Creating a plasma coordination center to support COVID-19 outpatient trials across a national network of hospital blood banks

Abstract

Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

Results: We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

Conclusion: The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Keywords: COVID-19; clinical trial management; cloud-based platform; convalescent plasma; decentralized clinical trial; investigational drug services; supply chain management.

Figure 1.

Pandemic research study startup. The events for the postexposure prophylaxis study for infection prevention are shown above the 4-month timeline for first patient visit and nationwide site activation with donor plasma distribution. Similar events for the outpatient early treatment study are shown below the timeline.

Figure 2.

Viral specific antibody levels by collection date and transfusion date. Anti-spike receptor binding domain immunoglobulin G area under the curve (Anti-Spike-RBD IgG AUC) levels among 650 donor units transfused into recipients segregated by A) month of collection and B) study month of transfusion. The transfusion number by month and anti-Spike-RBD IgG AUC geomean are depicted. Comparison of log10 transformed values indicated no differences by 2-way ANOVA with multiple comparisons.

Figure 3.

Time from collection to transfusion for COVID-19 convalescent plasma (CCP) or control. The 2019 control plasma was used first, then the 2020 collected SARS-CoV-2 seronegative control plasma. The interval from donor collection date to recipient transfusion date for (A) control plasma and (B) CCP. (C) FDA granted CCP a 3-month shelf-life extension to 15 months based upon antibody stability data submitted under IND19725. Donor plasma samples collected in early 2020 were diluted 1:320 for the Euroimmun assay. Fifteen months later, the same samples were thawed with repeat SARS-CoV-2 S1 Spike antibody levels measured after 1:320 dilution.

Figure 4.

Flow of both COVID-19 convalescent plasma (CCP) and control plasma units from donor collection centers to site blood banks and 26 transfusion locations. The width of each line in the figure indicates the volume or the quantity of plasma units distributed, while the line color corresponded to the U.S. census collection region by blood unit WDIN. After name of blood banks or study site is the column percent of total (absolute number). EHBB = Endeavor Health Blood Bank, NS = Northshore, NYBC = New York Blood Center Enterprises, Hoag MH = Hoag Memorial Hospital in Newport Beach, CAIH = Center American Indian Health, MS Washington DC-Medstar, WSU = Wayne State University Detroit, WCHN = Western Connecticut Health Network aka Nuvance, AAMC = Anne Arundel Medical Center, GT = Georgetown.

Figure 5.

Flow of COVID-19 convalescent plasma (CCP) plasma units per study. (A) Infection Prevention RCT with 70 unique CCP donations were acquired and transfused to 82 recipients. CCP was collected at regional supply centers: Annapolis, Maryland (35%), New York Blood Center, NY, NY (27%), Blood Bank of Delmarva, Newark, NJ (22%) and Evanston, Illinois (12%). Additionally, locally sourced plasma was collected in Los Angeles, California, Danbury and Norwalk, Connecticut, and Poughkeepsie, New York (4%). (B) Early treatment RCT where 333 unique CCP donations were acquired and transfused to 592 recipients. CCP was collected at regional supply centers: Annapolis, Maryland (31%), Evanston, Illinois (24%), the New York Blood Center, NY, NY (21%), and Blood Bank of Delmarva, Newark, NJ (14%), ImpactLife, Davenport, Iowa (2%). The remaining 8% (46) units were locally sourced at study sites. After name of blood banks or study site is the column percent of total (absolute number).