Fifty-Seventh ACBTSA Meeting July 7, 2023 - Meeting Summary

Executive Summary

The Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA) convened the second day of its 57th meeting to address four agenda items: a presentation on the Alloantibody Exchange; a presentation on United States Core Data for Interoperability (USCDI) and the Office of the National Coordinator for Health Information Technology (ONC) Health IT Certification program; updates from the Tissue Tracking Work Groups; and an update from the Giving = Living campaign. The ACBTSA received a presentation on methods to extend the expiry dates of blood collection materials, which informed their discussions of Surge Capacity Recommendations. Due to limited time at the meeting, the ACBTSA did not vote on the Surge Capacity Recommendations.

Action Items

Scott Brubaker will add the discussion of informed consent for recipients of tissue with live cells to either the Tissue Recipient Adverse Events/Reactions Working Group or the End User/Consignee Receipt and Use Working Group.

Claudia Cohn will reassemble the working group that developed the Surge Capacity Recommendations to revise the stockpile recommendations.

Claudia Cohn will revise the language of the Surge Capacity Recommendations related to the Giving = Living campaign and redistribute the edited versions to the ACBTSA for revision and vote.

Meeting Summary

Welcome and Opening Remarks

Claudia Cohn, MD, PhD, provided brief welcoming remarks, and James Berger, MS, MT (ASCP) SBB, conducted roll call to confirm a quorum.

Claudia Cohn thanked the HHS and RLA staff who helped with planning and running the meeting. She provided an overview of the agenda for Day 2 of the meeting. She also addressed the usefulness of the ACBTSA despite the challenges in getting recommendations to the ASH and the delays in seeing the results of recommendations. She highlighted the HOPE Act as one of many successes to which ACBTSA contributed. James Berger added that ADM Rachel Levine, MD, has been a strong advocate for ACBTSA, particularly in her role as the chair of the Blood, Organ, and Tissue Senior Executive Council (BOTSEC). He added that her contribution extends to involving other federal agencies (e.g., CDC, HRSA, ASPR) to leverage their assistance in key issues that concern ACBTSA as well.

Alloantibody Exchange Presentation

Christina Deuschle, MA, Rose Li & Associates

Christina Deuschle stated that the goal of the Alloantibody Exchange project is to address the risk to patients created by the lack of a nationwide RBC antibody data exchange in the United States. Only one national registry exists, in the Netherlands; thus, there is limited available information and process knowledge for setting up a U.S. exchange for RBC antibody data. While researchers have identified several barriers to establishing a registry, none of them have been systematically investigated. To address the gaps in research, the Alloantibody Exchange team performed an environmental scan to inform the strategic planning process toward the establishment of a national patient data exchange.

Background

Blood disorders (e.g., sickle cell disease, thalassemia) and complications during childbirth disproportionately impact historically underserved populations. To address this inequity, the OASH chose to develop an RBC antibody exchange as part of HHS Secretary’s “Challenge on Equity” award. The exchange is one of 24 projects selected to advance equity in programs, policies, and processes across HHS.

Method

The Alloantibody Exchange team performed an environmental scan in two phases to inform their report. Phase I included (1) a review of published and unpublished literature of existing exchanges, registries, data health systems, and their implementation and sustainability; and (2) the establishment of the RBC Alloantibody Working Group. In setting up the Working Group, OIDP helped identify relevant subject matter experts (SMEs) and representatives of impacted patients who could serve as members. Phase II included the construction of interview schedules and formal and informal stakeholder interviews, data analyses, and presentations to the Working Group by SMEs who were both part of and separate from the working group. This process will result in a report that will include lessons learned regarding barriers and obstacles, recommendations for success, and planning for the next steps to establish a national data exchange.

Case Studies

Christina Deuschle provided an overview of key takeaways from the case studies included in the report. She provided an overview of several systems, including successful programs such as the Transfusion Register of Irregular Antibodies and Cross (X)-match Problems (TRIX) and the European Union eHealth Digital Service Infrastructure (eHDSI), as well as attempted programs that did not come to fruition such as the Georgia Pilot Red Blood Cell Antibody Exchange and Santa Barbara County Care Data Exchange.

Across all presented case studies, main characteristics of success included a well-established pilot, broad stakeholder buy-in and engagement, sustained funding from government and industry partners, leadership from an established and reputable organization, inclusion of the exchange or registry in national guidelines, and providing service to areas previously under- or unserved. Across the case studies, main barriers to success included lack of implementation and expansion planning to move beyond a pilot program; slow expansion due to voluntary participation; limitations to technical and legal interoperability across organizations and states; difficulty monitoring costs and timelines; lack of standard adoption of data privacy regulations; lack of information technology (IT) implementation or support; lack of sustained funding; and lack of value proposition to stakeholders.

Conclusions

An RBC alloantibody exchange would improve individual health outcomes, particularly for individuals in underserved communities; create a clinical research data set; and provide an opportunity for patient education and empowerment. However, there are multiple obstacles to establishing a national patient data exchange, and plans must be in place to anticipate and address them.

