ACBTSA April 15, 2019 - Meeting Summary

Committee Business

Welcome and Roll Call

Jacquelyn (Jackie) Fredrick, MT(ASCP)SBB, PhD, retired CEO of Versiti, Inc., Chair of the Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA), called the 50^th meeting to order. She welcomed and thanked all Committee members and speakers for attending the meeting.

James (Jim) Berger, MS, MT(ASCP)SBB, Designated Federal Officer, ACBTSA, Senior Advisor for Blood and Tissue Policy, Office of the Assistant Secretary for Health, Department of Health and Human Services, conducted roll call and stated that the meeting had a quorum.

Dr. Fredrick reminded the meeting attendees of the mission of ACBTSA and introduced the first speaker, Dr. Carlos Villa.

The Food and Drug Administration (FDA) Update

Carlos Villa, MD, PhD, Medical Officer, Division of Blood Components and Devices, Office of Blood Research and Review

Dr. Villa updated the Committee on the 120^th Meeting of the Blood Products Advisory Committee (BPAC), which took place in March 2019. He highlighted the 2 of the 3 topics related to blood safety, shared BPAC’s recommendations regarding the proposed questions in the human immunodeficiency virus (HIV) Risk Questionnaire study and reported what the FDA has learned.

Evaluation of strategies to reduce the risk of Zika Virus transmission by blood and blood components

BPAC supported continuing the current strategy of universal testing by minipool or individual donation testing. The committee felt that additional information and continued surveillance are needed before implementing further policy change.

Blood donation policies regarding men who have sex with men (MSM)

BPAC was asked to comment on 1) what has been learned from implementing other MSM policies internationally and how the information can inform current U.S. MSM deferral policy, and 2) the questions proposed for study in the HIV Risk Questionnaire. BPAC members discussed the difference in HIV epidemiology and donor screening practices between countries, provided recommendations regarding the proposed questions in the HIV Risk Questionnaire study, agreed that FDA should pursue data to consider alternative deferral strategies while ensuring the current level of safety, and supported improved assessment of risk for all individuals.

BPAC also discussed pathogen reduction of platelet donation as an alternative procedure to MSM donor deferral. The majority of the BPAC members expressed the view that pathogen reduction as an alternative to MSM deferral would result in safe products intended for transfusion, while noting that care needs to be taken to implement this approach. BPAC also emphasized the need to engage stakeholders and re-emphasized the need to study and develop individual risk assessment.

Discussion

In response to Dr. Fredrick’s question regarding that data presented at BPAC’s 120^th Meeting, Dr. Villa clarified that the data are currently being analyzed and will become available to the public. Regarding individual risk assessment questionnaire, they are still in the process of gathering proposals for the study. He anticipated that the results will be made available to the public as well.

Mark Skinner, JD, President and CEO, Institute for Policy Advancement Ltd., asked a question regarding timelines for the studies. Dr. Villa replied that no specific timelines were given. It would depend on how soon the studies will be completed and data analyzed. The general agreement was it will be a data-driven approach.

Mary Gustafson, Vice President, Global Regulatory Policy, Plasma Protein Therapeutic Association, commented that she would like to see broader discussion around pathogen reduction as an alternative procedure to MSM donor deferral.

Purpose of the Meeting

Emily Blumberg, MD, FACP, Director, Transplant Infectious Diseases, University of Pennsylvania; Professor of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania

Dr. Blumberg, ACBTSA Co-Chair, thanked all meeting attendees. She noted that in 2013, the U.S. Public Health Service (PHS) published the first version of its guideline, which took several years to develop. At that time no data were available to guide the developing process. She stated that the purpose of the 50^th ACBTSA meeting is for the Committee to see where we were and where we are today, and to make their recommendations after the invited presentations. The recommendations will be reviewed by the Blood, Organ, and Tissue Senior Executive Council, which will make their own recommendations and solicit public input.

Landscape of Theme

Organ and Blood Stem Cell Transplantation in the United States: The Role of the Health Resources and Services Administration (HRSA)

Marilyn Levi, MD, Medical Officer, Division of Transplantation, Healthcare Systems Bureau, HRSA

Dr. Levi provided an overview of the role of PHS, particularly the role of HRSA. She noted that HRSA is the primary federal entity responsible for oversight of the solid organ and blood stem cell transplant systems in the U.S. It is also responsible for initiatives designed to increase the level of organ and tissue donation in the country. HRSA exercises its oversight through statutory requirements, federal regulations, and federal contracts.

Dr. Levi briefly reviewed solid organ transplantation-related statutory authorities through HRSA, including the 1984 National Organ Transplant Act, the 2004 Organ Donation and Recovery Improvement Act, the 2007 Charlie W. Norwood Living Organ Donation Act, and the 2013 HIV Organ Policy Equity Act (HOPE), which enables the development and publication of research criteria relating to transplantation of HIV-positive organs (living and deceased kidney and liver transplantation only) to HIV-positive individuals.

The entire solid organ transplantation oversight involves multiple agencies, including FDA, the Centers for Medicare and Medicaid Services (CMS), the National Institutes of Health, the Centers for Diseases Control and Prevention (CDC), and HRSA.

Dr. Levi introduced the divisions within HRSA that provide oversight on transplantation, including the Organ Procurement and Transplantation Network (OPTN), the Scientific Registry of Transplant Recipients (SRTR), the National Living Donor Assistance Center, the Advisory Committee on Organ Transplantation, the Organ Donation Public Awareness Program, as well studies and demonstration projects to increase organ donation and recovery rates.

In addition to organ transplantation, HRSA also provides oversight on blood stem cell transplantation through the CW Bill Young Transplantation Program, the National Cord Blood Inventory Program, and the Advisory Council on Blood Stem Cell Transplantation.

Dr. Levi presented data on ongoing crisis related to solid organ transplantations. Available data demonstrate that the waiting list for solid organ transplantation is rather long compared with limited donors available. As of March 3, 2019, there were 113,727 patients on the waiting list. Every day, about 20 people in the U.S. die while waiting for an organ transplant.

Dr. Levi noted that while we need more organs, critical balance needs to be maintained to ensure safety. HRSA facilities efforts in biovigilance monitoring and safety through multiple channels, including the OPTN ad hoc Donor Transmission Advisory Committee (DTAC), the United Network for Organ Sharing (UNOS) Patient Safety Portal, the PHS Biovigilance Working Group, the PHS guidelines, the National Marrow Donor Program (NMDP), and the Donor Patient Safety Monitoring Advisory Committee of the NMDP.

