Tissue Donation & Processing: Current Issues

Introduction

While the federal contractors charged with organ recovery are called Organ Procurement Organizations (OPOs), most OPOs also recover tissue, cornea, skin, bone, and other medical products of human origin. Because of well-documented failures of regulatory accountability for OPO organ recovery performance¹, coupled with a financial reimbursement structure which often incentivizes OPOs to invest more heavily in tissue recovery and processing over organs², there is a long-standing conflict of interest which has yet to be addressed and resolved. For many OPOs, tissue recovery and processing has become their core business, while lifesaving organ recovery has been largely deprioritized. Additionally, the siloing of federal oversight between the Centers for Medicare and Medicaid Services (CMS, which oversees OPOs) and the Food and Drug Administration (FDA, which has jurisdiction over tissue) does not allow for a fulsome picture of conflicts of interest between OPO organ and tissue activities, or meaningful scrutiny into the ways in which intertwined business interests can present harm to patients.

Tissue procurement and processing is a multi-billion dollar international industry. Tissue procurement can refer to a wide variety of materials and be used in many different procedures, including:

• Skin grafts can be used in wound repair, for burn victims, or during cosmetic procedures.
• Bone can be used with minimal processing for bone grafts, or it can be turned into plates, screws, or putties. Bone grafts are commonly used in fracture repair and reconstruction after cancer. One of the most common uses of bone-based putty is dental implants.
• Veins are often used during heart surgeries, such as a bypass.
• Connective tissue includes tendons, ligaments, and cartilage. Tendons are frequently used in orthopedic surgeries, such as a knee or shoulder repair, while cartilage can be used in cosmetic procedures like facial surgery.
• Birth tissue is material from the placenta, umbilical cord, or amniotic fluid. Most commonly, these materials are used to create wound coverings. This is the only type of living tissue donation.
• Heart Valves are used in two main procedures: heart valve replacement surgery and reconstructive cardiac surgery.
• Cornea is the transparent, dome-shaped surface of the eye. A cornea transplant is most often used to restore vision to a person with a damaged cornea, though can also relieve pain or other symptoms associated with cornea diseases.

Safety and ethical issues within the tissue industry have been written about and investigated for decades, with few changes to practice or policy produced; over this time, the industry has only continued to grow. Our research highlighted numerous issues that directly affect patient care and public trust in the tissue procurement system:

• Safety in tissue processing
• Consent in tissue donation
• Financial incentives and conflicts of interest
• Potential inequities in care

Tissue procurement, processing, and transplantation is a rapidly growing field of medicine. The current regulatory gray areas make it all the more urgent that these issues be addressed for the sake of patient safety and public trust in the system.

Differences between organ and tissue procurement

• Biological differences: The difference between organs and tissues is, in the words of one expert we spoke to, that “organs are vascularized and have a ‘crude shelf life’ that limits their viability outside the body, and when they’re transplanted a recipient needs to be on immunosuppressants. Tissues are generally not vascularized.”
• Clinical requirements: Many more people can become tissue donors than organ donors because tissue donation lacks the strict clinical requirements that apply to organ donors.
• Scope: One person can donate organs for up to eight other people, while one tissue donation can help anywhere from 50 to 100 other people.³
• Processing: The breadth of tissue products is reflected in the list of example processing actions the FDA offers, from preparation and sterilization to “cutting, grinding, shaping, culturing, enzymatic digestion, and decellularization.”⁴ One tissue processing company, MTF Biologics, lists 75 pages of orthopedic tissue products.⁵
• Allocation: Allocation decisions about where OPOs should send tissues are at the discretion of the OPO, because—unlike for organs—allocation is not prescribed by an oversight body.
• Financial incentives: Current OPO reimbursement structures do not provide meaningful financial incentive for OPOs to increase organ volume, while there is tremendous financial incentive to recover more tissue.⁶
• Legal structure: While OPOs are technically structured as 501(c)3 non-profits, tissue processors are often for-profit, and therefore without any meaningful transparency related to their financials.
• Industry demand: Organ transplants are often lifesaving, but tissue transplants can be used for lifesaving, life-enhancing, or cosmetic purposes. As one expert noted, “while there are things like bone grafts, the truth is we as a society have used more body parts for cosmetic enhancements,” rather than lifesaving procedures.

The tissue procurement process

In the United States, tissue procurement is often handled by Organ Procurement Organizations (OPOs), the same organizations tasked by the Centers for Medicare and Medicaid Services (CMS) with recovering organs. (Donor hospitals decide which entities they will work with for tissue procurement, though most choose to work with the local OPO for operational streamlining and political expediency.) Tissue recovery and processing companies, as well as tissue banks, may also play a role in the process, which varies widely between organizations and locations. Some OPOs handle every step of the process, from tissue procurement to creating and selling human tissue-based products; others only make referrals to tissue banks. In a few places in the U.S., hospitals work directly with tissue recovery organizations separate from OPOs. There are currently 128 accredited tissue banks in the United States, including 33 OPOs.⁷

The process from tissue donation to transplant includes:

