ACBTSA August 26, 2020 - Meeting Summary

Opening Remarks and Member Swearing In

Welcome and Roll Call

Purpose of the Meeting

Introductory Presentations

Current Experience During the COVID-19 Pandemic

Meeting Adjournment

51st ACBTSA Meeting: Day-1 Attendees

Opening Remarks and Member Swearing In

James (Jim) Berger, Designated Federal Officer for the Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA), welcomed all meeting attendees and introduced ADM Brett Giroir, Assistant Secretary for Health, U.S. Department of Health and Human Services (HHS).

ADM Giroir welcomed all meeting attendees. He noted that ACBTSA has been providing critical recommendations to the HHS leadership since 1997. In 2019, the Committee’s recommendations helped inform the revisions to the U.S. Public Health Service (PHS) Guideline for Reducing Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Through Organ Transplantation. He noted that the revised guideline was release in June 2020.

ADM Giroir noted that ACBTSA plays a critical role in helping ensure the nation’s preparedness and resiliency for public health emergencies such as the COVID-19 pandemic. He applauded the Food and Drug Administration’s and the industry’s collaborative efforts in monitoring and maintaining the blood supply while advancing treatment options. He explained that FDA, the Biomedical Advanced Research and Development (BARDA), worked closely with Mayo Clinic and the blood community to support the collection, distribution of, and expanded access to COVID-19 convalescent plasma (CCP), which has recently been authorized for emergency use for the treatment of COVID-19 in hospitalized patients.

AMD Giroir stated that HHS is committed to ensure the blood supply. Under the CARES Act, HHS will carry out a national campaign to improve awareness and to support outreach to the public and health providers about the importance of safety and the need for blood donation during public health emergencies. He noted that within two years, HHS will provide a report to Congress describing the Campaign’s activities, trends in blood supply donation, and evaluation of the campaign.

ADM Giroir noted that the Committee’s discussion and recommendations in the next two days will help strengthen the nation’s response to the current pandemic and prepare for future public health emergencies. He expressed his eagerness to read the Committee’s recommendations, and he thanked all members for serving on this Committee.

ADM Giroir welcomed and swore in the following 11 new public members.

  • Biree Andemariam
  • Sally Caglioti
  • Andrew P. Cap
  • Claudia S. Cohn
  • Raymond P. Goodrich
  • Elisa Gordon
  • Jed B. Gorlin
  • Daryl Kor
  • Jim MacPherson
  • Paul Ness
  • David Perez

Welcome and Roll Call

Jacquelyn (Jackie) Fredrick, Chair of ACBTSA, welcomed everyone to the meeting and encouraged all attendees to make recommendations.

Mr. Berger conducted roll call. ACBTSA members introduced themselves and clarified the organizations they represent (see Appendix A for Committee members).

The meeting started with a quorum.

Purpose of the Meeting

Ms. Fredrick highlighted the importance of blood transfusion and stressed the need for innovation and modernization of the blood system to ensure the robustness and safety of the U.S. blood system and transfusion medicine practice.

Ms. Fredrick pointed out that the blood community has a unique opportunity to learn from the community’s response to the COVID-19 pandemic and to build a stronger foundation for the future. Ms. Fredrick encouraged the Committee members to think and provide answers to the following two questions.

  • What recommendations should be made to the Assistant Secretary for Health to further improve the blood community’s response to public health emergencies and can be acted on in the next 2-4 years?
  • What additional resources are required to act on the recommendations?

Ms. Fredrick explained that the Committee will discuss, finalize, and vote on their recommendations during the day-2 meeting. She encouraged all speakers and the public to help address the following questions.

  • What worked well and are strengths to build upon for future public health emergencies?
  • What weaknesses were identified that threatened or could threaten the safety and availability of the blood supply and patient care?
  • What are the top three to five recommendations to achieve in the next 2-4 years to increase our preparedness and care for patients?

Dr. Jay Menitove explained that to ensure a productive recommendation development process, the Committee Chair formed a Writing Committee to help draft recommendations based on the presentations and discussions for ACBTSA to use as a starting point; ACBTSA members will review, discuss, revise, and vote on the recommendations at the end of the meeting. Dr. Menitove encouraged the ACBTSA members to think about recommendations from their perspectives and help finalize the recommendations the next day.

Ms. Fredrick briefly reviewed the meeting agenda and introduced the first speaker.

Introductory Presentations

Overview of the Public Health Emergencies

Dr. Merlyn Sayers, President and CEO of Carter BloodCare and a professor at the University of Texas Southwestern, reviewed the state of the nation’s blood programs and discussed the vulnerabilities and opportunities faced by the blood programs. Regarding recommendations for the Assistant Secretary for Health, Dr. Sayers addressed emergencies that are not immediately related to the COVID-19 pandemic.

Dr. Sayers reviewed the following “tipping points” that have transformed the blood centers.