Findings suggest that an RBC alloantibody patient data exchange is possible with 11 key considerations and steps, including a pre-defined implementation plan, a pre-implementation pilot, a clear leadership structure, funding and staffing for start-up and sustainability, stakeholder engagement and buy-in, an exchange interface with user data systems, an exacting viable data set, interoperability, automation whenever possible, data accuracy and validation, and a systematic evaluation of the framework. Creation of an exchange will also require additional research to answer outstanding questions, including whether nationwide interoperability should be mandatory or incentivized, whether patient-identifying data should be included, how to ensure and verify data accuracy, how to address resistance and hesitancy to implementation, and what guidelines and recommendations should accompany an exchange. These questions will be a primary focus of the Alloantibody Exchange project in its next phase.

Next Steps

The information presented above covers Phase I of the RBC Antibody Exchange Strategic Implementation Plan. Phase II will include pilot readiness and implementation activities, including a readiness assessment, implementation of a chosen model, and pilot implementation and evaluation. Phase III will include data exchange readiness and implementation, including readiness assessment, refinement of the pilot model, launch, and continued management of the RBC Antibody Exchange with the aim of sustainability and improvement.

Immediate next steps for the RBC Antibody Exchange project and Working Group include identifying feasible pilot options to test a national data exchange and determine readiness for pilot implementation. Contributors to these efforts include the RBC Working Group and stakeholders and subject matter experts who will utilize interviews, focus groups, and literature reviews to design and develop a pilot.

Discussion

Raymond Goodrich noted that the spread of the financial support for set-up of the case study exchanges and data systems ranged from $24,000 plus an administrator salary to $10 million. He asked what the financial balance would be to affordably implement and sustain an RBC antibody data exchange. Christina Deuschle noted that the lowest cost quoted is a regional register with a narrow scope that requires manual data entry, limiting the scalability of the program. However, the highest amount quoted was for a program that was unable to achieve sustainability due to lack of continued funding. An exact funding range for implementation and sustainability will need to be determined based on the implementation and sustainability plan for an exchange.

Based on her own experience in trying to develop an exchange, Cassandra Josephson underscored the obstacles of IT support, hospital buy-in, and liability. She noted that some of those barriers are less challenging to address as electronic health records (EHR) become more accessible to patients. She also noted that cost is decreasing for data portals and exchanges. The greatest obstacle is the lack of a single, national system for establishing and maintaining health records, but even so, the field is in a much stronger position now than it ever has been for establishing a nationwide exchange.

Claudia Cohn noted that the Yale group’s current initiative began with developing software to utilize with laboratory information systems (LIS) nationwide. There are only 9 major LIS that cover the U.S.; connecting some of those would be a strong start to creating an exchange. She asked how the RBC Alloantibody Exchange and the Yale LIS software could dovetail. Christina Deuschle responded that the lead of Yale’s software development is on the working group for the RBC Alloantibody Exchange and has shared knowledge gained from the development and launch of that software to aid in the development of the exchange.

Paul Ness asked which party (e.g., hospitals, blood centers) would be entering data into the exchange. Christina Deuschle responded that it has not yet been determined whether data entry will be utilized in the pilot. Cassandra Josephson noted that the field is moving towards a common model of data entry and standardized language that could provide guidance on these decisions. Deuschle noted that the project team is still working to identify experts in modeling to help inform the pilot exchange.

Daryl Kor asked whether EHR vendors could play a role in accomplishing the goals of the Exchange. Christina Deuschle replied that the project team plans to work with several stakeholders during Phases II and III, including EHR vendors. Daryl Korf noted that a challenge to developing an exchange is that many hospitals do not accept antibody data from outside testing locations, and wondered how that challenge would be addressed. Cassandra Josephson explained that the type and screen conducted at some outside testing locations may not provide sufficient information for hospitals to be able to utilize the data for their purposes of matching; an exchange would ensure that all the data necessary would be captured in the system.

USCDI and ONC Health IT Certification Program

Albert Taylor, MD, Senior Medical Informatics Officer Standards Division, Office of the National Coordinator for Health Information Technology, HHS

Albert Taylor explained that the United States Core Data for Interoperability (USCDI) is a dataset that was established in response to the Office of the National Coordinator for Health Information Technology (ONC) Cures Act Final Rule of 2020, which required the development of a new application programming interface (API) enabling access to patient data. USCDI was designed to be this new application. The primary use case for USCDI is patient care and patient access to their health care data, but other reporting programs (e.g., data exchanges) may utilize USCDI as their core guidelines, as well.