• A referral to an OPO is initiated (usually by a hospital, hospice, funeral home director, death investigator, coroner, or medical examiner) when staff have identified a patient who may be able to donate, at which point an OPO coordinator will make an assessment about organ and tissue donation viability. If the patient is ventilated, the priority evaluation should be for organ procurement potential. If the patient is not ventilated (the patient is already extubated, was never intubated, or already has a cardiac time of death), then the clinical evaluation is for tissue and eye procurement.
• It’s important to note that evaluation for tissue procurement is dependent on which tissue processors and eye banks the OPO works with. Evaluations for tissue procurement are not standardized. Also, OPOs may collect the same types of tissue for multiple processors with different criteria.
• If a tissue donation is possible, the OPO will approach the patient’s family or next of kin for consent. If the patient has organ and tissue procurement potential, most OPOs approach the family at the patient’s bedside (in person).
• If the patient has only tissue and eye procurement potential, the conversation with their family is often done over the phone (usually on a recorded line).
• If the family consents to tissue donation, a procurement team from the OPO or tissue bank will surgically recover tissues. Staff often rely on on-the-job training, rather than formal medical training; tissue procurement can be done by any staff the OPO deems qualified.
• The OPO either sells the donated tissue to a separate tissue processor, or handles processing itself.
• Tissue processors, whether an OPO or a separate business, then sell tissue products directly to hospitals and clinicians. Skin and bone grafts are often priced by size, while highly processed products vary in price. Researchers have estimated that human tissue has been priced at up to $500 per gram.⁸ The tissue procurement process can be managed by a single organization, or can involve both a nonprofit OPO and a for-profit tissue processor. For example, MTF Biologics, one of the largest tissue companies, receives referrals from 27 different OPOs.⁹

Regulation and the role of lobbying

Federal oversight

Tissue procurement and processing is primarily overseen by the Food and Drug Administration (FDA), rather than CMS, which regulates organ procurement and transplants.

(Note: the Health Resources Services Administration (HRSA) oversees the contract for the organ procurement transplantation network (OPTN), a contractor tasked with managing the national organ donation/procurement system. Learn more about issues of oversight gaps and conflicts.)

CMS requires that OPOs work with tissue banks and cooperate in:

• Screening and referral of potential tissue donors
• Obtaining informed consent from families of potential tissue donors
• Retrieval, processing, preservation, storage, and distribution of tissues
• Providing designated requestor training¹⁰ Beyond setting these requirements, CMS is not directly involved in oversight of the tissue industry. One former CMS staff member noted that, in the early 2000s, there was concern that not enough tissue banking was happening, which led to these requirements. However, multiple former HHS staff and industry experts we spoke with told us that, as the industry has grown, the incentives and scale of tissue procurement now create worrying distortions where some OPOs unofficially consider themselves “tissue-first and organs-second.”

FDA regulates the clinical practice of tissue procurement—focusing primarily on the safety of the tissue being procured and procurement process—but not the business practices around it. Researchers heard from former government staff members that tissue procurement oversight is extremely siloed. No agency routinely has insight into tissue processor financials or business operations. In practice, this means there is little to no oversight over either key procurement practices (such as approaching families for donation) or over potential conflicts of interest for OPO leadership, such as a compensated consulting role at a tissue processor or ownership of stock in a publicly-traded tissue processor such as CryoLife.

There is no single government agency with oversight over both organ and tissue procurement, despite how intertwined these activities are. This exacerbates the overall opacity of OPO operations, financials, and conflicts of interest. There is often cost-shifting within OPOs related to organ and tissue finances, including using taxpayer dollars meant for organ recovery to essentially subsidize private tissue processing interests.¹¹

Classification and regulation

FDA’s Center for Biologics Evaluation and Research (CBER) regulates tissue products under CFR Title 21, Part 1271, which includes any “human cell, tissue, and cellular- and tissue-based product,” referred to as HCT/Ps.^12,13 The FDA’s primary focus is on safety during processing, requiring tissue processors “to screen and test donors, to prepare and follow written procedures for the prevention of the spread of communicable disease, and to maintain records.”¹⁴

Tissue products are regulated differently depending on their classification as “minimally manipulated” or not. The FDA defines “minimally manipulated” products as:

• Products that retain the original characteristics of the tissue
• Products that are intended to serve the same function in the transplant recipients’ body (described as homologous use)
• Tissue that is not combined with any additional products, except for water or an agent for sterilization or storage (provided that agent does not alter the original characteristics of the tissue)
• Products that do not have a systemic effect on the transplant recipient¹⁵ In practice, this means that a bone shaped into a screw or ground into chips would be considered minimally manipulated, while demineralized bone turned into a gel would be more than minimally manipulated. Products that are more than minimally manipulated are regulated as both HCT/Ps and as drugs, devices, and/or biological products. The additional regulations as a medical device mean that the product must undergo a pre-marketing approval process, including clinical trials. The different regulations were developed under a tiered, risk-based approach, with the understanding that the lengthier or more detailed the processing, the more areas there are for manufacturing errors.

In effect this means that the less the product is processed, the less it is subject to regulation — and tissue processors have a clear stake in maintaining the definitions of minimally manipulated and homologous use.