  • Regulations and compliance. In the 1970s, the FDA published a final ruling with the intention of regulating blood as a “drug.” While the demand for compliance required and continues to require significant financial investment, the safety of transfusion products has been improved. Dr. Sayers commented that regulation of the blood industry has been a dominating success.
  • Blood supply instability and vulnerability. Dr. Sayers noted that cancellations of blood drives and decline in sales have significant effects on the blood programs’ financial margin and failure to recruit younger donors is a continuing costly vulnerability.
  • Preventive medicine opportunities and the role of epidemiology. Dr. Sayers commented that while the COVID-19 pandemic has taken a center stage as a public health emergency, other diseases such as diabetes are also public health emergencies that deserve attention. He noted that blood centers have a great opportunity to contribute to individual and community health. For example,
    • Conduct prediabetes screening (e.g., measure A1C) and inform the individuals (e.g., high school students) of the risk
    • Identify individuals at risk of fatal but treatable cardiovascular diseases
    • Perform coronavirus antibody testing and contribute to understanding the epidemiology of the coronavirus pandemic.

Recommendations

Dr. Sayers recommended the following actions to address the vulnerabilities and achieve the best outcomes.

  • Regulation: Include cost-effectiveness into regulatory consideration. Given that cost-effectiveness is hinged upon risk, Dr. Sayers noted that perhaps it is time for a national debate over risk tolerability.
  • Blood supply challenges: Fund psychosocial research to increase participation in donation (at all ages), and review by the Centers for Medicare and Medicaid Services (CMS) reimbursement for transfusion products.
  • Preventive medicine opportunities and epidemiology role: Promote relationships between blood centers and the Centers for Disease Control and Prevention (CDC), academia, pharma, health departments, hospitals, and insurers. Dr. Sayers noted that there is an opportunity for the blood programs to rebrand as centers for individual and community health and education.

Microbial Safety of the Blood Supply, 1990-2020

Dr. Roger Y. Dodd, Executive Scientific Officer of the American Red Cross, reviewed the mechanisms and systems used to prevent transfusion-transmitted infections and to ensure patient safety.

Dr. Dodd briefly reviewed the phases of transfusion-transmitted infections (traditional, chronic infections such as HBV, HCV, and HIV; and emergent infections that are generally acute and arthropod-borne such as vCJD, WNV, T. cruzi, Babesia, and ZIKV). He highlighted the key elements of microbial blood safety, and explained the nature of blood testing technologies. He noted that because of the advances made in testing, the overall risk of transfusion-transmitted known infections is about one in a million. And he highlighted the important role of blood research in ensuring blood safety and supporting and monitoring the effect of policy changes.

Dr. Dodd pointed out that while the requirements for testing are ultimately set by FDA, the “nexus” for decision-making in transfusion medicine is unclear. In addition to FDA, other federal agencies (e.g., CDC), accrediting organizations, blood collection entities, and hospitals also play a role.

Dr. Dodd reviewed the pivot points of the microbial safety of blood. He noted that the pandemic planning resulting from the SARS and H1N1 influenza threats helped the preparation for and supported the response to sustaining the blood supply during the COVID-19 pandemic. He pointed out that the financial stress within the U.S. medical system led to the transition of blood supply to commodity status, which inhibits innovation.

Dr. Dodd highlighted issues that need to be considered for decision-making and made the following suggestions for the Committee to consider.

Considerations for the Near Future

  • Stable funding is needed to ensure continuity and innovation.
  • A defined decision system and locus for blood safety issues are needed.
  • Social underpinnings to donation need to be understood and managed, with particular attention to donor motivation and perceived inequities in donor suitability procedures.
  • Blood safety has evolved into a complex, multilayered, and redundant system that could be radically simplified.

At the end of his presentation, Dr. Dodd asked the Committee to think about the following questions.

  • If it was necessary to establish a blood safety program today, what would it look like? Would it have the current level of complexity?
  • Could a satisfactory program be based upon new technologies such as pathogen reduction technology and nucleic acid testing alone?

Current Experience During the COVID-19 Pandemic

AABB: Interorganizational Disaster Task Force on Domestic Disaster and Acts of Terrorism

Brain Gannon, Chief Executive Officer of the Gulf Coast Regional Blood Center and Chair of the AABB Interorganizational Disaster Task Force on Domestic Disaster and Acts of Terrorism, provided background information of the Task Force. He highlighted what worked well and what the challenges were.

What Worked Well

  • The Task Force enabled the exchange of timely information on the status of the blood supply and facilitated a rapid, organized response to the COVID-19 pandemic.
  • The Task Force is uniquely positioned to provide a consistent message to the blood community and the public on the status of the blood supply during a disaster or public health emergency.
  • Individual blood centers have been responsive throughout the pandemic, and should be commended for ensuring the continued safety and adequacy of the blood supply.