USCDI

USCDI was developed to replace the Common Clinical Data Set and includes guidance for transition of care documents; clinical information reconciliation and incorporation; patient view, download, and transmission of their health data to a third party; electronic case reporting to public health agency; creation of C-CDA documents; access to data via APIs; and other uses (e.g., federal reporting). USCDI has expanded available guidance over time via a predictable, transparent, and collaborative public process to (1) support advancing health equity; (2) reduce disparities and support public health data interoperability; (3) propose new detailed lab data elements; and (4) add alcohol use, substance use, and physical activity assessments, treatment intervention, care experience preferences, and medication adherence data elements.

USCDI has several data elements captured in the upcoming version 4 draft, including capturing lab tests (e.g., antibody testing, antigen testing) via Logical Observation Identifier Names and Codes (LOINC), values and results, result status, and result interpretation. LOINC allows providers to query an EHR for data related to a given test. As the public submits additional recommendations for data elements, USCDI will sort these recommendations by prioritization criteria. These criteria include whether the data addresses healthcare disparities and inequities; helps underserved communities; or is burdensome for standards and implementation guide developers, health IT developers, or providers and health systems implementing updates. USCDI data elements proposed include product code, unique identifier, source identifier, and processing facility.

Additional ONC Programs

In some cases, unique program needs or case-specific data needs are not fully met by USCDI. To address these cases, ONC developed a program to help government and industry partners build on USCDI to support specific program needs. This program, USCDI+ for Quality Measurement and Public Health, applies USCDI processes of submission and harmonization while leveraging programs and authorities across HHS. USCDI+ for Quality Measurement and Public Health kicked off with CDC, CMS, and HRSA.

ONC also has an Interoperability Standards Advisory that identifies recognized interoperability standards and implementation specifications for industry use to fulfill specific clinical health IT interoperability needs. This system is flexible and responsive to key stakeholder input on specific areas, such as terminology, structure, and services.

Discussion

Cassandra Josephson asked for additional details on how ONC ensures compliance with USCDI or other programs. Albert Taylor explained that ONC has a voluntary certification program that includes USCDI as a certification criterion, which requires programs to demonstrate that they can exchange data in a way that meets USCDI standards. Programs that do not seek certification are not monitored; however, USCDI is part of a real-world testing program, meaning that if a user of an EHR notices that an element is not working the way it is meant to, this issue can be reported to ONC and certification bodies will work with the EHR system to ensure it is USCDI compliant. Cassandra Josephson expressed concern that the reporting of errors is voluntary as she noted that some EHR systems she has interacted with do not seem compliant. Taylor reiterated that it is the responsibility of the health IT or EHR vendors to do the development and testing to ensure that their programs are compliant.

Scott Brubaker asked whether the USCDI was flexible enough to be able to accept other systems beyond the applicable standards. He provided an example, noting that the listed product code applicable standard is ISBT-128, and asked whether another product code could be used. Albert Taylor first clarified that product code is not yet included in USCDI; it is one of the proposed data elements. He then explained that the applicable standards for USCDI mean that the EHR must, at a minimum, be able to represent a product code as ISBT-128 but does not preclude an EHR from using additional forms of representation. These applicable standards are not requirements unless the standard matches a requirement from CDC's National Healthcare Safety Network (NHSN). NHSN would need to create a requirement for any of USCDI’s data element standards to become mandatory nationwide. ONC does not dictate NHSN requirements. However, should NHSN decide to make a set of required standards for EHRs, USCDI could be used as a source for creating a set of guidelines that has a built-in standard for exchanging data.

The committee discussed using USCDI data elements to conduct tissue and organ tracking. Albert Taylor explained how tissue and organ transplant codes could be organized within the Summary of Data Classes and Data Elements document, providing implantable devices as an example. Sridhar Basavaraju asked what the barrier is for adopting additional data elements for tissue into USCDI. Albert Taylor noted that the USCDI has received hundreds of recommendations for data elements to add to USCDI, which has required ONC to be selective about which data elements are because each new data element is a burden on developers, standards developers, and implementers to accommodate. The prioritization criteria help ONC determine which elements to implement most urgently. Sridhar Basavaraju asked whether the proposed data elements listed on the slide will eventually be implemented in USCDI. Albert Taylor noted that every year ONC completes a cycle of consideration and adoption of new data elements.

Update from the Tissue Biovigilance Subcommittee

Timothy L. Pruett, MD, Professor of Surgery and Internal Medicine, University of Minnesota
Scott Brubaker, Director, Division of Human Tissues, FDA

Timothy Pruett described the substantial differences between tissue biovigilance and organ biovigilance. Tissue transplant involves several additional steps between removal from the donor and transplant in the recipient. Tissue transplants are more similar to blood transfusions, which also require multiple steps of processing and testing prior to transfusion to the recipient. The Tissue Biovigilance Subcommittee was formed in response to the nationwide Mycobacterium tuberculosis outbreak in the United States during 2021, linked to a viable bone allograft that resulted in significant recipient morbidity and mortality and placed at risk healthcare workers who provided care to infected recipients. The Tissue Biovigilance Subcommittee formed four working groups, comprised of stakeholders and subject matter experts, to analyze each step of biovigilance: tissue source, tissue processing, end use or consignee receipt and use, and tissue recipient adverse events and reactions. The goal is for each working group to identify and document gaps for processes within their assigned area of focus.

