial drugs. The absence of competition, at least initially, will also escalate the price and discourage innovations in islet processing, to the detriment of patients who could benefit from this life-saving therapy.
- Allowing the commodification of islets runs counter to the ethical norms underlying the organ and tissue transplantation framework, under which the sale of organs and tissues is prohibited and organ donation is viewed as an altruistic act.
We propose to harmonize the U.S. approach to allo-ITx with that of many other countries, which would allow for implementation of safe, effective, affordable, and widely accessible islets for transplantation as a standard of care procedure.
- Specifically, we seek urgent modification of the FDA regulatory status of allo-islets, before a BLA is issued and orphan designation is awarded to a single commercial sponsor (which could happen as soon as March 2021).
- Allo-islet regulation should be consistent with the regulation of auto-islets and other minimally-manipulated human tissue for transplantation.
We recommend that the FDA:
- Confirm islet allografts are “minimally manipulated” HCT/Ps as that term is defined in FDA regulations, because they are subject to only short-term incubation prior to allograft infusion that does not alter their relevant biological characteristics.
- Allow allogeneic islets from unrelated donors to be eligible for regulation as HCT/Ps exclusively under Section 361/Part 1271, provided that donors and recipients are immunologically compatible as determined by current clinical standards for immunological matching in organ and tissue transplantation.
We recommend that HRSA, through the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN), continue to oversee pancreas allocation and procurement and extend its oversight of transplant programs to include those that perform islet transplantation, which would allow HRSA to monitor the outcomes of patients receiving allo-ITx.
Allo-islets is a “poster child” for archaic over-regulation. Adjusting the regulation would remove regulatory barriers, reflect our current clinical practice, and deal with our upcoming challenge. ASTS proposes the forementioned updates to current regulations as critical for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.
ASTS Statement on Procurement of HIV+ Organs
Drafted by the ASTS Ethics Committee and approved by the Executive Committee, September 2020
The issue of surgeons declining to procure organs from HIV+ donors came forth to the leadership of the ASTS who asked the Ethics Committee to address this situation.
Definition of the problem:
HIV was once considered an absolute contraindication to organ donation. As the fields of transplantation and infectious diseases have advanced, protocols have been developed to consider utilization of organs from HIV+ donors, as organs continue to be a scarce resource. It came to the attention of the leadership committee that some surgeons have refused to procure organs from these donors. The leadership asked the Ethics Committee to address this concern.
ASTS Principles regarding procurement of organs from HIV+ donors
- HIV was once considered an absolute contraindication to organ donation. More recent data and protocols support the utilization of these organs for appropriate recipients to optimize beneficence.
- The United States government expressly endorses transplantation of HIV+ donor organs with the HIV Organ Policy Equity (HOPE) Act. Given the shortage of organs for transplantation, using HIV+ donor organs increases the availability of organs for transplantation for appropriate recipients (utility).
- The wishes of individuals with HIV who elect to donate their organs, either through living or deceased donation pathways, and are deemed appropriate donor candidates, should be respected based on the ethical principle of autonomy.
- There is excellent data that demonstrates the low risk of transmissibility of HBV, HCV, and HIV to health care workers. HIV is well-documented to be the least transmissible of the three. HCV is a common indication for liver transplantation and is an acceptable donor-derived infectious disease for deceased donor heart, lung, liver and kidney transplantation. Transplant surgeons are frequently exposed to HCV and do not cite this infection as a reason for refusal to perform donor or recipient operations, thereby suggesting that this reasoning is not valid for HIV+ donors.
- There is strong data to support the use of post-exposure prophylaxis in the setting of an actual or potential exposure. There has been no well-documented health-care worker seroconversion in surgery from direct patient contact since 1999.
- The ethical principle of beneficence is generally cited to support operating on patients with HIV who stand to benefit from the operation. While organ donors do not directly benefit from the procurement operation, organ transplant recipients do, so the principle of beneficence (e.g., maximizing benefits and minimizing harms) supports organ procurement from HIV+ donors.
- It is the position of the ASTS that refusing to procure organs from an HIV+ donor or refusing to operate on an HIV+ recipient is neither ethical nor scientifically sound. Utilization of organs from HIV+ donors should be encouraged and facilitated within the confines of well-designed protocols. Moreover, surgeons should utilize universal precautions when operating on all donors and recipients, not just those with known HCV, HBV or HIV, to reduce the risk of infectious disease transmission as recommended by the CDC since 1987, and part of standard precautions since 1995.