Weaknesses and Challenges

  • Lack of accurate, comprehensive, and timely data on the blood supply
  • Lack of real-time data on blood utilization and inconsistent coordination between blood centers and hospitals on the evolving changes in the demand and utilization of blood supply
  • Challenges with effectively communicating the status of the blood supply to the public
  • Vulnerabilities throughout the blood supply chain, including challenges associated with the continuous recruitment of eligible donors, not prioritizing blood centers for supplies, and blood centers’ reliance on sole-source products.

Recommendations

  1. HHS should dedicate funding to modernize the system used to report the available blood supply, and maintain an automated system that includes real-time, comprehensive, accurate data on blood inventories.
  2. HHS should develop policies and invest resources to strengthen the resiliency of the entire blood supply chain.
  3. HHS should dedicate funding to support the Task Force’s infrastructure, which would enable innovation and potential automation of some of the Task Force’s activities.

Discussion

Following the presentation, Mr. Gannon and Mr. Leo Debandi, Vice Chair of the Task Force, answered a range of questions from Committee members.

Funding

In response to Ms. Fredrick’ question on funding, Mr. Gannon explained that they and other members serve on the Task Force as volunteers and the individual organizations pay for the services provided to them (for example funding needed for transporting samples from Hawaii to mainland for testing is worked out with the specific blood center).

Mr. Debandi added that the Task Force needs to know where blood supply is; however, they neither have the data from the blood centers nor have data from the hospitals.

Supply chain vulnerability and solutions

Regarding supply chain vulnerability, Dr. Raymond Goodrich asked if there are plans for considering policies to address sole sourcing versus the distribution of the supply from various blood centers.

Mr. Gannon responded that the Task Force has not discussed policies to be created that would require multiple providers in different geographic locations. He acknowledged that there might be an opportunity to discuss the topic, and that the Task Force has discussed the possibility of setting up stockpiles of products that are not perishable.

Mr. Debandi added that decisions around sourcing is for the individual organizations to make, and he agreed that stockpiling might be a possible solution.

Mr. Dave Perez shared that in one of the recommendations from the Blood Centers of America (BCA), they noted that BCA would like to work with FDA to identify certain blood product codes and identify other manufacturers that can produce those products in the event of a disaster.

In response to Dr. Lynne Uhl’s question regarding using Emergency Use Authorization (EUA) to address supply issues, Mr. Gannon responded that the Task Force has not discussed the topic, and he agreed that it is a good idea and should be considered.

Decision-making

In response to Ms. Fredrick’s question on the Task Force’s authorities and decision-making process, Mr. Gannon and Mr. Debandi explained that the Task Force makes mostly operational decisions, and they rely on the individual members to take actions and make decisions.

Dr. Daryl Kor wanted to know if the Task Force has worked with hospitals to better understand the demand (e.g., days of inventory or days on hand).

Dr. Gannon acknowledged that it is an ongoing challenge. He pointed out that hospitals are protective of their data, and the Task Force does not have the authority to manage such data. However, if the data can be protected and data reporting can be automated, the Task Force could have that information, he said.

Dr. Paul Ness commented that the Task Force and the blood community have to deal with some challenges such as how to obtain comprehensive and accurate data regarding inventory. He pointed out that if the blood community continues to compete with each other and does not share information, it will require a lot consensus building to convince the federal government to provide funding.

Dr. Jed Gorlin commented that the stockpile strategy would be helpful in the event of a surge in demand, and the Task Force is effective for regional, localized events. He asked about strategy planning for nation-wide events such as the COVID-19 pandemic, which affects blood collection across the nation.

Mr. Debandi explained that they used the same approach for the COVID-19 pandemic and were able to react quickly based on their resource.

Experience of Hospitals and Transfusion Services

Dr. Claudia Cohn, Associate Professor of the University of Minnesota Medical School and Chief Medical Officer of the AABB, shared her hospital’s experience and her own observations on blood supply during the COVID-19 pandemic.

Weakness

Dr. Cohn pointed out the following two interlinked weaknesses, and she noted that demand and supply were completely out of sync during the earlier months.

  • Lack of information about blood supply and demand led to poor planning and wastage
    • For example, AABB weekly survey showed that the wastage was up to 54% after the surge of blood donation and cancelled elective surgeries
  • Lack of a steady blood supply affected patient care
    • Dr. Cohn pointed out that the blood shortage forced hospitals to cancel certain surgical procedures that use high volumes of blood (e.g., liver transplants), and affected hospitals’ care for many patients, including trauma victims, individuals with sickle cell disease, and patients who need stem cell transplants.
  • Patient outcomes are directly related to blood availability, but the information is not tracked.
    • Dr. Cohn explained that FDA requires all blood-related fatalities to be reported; however, when a patient dies because of blood is not available, not reporting is required.

Strengths

Dr. Cohn highlighted the following strengths.

  • National support ( e.g., the calls for blood donations)
  • Communication between hospitals and blood centers
  • Blood centers’ rapid response in collecting COVID convalescent plasma

Recommendations

Dr. Cohn made the following recommendations.