Lobbying and industry influence on regulation

The American Association of Tissue Banks (AATB) is an influential industry membership association that promotes the use of donated tissue and sets some voluntary standards. Tissue banks can be accredited through the AATB, but accreditation is entirely voluntary.

The AATB has also emerged as an influential lobbying voice for the tissue industry. Investigative reporting in 2012 detailed that Kevin Cmunt—then an official at the tissue bank AlloSource, and subsequently an OPO CEO—bragged during a panel session at an AATB meeting that “AATB has traditionally worked very closely with FDA, and in many cases led the FDA in regulatory requirements.”¹⁶ The AATB has also threatened litigation against FDA to prevent further regulation.¹⁷

In 2007, Sen. Chuck Schumer (D-NY) introduced legislation that would have established mandatory requirements for what banks had to tell donor families, as well as try to limit the profits companies can make from the donation¹⁸, but later confirmed the bill died after heavy lobbying by the industry.¹⁹

This seems to be part of a pattern: in 2019, the LA Times published a 7-part investigative series into a decades-long effort from the “multibillion-dollar global body parts industry” to influence policy.²⁰ The LA Times outlined tactics including giving Medical Examiners gifts, sponsorships, and other payouts to enlist their support for regulatory and legislative efforts to increase OPOs’ access to tissue recovery at county morgues, even while compromising death investigations²¹ and amid donor family complaints of misleading consent tactics.²²

The LA Times even noted that Christina Strong—an OPO General Counsel “who has long worked for the nation’s human tissue procurement industry”—attempted to coordinate efforts to obstruct the paper’s investigation.²³

Most recently, the AATB argued against CMS’s decision in the 2020 Final Rule to use improved outcome measures and set higher performance standards for OPOs.²⁴

Safety in tissue processing

FDA enforcement reports, warning letters, and recalls from the past twenty years detail numerous issues at tissue processors and tissue banks across the country. Enforcement reports from 2022 alone include near-weekly issues, from skin, bone, and tendons being distributed from donors who were not adequately tested to possible contamination of amniotic fluid.²⁵

Previous issues identified by FDA inspectors have included such quality control failures as tissue materials contaminated by Clostridium and Staphylococcus bacteria, dirty cleaning materials left out in areas where tissues were stored,²⁶ and tissue processors failing to maintain adequate screening procedures to prevent the spread of infectious disease.²⁷

Safety issues such as these have proved fatal to patients. In 2020, Azyio Biologics recalled a bone-based product after four patients who received transplants tested positive for tuberculosis.²⁸ Subsequently, CDC found that 113 people received transplants from a single donor who had undetected tuberculosis. Three people died from tuberculosis as a result. For all other transplant recipients, treatment for tuberculosis did not start until an average of 69 days after the transplant—a dangerously long delay.²⁹

Unfortunately, as Professor Michele Goodwin has written, these “scandals are treated as episodic rather than systemic of a renegade, unregulated industry.”³⁰ When coupled with financial incentives that reward volume, the lack of safety standards become particularly problematic. As one tissue coordinator told us: “When it comes to the quality of tissue we send out, there has been a definite trend toward accepting more and more questionable tissue with regards to disease processes, decomposition, infections, and the like. I’ve actually been told by the director of the tissue department to send in questionable tissue that has obvious concerns, because ‘Even if they throw it out, we’ll still get paid something for it.’”

Serious safety issues like these make it clear that there are major gaps in federal oversight.

For instance, there is no easy, expedient way to track donated tissue materials from a single donor to the hundreds of recipients who may receive a transplant. Although imperfect, such a system does exist in organ donation. However, FDA does not regularly have jurisdiction over end users of the products it regulates, except during recalls. The agency can and does require that tissue banks track the hospitals and clinics to which products are distributed, but can only encourage tracking to the final transplant recipient,³¹ which is arguably the most important step, especially when tissue product recalls can involve tens of thousands of grafts.³²

While an August 2022 bipartisan Senate Finance Committee hearing detailed deadly failures in oversight of organ donation in the United States,³³ tissue processing may actually contain even fewer safeguards. In both systems, the result is potentially fatal for patients as well as emotionally damaging for families who have no assurance that their loved ones will be treated with respect and dignity.

CryoLife: a history of deadly failures

In November 2001, 23-year-old Brian Lykins died following a routine knee surgery after contracting an infection from a contaminated tissue transplant. A Centers for Disease Control and Prevention (CDC) investigation found that CryoLife, one of the country’s largest tissue processors, had processed and shipped tissues from a donor whose body had not been refrigerated for over 19 hours and was infected with Clostridium bacteria. In addition to Mr. Lykins, 27 other patients contracted severe infections from tissues processed by CryoLife during this time.³⁴ An FDA inspection the following year found numerous process failures, including a “failure to adequately inspect or test incoming product.” ³⁵

This was neither the first nor the last time a patient would become seriously ill or die because of CryoLife’s failure to adhere to safety protocols. Just two years after Mr. Lykins’ death, another teenager became seriously ill after receiving a knee ligament transplant that was infected with Staphylococcus bacteria.³⁶