The scope of the Tissue Source Working Group includes donor identification; donation authorization and informed consent; donor screening and decision to proceed; chain of custody; tissue recovery and acquisition; and donor testing. The Tissue Processing Working Group scope includes chain of custody; bioburden assessment and culture method suitability; preservation and storage; processing validation; donor eligibility determination for release; and product distribution. The End User/Consignee Receipt and Use Working Group scope includes tracking, coding, and records; inspection, storage, and preparation for use; EMR and biovigilance, including linkages between inventory and recipients; and final disposition. The scope of the Tissue Recipient Adverse Events/Reactions Working Group includes procedures, recognition, investigation, and reporting. The scope of the working groups is subject to change via input from Tissue Source Working Group members.

The four working groups have begun meeting regularly and will contribute to a gap analysis report that will be sent to the full committee for review. The final report may also include a gap analysis versus other biovigilance efforts in the United States (i.e., for blood and blood product transfusions).

Discussion

Jed Gorlin noted that his center is the testing site for the Iowa and Minnesota Mother’s Milk Bank, and asked if milk banks are included in tissue biovigilance or a separate system. Cassandra Josephson noted that donor milk is tested and also pasteurized; whereas maternal milk is only tested. She noted that she was not sure which entity regulates milk testing and pasteurization, but that blood, tissue, and mother’s milk all face similar biovigilance issues, including documentation and standardization. Timothy Pruett agreed that there is an overarching issue of moving products from one person to another, whether they are blood, tissue, organ, or other products. He emphasized the need for common language and good practice on an international level.

David Stroncek noted that the field of gene manipulative immunotherapy for cellular cancer is a is currently experiencing a steep rise in research popularity. He asked whether those products were tracked as well. Timothy Pruett noted that they are not as ideally tracked as researchers and clinicians would want.

Sridhar Basavaraju asked if the Tissue Biovigilance Subcommittee was considering the requirement for informed consent, because most individuals who receive a tissue product are not subject to informed consent in the same manner that blood transfusion and organ transplant recipients are. Timothy Pruett noted that one of the working groups is including an evaluation of informed consent for the recipient. He noted that this issue is of concern to him personally because when he received a bone implant, he did not receive a consent form for the procedure. He continued to note that some practitioners may not see tissue as a transplant but instead as a tool, like screws or other materials used in surgery. He added that this disconnect is more an educational issue than a regulation issue. Sridhar Basavaraju emphasized that if someone is receiving tissue with live cells, they should be subjected to informed consent in the same way that an organ transplant recipient would be. Scott Brubaker suggested that this issue could be added in more specificity to the work of either the Tissue Recipient Adverse Events/Reactions Working Group or the End User/Consignee Receipt and Use Working Group.

Lou Barnes noted that accredited member tissue banks have informed consent at the forefront of the education of their customers. Most tissue banks provide materials to patients; however, Barnes noted a gap in how well patients understand the materials and how well the providers use the materials to educate patients. The effectiveness of the education is often associated with the provider’s perceived risk of the tissue being collected or transplanted. The risk is perceived as lower for terminally sterilized and decellularized products. Timothy Pruett explained that extensive literature has been published likening terminally sterilized and decellularized to devices. He expanded that cellular products are considered to have higher risk than decellularized products.

Giving = Living Campaign Final Update

Ann Aikin, MA, Communications Director, OIDP

Ann Aikin emphasized that blood and plasma are invaluable, life-saving products that are needed to treat a variety of conditions. While every two seconds someone in the United States needs blood, its shelf life is only 42 days. In early 2022, the American Red Cross declared that the United States is facing a national blood crisis, with a severe shortage due to the COVID-19 pandemic. When Congress passed the CARES Act, it called for HHS to undertake a national communications campaign to address the unprecedented blood and plasma shortages. In response, HHS developed Giving = Living, a national blood and plasma donation campaign launched in August 2022. While the contract for Giving = Living ended in March 2023, HHS is still supporting parts of the campaign.

Campaign Development

HHS performed formative research and convened an expert panel to inform development of a campaign to address the blood and plasma shortages. These activities included a literature review, environmental scan, focus groups, and expert panel meetings. From these activities, HHS learned that the public is generally uneducated about both the donation process and the eligibility requirements. Barriers to donation include negative donation experiences, lack of trust, perceived inconvenience, and mistrust of the health care system; while motivators for donation include altruism, incentives (e.g., monetary, gift card), personal connection to an individual in need, and an understanding of the donation process.