  1. HHS should work with Congress to create, implement, and fund a comprehensive, sustainable, minimally burdensome system that monitors and makes available real-time data on the blood supply and real-time data on utilization by hospitals.
  2. HHS should work with Congress to stabilize the blood supply by developing a sustained campaign to heighten blood donor awareness, developing a coordinated system for blood donations, and developing a system that will strengthen the supply chain for blood collections.
  3. HHS should work with Congress to link data on blood product availability, transfusions, and patient outcomes to ensure patients have access to vital and life-saving blood products.

Experience of Blood Centers: Donor Engagement, Blood Donors and Donation Process, and Public Awareness and Communications

Mike Parejko, President and CEO of Mississippi Valley Regional Blood Center and President of the America’s Blood Centers (ABC), shared his center’s experience. He noted that his message is in-line with the previous speakers.

What Worked Well

  • National messaging from influencers and top government officials
    • However, ad hoc messaging is not optimal and constant, ongoing messaging is needed to cultivating donors
  • Collection and distribution of coronavirus convalescent plasma

Weaknesses

Mr. Parejko highlighted the following challenges blood centers faced during the pandemic.

  • Lack of real-time data and data exchange between hospitals and blood centers
  • Cancellations of mobiles collections
  • Conflicting public health positions/messaging caused confusion
  • Pandemic impact on staffing and operation
  • Impact on transportation and logistics
  • Supply chain disruption and lack of access to personal protective equipment

Recommendations

  1. Support research studies to understand the predictive social and psychographic motivation for blood donors focusing on attracting and retaining blood donors
  2. Support the creation of a national blood donation campaign designed to build a broad-based commitment to regular blood donation that achieves a diverse and robust donor base
  3. Establish and support a real-time, structured data collection and reporting system
  4. Leverage data and information to optimize current FDA licensure process

Discussion

Mr. Jim MacPherson asked if the Mississippi Valley Regional Blood Center uses BloodHub to monitor hospital inventories.

Mr. Parejko responded that they do use BloodHub but they do not have electronic transfer of data regarding hospital inventories.

Regarding the need for consistent, ongoing messaging for blood, Dr. Elisa Gordon asked what organizational level is responsible for the campaigns.

Mr. Parejko responded that right now local and national messaging and awareness campaigns are disjointed, and they are taking “thinking nationally and acting locally” approach.

Dr. Andrew Cap shared that in the Military, one of their solutions is “a walking blood bank.” The strategy, he noted, has been evaluated and used in Europe, and he suggested that the blood community in the U.S. consider it as well.

Experience of Blood Centers: A Panel Discussion of Blood Inventories, Supply Chain, CCP, and Financial Impact

The panelists first shared their organizations’ experiences. They then answered questions from the Committee members.

BCA Presentation

Bill Block, President and CEO of BCA, explained BCA’s efforts in addressing the challenges the independent community blood centers faced, shared what worked well, and presented a comprehensive list of recommendations.

What worked well for blood donation

  • The U.S. Surgeon General’s call for donation
  • Blood centers’ adjustment to fixed donation sites
  • Data-driven software used to help centers find where the donors are
  • Establishment of COVID-19 donor registry
  • Innovative promotion strategies to attract donors

What worked well regarding the supply chain

  • Proactive response to addressing shortage of personal protective equipment
  • Leveraged over 500 fixed sites
  • Availability of blood collection devices such Alyx and Trima
  • Developed strategy for communicating with key suppliers
  • Utilization of interactive maps for test tube transportation logistics, supply chain key manufacturers, and COVID-19 Hot Spots
  • Strong communication with FDA, BARDA, the Armed Services Blood Program, ABC, AABB, American Red Cross (ARC), and principal investigators for CCP
  • Rapid collection of COVID convalescent plasma

What worked well regarding finance and business model for CCP

  • Developed a new cost recovery model for CCP that factored in all relevant costs to the blood centers and accounted for opportunity cost of not collected multiple components
  • Developed new pricing procedures for collections and distributions
  • Developed forecast for each blood center showing CCP Surge Capacity

Overall Recommendations and Summary
Surge capacity

  • Automation: Have a diverse set of pre-validated machines to give the industry flexibility to rapidly expand the capacity across the U.S.
  • Donors: Develop a National Awareness Campaign on the status of the industry and the importance of blood donation
  • Infrastructure: Leverage fixed site and mobile capabilities to deploy to “Hot Spots and others”
  • Data/Technology Infrastructure: Leverage BCA’s existing industry data collection and expand it to include all blood types for use during disasters and pandemics and support the BioLinked COVID-19 Registry
  • Personal Protective Equipment and Strategic Stockpile: Prepositioned and managed by BCA for independent centers supported by HHS to accelerate capability
  • Accounts Payable/Receivables: BCA is the single point of billing and payment for 71 independent collectors

Research and development support

  • Encourage industry innovation (e.g., co-development opportunities with industry and financial support from the government)

Testing/Community health

  • Leverage blood centers’ community-based testing capability and bolster national testing entities
  • Provide back-to-work testing support
  • Blood centers can offer antibody testing, screening, and other services as an expansion of the public-private healthcare infrastructure during pandemics
  • Blood centers could serve as community life centers to offer services such as HIG infusions, A1C testing, and vaccinations

ARC Presentation

Mr. Chris Hrouda, President of the American Red Cross’ Blood Services, highlighted the impact of COVID-19 across the industry and shared what worked well and what did not work as well.