Between 1996 and 2002, 33 patients became ill and four patients died from fungal infections contracted from CryoLife-processed heart valves.³⁷ At the time, CryoLife processed 70% of the nation’s heart valves. However, after Mr. Lykins’ death in 2001, the FDA only recalled soft tissue products — not heart valves.³⁸

The problems at CryoLife did not stop there, even after two more patients died in 2009 and 2013. A 2013 FDA warning letter to the company details numerous safety violations, including: a lack of “active environmental monitoring…in critical classified areas;” the use of municipal water when preparing disinfectant solutions, even when testing revealed “consistent bioburden levels too numerous to count” in the water supply; and a lack of adequate staff training, such as “poor aseptic techniques.”³⁹

Despite being plagued by countless safety violations, FDA recalls, and warnings — and despite being directly responsible for harming and even killing patients — CryoLife continues to operate. In 2022, the company rebranded as Artivion and reported almost $300 million in revenue.⁴⁰

Consent in tissue donation

Much of the public are unaware of the specifics of tissue procurement, and studies have found that family approaches for tissue donation routinely lack key elements of informed consent. Some families may not even know that they are working with more than one organization or that their loved one’s tissues are being used to generate thousands of dollars of revenue.

As one expert told us, “the general public has no idea what’s going on in the tissue world, even donor families who are interacting with an OPO or tissue bank. From some conversations I’ve had with donor families, [it’s clear] they don’t realize there’s a distinction between OPOs and tissue banks, since there’s just one person they talk to.”

A 2001 report on tissue donation consent from the Office of the Inspector General (OIG) found issues including:

• “Tissue banks often request consent over the telephone, rather than in person.
• Many tissue banks rely on staff from other organizations to obtain consent. There may be little training and accountability of external tissue requestors.
• Tissue banks provide donor families with little written material at the time of donation.”⁴¹

The OIG recommended a number of improvements to how the tissue banking industry approaches informed consent, including providing written disclosures, better marking of donated tissue throughout the processing process, more accountability for those requesting consent, and periodic public disclosure about tissue banks’ financing.

In our conversations with experts, they described a system that has changed little in the past twenty years:

• In a 2010 study by researchers Laura Siminoff and Heather Traino, 70 percent of donor families said they would object to a loved one’s tissue going to a for-profit business, yet fewer than one in five said they’d been told that the harvested tissues could go to a for-profit company.⁴² The LA Times reported that “Some families say they feel [OPOs] misled them into agreeing to [tissue] procurements.”⁴³

• A 2013 study of over 1,000 consent conversations found that only three families were offered written materials explaining donation, and no conversation included the fact that tissue materials may be sent internationally. This study also found that conversations with younger, white family members were more likely to have more elements of informed consent than conversations with older family members and people of color.⁴⁴

• A 2015 study found that roughly half of tissue banks surveyed did not include the fact that tissue may be used for cosmetic purposes on an authorization form.⁴⁵

Case study in consent-related issues: Nevada Donor Network

In one case involving the Nevada Donor Network—which is currently under investigation from the House Oversight Committee regarding conflicts of interest in its tissue processing business⁴⁶—a donor family alleged that the OPO “made [representations] in order to induce consent, were false, misleading, contained material misrepresentations and omissions of fact, and were undertaken in bad faith” and that the OPO “exceeded the scope of their consent and substantially disfigured their mother’s body”.⁴⁷

The OPO’s handling of this case prompted one of the Nevada Donor Network’s founders to remove herself from the Nevada organ and tissue donation registry, citing concerns about a lack of transparency regarding the for-profit nature of tissue processing, and telling the Las Vegas Review-Journal: “The revenue-generating business venture of tissue donation has sullied the charitable desire of good people to donate lifesaving solid organs, like kidneys and hearts and lungs. They should not be linked in consent forms, in business operations or in patient education…The fact that you can’t say no and have it stand after you die horrifies me…‘No’ doesn’t mean ‘no’ here, and ‘yes’ has no boundaries.”⁴⁸ The OPO subsequently settled this claim out of court.⁴⁹

Misleading tactics

Experts we spoke to cited a number of misleading tactics routinely used to obtain “consent” from families. The AATB’s own guidance suggests refraining from any mention of processing tissue, processors, or products, and instead focusing on “sharing” and “gifts.”⁵⁰

The unclear language used in consent conversations may contribute to confusion, as families may not question the need to “prepare the body” ahead of a potential donation. One expert said, “It was so frequent it became normalized within the system, framed within the context of…’preparing the body.’ The [organization would] claim that they’re just getting standard medical information…but as part of that process, they were stealing from the body.”

A coordinator from the Midwest Transplant Network OPO in Kansas shared information regarding a case in which “a family was lied to so our call center could get them on the phone to pressure them into donating.” Specifically, the coordinator wrote that ”When the [donor’s] family responded to a text by texting, they were told the phone didn’t accept text messages. It appears that the family was only interested in donating the brain to a university for research purposes, so we told them they had to call, and pretended not to acknowledge what they said. The brain donation would have offered no financial benefit to our organization.” The family was told they could only communicate with the OPO by calling (which was untrue; the OPO could read their texts), because the OPO wanted the opportunity to verbally pressure the family into a broader consent for donation than they’d initially indicated they were comfortable with.