The number of potential donor-derived transmission—reported through the UNOS Patient Portal—peaked in 2015 with 290 reported potential events. Further review conducted by DTAC showed that actual transmissions did not increase from 2011 to 2018, and the number of cases ultimately proven and probable is small (ranging from 26 to 47 each year from 2011 to 2018).

Summary of 2013 PHS guidelines

Dr. Levi provided a brief overview of the guidelines on increased risk donors. The criteria for increased risk donor classification include exposures to the following within the past 12 months.

Intravenous drug use
Imprisonment for 72 hours
Sexually transmitted infection
Sexual activity:
- MSM
- Exchange of sexual activity for drugs or money
- HIV, hepatitis B or hepatitis C infected partner
- Sexual partner with history of IVDA
Hemodiluted blood sample
Hemodialysis (for hepatitis C virus [HCV] risk only)
Children <18 months of age born to mother infected with or at increased risk for HIV, hepatitis B virus (HBV) or HCV
Children breastfed from mother with known HIV infection or at increased risk

Following the PHS guideline on IRD, more donors are identified as with “increased risk.” She explained that 1 in 4 donors considered IRD is because of opioid.

The 10-year review of probable/proven donor-derived transmission events showed that although the number of transmissions seem high, the reality is that the percentage of recipients had donor-derived disease is small (0.14%).

Dr. Levi explained that HRSA, CDC, and FDA coordinate issues related to donor screening, and that multiple pathways exist for data and issues to be reported to the OPTN. If there is concern of disease transmission, NMDP will review the events, determine if it is donor or procedure related, and report the findings to HRSA and FDA.

Committee Address 1

Admiral Brett Giroir, MD, Assistant Secretary for Health, HHS Office of the Secretary

Admiral Giroir thanked all meeting attendees and expressed his gratitude for the Committee’s role in ensuring the safety of America’s blood supply as well as safety and availability of organs. He highlighted the following accomplishments of the Committee.

Advocating for the creation of a sentinel system to monitor production, demand, and utilization of blood products.
Making blood donation a national priority.
Recommending, after an extensive review, that the FDA amend its policy of “indefinite deferral” of blood donations from men who had sex with men to a 12-month deferral period.

As a physician who cares patients in need and as the Assistant Secretary for Heath, Admiral Giroir said he is committed to ensuring that the work the Committee is doing syncs with the overall mission of “Leading America to Healthier Lives.”

Admiral Giroir noted that the high demand for organs, combined with a small increase in organ availability, has resulted in increased acceptance of donors with risk factors for HIV, HBV, and HCV. However, the gap between available organs and those who need continues to widen. In 2018, more than 17,500 donors donated organs, which resulted in more than 36,500 transplants. However, nearly 114,000 Americans remain on the waiting list and an average of 20 Americans die every day from the lack of available organs to transplant.

Admiral Giroir asked the Committee to carefully consider the balance of organ safety and availability. The goal is to reduce risk as much as is feasible while preserving the availability of as many high-quality organs as is possible.

Admiral Giroir noted that during this meeting, the Committee will be tasked with recommending revisions to the PHS guidelines by answering the following 3 questions.

Does the available information support a reduction of the current 12-month risk behavior time frame for determining increased risk donor designation?
Is there a more appropriate term than “increased risk donor” to designate donors with risk factors for undetected HIV, HBV, or HCV infection?
Should some criteria for increased risk donors be modified (eg, hemodilution of specimen used for HIV, HBV, or HCV testing, history of sexually transmitted infection, or outpatient hemodialysis)?

Admiral Giroir asked the Committee to work with HHS on increasing opportunities for prevention, improving treatment of disease, and enhancing the safety and availability of transplants.

Committee Address 2

Robert R. Redfield, MD, Director, Centers for Disease Control and Prevention (CDC)

Dr. Redfield stressed that transplantation is important public health prevention. He expressed his appreciation for the Committee’s work. He said that more than 100,000 American people are on the waiting list of organ transplantation, most patients suffer the consequence of dialysis while on the list and about 20 people die while waiting for available organs. The overall survival rate is about 35% without transplantation, and the rate increases to 75% with transplantation.

Dr. Redfield noted that the decisions we make will impact patients. He urged the Committee to embrace science, review scientific evidence, balance organ safety and availability, and improve organ utilization. “Transplantation is a critical tool, which is currently underutilized,” he said.

Dr. Redfield thanked the Committee for working on the complex issue. He urged the Committee to use the opportunity to advance the guidelines and to help patients.

Overview of the Organ Procurement and Transplantation Network (OPTN)

David Klassen, MD, OPTN Medical Director, Chief Medical Officer, UNOS

Dr. Klassen provided an overview of the history of OPTN, explained its current structure, and presented available data.

From 1970s to early 1990s, there was no coordinating national system. The National Organ Transplant Act of 1984 established OPTN, created the Organ Procurement Organization (OPO) system, and created SRTR for data analysis.

Key responsibilities of OPTN are to:

Maintain a national transplant list;
Facilitate organ distribution and transplantation;
Establish equitable policies and membership standards;
Monitor members for compliance, safety, and quality;
Collect/validate/report transplant data; and
Promote most/best use of available organs.

OPTN is a membership organization made up of transplant hospitals, OPOs, histocompatibility laboratories, public organizations, medical/scientific organizations, and individual members. It is governed by the Board of Directors and conducts its activities through various committees.

OPTN high level data showed that 36,527 solid organ transplantation procedures were performed in 2018. More than 250,000 transplant recipients are alive today. About 114,000 transplant candidates are currently listed nationwide, which is below the historic peak in 2014. On average, about 150 candidates are added to the list each day, and about 18 die while waiting.

Dr. Klassen then introduced UNOS, a private, 501(c)3 organization that manages the OPTN system under cost-share contract with the federal government. UNOS has a 24-hour call center for organ matching, and it provides research, technology, and education to the transplant community.

OPTN’s core functions include running the “match,” managing the data, and providing quality oversight. OPTN’s transplantation allocation systems are based on the organ type. Its database contains 24 billion records, 8 database environments, 30,000 database elements, and 8 terabytes of data storage. OPTN provides quality oversight on patient safety, disease transmission, clinical transplantation outcomes, and policy compliance.

OPTN’s policy pertaining transmissible disease risk and consent requires consent by recipients to 1) general risks of potential malignancy or infectious disease transmission, 2) donors with risk identified pre-transplant, and 3) organs from donors with increased risk of disease transmission as specified in the PHS guideline.