What was the most effective in achieving blood inventory and critical supply adequacy during the early phase of the pandemic?

  • Ability to recover from significant cancellations with media visibility, administration, and elected official support for blood donation, and antibody testing
  • Internal ability to quickly stand up infrastructure and processes to support response operations and balance production, including the introduction of an entirely new product line
  • Built Concept of Operations plans for COVID19 complete with trigger levels and daily dashboards, which allowed ARC to quickly analyze and adjust to changing operating environment due to the pandemic

What was the least productive use of time and resources involved in achieving blood inventory and critical supply adequacy during the early phase of the pandemic?

  • Attempting to mitigate cancellations with additional sponsored drives has been less impactful than direct-to-donor tactics for fixed sites and regularly scheduled mobile operations
  • Navigating changing local and state regulatory requirements (shelter-in-place, PPE, etc.) while operating as a national system
  • Managing eligibility changes in the middle of the pandemic
  • Managing the process of getting the staff to be considered essential service employees at a state-by-state level
  • Given that PPE was a critical component of the safety response, delaying or changing guidance made it difficult to commit to and source necessary supplies; additionally frontline access to PPE received by hospitals and other healthcare providers did not include blood providers
  • Managing a challenging process to nationally source CCP donors

Recommendations

  • Establish a process or framework to coordinate across the local, state, and national level issues such as shelter-in-place orders
  • Create a unified approach to mandates regarding cancellation of elective procedures and identify systems and processes to aid the industry’s ability to forecast and understand demand
  • Classify blood center employees as essential staff
  • Include blood providers in the National Disaster Framework and clearly spelled-out in all emergency support functions at the federal and state levels
  • Work with the industry and government partners to enhance response planning to focus on large scale loss of sponsored blood drives, large scale loss of trained staff, and significant disruptions in transportation routes
  • Evaluate innovative solutions to a more focused and productive industry-wide donor engagement process. Mr. Hrouda noted that public campaign alone will not solve the supply problem, and other solutions to engage donors are needed.

Vitalant Presentation

Dave Green, President and Chief Executive Officer of Vitalant, explained Vitalant’s early (first 3 months) experience of dealing with the COVID-19 pandemic, during which they tackled a wide range of issues and challenges similar to those experienced by other blood organizations. Mr. Green then shared what worked well and what did not work as well for Vitalant.

What was the most effective in achieving blood inventory and critical supply adequacy during the early phase of the pandemic?

  • Public messaging (from FDA and the U.S. Surgery General) made a huge difference.
  • Vitalant Research Institute’s following efforts helped.
    • Search for SARS-CoV-2 RNA in blood donations and post-donation-reported, transfused units
    • Use antibody-positive samples for test development and validation
    • Examine the time course of the U.S. population infection through changing donor antibody prevalence
    • Use donors with post-donation-reported illness and CCP donors to estimate infectivity, the time course of antibody development, and antibody persistence (immunity to reinfection)
    • Build on REDS-funded studies to identify biomarkers of COVID-19 progression or protection, and determine impact of recent infection on red blood cell (RBC) and platelet function and transfusion product efficacy
    • Develop a linked model of CCP supply, production, and demand

Mr. Green noted that CCP is the first product to have cost recovery, and the success of CCP was a huge moral lift among the employees.

What was the least productive use of time and resources involved in achieving blood inventory and critical supply adequacy during the early phase of the pandemic?

  • Finding reliable sources for new PPE requirements
  • Figuring out a work-from-home approach during the crisis, including new cybersecurity threats
  • Reviewing new legislation (in consultation with external support)
  • Intense pressure to manage cash flows when revenue dropped quickly by 30%
  • Managing multiple and varied state-level requirements while delivering services at a national level
  • Issuing multiple communications on masks, shelter-in-place orders, and expense reduction measures

Recommendations for future preparedness

  • Adopt blood donation now as a priority focus at state and federal government levels to build a more robust and committed workforce to blood donation and to serve as an emergency resource during times of stress
  • Establish a quick access cash fund to sustain operations during an extreme and prolonged crisis to avid disruption to the blood supply
  • Facilitate national pandemic response planning that includes instances with complete disruption of external social structures to evaluate coordination and communication gaps
  • Design coordination systems for public health emergency management that connects blood centers to information exchanges and aligns communications
  • Direct as part of Joint Commission reviews, the evaluation of regular coordination meetings/contacts with blood suppliers and recurring exchange of critical blood supply and demand information

Suggestions for government assistance during public health emergencies

  • Keep selected key government leaders prepared to act as blood donation advocates (e.g., U.S. Surgeon General, FDA, and local Public Health Departments) when needed, and design a system to coordinate messaging
  • Establish a standing framework for state and federal orders (such as shelter-in-place orders) that include clarification of the need for continued blood donations and administrative measures to ensure continued access by blood providers to hospitals and donor sites
  • Help ensure local, state, and national logistics considerations include provision for continued movement of blood stocks, testing materials, and supplies when transportation networks are stressed
  • Help connect blood centers to local, state, and national reserve stocks and/or emergency funding to sustain essential operations

Discussion

Dr. Menitove asked if the donors understood the antibody testing results and how they used the information.