As one researcher noted: “You only have to listen to a few [consent] calls. [Families] can’t bury loved ones due to funeral costs, even though they’re giving an enormous amount of money to tissue banks and OPOs.”

Although experts told us that tissue recovery organizations may invest in improving these conversations, the motives are not necessarily altruistic. As one expert told us: “[Organizations] invest in how to communicate across different communities, which you could say is helpful, if there are language barriers. But that’s not what they’re getting at. It really is about how to maximize the return on the ask, and doing so as expediently as possible.”

Financial incentives and conflicts of interest

Current OPO financial reimbursement structures create a greater financial incentive for tissue recovery than for lifesaving organ procurement.⁵¹

Tissue companies like Stryker and Becton, Dickson and Company (BD) reported over $17 billion and $20 billion in total 2021 revenue, respectively, and operate in up to 190 countries.^52,53 Demand for tissues is driven by the medical community, in addition to biomedical researchers, pharmaceutical companies, and cosmetic companies, which need human tissue samples for testing and research.

Organs vs. tissues: balancing revenue and resources

According to one former CMS staff member, it’s up to individual OPOs to balance their tissue and organ procurement work — except that tissue procurement relates to a multi-billion dollar for-profit business with clear financial incentives for increased volume, while organ procurement is a non-profit business. Because organ procurement - unlike tissue procurement - is funded on a cost reimbursement basis by Medicare, OPO finances are not nearly as affected by the volume of organs recovered as tissue, so there is much less direct financial benefit for higher procurement/performance.⁵⁴

There are organizational benefits to maintaining status as an OPO, because it creates access to hospitals and ensures the OPO will receive patient referrals—which are highly lucrative for tissue procurement. However, as one expert noted, “underperformance as an OPO has zero impact on the bottom line.” Issues found on the organ procurement side—up to and including decertification—would not keep an OPO from continuing tissue procurement (though it could make it more difficult by impacting hospital access). For many OPOs, this means “tissue becomes the safety net,” as we heard from one expert, in the event of decertification—meaning that a decertified OPO could keep operating its non-organ recovery business lines. This may contribute to the feeling that decertification is an empty threat for OPOs whose primary revenue driver is tissue.

OPO annual revenues from tissue procurement vary widely, from $4.5 million at Kentucky Organ Donor Affiliates up to $411.9 million at LifeNet (Virginia).^55,56 (Note: not all OPOs report these numbers publicly.)

Massive tissue revenues led experts we spoke with to describe some OPOs as “tissue banks with an organ procurement side business.” One expert told our researchers they saw several cases of “serious leadership issues” at OPOs while working with the OPTN Membership and Professional Standards Committee. At these OPOs, executives were “taking money out of OPO operations to support tissue [procurement], to the detriment of organ procurement.” These were described as the “sloppy, extreme cases,” which only came to light because of serious safety issues at the OPO.

LifeNet, one of the largest OPO tissue processors, was described as treating organ procurement as their “side hustle,” while they made “tons of money” on tissue procurement.⁵⁷

In lobbying materials, OPOs and UNOS often try to obfuscate this dynamic by highlighting that organs and tissue can both be recovered from the same donor, implying that OPOs do not need to choose between the two goals.⁵⁸ However, the tension most often presents in staffing and resource allocation decisions, rather than on a case-by-case basis.

Specifically, OPOs are often grossly understaffed on frontline coordinators for organ donation, and heavily resourced and staffed for tissue recovery operations.⁵⁹ This problem is further compounded by the lack of transparent data about donors who might have become organ donors but who instead only donated tissue. Interviewees we spoke to routinely talked about staffing discrepancies at some OPOs between organ procurement and tissue procurement. One former transplant nurse coordinator described how her organ procurement team had three staff members, while the tissue procurement team had eight. While her staff were working 24 hour shifts because the OPO refused to pay for the additional staff necessary to cut shifts to a safer 12 hours, the tissue procurement teams had enough staff to be “stumbling over each other.”

This directly impacts the thousands of patients waiting for a lifesaving organ transplant: studies have shown that the timing of a donation request directly affects the likelihood of a family or next of kin consenting to donation, suggesting that an overworked, understaffed department cannot successfully recover the true number of potential organ donors — the very mission an OPO is tasked with.⁶⁰ CMS could mitigate some of these issues by transparently publishing staffing data for all OPOs for both organ and tissue procurement, as well as by publishing OPO process data (e.g., how often and how quickly OPOs respond to referrals) as suggested by the Senate Finance Committee.⁶¹

Conflicts of interest

Different parts of the tissue processing industry are deeply entwined, which can create conflicts of interest.

OPO executives make up the AATB Board, along with representatives from tissue processing companies.⁶² The immediate past Chair is the current Senior Vice President of New England Donor Services; other Board Members have included the Director of Tissue Donor Services for LifeCenter Northwest, the Vice President of Tissue Operations at the Nevada Donor Network, and the Chief Clinical Officer for Kentucky Organ Donor Affiliates.