The organ discard rate gradually rose in the past years. In 2018, about 20% kidney procured were not being transplanted, indicating an opportunity to improve. Meanwhile, 2-year graft survival rate gradually declined. While the number deceased organ donors with standard risk remained relatively stable, the number of deceased organ donors classified as PHS IRDs are on the rise—about 25% of the deceased donors met the PHS increased risk status in 2017.

Dr. Klassen pointed out that the environment for organ transplantation is unique. Decisions generally need to be made within 30 minutes, and the decision to accept or decline an organ can affect survival. Compared to patients who declined IRD kidney offers, patients who accepted kidney from IRDs had significantly improved survival benefit.

Discussion

In response to Dr. Fredrick’s question regarding regional differences and what can be done to increase organ utilization. Dr. Klassen noted that waiting time varies across the country. He pointed out the importance of clearing negative connotations associated with IRD. He noted that we need to balance how the guidelines are structured, and broadening education about risk could make an impact.

In response to a question from Richard Benjamin, MBChB, MS(HCM), PhD, FRCPath, Chief Medical Officer, Cerus Corporation, Dr. Klassen clarified that risk status is defined by clinical categories listed on the PHS guidelines and is communicated with the centers.

Dr. Blumberg commented given that donor data are confidential, centers must be careful about how to communicate without disclosing private information. She noted that the tasks of the Committee are to define the risk based on current information and provide recommendations accordingly, and there will be certain areas that are outside of the Committee’s purview.

In response to Dr. Fredrick’s question, Dr. Klassen noted that it is not clear why patients decline organ offers.

Marian Macsai, North Shore University Health System, Glenbrook Hospital; Eye Bank Association of America, asked a question regarding HCV related risks and consent. Dr. Klassen replied that utilization of organs from donors with HCV has been increasing, but utilization of organs from donors with PHS designated “increased risk” hasn’t.

Dr. Blumberg added that transplants from donors infected by HCV is complicated. Donors with NAT-positive and antibody-positive results are 2 different categories. She clarified that currently there is no universal consent to accept organs from HCV-positive donors, and that each center has their own process.

Dr. Klassen added that there is separate consent to receive transplants from HCV donors. There are multiple consents to be made. He clarified many of the consents were conducted before transplantation.

Dr. Skinner asked if clinician behaviors play a role in the regional differences, and what changes can be made. Dr. Klassen replied that it is challenging to predict clinicians’ behaviors, which vary across the country. Different centers have different levels of tolerance to risk. Education could make a difference. He suggested the Committee address the PHS risk criteria in order to decrease PHS risks while maintaining the safety level. He stressed that the transplantation environment and decision-making process are different from blood and tissue.

Historical Background of PHS Role in Prevention of HIV and Hepatitis Transmission Through Organ Transplantation

Matthew J. Kuehnert, MD, Medical Director, Musculoskeletal Transplant Foundation

Dr. Kuehnert provided a brief overview of the historical background of PHS’s role in prevention. To address transmission of HIV through organ transplantation occurred despite antibody testing, the PHS Work Group on Organ and Tissue Transplantation was formed in 1991. The CDC guideline for preventing transmission of HIV through human tissue/organs was subsequently published. Despite antibody screening, transmissions involving HIV as well as HCV, however, continued in the following years.

The nucleic acid test (NAT) was developed to reduce the “window period,” a time period during which a patient is infected with transmissible virus but test is false negative. NAT was implemented in 1999 for blood donor screening and tissue donor screening in 2005. However, by 2007, organ donors still were not being tested using NAT.

Dr. Kuehnert presented 2 examples of HIV and HCV transmission from donors. In 2007, a deceased donor with increased risk (MSM) who died after being hit by a car transmitted both HIV and HCV to 4 organ transplant recipients, 2 of whom died and the other 2 lost graft because of complications. In 2009, a donor who was screened and tested 79 days before transplantation transmitted HIV by kidney transplant to a living donor. The donor was diagnosed with HIV one year after the kidney transplantation. The incident highlights the need that living donors should be screened no more than 7 days before recovery.

Currently, the opioid use in the U.S. continues to increase. Meanwhile, HCV infections are increasing across populations, including organ donors. HCV prevalence in potential organ donors is high. Residual risks of infectious disease transmission for organ transplantation are higher than tissue and blood. As a result, the PHS Guidelines for Preventing Transmission of Human Immunodeficiency Virus through Transplantation of Human Tissue and Organs were developed and published in 1994.

To preserve availability while keeping organs as safe as possible, Dr. Kuehnert suggested looking at both donor eligibility-associated issues and organ suitability-associated issues.

Dr. Kuehnert noted that the focus of the 1993 guideline was on HIV prevention, whereas the focuses of the 2013 guideline was expanded to include HIV, HBV, and HCV. The criteria for IRD designation were updated to include 12 categories and special requirement for recipients to consent prior to IRD organ transplant. In addition, HCV NAT testing was recommended for all donors and HIV NAT or HIV p24 antigen for IRD, and post-transplant HIV, HBV, HCV testing was recommended for all recipients. He explained that the revision was conducted through an evidence-based process. When data were not available, external experts from the transplant community were consulted.

Dr. Kuehnert explained that issues were raised during the guideline development process, including the possibility of reduced acceptance of organs due to more donors defined as at increased risk, decreased organ availability caused by false-negative tests, and increased costs associated with pre- and post-transplant testing. Changes were made in response to public comments and external input, and the final guideline was published in 2013.

Dr. Kuehnert noted that the risk of undetected HIV and HCV infection despite NAT test can be modeled. However, it is challenging to identify the risk of donors and find the “safe subset.” In terms of organ safety, he pointed out that the following information is needed.

Knowledge of how many transmissions have been prevented
Outcomes of managing known infected donors
Need for better informed consent, including understanding by physicians and discussion with patients
Models to understand what donors at risk of

He warned the danger of eliminating risk factor assessment entirely and rely on lab screening only because all currently available tests have eclipse period and there are other pathogens (eg, human herpesvirus 8, Hepatitis E virus, and Peg virus 2) besides HIV, HBV, and HCV.

He suggested that the following actions need to be taken to ensure organ safety.

Testing all recipients receiving transplant from increased risk donors
Managing transplant from known infected donors
Developing models for risk quantification

In summary, Dr. Kuehnert noted that the risk of transplant-derived disease transmission is small but it is important to ensure trust in the system. He said that risks at bed side are poorly understood, and informed consent and assessment tools are key to improve understanding.