Mr. Green responded that their staff members were very clear about the limitations of the information and they communicate the information through their medical group. He pointed out that their primary focus was to identify potential CCP donors.

Mr. Hrouda agreed that antibody testing is a way to identify CCP donors. He shared that ARC’s scientific and medical teams follow up with donors and properly inform them about test results, and local and state health departments showed great enthusiasm.

In response to Dr. Menitove’s comment on the assistance that BCA provided to the independent blood centers, Mr. Block noted that BCA helped the independent blood centers with their procurement process so that the centers could focus on patients instead of management issues such as vetting suppliers. He commented that having one focal point was critical in helping drive solutions more quickly.

Experience of FDA

Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research (CBER), shared FDA’s responses to the pandemic.

Donor Deferral Updates

Dr. Marks explained that FDA revised the donor deferral criteria in response to the pandemic to expand the donor base, and they also used the opportunity to update recommendations for reducing the risk of HIV, CJD, and malaria transmission by blood and blood products.

ADVANCE Study

Dr. Marks shared that the ADVANCE study was designed by collaborative process with advocacy organizations, blood collectors, community health centers, health agencies, and academics. He explained that results of the study may help determine the feasibility of larger study assessing utility of new questions to eliminate donor deferral for men who have sex with men (MSM).

U.S. Convalescent Plasma Expanded Access Program

Dr. Marks briefly explained the rationale for program, reviewed the protocol, and shared evidence gathered so far.

Protocol

  • Single arm protocol with sites across the U.S.
    • Investigational New Drug (IND) held by Mayo Clinic, Funding from BARDA
    • Plasma from ARC/ABC
  • Demographics and simple endpoints captured
    • Safety
    • 7 day, 28 day survival
  • Statistical analysis of dose response by titer could possibly support demonstration of efficacy

Objectives

  • Primary objective
    • Provide access to COVID-19 convalescent plasma
  • Secondary objective
    • Assess safety of convalescent plasma transfusion
  • Tertiary/exploratory objectives for efficacy
    • Assessment of health care utilization (e.g., days in ICU)
    • Correlate antibody titers with clinical outcomes

Summary of Available Evidence

Dr. Marks explained that the collective evidence may support the safety and efficacy of convalescent plasma for the treatment of COVID-19 early in the disease course

  • Efficacy of convalescent plasma in prior outbreaks
  • Supportive pre-clinical evidence in COVID-19
  • Supportive evidence from small clinical trials
  • Data from the U.S. Expanded Access Program
    • In a subgroup of patients who were less than 80 years of age, were not intubated, and were treated early (within 3 days of diagnosis), there was a 37% relative reduction in mortality in those treated with high titer convalescent plasma (p=0.03).

Sustainability of Blood Supply

Dr. Marks noted that FDA will continue to work to address the unique challenges to the blood supply brought about by COVID-19, and that the safety and sustainability of an adequate blood supply remains a very high priority for the agency. FDA will also continue and expand its applied scientific research programs and its collaborations on pathogen reduction efforts. Dr. Marks stated that FDA wants to see pathogen reduction broadly applied without interrupting blood centers’ work.

Dr. Marks stressed that blood is national resource and is import for everyone and the whole county. He reiterated that FDA will continue to work with the whole community.

Discussion

Ms. Mary Gustafson noted that she was interested in FDA’s efforts in pathogen reduction, and if FDA looks at behavioral risks in term of lowering or getting rid of deferrals using pathogen reduction.

Dr. Marks responded that they are considering it, and they would like to get more data in the area to ensure robustness. He explained that they removed deferrals in the Malaria Guidance. Regarding pathogen reduction and HIV deferrals, he noted that blood centers showed interest in the past; however, related efforts were delayed due to COVID-19. He agreed that it would be nice to look at that again.

Dr. Raymond Goodrich asked Dr. Marks to comment on the effect of CCP on 28-30-day mortality, and he asked Dr. Marks to share his thoughts on randomized study designs that could be implemented during the pandemic.

Dr. Marks replied that depending on the assay and methodology used, the relative risk reductions in 30-day mortality is about 20-25%, and the benefit appears to be durable in the group of people who were treated early, were less than 80 years of age, and were not on a ventilator. Regarding clinical trial design, he noted that conducting randomized clinical trials during the pandemic is challenging, and he agreed that if convalescent plasma is going to be considered as a future agent, there needs to be something that is well thought out and could be easily used.