Other overlaps between OPOs and tissue processing companies include:

• Executives from five OPOs (Donor Alliance Network, Iowa Donor Network, Mid-America Transplant, ConnectLife, and Gift of Hope) also sit on the Board of Allosource, a large tissue processing company. These OPOs own stakes in Allosource ranging from $8 million to $26.4 million.^63,64

• Executives from Midwest Transplant Network, LifeShare of Oklahoma and New Jersey Sharing Network sit on the board of MTF Biologics, another large tissue processing company.⁶⁵

• LifeNet Virginia operates seven subsidiaries, five of which are focused on tissue procurement and processing.⁶⁶

• Nevada Donor Network, in “joint venture” with Australian company Australian Biologics, owns a 22,000 square foot tissue processor called Origin Biologics, a conflict which is currently being investigated by the House Oversight Committee.⁶⁷

• LifeLink of Georgia has paid almost $2 million in fees to TransLife Tissue Bank, a tissue bank run by a LifeLink Board Member.⁶⁸

Some OPOs have multiple subsidiaries and a global presence. LifeNet, for instance, spends nearly $1 million on global sales representation, while LifeLink of Georgia owns a $250,000 stake in HCT Regenerative (a tissue processing company based in Hong Kong).^69,70 LifeLink sells this company tissue and bone material, and receives a royalty on any allografts sold.

Instances of corruption

While industry opacity prevents many abuses from coming to light, some high-profile examples have emerged.

For example, in one case—which eventually resulted in the criminal conviction of two OPO executives in Alabama,⁷¹ and for which the whistleblower was threatened with being “cremated alive”⁷² —an OPO staffer filed a complaint with the OPTN’s Membership and Professional Standards Committee (MPSC) regarding allegations of a money laundering scheme. As NPR later reported, the OPO had given a contract to a local funeral home to be ”the one place where tissue was taken from corpses” in exchange for kickbacks.⁷³ The complaint filed with the MPSC called on UNOS to conduct a full investigation,⁷⁴ but the MPSC did not take meaningful action. As summarized by the Senate Finance Committee in its August 2022 investigation memo: “The Committee was unable to identify what, if any, steps UNOS took to investigate the financial improprieties reported to them in March 2011. Instead, it seems UNOS simply rolled the complaint into a broader ongoing review of the OPO for OPTN policy and procedure violations.”⁷⁵

An expert we spoke with noted that it’s “unclear how regularly these cases are happening under the radar, because HRSA and CMS do not look at the financials of tissue at all, except in extenuating circumstances.”

Separately, we heard from one OPO CEO who had been in front of the MPSC for an apparent violation related to organ recovery who said that “after the first day of MPSC proceedings, [a senior member of the MPSC] pulled me aside at the hotel bar and said ‘this will go on for two years and cost your OPO millions of dollars; or else it can all just go away if you give me your OPO’s tissue business.’” Because there are no public disclosures related to financial interests in tissue procurement and processing, there is a risk that members of MPSC, rather than providing oversight of OPOs, could actually be engaging in business development to further their own personal interests.

Compounding the problem is that the MPSC does not make case details publicly available. In fact, at the August 2022 Senate Finance Committee hearing, Senator Elizabeth Warren characterized UNOS’s current oversight as “sitting on your hands while people die.”⁷⁶

In a separate incident around the same time as the Alabama case, a New Jersey-based body broker named Michael Mastromarino pleaded guilty to enterprise corruption, reckless endangerment and body stealing. As part of the scheme, Mastromarino established a network of undertakers, whom he paid up to $1,000 per corpse, and harvested tissue from bodies without consent. According to filings, Mastromarino also harvested body parts from people with cancer, H.I.V. and other communicable diseases, and forged paperwork - including consent forms and death certificates - to make it appear as if the donor met clinical and legal requirements for tissue donation.⁷⁷ As NPR later reported, “a lot of the things that seemed so shocking about his case turned out to be routine aspects of the business. They were surprising only because so little is known about human tissue donation.”⁷⁸

Inequities in care

There’s no regulatory requirement for tissue donation to benefit the community the tissue comes from, and allocation decisions about where OPOs should send tissues are at the discretion of the OPO, because—unlike for organs—allocation is not prescribed by an oversight body. This means that allocation is governed by the market for tissues, rather than by impact or patient need.

Major users of donated tissue materials include biomedical companies, cosmetic companies, and research centers that need human tissue samples for research purposes. At times, this has meant that skin banks for burn victims have been unable to get the tissue needed to serve their patients, as tissue processors could sell it at higher prices to biomedical and cosmetic companies.⁷⁹

As one researcher told us, “It’s absolutely, deeply unethical that we don’t know how many times someone in our community is asked to give tissue and we can’t track where that tissue goes and if there is a return to community benefit.”

Studies have found that patients in high socioeconomic status areas have increased access to organ transplants;⁸⁰ that the organ donation system does not adequately, equitably serve patients, donors, and families of color;⁸¹ and that organ transplant recipients are more likely to be white, highly educated, and live in higher socioeconomic status zip codes.⁸² In contrast, Black patients spend a longer time on the waitlist,⁸³ and are less likely to be rated an “appropriate candidate” for a transplant than a white patient.⁸⁴

These disparities are seen in tissue procurement and transplantation as well, where communities that donate the most are not seeing the most impact or benefits. Tissue transplants are frequently used in cosmetic, reconstructive, or joint surgeries that may only be available to wealthier patients with private insurance.