Historical Perspective on the Establishment of DTAC

Michael Ison, MD, MS, FIDSA, FAST, Professor, Division of Infectious Disease and Organ Transplantation, Transplant & Immunocompromised Host Infectious Diseases Service, Northwestern University Feinberg School of Medicine

Dr. Ison, a former member and the second Chair of the Disease Transmission Advisory Group (DTAG), the predecessor of DTAC, provided a historical perspective on the establishment of DTAC, whose main focus is on unexpected transmissions derived from organ transplantation.

DTAC was first established in 2006 as an advisory group to the OPTN/UNOS Operations Committee to identify and evaluate potential donor-derived disease transmission events.

Transmissions of a rodent-borne virus from an organ donor to multiple recipients led to the development of OPTN Policy 4.6, which requires donor testing using an FDA licensed, approved, or cleared serologic test, “high risk” donor assessment, and risk communication to transplant centers.

OPTN policy 4.7 further requires reporting donor-derived events as soon as possible and not to exceed one complete working day to the procuring OPO, which shall then communicate the results to all recipient Transplant Centers and Tissue Banks, manage the investigation, notify OPTN, and submit a final written report to the OPTN within 45 days.

Dr. Ison explained the focus in increased risk donors started with an unexpected HIV and HCV transmission from an HIV and HCV serology negative donor to an HIV and HCV antibody negative recipient. The donor was labeled as “high risk” based on PHS guidelines and was subsequently tested HIV positive using post-transfusion serum and HCV positive by polymerase chain reaction. The community responded with processes to improve consent and monitoring. In response to the HIV/HCV transmission event, DTAG was transformed into the ad hoc OPTN Disease Transmission Advisory Committee to review all potential donor-derived transmission events.

During the first years, they formalized the DTAC’s structure and function, partnered with other experts, collected data, and continued working with CDC. They also established a U.S. Organ vigilance system to help develop real-time guidelines, and they were involved in the 2013 revision of PHS increased risk guidelines.

DTAC’s main accomplishments from 2005-2010 include the following.

Established the epidemiology of donor-derived disease transmission
Increased organ availability
Provided guidance on key issues associated with H1N1, Dengue, and West Nile virus
Provided education through journal publications and meeting presentations
Collaborated with key transplant players
Established the importance of infectious disease expertise within UNOS

Dr. Ison pointed out that the biggest accomplishment of DTAC is that today DTAC has become the gold standard for organ vigilance systems in the world.

Discussion

Dr. Fredrick asked if DTAC’s work is funded. Dr. Ison replied that it is run through UNOS, and it has changed over time. Dr. Klassen added that UNOS staff members are supported by UNOS, but DTAC member are all volunteers. And there is no specific grant supporting the work.

The 2013 PHS Guideline to Reduce the Risk of Unintended HIV/HBV/HCV Transmission Through Organ Transplantation: Opportunities for Improvement

Sridhar Basavaraju, MD, CDR-U.S. PHS; Director, Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC

Dr. Basavaraju first provided a brief summary of the 2013 PHS guideline recommendations. The goal of the guideline is to reduce the risk of unintended HIV, HBV, or HCV transmission through transplantation. The guideline recommends all donors should be tested using HIV, HBV, HCV serology as well as HCV NAT. Donors are classified IRDs if they have more than one of the 12 medical/social risk factors for undetected HIV, HBV, or HCV infection, or unknown medical/social history, or hemodiluted blood sample used for testing. No donor exclusion is recommended.

Since it was implemented in 2014, CDC has received various comments and feedback from the community. In response, CDC conducted the 4 analytic projects with a goal to publish the revised recommendation in 2020.

Dr. Basavaraju then presented data comparing donors with standard risk to IRD and provided takeaways from each project.

Analytic project 1: Trends in deceased solid organ donor characteristics and hepatitis B and C, and HIV screening results in the U.S. between 2010 and 2017

The study showed that while standard risk donors remained flat over the years, the number of deceased increased risk donors who died from drug intoxication gradually increased. In 2017, increased risk donors had about 16 times the prevalence of detectable HCV compared to standard risk donors.

Analytic Project 2: Description of all CDC-led outbreak investigations (2014-2017) of HBV/HCV transmission through transplantation

The study investigated transplant-associated HCV and HBV transmissions in the U.S. from 2014 to 2017. All donors were designed IRDs, and the majority of them had a history of drug use. Post-transplant screening of IRD organ recipients led to early detection of transmission and treatment.

Analytic project 3: Impact of PHS increased risk deceased donor designation on organ utilization—analyzing data from the OPTN

The analysis found that when excluding HBV/HCV-positive donors, the IRD designation had no statistically significant impact on utilization rate. However, quantified analysis revealed that IRD is associated with underutilization of adult kidney (148 per year), adult lungs (34 per year), and pediatric hearts (12 per year). Further analyses showed that underutilization of adult kidneys was driven by a subset of centers, suggesting an opportunity to work with the community to develop education programs.

Analytic Project 4: Models to describe risk of undetected HIV, HBV, and HCV infection among PHS increased risk donors with negative NAT result

The study showed that for IRDs, the risk of undetected infection is less than 1/1,000,000 for

HIV, HCV: > 2 weeks after most recent exposure
HBV: > 5 weeks after most recent exposure

Even if a donor is infected with one virion, the risk of undetected infection is still less than 1/1,000,000 for

HIV, HCV: > 3 weeks after infection
HBV: > 10 weeks after infection

The results suggested that the period during which reported donor risk behaviors result in IRD designation can be safely shortened.

Data from DTAC identified 9 of the 12 criteria implicated in transmission, and 3 criteria that can be considered for removal, including

Newly diagnosed or have been treated for syphilis, gonorrhea, Chlamydia, or genital ulcers
Hemodialysis (only increased risk for HCV)
Hemodiluted blood specimen used for infectious disease testing

Evaluation of sexually transmitted disease (STD) as an IRD criteria suggested that STD is a risk factor for HIV infection, and the risk of subsequent HIV infection can persist for up to 10 years after STD diagnosis.

Hemodialysis

An analysis of data from DTAC, CDC outbreak reports, the National Healthcare Safety Network, and the Dialysis Outcomes and Practice Patterns Study showed that outpatient hemodialysis has a small risk of HCV infection. However, the risk has declined since 2001 because of improved infection control practices. As a result, the likelihood of acute, undetected HCV infection resulting from most recent outpatient dialysis exposure is small.