Mr. Jim MacPherson commented that Israel has approved intravenous immunoglobulin (IVIG) and other countries are trying to study and use IVIG and even vaccines using mechanisms similar to the approach that FDA used for CCP. He asked if FDA is going to apply the approach used for CCP to other agents such as IVIG and vaccines.

Dr. Marks responded that each product is different. For vaccine, there are several ongoing large trials for vaccines. He noted that vaccines will need data in which people have confidence. For monoclonal antibodies, there are also large randomized trials. There are also trials on immunoglobulin. He commented that every country does its own benefit/risk calculation based on data available to them.

Dr. Andrew Cap commented that the Military faced a similar situation in the past regarding resuscitation of combat casualties in the field. He explained how they built a registry to give people blood products earlier, and how the registry data were used to inform decision-making in a manner similar to how the Expanded Access Program is used. He explained that eventually they were able to sponsor clinical trials in a un-wartime setting. He pointed out that when faced with emergency situations, alternative ways are needed to assess products’ clinical utility. He suggested there should be a national debate over how we prepare for future emergencies.

Dr. Marks responded that they are very cautious to ensure people believe the results. He applauded the Mayo Clinic team’s work that was able to get efficacy signal out of a trial that was not intended for that purpose. He explained that the trial started in April, and at that time there was no way to get high titers. He agreed that they need to think of alternative ways to do things (e.g., beyond randomized clinical trials).

COVID-19: A Manufacturer’s Perspective

Dean Gregory, President of Medical Devices, Fresenius Kabi North America Region, explained Fresenius Kabi’ business continuity plan and answered the Committee’s questions from a manufacturer’s perspective.

What worked well for the industry

  • Transparency of communication with BCA, ARC, and the industry on inventory
  • Open communication with the FDA to allow alternative collection/sourcing considerations
  • Being part of the discussion and solution with governmental initiatives

What worked well internally

  • Proven business continuity plan developed based on experience with past disasters such as Hurricane Maria in 2017
  • Strength of product portfolio
  • Strong company philosophy of protecting employees while keeping critical operations going

Weaknesses

  • In a global pandemic, geographic back up may become irrelevant.
  • In recovery, inventory levels are the most important factor.
    • Some blood centers had only 2-3 weeks of inventory on hand.
    • In this situation the recovery time was very short. While the company didn’t risk a supply shortage, manufacturing yields were affected.

Recommendations

Mr. Gregory pointed out that blood centers carry various levels of inventory. Across the U.S. there is not a sufficient level of BPU inventory to accommodate multiple failure points of disastrous effects. He noted that the current blood bank economics makes it difficult for the company to financially justify carrying additional inventory beyond 60 days.

Mr. Gregory recommended that the industry

  • Target 6 months of BPU stockpile (finished goods)
    • Set up a system to test 10% of a lot prior to being placed in a reserve inventory and rotated to manage expiration.
  • Develop a single, dedicated, and well-funded business continuity plan for the industry

Discussion

Mr. Dave Perez commented that his group used Mr. Gregory’s example of Hurricane Maria as a case study and would also like to use the Czech Republic example to illustrate how companies in the event of a pandemic could get certain coded products manufactured.

Mr. Gregory expressed his willing to share his insights and work together to advance the industry.

Regarding a stockpile, Mr. Jim MacPherson asked Mr. Gregory’s thought on asking Congress to pay for a stockpile and letting industry manage it, and what potential disadvantage of a national strategic stockpile would be.

Mr. Gregory noted that products have expiration dates and need to be rotated to remain usable. He shared that his company developed a strategic reserve inventory to allow companies that are willing to pay extra fees for incremental units. He explained that for his company, it needs to be hand-in-hand with the actual user to ensure that the inventory is updated and fresh. He noted that the blood industry can build a system that does not allow waste. For example, build a one-time value of inventory and then continue to rotate through the existing supply chain system.

Regarding communication with FDA, Dr. Lynne Uhl asked if there is an opportunity to work with FDA and put things in place to ensure more effective discussion in the event of emergency.

Mr. Gregory responded that after Hurricane Maria, his team met with Dr. Marks’ team and presented a proposal, and everything is in place now to do what they previously struggled to do. In the case of COVID, Mr. Gregory noted that plasma would be beneficial in other situations and needs to be an entity. He noted that his team has discussed with FDA regarding how to leverage devices that are approved for source plasma, and how to put in place a very simple ability for the blood banks or plasma centers to effectively get one-time variants to leverage existing resources. He noted that those are ongoing discussion topics with FDA.

At the end of the discussion, Ms. Fredrick thanked everyone and encouraged the Committee members to think about the recommendations.

Meeting Adjournment

The meeting was adjourned at 5.42 pm.

