Optimized Protocol for Producing Pathogen-Inactivated Double-Dose Platelet Concentrates From Six Pooled Buffy Coats.

Abstract

Background: Pooled platelet (PLT) production methods differ worldwide. In Europe, the buffy coat (BC) method is predominantly used, with four to eight BCs being pooled to produce single- or double-dose PLT products. The European Directorate for the Quality of Medicines & HealthCare (EDQM) blood guide and Austrian legislation define a therapeutic PLT unit as ≥ 2 × 10¹¹ PLTs/unit. We optimized the manufacturing steps to produce doubledose PLT products from six BCs, aiming to enhance production efficiency while maintaining product quality.

Methods: We stepwise optimized our protocol starting from five BCs (BC5) (N=107). First, we included an additional BC (BC6) (N=110). Second, we used a hematology analyzer (Sysmex XN-1000) equipped with blood bank mode, which is a novel software application for measuring PLT counts in PLT units (BC6+XN-1000) (N=106). Third, we optimized the blood cell separator (BCS) settings to produce higher-volume BCs (BC6+XN-1000+BCS) (N=107). Fourth, we adapted the centrifugation (BC6+XN-1000+BCS+CF) (N=197). All units were pathogen-inactivated using the INTERCEPT blood system (amotosalen/ultraviolet A).

Results: Each optimization step significantly increased the yield ( × 10¹¹/PLT concentrate) (P <0.001). The mean yield increased from 2.83 (SD 0.39) for BC5 to 4.81 (SD 0.58) for BC6+XN-1000+BCS+CF. The mean BC volume increased from 47.78 mL (SD 5.09) to 55.59 mL (SD 5.11) following BCS adaptions (P <0.001).

Conclusions: After stepwise protocol optimization, we could produce pathogen-inactivated double-dose PLT concentrates by pooling six BCs, complying with national regulations and EDQM quality requirements while reducing costs and minimizing blood wastage.