Hemodilution

Hemodilution can result in false-negative test results. Studies showed that hemodilution of a sample tested by HIV, HBV, or HCV NAT can result in undetected infection, and the effect on NAT detection is most likely to occur during the early infection phase and will result in prolonged window period.

In summary, analyses conducted by CDC showed that

IRDs are more likely to be infected with HCV than non-IR donors
Transmissions of HBV and HCV from recently infected IRDs to organ recipients continue to occur
- As a result of opioid epidemic, might be occurring with greater frequency
- Post-transplant screening of IRD organ recipients led to early identification and treatment
- Risk of death and graft failure was likely reduced
IRD designation is associated with underutilization of adult lungs and kidney and pediatric hearts
Magnitude of underutilization is lower than previous estimates
About 200 organs underutilized per year, a small proportion of total unmet need
Period during which reported donor risk behaviors result in IRD designation can be safely shortened
Hemodialysis can be removed as IRD criteria while preserving safety

Discussion

In response to Dr. Benjamin’s question regarding HCV and other factors affecting utilization, Dr. Basavaraju acknowledged that the data they received showed some bias and cannot be extrapolated to the general population. He said that there may be other factors contributing to underutilization. Dr. Klassen added that that the environment for organ transplantation is unique and complex. It is challenging to assess the reasons for organ underutilization and why organs are discarded.

Dr. Skinner asked if recipients should continue to be tested/monitored after transplantation if the criteria for IRD were changed. Dr. Basavaraju replied that they are not asking ceasing testing entirely. Dr. Klassen added that current policy mandates follow up and the policy would still be in effect even if the criteria for IRD were modified.

Louis Katz, MD, Chief Medical Officer, Biomedical Services, America’s Blood Centers, asked how many more organ donors would be labeled as “high risk donors” if the 12-month risk behavior timeframe were changed from the 12-month deferral to 3-month deferral, and how many of the donors in the studies have a history of hemodialysis.

Dr. Basavaraju responded that current OPTN data do not provide such information, and they cannot calculate how more donors would be identified as IRD if they reduce the timeframe. The data do show the number of IRDs goes up. Given that intravenous drug and opioid users tend to use drugs regularly, he said, from the opioid perspective reducing the window period will unlikely change much. However, reducing the window period could affect the number of donors labeled as high risk because of incarceration. He added there will be data later on how many donors considered IRD due to hemodialysis.

In response to Dr. Blumberg’s question regarding antibody testing for HCV, Dr. Basavaraju agreed that antibody testing could underestimated the number of cases of HCV. They do not have data to show how many are underestimated.

In response to Dr. Blumberg’s question on HBV detection, Dr. Basavaraju noted that changing timeframe would impact HBV more than HCV and HIV. He added that for HBV, 1/1,000,000 probability would result in about 80 days.

Dr. Blumberg asked the impact of incarceration. She wondered if Dr. Basavaraju could provide more granularity to help the Committee better understand the issue. Dr. Basavaraju replied that the data they have do not provide such information.

Stakeholders

DTAC Experience in Disease Transmission and Outcomes

Cameron Wolfe, MBBS (Hons), MPH, FIDSA, Associate Professor of Medicine, Infectious Disease Division, Duke University School of Medicine

Dr. Wolfe, immediate past chair of DTAC, introduced DTAC’s vigilance in ensuring organ safety, explained current communication channels in the transplant community, and reviewed recent trends in disease transmission.

Dr. Wolfe stated that DTAC’s goals are to notify transplant centers about issues arising in real time, evaluate long-term trends, inform and educate the public, and drive policy change when necessary. OPOs and transplant centers report to DTAC infections and transmissible diseases diagnosed after transplantation, as well as unanticipated conditions that might be donor-derived. DTAC reviews and evaluates the reported cases and issues and communicates with government agencies, including CDC, HRSA, and FDA.

Dr. Wolfe reviewed infections and conditions that could occur through transplantation. He emphasized that the chance of transplant-derived transmission infection is small. He noted that transmission of malignancy is possible, and pathologists are working on stratifying risks for different donor malignancies.

He pointed out that the solid organ transplant field and the blood and tissue world handle emerging threats (eg, Zika, Chagas, and West Nile virus) differently, with different levels of risk acceptance. Given that the epidemiology of infectious disease constantly changes and no tests are perfect, he said that “we may need to learn to live with some risks.”

The opioid epidemic has increased the prevalence of HCV infection in the general population as well as in potential donors. In 2017, up to 25% donors in different parts of the country were HCV positive. However, unanticipated HCV transmission is rare largely because of effective testing. The opioid epidemic has a less significant impact on HIV infection rates than HCV, and the risk of unanticipated HIV transmission derived from organ transplantation remains small.

Studies have shown that accepting the first available organ, regardless of the donor’s behavioral risk factors and the donor’s PHS risk status, is associated with better survival benefit than remaining on the waiting list.

At the end of the presentation, Dr. Wolfe provided the following conclusions.

Donor-derived transmission events remain rare in the U.S., although they can be significant.
OPTN/DTAC can assess real-time changing trends in transplant and disease transmission and help explain and mitigate risk.
Unknown risks in solid organ transplants are balanced with the risk of doing nothing.

Discussion

Dr. Basavaraju asked Dr. Wolfe to comment on concerns around universal testing HIV. Dr. Wolfe pointed out false-positive results and increased costs.

In response to Dr. Macsai’s comment on testing recipients after transplantation, Dr. Wolfe responded that it is possible that a recipient is infected with HBV or HCV following organ transplantation but the infection is not donor-derived. However, it is still for the patient’s best interest to detect the infection regardless of the source of the infection.

PHS IRD Discussion: OPTN Perspective

Marian G. Michaels, MD, MPH, Chair, ad hoc OPTN DTAC, Professor of Pediatrics and Surgery, UPMC Children’s Hospital of Pittsburgh

Dr. Michaels presented DTAC’s view on PHS guidelines and their suggestions to the questions they were asked to address.

Questions 1: Is a new term needed to replace the current term “PHS increased risk donor”?

DTAC’s response is yes because the term has an unintended negative connotation and is associated with biases that may lead a potential recipient to reject an organ despite the probability of better outcome of accepting the organ offer than rejecting. However, they did not have a specific new term to recommend.

DTAC suggested reframing the question by using a neutral term, consulting with public relations specialists or behavioral psychologists, and giving the following options.