Appendix A: 51st ACBTSA Meeting: Day-1 Attendees

ACBTSA Members in Attendance (in alphabetical order)

Chair

Jacquelyn (Jackie) Fredrick, MT (ASCP) SBB, MBA, Hon DB/DPH, Retired CEO, Versiti, Inc.

Public Members

Biree Andemariam, MD, Associate Professor, Department of Medicine, Neag Comprehensive Cancer Center, Division of Hematology/Oncology, University of Connecticut Health (UConn Health); Chief Medical Officer, Sickle Cell Disease Association of America, Inc.

Sally Caglioti, MS, MT (ASCP), President & CEO, Creative Testing Solutions

Andrew P. Cap, MS, MD, PhD, FACP, Colonel, Medical Corps, U.S. Army; Director of Research, U.S. Army Institute of Surgical Research; Hematology-Oncology Consultant to the U.S. Army Surgeon General; NATO Blood Panel Co-Chair; Professor of Medicine, Uniformed Services University; Hematology/Oncology/BMT Staff, San Antonio, Military Medical Center

Claudia S. Cohn, MD, PhD, Associate Professor of Laboratory Medicine and Pathology; Director, Blood Bank Laboratory; Associate Director, Clinical Laboratories, University of Minnesota; Chief Medical Officer, AABB

Raymond P. Goodrich, PhD, Executive Director, Infectious Disease Research Center, Office of the Vice President for Research; Professor, Department of Microbiology, Immunology and Pathology, Colorado State University

Elisa Gordon, PhD, MPH, Professor, Department of Surgery, Division of Transplantation; Center for Health Services and Outcomes Research, Institute for Public Health and Medicine; Center for Bioethics and Medical Humanities, Department of Medical Education, Feinberg School of Medicine, Northwestern University

Jed B. Gorlin, MD, MBA, Vice President and Medical Director, Memorial Blood Centers

Daryl Kor, MD, MSc, Professor of Anesthesiology; Director, Patient Blood Management Program, Mayo Clinic College of Medicine

Jim MacPherson, MS, MPh, President/CEO, MacPherson Strategies; President, Global Healing

Paul Ness, MD, Professor, Pathology and Medicine, Johns Hopkins University

David Perez, BA, Retired CEO, Terumo BCT

Representative Members

AABB
Lynne Uhl, MD, Vice Chair, Division of Laboratory and Transfusion Medicine, Department of Pathology, Beth Israel Deaconess Medical Center; Associate Professor, Harvard Medical School

American Association of Tissue Banks
Matthew J. Kuehnert, MD, FACP, FIDSA, Chief Medical Officer, MTF Biologics

Association of Organ Procurement Organizations
Gary Marklin, MD, Chief Medical and Research Officer, Mid-America Transplant

Eye Bank Association of America
Bennie H. Jeng, MD, MS, Professor and Chair, Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine; Past member, Board of Directors, Eye Bank Association of America

Major Blood Supplier
J. Chris Hrouda, MT (ASCP), President, Blood Services, American Red Cross

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

Manufacturer/Supplier of Blood Donor Testing and Screening
Susan Galel, MD, Senior Director of Medical Affairs, Blood Screening, Roche Molecular Systems

Ex-Officio Members

Center for Disease Control and Prevention
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

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

Food and Drug Administration, Office of Blood Research and Review
Nicole Verdun, MD, Director, Office of Blood Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration

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

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

National Institutes of Health
Kathleen (Cathy) Conry Cantilena, MD, Acting Chief/Senior Research Physician, Department of Transfusion Medicine, Clinical Center, National Institute of Health

ACBTSA Members Absent from the Meeting

Matthew J. Keuhnert, MD, FACP, FIDSA, Chief Medical Officer, MTF Biologics                                                                                                                     

HHS Support Staff in Attendance

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

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

Jordan Broderick, MA, Health Communication Specialist, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Health and Human Services

Allison Petkoff, ORISE Fellow, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Health and Human Services

Presenters and Panelists at Day-1 Meeting (in the order of presentation)

Merlyn H. Sayers, MBBCh, PhD, Carter BloodCare, Dallas-Fort Worth, Texas, University of Texas Southwestern, Dallas, Texas

Roger Y. Dodd, PhD, Executive Scientific Officer, American Red Cross, Adjunct Associate Professor, Johns Hopkins University

Claudia S. Cohn, MD, PhD, University of Minnesota

Mike Parejko, MS, MT(ASCP), President & CEO, Mississippi Valley Regional Blood Center; President, America’s Blood Centers

Bill Block, CEO, Blood Centers of America

Chris Hrouda, President, Biomedical Services, American Red Cross

David Green, CEO, Vitalant

Jay Menitove, MD, Retired CEO and Medical Director of the Community Blood Center-Kansas City

Peter Marks, MD, PhD, Director, Center for Biologics Evaluation and Research, FDA

Dean Gregory, President, Medical Devices, Fresenius Kabi North America Region

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