ASTS Statement on OPO Metrics
Drafted by the ASTS Executive Committee, September 2020
The American Society of Transplant Surgeons strongly supports efforts to increase the availability of life-saving organ transplants, which requires increasing the number of organs available for transplantation retrieved by Organ Procurement Organizations (OPOs). ASTS believes it is important not to significantly delay long-overdue modification of OPO metrics, which are currently subjective and self-reported. At the same time ASTS cautions that development of updated metrics must occur with appropriate involvement of the transplant and OPO community, with a thoughtful transition to new metrics that avoids unintended consequences that would adversely affect patients, such as simultaneous decertification of multiple OPOs.
OPO metrics must be put in place based on a potential donor “denominator” that is calculated based on a verifiable, objective methodology. Assuming that no existing accurate alternative source of data reflecting hospital inpatient deaths can be identified, ASTS believes that that the CDC’s National Center for Health Statistics’ Detailed Multiple Cause of Death (MCOD) data (with appropriate exclusions) should be utilized to identify potential donors, and that the transplant community should work with appropriate governmental organizations to address the shortcomings of this database.
When significantly altering a complex system, both short- and long-term impacts must be considered. At least during the transition to the new metrics, care should be taken to ensure that any new regulatory requirements encourage improved OPO performance without resulting in widespread and simultaneous decertification of a significant number of OPOs, which would be inconsistent with the needs of our patients. For this reason, any new system that is put in place should establish realistic standards and should retain sufficient flexibility to enable an OPO that is continuing to make substantial improvement in meeting applicable outcomes requirements to retain certification, so long as it meets threshold and other improvement benchmark required by CMS that are tailored to take into account the circumstances of the particular OPO involved. This will hopefully mitigate the potential disruption and adverse impacts to patients resulting from the decertification of an OPO, while improving OPO performance.
ASTS looks forward to working collaboratively with the OPO community, HRSA, and CMS in future discussions for development and updates on such metrics to ensure continued focus on the goal of maximizing the number of patient lives saved.
public comments on the CMS OPO Conditions for Coverage Proposed Rule
ASTS Statement on Conscious DCD
Drafted by the ASTS Ethics Committee and finalized by the ASTS Executive Committee, June 2020
The issue of conscious DCD came forth to the leadership of the ASTS from a member who inquired whether the ASTS had a policy that would help guide members through these potentially emotionally charged situations. The leadership asked the Ethics Committee to address the member’s concern.
Definition of the problem:
There may be clinical situations in which the patient is able to communicate his/her wishes to be an organ donor upon actions that the patient desires the medical team to make that would facilitate death. Such conditions would include high c-spine fracture and cord injury, amyotrophic lateral sclerosis.
ASTS Principles Regarding Conscious DCD
- Donation from the conscious donor who dies after withdrawal of ventilator support with either a high c-spine fracture or with an illness such as amyotrophic lateral sclerosis is ethically appropriate based on the ethical principle of Autonomy.
- If members or programs feel an ethical or moral obligation to not participate in this donation process, they should be able to decline to participate in the process of donation or the utilization of organs from such donations without penalty.
- Programs or members who decline to participate in the process of donation and utilization of organs from the “conscious donor” should prospectively notify the Organ Procurement Organization, which is responsible for identifying a willing surgeon or program.
- In the acutely injured patient, it is likely that deferment of authorization of donation should take into account the emotional vulnerability of the injured patient and how it may impact decision-making. There should be a “cooling off” period between injury/diagnosis and the decision to initiate action that would lead to death and donation.
- There is a need for assurance that processes are in place to proceed with DCD donation in an ethically and clinically appropriate circumstance through the OPO.
- ASTS members should adhere to the dead donor rule.
- ASTS members do not condone euthanasia or assisted suicide.
- ASTS members are compelled to maintain the public trust.