PHS A: No further testing is required based on PHS risk identification
PHS B: Further testing is required based on identified possible risks
PHS C: Further testing/Px required based on positive donor test (eg, positive HCV NAT testing)

Question 2: Should donors continue to be identified based on risk factors for HIV, HBV, HCV?

Dr. Michaels stated that OPTN supports education on all risks associated with donor transmission, not just PHS IRD; however, OPTN also supports maintaining a classification specifically for HIV, HBV, and HCV to inform transplant centers and recipients of the need for post-transplantation testing, and to keep transparency.

Question 3: Should time be shortened from 12 months?

Their answer to the question is yes because the 12-month period was determined before all OPOs began using NAT, which substantially decreases the eclipse period. Data from CDC showed that the window or eclipse period is shorter than 30 days for HIV, HBV, and HCV viruses.

Question 4: Are there specific criteria that should be eliminated or revised?

Dr. Michaels noted that this question is challenging to answer because there was no easy way to obtain statistics on why the donors were listed as PHS IRD. Evaluation of data from 2018 suggested most deceased donors (62%) met only one criterion for being classified as an increased risk donor, and IV drug use and incarceration accounted for the majority of and were listed as the most common risk factors.

In comparison, hemodialysis and hemodilution were implicated in fewer cases (12%). Between 2008 and 2018, there was no transmissions of HIV, HCV, and HBV because of hemodialysis or hemodilution as a risk factor. Further analysis showed that a significant percentage of the deceased donors were pediatric (less than 12 years of age) for whom hemodilution was the only risk factor.

In conclusion, Dr. Michaels stated that DTAC believes there is worthiness to remain donor risk assessment for transparency and for further evaluation. They suggest changing the term, recommend shortening the time, and suggest considering removal of hemodialysis and hemodilution as risk factors for pediatric donors.

Discussion

Dr. Basavaraju raised concerns over the 3^rd option that DTAC suggested in response to the first question. He wondered if that would be outside of the Committee’s charge.

Dr. Michaels responded that providing more options while keeping the tiered classifications could make PHS IRD less threating. Dr. Ison commented that the terminology perhaps should be more patient-oriented.

HIV and HCV in Organ Transplantation: Clinical Trials and Outcomes

Christine M. Durand, MD, Associate Professor of Medicine and Oncology, Johns Hopkins University School of Medicine

Dr. Durand first reviewed the biology and epidemiology of HIV and HCV, and the effect the evolution of HIV and HCV treatment on organ transplantation.

HIV in Organ Transplantation

HIV affects about 1.1 million people in the U.S. The incidence of HIV remains stable since 2012, with estimated 38,700 new cases in 2017. Treatment options for HIV have greatly evolved over the years.

HIV in a donor or recipient was a contraindication for transplant in the ’80s and ’90s. However, clinical studies and national real-world data shown that, in the era of the effective antiretroviral therapy, the relative risk of mortality resulted from transplantation of kidney from HIV-negative donors to HIV-infected recipients is lower than mortality associated with dialysis. Studies have also shown encouraging patient and graft survival rates following transplantation of kidney from HIV-positive donors to HIV-positive recipients.

Transplantation of organs from HIV-positive donors to HIV-positive recipients currently is limited to research only to reduce potential risks (eg, HIV superinfection, HIV-associated organ diseases in allograft, and increased rejection and infections), and requires institutional review board approval and OPTN approval.

Dr. Durand then presented data from HOPE in Action, a multicenter clinical trial to determine if transplantation of kidney or liver from HIV-positive donors to HIV-positive recipients is safe and effective. Early results showed encouraging patient and graft survival rates. Rare HIV breakthroughs occurred because of non-adherence. The study also found that rejection was common in kidney transplantation.

Dr. Durand pointed out that people with false-positive HIV test results can serve as a potential donor pool. They estimated about 50-100 HIV false-positive donors per year. Data from the first 3 years of HOPE in Action showed that half of donors were false positive.

HCV in Organ Transplantation

HCV infects liver hepatocytes and is transmitted primarily through blood contact. Unlike HIV, HCV is considered a curable infection because of effective treatment options. The incidence of HCV continues to increase since 2010, with estimated 41,200 new cases in 2016. Transplantation of kidney or liver from HCV-positive donors to HCV-positive recipients is common.

The opioid epidemic has increased the number of deceased donors who died from opioid overdose. In 2017, more than 30% of the deceased donors who died from overdose were HCV positive. Outcomes of transplants of organs from donors who died from drug overdose appeared similar to or better than organs from donors who died from trauma. However, HCV-positive organs remain underutilized.

Multiple studies have shown that with direct-acting antiviral management, transplantation of kidney from HCV-positive donors to HCV-negative recipients appear to be safe.

However, complications do remain and long-term data are lacking. Some publications suggest increased allograft rejection and HCV treatment failure.

At the end of her presentation, Dr. Durand noted that

Novel strategies are needed to expand the current donor pool, and
The evolving landscape of HIV and HCV treatment has altered risk-benefit for those on the waiting list.

Discussion

Dr. Basavaraju asked if there are data on timeframes around treatment. Dr. responded that some of the observational studies have delay of 30-60 days. There appeared to be a trend that shows the longer the wait period, the more complications. She noted that she prefers to treating patients as soon as possible, preferably within the first month.

Ethics of Informed Consent of Potential Recipients of IRD Organs

Peter P. Reese, MD, MSCE, Associate Professor of Medicine and Epidemiology, University of Pennsylvania

Dr. Reese presented ethical principles at the bedside. He noted that “do no harm” is an oversimplification, but too much information has consequences as well. Informed consent needs to balance the duties of beneficence and the respect for autonomy.

Dr. Reese noted that many viable organs are declined or discarded. He said that patients may not realize that transplant-derived HCV transmission may be less risky than transmission of cytomegalovirus, a common virus that can infect almost anyone.

Dr. Reese expressed his view that cognitive biases play a role at the bedside. For example, physicians may feel worse about doing something that leads to a bad outcome than doing nothing. However, turning down organs needlessly also harms the patient, he pointed out. In addition, many transplant staff can picture the patient with a post-operative complication but in many cases, they rarely see the patient who suffer on the waiting list.

Dr. Reese noted that studies assessing patients’ opinions on IRD organs found out that many patients thought that IRDs would be in poor health because of having chronic diseases such as diabetes, hypertension, or cancer. He suggested that informed consent should take place at regular intervals. If a patient has prospectively agreed to accept an IRD organ, only minimal amount of specific information about donor is necessary at the time of organ offer. He suggested shifting the language towards the most relevant comparisons and away from the hypothetical ideals.