Based on these findings, the HHS developed the Giving = Living charge to increase the number and diversity of Americans who (1) understand why blood donation is important, what blood donations are used for, and what the blood donation process is and eligibility requirements are; (2) believe donating blood is important and the right thing to do; and (3) donate blood and continue to habitually donate blood. To meet these goals, HHS created campaign brand testing around the themes of altruism (underscoring how donations help others), social norms (driving the perception that donating routinely is the right thing to do), and peer-to-peer connections (reinforcing the value of working together and social support). Based on brand testing, the Giving = Living brand was developed, using a “dear hero” approach that features testimony from individuals who received blood transfusions, highlighting their personal stories via the campaign website, public service announcements, and digital ads.

Media Campaign

Ann Aikin highlighted three of the individuals whose stories were included in the campaign. Each of the stories was tested with an audience and were well received. In addition to appreciating the clear and compelling message that blood donation saves lives, the test audience also reported that statistics and references to specific conditions that require blood donation increased the understanding and impact of the messaging. The audience shared that understanding how donations help the recipient and their families and how the donations allow these individuals to live normal lives, facilitated relatability, empathy, and motivation to learn more. Ann Aikin proceeded to share one of the long form videos and one of the 30 second videos from the Giving = Living campaign, demonstrating the list of videos available for the campaign and the ease of sharing these videos virally.

The Giving=Living website is split into three main sections. The landing page shares details about the campaign, including materials to increase support for blood and plasma donation. The website also includes pages where individuals interested in donating blood or plasma can learn more about the process, benefits, and local resources. Throughout the different available webpages, there are also several calls to action to find a local donation center.

The Giving = Living campaign has leveraged both social media and traditional media for spreading their message. The campaign designed several gifs (through GIPHY), as well as frames to use on Instagram and Facebook profile pictures. Additionally, Admiral Levine, as the spokesperson for the campaign, participated in media interviews with select news stations around the country.

Finally, the campaign held the Giving = Living Blood and Plasma Donation Innovator’s Challenge, which called for community-drive strategies to increase and diversify blood and plasma donations. The challenge closed on December 5, 2022, and awarded nine winning organizations, teams, or individuals between $1,800 and $10,000.

Metrics

Ann Aikin shared the metrics for the Giving = Living campaign from launch through the middle of March 2023. Organic social media content reached more than 66.7 million people and generated more than 11,800 engagements. In addition, YouTube videos generated more than 4.5 million views. Paid media generated over 676,000 clicks and delivered over 54 million impressions. Donated media received more than 328.7 million impressions for a total value of over $4.3 million.

The CARES Act also required tracking geographic markets and performance, so Giving = Living tracked performance by geographic region. At the city level, Giving = Living performed best in the small- to medium-sized markets, with highest engagement in Eugene, Oregon and Yakima-Passo-Richard-Kennewick, Washington. Television marketing for English-language blood donation was aired most often in Montana, Virginia, and Mississippi. The Spanish-language blood donation television ads were most often aired in Connecticut and Massachusetts.

The Giving = Living campaign also tracked engagement of media by race, comparing performance to common benchmarks for similar ads among the general market, Hispanic audiences, and Black audiences. Overall, the Giving = Living campaign ads exceeded benchmarks. Display ads overdelivered on impressions by 8 percent in all three demographics (general, Hispanic, Black). Pre-roll ads (i.e., marketing before videos played) overdelivered by 9 percent in the general market and Hispanic audiences and overdelivered by 2 percent among Black audiences. Connected TV (CTV) ads overdelivered impressions by 7 percent in the general market and 2 percent among Black audiences. Surprisingly, these CTV ads exceeded benchmark expectations among Hispanic audiences by 38 percent.

Next Steps

HHS will continue to promote the campaign on social media and at events. HHS is looking for opportunities and events for promotion, such as National Blood Donor Month and National Women’s Health Week. Giving = Living has promotional and educational materials available for other organizations to utilize. Organizations can disseminate fact sheets, videos, and other materials via social media using #GivingEqualsLiving or in blogs or newsletters. The materials can also be used to host blood or plasma drives.

Lessons learned from the campaign include that testimonials and materials performed well when they made people feel connected to the stories. Additionally, the materials were successful because they were relevant, demonstrating to audiences how donations help recipients and their families. Finally, stories were most impactful when paired with statistics and related to familiar conditions, helping the audience understand the urgency for donations.

Ann Aikin asked for the ACBTSA members to spread the message about the availability of materials for use. She emphasized that more time in the market would create additional, needed opportunities to address barriers to donation (e.g., myths that may confuse potential new donors). Clear and memorable messages are needed from a variety of sources to reach a wider audience, reinforcing that blood and plasma donations save lives. Future materials also need to address personal risk to donors, a concern among the audiences who reviewed the Giving = Living campaign materials.

Discussion

Cassandra Josephson asked whether messages about cancer or small children were well received. Ann Aikin noted that stories about cancer patients, including one child cancer patient, were well received and were included among the stories in the campaign. Another story included in the campaign is the child of a cancer patient who died, but who benefited from blood transfusions late in treatment.

