Abstracts

Introduction: INTERCEPT plasma (I-FFP) for transfusion is prepared with a photochemical treatment (PCT) system using amotosalen (S-59) and long-wavelength UVA light to inactivate a broad spectrum of blood-borne pathogens. For Phase 3 clinical trials, 6 US blood centers prepared an inventory of approximately 10,000 I-FFP units by processing ~250 mL whole blood (WB)-derived or apheresis (APH) plasma units using a prototype PCT system. I-FFP had sufficient retention of coagulation factor activity for support of patients with congenital and acquired coagulopathies or TTP. The prototype PCT system has been modified to treat up to 635 mL of plasma in a single PCT process, yielding up to three ~200 mL doses while maintaining pathogen inactivation efficacy. This modified PCT system intended for commercialization was evaluated in process validation studies in 3 European blood centers under routine operating conditions. After processing with the commercial PCT system, the effect on coagulation factor activity and retention was assessed in apheresis plasma (ASH, 2004) and recently in WB-derived plasma.
Methods: WB and/or apheresis plasma units were collected at the 3 European blood centers. Three-unit pools (~600 mL) of WB-derived plasma were prepared. Apheresis plasma (~600 mL) was collected using Autopheresis C (Baxter Transfusion Therapies) or Haemonetics MCS+ devices. Blood bank personnel processed a total of 60 WB-derived plasma pools and 90 APH plasma units using the commercial PCT system. Baseline and I-FFP plasma samples were collected, frozen below -60°C, and sent to Cerus for assay of factors I (fibrinogen), II, V, VII, VIII, IX, X, XI, and XIII, proteins C (PC) and S (PS), and antithrombin (AT). Alpha-2 antiplasmin (AP) was assayed by a reference laboratory. Comparative data from a representative subset of I‑FFP units prepared for the Phase 3 trials using the prototype PCT system were obtained from samples collected during PCT processing.
Results: Retention of coagulation factor activity in WB-derived and APH I-FFP prepared with the commercial PCT system (Comm) was 73-76% of baseline fibrinogen and FVIII activity, and 80-97% of baseline for factors II, V, VII, IX, X, XI, XIII, PC, PS, AT, and AP. Retention of activity is expressed as a proportion (%) of pre-treatment (baseline) activity remaining after PCT.
Conclusion: Retention of coagulation factor activity in WB-derived and APH plasma processed with the commercial PCT system was similar to that of I-FFP used in clinical trials that demonstrated sufficient levels of coagulation factor activity for treatment of congenital and acquired coagulopathies and TTP. The PCT system intended for commercialization provides multiple I-FFP doses with a single PCT process.