Dr. Reese suggested

Endorsing best practices in patient education,
Explaining how changes in practice align with ethical principles, and
Endorsing appropriate use of good tools in terms of patient and physician education.

Dr. Reese acknowledged that public trust is a real issue. However, robust informed consent at the time of wait-listing should be as good in maintaining public trust as consent in a hurry at the time of organ offer. Conducting similar surveillance for donor-derived, blood-borne viruses for all organ recipients would make it simpler and more logical, given that differences in risks are very small between IRD and non-IRDs.

In summary, Dr. Reese emphasized the following.

Beneficence means integrating risks and benefits for each patient at the bedside, and “do no harm” is not a useful concept for patients on the waiting list.
Informed consent for IRD organs is best implemented while the patient is on the waiting list, not at the time of organ offer.
Best practices for informed consent should address the following challenges.
- IRD organs may be declined because of patient preferences or lack of understanding.
- IRD organs may also be declined because of cognitive biases on the part of physicians or patients.

Discussion

In response to Dr. Katz’s question regarding patient’s social and medical history, Dr. Reese pointed out that how to communicate with patients matter. For example, a donor with 2 negative tests can be interpreted differently from IRD.

In response to Dr. Basavaraju’s question regarding how much information should be provided to the potential recipient. Dr. Reese cautioned that at the time of organ offer, providing too much detailed information could mislead patients.

Dr. Blumberg asked Dr. Reese’s perspective on the amount of information to be provided and how to remain balanced in the changing landscape.

Dr. Reese noted that in his view, informed consent as a 1-time education is not going to work. He added that we need to talk to patients at regular intervals. He said that many centers he works with brings patients back to re-educate risks.

Dr. Fredrick asked Dr. Reese to provide a recommendation that could address best practices across centers.

Dr. Reese pointed out that some centers would never use IRDs, and he suggested considering the following as 2 measures when assessing best practices of transplant centers: appropriately aggressive use of organ donations and robust evaluation of informed consent. He added that there are ways to change behavior.

OPO Experience with PHS Increased Risk Donors

Richard Hasz, MFS, Vice President, Clinical Services, GIFT of Life Donor Program

Mr. Hasz first introduced Gift of Life, a non-profit OPO/Tissue Recovery/Eye Bank established in 1974 in Philadelphia. He then shared their challenges and presented data.

Mr. Hasz noted there are 58 OPO donation service areas in the U.S. and over the years they have seen an increase in organ donors. Data from 2015 to 2016 showed that deceased donors died of different reasons across the country. However, data from 2017 to 2018 showed an increase in the percentage of deceased donors with PHS increased risk status. Regional differences were also observed for HCV seropositive donors.

Mr. Hasz pointed out that determination of increased risk donors using the medical-social history questionnaire has limitations. The questionnaire can take hours to answer, the information gathered may not be accurate, and it is unclear how the information is applied. Automation and electronic health record may help, he said. Regarding specimen qualification, Mr. Hasz noted that it can be challenging to determine when is the best time to collect the specimen.

Mr. Hasz said that based on the data from 2017-2018 data, they found out that the top factor for IRD designation was drug use, and donors classified as increased risk donors were mostly white male.

Mr. Hasz explained that communications with transplant centers can be conducted through DonorNet, or during pre-recovery time out and organ offer process. However, the process may not be always consistent, and the amount of information shared vary from center to center.

Mr. Hasz reported that the number of organs transplanted from PHS IRDs has greatly increased. The discard rate from IRDs was smaller than from non-increased risk donors and has gone down in the past years for all organs together.

In summary, Dr. Hasz said that they have seen a significant increase in the number of PHS IRDs and organ utilization since 2014. However, they do believe the medical-social questionnaire is complex, and they encourage simplifying the questionnaire given that family members are grieving at the time.

Discussion

In response to Dr. Basavaraju’s question regarding testing, Dr. Hasz noted that it would be hard to go backward regarding NAT testing, which is relatively inexpensive to conduct.

Dr. Gustafson asked if Dr. Hasz could point out any specific areas that need to be simplified, and how to make answering the medical history questionnaires a better process.

Dr. Hasz responded that questionnaires related to organ donation are often conducted face to face, and families may respond differently. Further studies involving more centers may be needed to assess how much value can be gained from the questionnaires.

In response to Dr. Macsai’s question on comparison of false-negative rates of tests, Dr. Hasz noted that it is easy to find current information; however, there are no data on how much additional value can be gained from donor history.

ASTS Perspective on Proposed Revision to Guideline Recommendations

Dixon B. Kaufman, MD, PhD, President, ASTS

Dr. Kaufman first provided a brief overview of ASTS and then presented their perspective.

Established in 1974 the ASTS serves approximately 1,800 surgeons, physicians, scientists, and other transplant professionals dedicated to excellence in transplantation surgery. ASTS understands the past value of current PHS guideline, which was implemented in 2013. However, the environment has changed in the past years. ASTS’s transplant programs routinely assess cases to ensure best practice and they have found that a lot recovered organs were discarded despite more patients than ever are waiting for a deceased donor transplant.

ASTS is concerned that the current PHS guideline might have contributed to the underutilization. Current PHS guideline focuses heavily on social and medical history. However, the significance of what were considered risks and how they should be mitigated back in 2013 are probably different today.

From the surgical perspective, the number of transmissions is smaller than complications from transplantation procedure itself. It may be prudent to develop a more precise definition of a reasonable likelihood of disease transmission of HIV, HBV, and HCV.

ASTS is also concerned that the usefulness of social history as an accurate parameter to assess viral disease transmission risk has limitations and could increase anxiety when NAT test is negative. ASTS believes that social and medical history give appropriate context to the interpretation of NAT screening results only when the individual donor is still within the serologic negative phase.

Dr. Kaufman noted that the emphasis on the donor’s social history may mislead the public about the potential for viral disease transmission through transplantation, which could result in individuals refusing to be listed to receive organs from donors classified as “increased risk donors.” He pointed out that current “increased risk” classification disproportionately affects pediatric patients. In addition, the social and history basis of increased risk also creates needless anxiety and concerns of disease transmission when NAT screening is negative.

Dr. Kaufman stated that ASTS appreciates post-transplantation monitoring and screening, supports surveillance, and is pleased that the guidelines would be revised. “We are here to help move the field forward,” he said.

Discussion

In response to Dr. Macsai’s question regarding NAT negative phase, Dr. Kaufman noted that a 12-month period is too long, and a 30-day period is more appropriate.