For example, studies have found that the average cost for a knee tendon repair is $13,000, a procedure that commonly uses a tissue transplant.⁸⁵ For a patient with Medicare, the out-of-pocket cost may range between $414 to $719.⁸⁶ Because few tissue transplants are lifesaving, families may be more likely to skip these costly procedures. Tissue transplants are used in surgeries that can be important for mobility and quality of life, but may not be affordable for families who cannot afford unexpected expenses.⁸⁷

One of the most common uses of donated bone tissue is dental putty, frequently used in dental implants. There are wide disparities in dental care in the United States: At least half of American adults do not have dental insurance,⁸⁸ while children from low-income families are three times as likely to have untreated cavities as children from high-income families.⁸⁹ Dental implants, which can cost thousands of dollars per tooth, are a costly use of donated tissue material that many Americans cannot benefit from.

Issues persist when tissue is sold internationally. A recent World Health Organization (WHO) report found that “long-term or ongoing reliance on external sources can expose the ‘importing’ national health system to an unpredictable supply in terms of quantity and quality and to commercialization, with imposed higher or unacceptable costs limiting access. Conversely, ‘exporting’ countries may be under-serving their own population of potential recipients by diminishing local availability.” ⁹⁰

Recommendations for better regulation

Part of the urgency, and difficulty, in developing stronger regulations for the tissue processing industry is because the field is a rapidly growing, developing area of medicine. Since the FDA finalized the Current Good Tissue Practices in 2005, there have been major developments in procedures like pancreatic islet cell transplantation and the transplantation of composite tissue allografts (which include procedures such as face or hand transplants).

Experts describe a field with “a lot of gray areas,” where regulation has not always kept up with changes in medical technology. For instance, the FDA’s definitions of “minimally manipulated” and “homologous use” may be challenged when products combine multiple types of human tissue or are used in complex procedures. Furthermore, oversight is split between multiple bodies. For example, veins taken in the context of organ procurement fall under the jurisdiction of the OPTN—yet those same veins would be classified as tissue if taken alone.

In one recent case, which is currently the subject of a legal battle in the Wayne County Probate Court in Michigan, the donor’s family had consented to donate organs but not tissue. However, tissue was recovered, which appeared to interfere with the autopsy; this was particularly important as the death had been flagged as “suspicious or unusual” by doctors at the hospital where the donor had died.

In a recorded phone call, the county Medical Examiner told the donor’s family: “In the state of Michigan, you can remove organs for donation and transplant into someone else without consent of the Medical Examiner. That only requires the next-of-kin, and it’s my understanding that some organs were donated, and unfortunately, in this case, [the OPO] removed tissue which would’ve been vertebral column, like the backbone… [The problem is that] how we classify the organs and tissues may need some clarification… How I classify [backbone] is a tissue. How [the OPO] classif[ies] that is an organ.”⁹¹

This is emblematic of the fragmented, siloed nature of tissue regulation. Changes are urgently needed to increase patient safety and restore public trust in the system.

Information sharing between government agencies

To address the fragmented nature of tissue industry regulation, stronger information sharing is needed between FDA, CMS, and HRSA. It is crucial to close these gaps in oversight and ensure that all aspects of tissue procurement and processing are being properly overseen.

Government agencies and Congress should support:

• Sharing OPO and tissue processor audit reports between FDA and CMS. Issues found by either agency should trigger further investigation by the second agency. The ultimate goal should be to increase patient safety by fully monitoring each aspect of procurement and transplant.
• Faster, more responsive information sharing between FDA, CMS, HRSA, and CDC when responding to adverse event reports and deviations from best practices. These agencies must be able to quickly and accurately notify hospitals and patients in the event of adverse events. Historically, recalls can take months, with agencies unable to accurately track every recipient of potentially hazardous tissue.

Increase traceability of tissue products

A key component of adverse event reporting and tracking is traceability. The WHO has called traceability of human-based tissue products an “absolute prerequisite” for ensuring patient safety.⁹² And while the OPTN does implement a system for tracking organs from donor to recipient, there is currently an inadequate tracking system for tissue donations and transplants. The European Commission updated traceability guidance in 2022, after finding the original 2001 guidance was now “outdated” and not keeping “pace with this rapidly changing sector.”⁹³ The U.S. should follow this example and update the 2005 tissue product guidance as well.

Specifically, FDA should require a universal tracking system for all human-tissue based products that is easy to integrate with global standards, and covers the entire process from recovery to transplant. Currently, many tissue banks voluntarily use the ISBT 128 code system for donor identification, but this labeling standard only covers the final label present during distribution; it’s optional for tissue processors to use the same label during recovery and processing.⁹⁴ A 2015 survey of 112 tissue banks found that only 27 banks tracked incoming transplant records from hospitals and clinicians.⁹⁵ The use of multiple labels throughout procurement and processing has the potential to create serious tracking issues in the event of an adverse event report. With thousands of tissue products shipped internationally every year, it’s critical that these products be easily and quickly traceable back to the country and donor of origin.

