Characterization and Stability of Spray Dried Plasma Manufactured with the Frontlineodp™ System

Background: Prehospital intervention with plasma reduces mortality in trauma. Providing plasma when needed is challenging. Spray-dried plasma provides storage and logistical advantages for the provision of plasma at the point-of-care in the treatment of hemorrhagic shock. The FrontlineODP™ System is a novel, decentralized, manufacturing technology designed for use by blood centers for producing spray dried plasma (ODP - OnDemandPlasma) from conventional plasma in a flexible bag configuration. ODP is rehydrated with sterile water for injection and within minutes is ready for transfusion. ODP characterization studies were conducted to support initiation of a Phase 1 Clinical Safety study.

Methods: ODP (n=60) and its paired control plasma frozen within 24 hours (PF24) were evaluated for 45 assays of coagulation factor activities/antigens, clotting times, complement, markers of activation and chemistries. Moisture content of ODP was determined by coulometric Karl Fischer titration. Shelf-life study was conducted by pooling PF24 and manufacturing eight ODP units from each pool. Three pools were stored at each storage conditions (n=3 at each timepoint). Storage conditions include refrigeration, room temperature (RT), 30°C, 37°C excursion followed by RT, and -80°C excursion followed by RT. Mean percent change was calculated for ODP values at each timepoint and compared to the ODP at t=0.

Results: ODP characterization assays were within ±20% of the paired control or within clinical reference ranges for all assays except von Willebrand ristocetin cofactor activity (vWF:RCo) and C5a. Comparability of ODP vWF adhesion function to fresh frozen plasma was demonstrated through a Bioflux microfluidic platelet adhesion assay as well as C5a values that were within ranges reported for apheresis plasma. Mean rehydration time was 4 minutes 39 seconds (SD=0.75, n=184) for initial studies and further optimization of rehydration method resulted in a mean of 2 minutes 48 seconds (n=21). Moisture content of ODP at t=0 was 1.46% (n=20) and maintained ≤1.58% through storage at 1-6°C for 2 years and at 20-25°C for 1 year. After 24 months refrigerated storage, ODP was ± 25% compared to t=0 or within the normal reference range for all test parameters except thrombin anti-thrombin (TAT) and prothrombin fragment 1.2 (PF1+2). Six months RT storage studies demonstrated that ODP was within ± 25% compared to t=0 or within the normal reference range for all test parameters except aPTT and PF1+2. PF1+2 shows increase over time and similar levels are observed in both ODP and its paired frozen control over shelf life. ODP stored at 37°C for 24 hours + RT for 3 months and at -80°C for 24 hours + RT for 3 months were within ± 25% compared to t=0 or within the normal reference range for all test parameters. Storage at 30°C for 3 months demonstrates ODP is ± 25% compared to t=0 or within the normal reference range for all test parameters except aPTT, TT, FVIII, and vWF:RCo.

Conclusion: ODP is comparable to PF24 plasma and has similar levels of coagulation factor activities, clotting times, balance of pro- and anticoagulation factor activities, markers of activation, and chemistries. Shelf-life studies demonstrate stability of ODP with mean values comparable to t=0 units with respect to coagulation profiles when stored at 24 months at refrigeration, 6 months at RT, 3 months at 30°C, and 3 months at RT following a high and low excursion. Additional studies are planned to extend the RT shelf-life to 12 months. A Phase 1 Clinical Safety study is currently ongoing.