PLoS One . Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality

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PLoS One


. 2020 Dec 22;15(12):e0243967.
doi: 10.1371/journal.pone.0243967. eCollection 2020.
Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality


Viola H?hnel ¹ , David Peterhoff ² , Veronika B?uerlein ¹ , Andreas-Michael Brosig ¹ , Irene Pamler ¹ , Christian Johnson ¹ , Adelina Bica ¹ , Monica Totir ¹ , Thomas Ossner ¹ , Barbara Stemmer ¹ , Martina Toelge ² , Anja Sch?tz ² , Hans-Helmut Niller ^{2 3} , Barbara Schmidt ^{2 3} , Ralf Wagner ^{2 3} , Andr? Gessner ^{2 3} , Ralph Burkhard ¹ , Robert Offner ¹



Affiliations

• PMID: 33351831
• DOI: 10.1371/journal.pone.0243967

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2-6?C) for up to 5 days or frozen (-30?C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100-1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.