Raymond Goodrich asked if the campaign, in addition to reaching the target audience, also resulted in the desired behavior change of people becoming regular blood donors. He asked whether Giving = Living was able to track conversion of non-donors to donors. Ann Aikin noted that tracking this conversion would require additional funding. The campaign is tracking the metrics available through the donation center locator on the Giving = Living website; however, those numbers do not accurately reflect a full conversion as not everyone who seeks out a donation location will choose to donate. Jim MacPherson asked whether Giving = Living had reached out to the Advertising Council (Ad Council) to see if they would assist in tracking pre- and post-advertisement attitudes on blood donation, or whether HHS had other plans for moving forward to track these non-donor-to-donor conversions. Ann Aikin noted that HHS has not worked with the Ad Council, as they do not have the funding available to ask the Ad Council to perform such metric measurements. HHS is working to find funding, and in the meantime continuing to promote the campaign via social media and through other organizations for free. If ACBTSA recommends that the work continue, there is still extensive work to be done to promote the campaign, develop materials, and evaluate impact.

Methods to Extend the Outdate of Blood Bags

Bryan Blickhan, Senior Vice President of Research and Development and Device Production, Fresenius Kabi

Bryan Blickhan explained that ACBTSA has previously discussed the need to extend the expiry date for blood collection products to improve supply and ensure broader availability of products nationwide. However, extending this expiry date impacts several stakeholders who are responsible for ensuring the safety of the affected products. When establishing expiration dates for blood collection and processing kits, for example, manufacturers demonstrate appropriate physical and functional characteristics over the shelf life of the materials, including product integrity (e.g., container closure), acceptable blood component storage, correct function with applicable system interfaces (e.g., clamps, sealers), acceptable materials safety profile, and solution stability per FDA’s Stability Testing of New Drug Substances and Product guidance protocol.

Due to the extensive number of physical and functional characteristics that determine a product’s shelf life, several key aspects may limit the ability to extend product expiry. First, material properties (e.g., strength, elasticity, permeability) can change over time, degrading and affecting product integrity and performance. Material properties will need to be considered and potentially tested to ensure that extending the expiry date would not impact product function, integrity, extractables or leachables, and blood product storage. Second, contained and packaging permeability means that water loss will occur over time, potentially affecting anticoagulants or processing solutions. Concentrations of anticoagulants and other solutions in materials change over time, and will continue to change after a products pre-determined expiration date. Any extension of the expiry will require careful consideration of solution specifications and their potential effects on the storage of blood components (e.g., red cell hemolysis, platelet pH).

Bryan Blickhan highlighted three main discussion points for ACBTSA to consider as they discuss the potential extension of expiry dates for blood collection products. First, ACBTSA will need to determine whether manufacturers have performed studies at time points beyond the existing labeled shelf life to determine whether the extent of challenges to extension are adequately documented or still unknown. Second, if testing for extending the shelf life has not been performed, ACBTSA will need to consider that costly and burdensome studies will be required to test blood storage, extractables and leachables, and product integrity and function over time. Finally, regulatory agencies may need to allow for exceptions to some of the currently established limits (e.g., blood storage quality metrics) and requirements for the type and size of studies required to gain acceptance of longer shelf lives for products. These discussion points represent the next steps for ACBTSA to consider in seeking an extension to expiration dates of products. Bryan Blickhan concluded by noting that Fresenius Kabi would be interested in continuing to collaborate with ACBTSA on extension of expiration dates for blood collection materials.

Discussion

Jed Gorlin noted that the European Union is looking to remove DEHP in blood collection bags, and asked Bryan Blickhan for his perspective on this possibility, both nationally and internationally. Bryan Blickhan noted that Fresenius Kabi has long-term plans to continue to monitor and address international needs. In regions without mandates, Fresenius Kabi is in discussion with major customer groups to calibrate interest in looking at alternative available materials and options as they become available.

Raymond Goodrich acknowledged that testing is a key component for manufacturers to expand expiry dates on products. He noted that the economic advantage of an extended shelf life may make it worthwhile for manufacturers to perform the testing. He then asked whether the original expiration date for blood collection materials was established based on initial testing or economic value. Bryan Blickhan explained that for products containing solutions, Fresenius Kabi based their expiration dates on testing to demonstrate that their products meet the requirements for the stability guidelines developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Fresenius Kabi aims to provide the longest possible shelf life that allows the products to remain within the guidelines’ limitations. These guidelines are often the limiting factor in extending the shelf life of blood collection products for the reasons discussed above (e.g., stability, degradation). Dry products without solution consideration are likely to have expiration dates based on historical norms. These dry products could be reassessed based on current standards; however, this testing would likely be burdensome on the manufacturers.

Lou Barnes asked what the average shelf life is for products containing solutions that limit the shelf life. Bryan Blickhan noted that Fresenius Kabi products have a 20- to 26-month shelf life, with most at the lower end. Lou Barnes asked if Bryan Blickhan would communicate back to the Fresenius Kabi manufacturing team his interest in better understanding manufacturing output capacity and manufacturing challenges. Bryan Blickhan agreed to follow-up offline to further this discussion.