To support these efforts, CMS should consider requiring hospitals and surgical centers to track tissue transplants and recipients. As a payer for these procedures, CMS may have authority over end users that FDA lacks. Currently, The Joint Commission voluntary standards for hospitals include patient-level tracing, providing a strong example for CMS to consider.⁹⁶

Require transparency to increase safety and equity

Currently, researchers cannot state with certainty the number of tissue donors in the U.S. last year, the types of grafts procured, the types of transplants received, or the communities procurement and transplant occurred in. However, as one expert noted, these are “knowable, countable numbers,” that are currently tracked in other countries. For example, Canada collects data on the types of tissue transplants, while Australia and New Zealand publish extensive monthly data, breaking down the number of tissue donors by gender, province, and age.^97,98 This data is crucial for identifying trends, accurately counting adverse events, and better understanding the inequities of tissue procurement and transplantation.

CMS should require OPOs to include data on tissue procurement in reporting to CMS. Because OPOs must provide this data to processors in order to clear tissue donors, providing this data would not require new processes. OPOs should report and aggregate existing data, such as:

• How many potential donors are evaluated, approached, and authorized
• The number and type of tissue procurement by location, donor gender, donor race and ethnicity, and donor age
• The number of transplants by tissue type (i.e., the number of skin grafts, the number of bone grafts, etc.)
• The number of tissue transplants, by recipient gender, recipient race and ethnicity, and recipient age in each OPO’s Donation Service Area (DSA)
• The number and type of adverse events reported to the company or OPO
• The number and type of referrals for tissue procurement in a given DSA
• The number and type of potential tissue donors identified in a given DSA stratified by demographic
• The number and type of authorizations for tissue procurement by type of graft (whole eye, cornea, full-thickness skin, bone, heart for valves, etc.) stratified by demographic
• The number and type of donors by graft in a given DSA stratified by demographic

This data could be de-identified and publicly shared for greater transparency.

With increased data collection and transparency—including financial resource allocation and OPO staffing data—CMS, Congress, researchers, and other stakeholders will be able to accurately identify trends in tissue procurement and transplantation, including inequities. This is a necessary step towards being able to address issues and ensure a more ethical system of procurement and transplant.

Regulators should also require OPOs to publish potential conflicts of interest related to tissue procurement. Pro-transparency OPO leaders have voiced support for CMS to require OPOs to publish a statement of financial relationships between OPOs, OPO leadership, and external tissue operations.⁹⁹ Doing so would bring increased transparency to a currently opaque system.

Conclusion

By some estimates, up to 2.5 million tissue grafts are transplanted every year.¹⁰⁰ Tissue procurement and processing is currently a multi-billion dollar industry that has grown rapidly since the first tissue bank was founded in 1949.¹⁰¹ By some estimates, the global tissue banking market may be as large as $3 trillion by 2026.¹⁰²

Although many patients do benefit from tissue transplants every year, the industry has been plagued by safety issues, inadequate oversight, and little accountability for patients and their families. Some OPO leadership have consistently made choices to prioritize tissue recovery over organ procurement, such as directing staff resources to tissue procurement rather than organ procurement. Decisions like this have a direct impact on the thousands of patients waiting for a lifesaving organ transplant.

The tissue industry urgently needs regulatory changes to bring increased transparency and safety to a necessary—yet currently opaque and unsafe—system. As medical technology advances, the tissue transplant field will continue to grow. It is crucial that regulations keep up with these changes, for the sake of patient safety, public trust in the system, and equity in transplantation.

Appendix A: List of OPOs registered as tissue banks

Organ Procurement Organization103	Region
Alabama Organ Center	AL
Center for Organ Recovery and Education	Western PA & WV
Donor Alliance	CO
Donor Network of Arizona	AZ
Donor Network West	Northern CA
Gift of Hope Organ & Tissue Donor Network	IL
Gift of Life	Eastern PA & Southern NJ
Gift of Life Michigan	MI
Indiana Organ Procurement Organization	IN
Kentucky Organ Donor Affiliates	KY, Western WV & OH
LifeBanc	Northeast OH
LifeCenter Northwest Organ Donation Network	WA, ID, MT
LifeCenter Organ Donor Network	Southwest OH & Southeast IN
LifeGift Organ Donation Center	TX
LifeLine of Ohio	Central OH
LifeLink of Florida	Western FL
LifeNet	VA & Northwest WV
Lifeshare of Oklahoma	OK
LifeSharing - A Donate Life Organization	CA
Lifesource Upper Midwest Organ Procurement Organization	MN, SD, Western WI
LiveOnNY	NYC
Mid-America Transplant Services	MO & Southern IL
Nevada Donor Network	NV
New England Organ Bank	CT, ME, NH, RI & VT
New Jersey Sharing Network	NJ
OneLegacy	CA
OurLegacy	FL
Tennessee Donor Services	TN, KY, VA
The Living Legacy Foundation of Maryland	MD
Upstate New York Transplant Services Inc	Western NY
Versiti	WI
Washington Regional Transplant Community	Washington, D.C., & Northern VA
We Are Sharing Hope SC	SC

Notes