American Society of Transplantation (AST) Comment on Increased Risk Donor Definitions

Nicole Turgeon, MD, AST Councilor-at-Large

Dr. Turgeon first provided a brief overview of AST, the largest transplantation organization in the North American with more than 4,000 members, and then answered the questions they were asked.

Dr. Turgeon noted that the comparative risk of transplantation versus the risk of HIV, HBV, and HCV transmission needs to be considered in the era of advanced treatment for these infections, and that it is time to revisit the PHS guidelines.

Question 1: Is a new term needed to replace current term “PHS Increased Risk Donor”?

Their answer is yes because the term emphasizes the negative connotation and can be confusing to patients as well as physicians. AST does not have a specific term suggestion. Instead they recommend working with psychosocial professionals to develop a new term. She pointed out the need to differentiate antibody test and NAT results given that the 2 types of testing have different window periods.

Question 2: Should donors continue to be identified based on risk factors for HIV, HBV, HCV?

Dr. Turgeon noted that AST believes inadvertent transmissions could affect public’s trust in the system. Continued transparency and understanding of anticipated risks based on donor behavior must be communicated with recipients through enhanced communication and education efforts.

Question 3: Should time be shortened from 12 months?

Dr. Turgeon stated that AST’s Infectious Disease Community of Practice, based on the best evidence available, strongly supports a significant shortening of the time period to substantially mitigate risk. They also support collecting information on timing of risk to further evaluate and improve the precision of the time period.

Question 4: Are there specific criteria that should be eliminated or revised?

Dr. Turgeon noted that published data are limited. However, at AST they believe that factors with relatively lower risks (eg, hemodialysis and hemodilution) could be safely eliminated.

Association of Organ Procurement Organizations (AOPO) Comment on Proposed Revision to Guideline Recommendations

Diane Brockmeier, BSN, MA, AOPO President

Incorporated in 1984, AOPO is a non-profit organization representing 58 federally designated OPOs in the U.S. OPOs are the primary organizations responsible for the identification of donors, safe and timely organ recovery, and preservation and transportation of organs for transplantation.

Ms. Brockmeier noted that organ donation from deceased donors and organ transplantation have increased in the last 6 years. The number of PHS high risk donors has also increased. The percentages of donors with PHS designated “high risks” vary markedly across the county. She commented that the accuracy of the medical-social questionnaire is limited. She said that NAT testing is routinely available for all OPOs.

Ms. Brockmeier said that AOPO suggests 1) speaking with donors’ families, and 2) replacing the term “increased risk donor” with a more neutral term. She added that AOPO supports reducing the time period.

Discussion

In response to Dr. Benjamin’s comment on perspectives from the donor’s family, Ms. Brockmeier agreed that given the stigma, “vulnerable” is an appropriate word to describe some donors.

Dr. Wolfe asked Ms. Brockmeier to share her interpretation on the inequality around donor utilization. Dr. Klassen commented that organ sharing can help improve utilization. Ms. Brockmeier agreed. She added that AST supports broader organ sharing.

First Day Wrap-up and Adjournment

Dr. Fredrick thanked all speakers for their presentations and noted that the slides of the presentations will be provide to all Committee members. She announced that the second day of the 50^th meeting will start at 8:30 am next day and the Deputy HHS Secretary will address the Committee.

The meeting was adjourned at 5:30 pm.

Appendix: Committee Members and HHS Support Staff

Public Members

Chair
Jacquelyn (Jackie) Fredrick, PhD, Retired CEO, Versiti, Inc.

Vice Chair
Emily A. Blumberg, MD, FACP, Director, Transplant Infectious Diseases, University of Pennsylvania; Professor of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania

Daniel Brennan, MD, Professor of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine; Medical Director, the Comprehensive Transplant Center

Brian S. Custer, PhD, MPH, Director, Epidemiology and Health Policy Sciences; Vice President, Research and Scientific Programs, Blood Systems Research Institute

Cassandra D. Josephson, MD, Professor, Pathology, Laboratory Medicine and Pediatrics, Emory University School of Medicine; Medical Director, Transfusion, Tissue and Apheresis Services, Children’s Healthcare of Atlanta (called in)

Mark W. Skinner, JD, President and CEO, Institute for Policy Advancement, Ltd.

Representative Members

Richard J. Benjamin, MBChB, MS(HCM), PhD, FRCPath, Chief Medical Officer, Cerus Corporation

Marian Macsai, MD, North Shore University Health System, Glenbrook Hospital; Eye Bank Association of America

Louis Katz, MD, Chief Medical Officer, Biomedical Services, America’s Blood Centers (Called In)

Mary Gustafson, Vice President, Global Regulatory Policy, Plasma Protein Therapeutic Association

Stefan Riedel, MD, PhD, D(ABMM), FCAP, Associate Professor, Pathology, Harvard Medical School; Associate Medical Director, Clinical Microbiology Laboratories, Beth Israel Deaconess Medical Center (Absent)

Gary F. Marklin, MD, Chief Medical Officer, Mid-America Transplant

Lynne Uhl, MD, Director, Division of Laboratory and Transfusion Medicine, Department of Pathology, Beth Israel Deaconess Medical Center

Frank S. Wilton, CAE, IOM, President and Chief Executive Officer, American Association of Tissue Banks (Absent)

Ex-Officio Members

Sridhar V. Basavaraju, MD, FACEP, CDR, USPHS, Director, Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention

Scott A. Brubaker, CTBS, Director, Division of Human Tissues, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration

Marilyn E. Levi, MD, Director, Division of Transplantation, Health Resources Services Administration

Carlos Villa, MD, PhD, Medical Officer, Division of Blood Components and Devices, Office of Blood Research and Review (alternate)

Diane H. Corning, RN, JD, Health Insurance Specialist, Center for Clinical Standards and Quality, Clinical Standards Group, Centers for Medicare and Medicaid Services (Absent)

Harvey Klein, MD, Chief, Department of Transfusion Medicine, Clinical Center, National Institutes of Health (Absent)

HHS Support Staff in Attendance

James Berger, MS, MT(ASCP), SBB, Designated Federal Officer, ACBTSA, Senior Blood and Tissue Policy Advisor, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Nicole Greene, Senior Public Health Advisor, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Kaye Hayes, MPA, Alternate Designated Federal Officer, Deputy Director, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Richard Henry, ML, MPH, MT(ASCP), Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Debbie Seem, RN, MPH, Public Health Analyst, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services