ASTS Statement on NKR Advanced Donation Program Drafted by the ASTS Ethics Committee and finalized by the ASTS Executive Committee, November 2017
The ASTS Ethics Committee was asked to opine on whether or not the NKR Advanced Donation Program constitutes “valuable consideration.” The ASTS is strongly in support of novel efforts to remove disincentives to live organ donation to increase the organ supply. In that the NKR Advanced Donation Program strives to remove such disincentives, the Society sees this program as in line with our goals and values. The success of the NKR program will be dependent upon the resolution of a number of logistical, operational, legal, and other challenges. Until these challenges have been vetted, and adequately addressed, the ASTS recommends that interested individuals proceed with caution. The question of whether advanced donation represents valuable consideration is a legal issue, and therefore, outside the purview of the ASTS. Additionally, the ASTS does not endorse any specific KPD program over the others, but rather sees KPD as an under-utilized avenue to increase access to transplantation.
ASTS Position on Global Kidney Exchanges
Drafted and finalized by the ASTS Executive Committee, October 2017
ASTS supports efforts to increase access to transplantation by increasing the organ supply and by removing biologic, logistical, geographical, and financial barriers. ASTS supports efforts by the global transplant community to increase access to transplant care through kidney exchanges across national boundaries. ASTS also supports constructive engagement with transplant stakeholders in the developing world. In that regard, the Society supports the conceptual basis behind Global Kidney Exchanges. Further, we commend Dr. Rees and colleagues for their creativity, integrity, beneficence, and tireless efforts to pioneer Global Kidney Exchange to demonstrate its feasibility. The Society acknowledges that there is potential for abuse, particularly in regard to patient selection, coercion, and equitable participation. ASTS encourages further investigation into the ethics, logistics, governance, and financial aspects of Global Kidney Exchange.
ASTS Position on Health Care Reform
Drafted and finalized by the ASTS Executive Committee, July 2017
The American Society of Transplant Surgeons is committed to supporting the health care needs of organ transplant patients, living organ donors, and those with end stage organ disease. To that end, ASTS strongly believes that health care should be accessible for all our patients. Specifically, we believe that the following principles should be carefully considered before making any changes to the health care system in the United States.
- Living organ donors should not suffer discrimination or financial burdens associated with their act of altruism. Donating an organ should never be a reason to charge higher premiums for health insurance or deny life or disability insurance.
- Transplantation is the treatment of choice for end stage organ disease, resulting in better health outcomes and cost savings for the payor over the mid- to long-term than other treatment options. There is no valid medical or financial argument for excluding it from insurance coverage.
- Transplant patients and those with end stage organ disease, particularly those on dialysis, can experience variations in their Medicaid eligibility and thus coverage gaps. ASTS believes this vulnerable patient population should be exempted from any insurance coverage requirements that may endanger their access to care and thus their lives.
ASTS urges Congress and the Administration to work with provider and patient groups to craft solutions to ensure meaningful coverage is available to this vulnerable population.
ASTS Statement on Executive Order on Immigration
Drafted and finalized by the ASTS Executive Committee, January 2017
In the American Society of Transplant Surgeons’ 43-year history, our members have trained hundreds of surgeons from around the world in pursuit of our mission to advance the art and science of transplant surgery. Many of our members were born outside the United States and have contributed richly to science and healing of people of all colors and religions. Banning visitors and legal immigrants due to origin and religion is inconsistent with our values as Transplant Surgeons and Americans. We call upon the Administration to carefully consider all factors, including the wellbeing of our patients and colleagues, in making and enforcing immigration policy going forward.
ASTS Statement of Professionalism May 2015
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Recent Living Donor Death June 12, 2012
PDF, 61.61 KB
Transplantation of Organs from HIV Infected Deceased Donors July 22, 2011
PDF, 133.54 KB
PDF, 56.22 KB
ASTS Confidentiality and Conflict of Interest Policy
PDF, 33.06 KB
Non-ASTS Fellows in Parallel Tracks at ASTS Accredited Programs June 30, 2009
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Recommended Guidelines for Controlled DCD Organ Procurement and Transplantation May 11, 2009
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Proposal - Health Insurance as Incentive for Living Kidney Donation February 6, 2009
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Draft - Definition of a Transplant Surgeon December 11, 2008
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Procuring Surgeon Criteria July 25, 2008
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Volunteer Non Directed Live Donations June 1, 2008
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Fellowship Workload Practices January 24, 2008
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Paired Kidney Donation May 29, 2007
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Directed Donation and Solicitation of Donor Organs October 23, 2006
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Live Vascular Grafts January 15, 2005
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