Discussion on Surge Capacity Recommendations

Claudia Cohn led the Committee in a review and live revision of the recommendations she had presented during the previous day’s meeting. Due to time constraints, the Committee did not vote on the recommendations.

Stockpile Recommendations

Recommendations 5 through 8 discuss the expansion of a stockpile of blood, plasma, and collection supplies.

Recommendation 5

Recommendation: The Committee therefore recommends that a list of key materials, developed by BCA as part of an ASPR grant, be used to create regional stockpiles that are maintained by third party vendors. The establishment of the stockpile would take into consideration the ongoing activities of BCA’s 3PL plan that will allow for consolidation of resources, which will be an important step toward the establishment of stockpiles.

Susan Galel provided several observations on this recommendation. First, the scope of the recommendation could be overwhelming if it includes all critical supplies. Additionally, testing reagents that require a cold chain and are licensed as biologic pharmaceuticals have quality management considerations for a stockpile, including responsibility for quality of the products in the stockpile, ownership of the products in the stockpile, and who is responsible for complaint investigation. Susan Galel also commented that existing agreements require manufacturers to have a certain supply available at distributor warehouses and asked whether the proposed stockpile would affect those supply requirements.

Cassandra Josephson noted the need for more specifics in the recommendations, specifically regarding quality control. She suggested that the recommendation be tabled until the Committee can define the scope and responsibilities more clearly.

Diane Corning explained that stockpiling responsibilities can be burdensome when assigned to a single entity and suggested that providers form coalitions that could share the responsibility of stockpiling.

Lynne Uhl agreed that the recommendation requires input from a broader array of stakeholders. Other blood collection facilities (e.g., The Red Cross) should be involved in defining the scope and responsibilities outlined in the recommendation. Additionally, hospital representatives, who require access to any aspect along the chain of blood collection, manufacturing, and distribution, should also be involved in these discussions to better understand the full impact of any changes. Claudia Cohn clarified that the working group that developed the recommendation included representatives from ABC, BCA, and the Red Cross. Susan Galel added that suppliers should also be considered stakeholders in the recommendation discussions. Sally Caglioti, a member of the working group that drafted the recommendation, agreed with the suggestion for the working group to revisit the recommendation with the new information brought forth at the meeting.

Jim MacPherson expressed concern that sending the recommendation back to the working group will not lead to discussions beyond those that have already occurred, given that many of the concerns raised during the meeting were already discussed at the working group level. Claudia Cohn emphasized the importance of making a recommendation about creating a national stockpile that does not solely rely on the private sector. Raymond Goodrich added that this recommendation only suggests the creation of a list of what materials would be included in a stockpile, utilizing BCA’s work as a starting point, which he felt was a reasonable scope.

Recommendations 6 through 8

Recommendation 6: The Committee also recommends that a Memorandum of Understanding (MOU) be negotiated with Canada to allow their blood and blood products into the U.S. and utilization of their testing laboratories to relieve transient strains in the blood supply brought about by emergencies. The MOU would be bi-directional. The FDA would participate in this work to assure the safety of the incoming blood from Canada or other countries.

Recommendation 7: The Committee also recommends that an HHS funding organization offer grant or contract funding that enables the development of novel means for extending the outdate of perishable materials in the stockpile.

Recommendation 8: The Committee further recommends that OASH or other HHS funding organization receive an enabling budget to be used for projects that stabilize the blood supply such as stockpile of key supplies and components. Funding from OASH or other HHS funding organization would be used as start-up funding for the establishment of a stockpile.

Susan Galel noted that recommendations 7 and 8 both address funding that enables the development of processes by which a stockpile can be established or that shelf life can be extended, but not the sustainability of funding to continue these projects over time. She asked that the working group consider the ongoing costs of maintaining a stockpile.

The Committee determined that, given the need to further discuss the business aspects of these recommendations, the recommendations would be revisited on the working group level to allow for a more thorough discussion with all relevant stakeholders present. Claudia Cohn will reassemble the working group members to this end.

Donor Recruitment Recommendations

Recommendations 12 and 13 focus on the continuation and expansion of blood and plasma donation efforts.

Recommendation 12: The Committee therefore recommends that [the Giving = Living] campaign be continued and expanded to encourage blood and plasma donations.

Recommendation 13: The Committee further recommends that investments be made in data analytics to continue to have donor numbers across the industry that allows for further advocacy and tracking of marketing/collection-recruitment campaigns associated with recruitment of donors. BCA has invested extensively in our analytics program.

Jim MacPherson noted that Ann Aikin stated that Giving = Living does not have additional funding and asked where the additional funding would come from to complete an evaluation or expand the campaign. James Berger explained that the recommendation should state that funding be provided to continue the program, perform the analysis, and increase minority donations.

Elisa Gordon highlighted that Giving = Living is a great campaign that should receive continued funding, but the campaign needs an evaluation component to accurately measure the campaign impact. She argued that HRSA campaigns for organ donation require analytics to be built into the campaign. Many ACBTSA members agreed with the need for an analysis of the campaign’s impact. Raymond Goodrich noted that Recommendation 13 includes language about investments into data analytics that are broader than Giving = Living but would include the campaign and would drive research on the effectiveness of all marketing and recruitment efforts.

Cassandra Josephson suggested that an analysis could still be performed retrospectively on the campaign’s activities to date using metrics from social media and other areas where the campaign components were integrated. Raymond Goodrich agreed with the possibility of a retrospective analysis and the continuation of the campaign. Elisa Gordon challenged the use of a retrospective analysis and instead encouraged implementing a campaign that requires a prospective analysis of impact to ensure rigorous results.

Lynne Uhl suggested combining recommendations 12 and 13. She also supported the suggestion of monitoring the outcome of the campaign. She asked whether ACBTSA can request funding for further advocacy programs. Jim Berger noted that ACBTSA can provide any recommendations that they feel are important, including funding for further advocacy programs.

The Committee members discussed potentially editing the language of recommendations 12 and 13. During the discussion, Committee members shared concerns about the need for a full study to demonstrate the effectiveness of campaigns and the counter argument that utilizing already limited funding for starting a new campaign would negatively impact already existing and successful campaigns for increasing blood and plasma donation. Those who shared the latter perspective pushed for continued funding of Giving = Living with an expansion to include analysis of impact, including converting non-donors to donors, increasing awareness of the need for donation, and improving attitudes toward donation.

Due to insufficient time at the meeting, the Committee tabled editing and finalizing the language of recommendations 12 and 13, as well as all other non-discussed recommendations. Claudia Cohn will work after the meeting to edit the language of Recommendations 12 and 13 in a way that addresses the concerns expressed during the discussion.

Wrap-up and Adjournment

James Berger officially adjourned the meeting at 12:54 PM ET.

List of Participants

Voting Members

Claudia Cohn (ACBTSA Co-Chair), University of Minnesota
Diane Wilson (ACBTSA Co-Chair), Community Blood Center Community Tissue Services (CBC/CTS)
Biree Andemariam, UConn Health
Louis E. Barnes, American Association of Tissue Banks (AATB)
Sally Caglioti, Creative Testing Solutions
Susan Galel, Roche Diagnostics
Ray Goodrich, Colorado State University
Elisa Gordon, Vanderbilt University
Jed Gorlin, Innovative Blood Resources & University of Minnesota
Bennie Jeng, University of Pennsylvania
Cassandra D. Josephson, Johns Hopkins All Children’s Hospital
Michelle Kameka, Florida International University
Daryl Kor, Mayo Clinic
Jim MacPherson, MacPherson Strategies
Gary Marklin, Mid-America Transplant
Paul Ness, Johns Hopkins University
David Perez, Terumo BCT (retired)
Glenn Ramsey, Northwestern Medicine
Eric Santiago-Justiniano, Fresenius Kabi
Lynne Uhl, Beth Israel Deaconess Medical Center and Harvard University

Ex-officio Members

Sridhar Basavaraju, Centers for Disease Control (CDC)
Scott Brubaker, Food and Drug Administration (FDA)
Diane Corning, Centers for Medicare & Medicaid Services (CMS)
Marilyn Levi, Health Resources and Services Administration (HRSA)
David Stroncek, National Institutes of Health (NIH)
Nicole Verdun, Food and Drug Administration (FDA)

Presenters

Ann Aikin, Health and Human Services Office of the Assistant Secretary for Health (HHS OASH)
Bryan Blickhan, Fresenius Kabi
Bill Block, Blood Centers of America
Scott Brubaker, U.S. Food and Drug Administration (FDA)
COL André Cap, US Army
Christina Deuschle (Meeting Host), Rose Li and Associates, Inc. (RLA)
Peter Marks, U.S. Food and Drug Administration (FDA)
Jay Menitove, Previous ACBTSA Chair
Timothy Pruett, University of Minnesota
Albert Taylor II, Office of Technology Office of the National Coordinator for Health IT

Additional Attendees

James Berger, Health and Human Services Office of the Assistant Secretary for Health (HHS OASH) Designated Federal Officer (DFO) for ACBTSA
Kaye Hayes, Deputy Assistant Secretary for Health and HIV and Infectious Disease (OIDP), Executive Director of President’s Advisory Council on HIV/AIDS (PACHA)
Lauren Overman, Health and Human Services Office of the Assistant Secretary for Health (HHS OASH), Alternate Designated Federal Officer (DFO) for ACBTSA  
Sara Parker, Health and Human Services Office of the Assistant Secretary for Health (HHS OASH)
Allison Petkoff, Health and Human Services Office of the Assistant Secretary for Health (HHS OASH)
             
Mike Kavounis (Meeting Host), RLA
Meghan Walsh (Project Manager), RLA
Jay Weixelbaum (Science Writer), RLA