Validation Studies in European Blood Centers To Evaluate Processing Whole-Blood-Derived or Apheresis Plasma Using the INTERCEPT Blood System Intended for Commercialization.

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 ~10,000 I-FFP units by processing ~250 mL whole blood-derived (WB) or apheresis (APH) plasma units using a prototype PCT system. In these trials, I-FFP effectively supported 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 APH plasma (Blood2004;104:746a) and, as reported here, in WB plasma. Methods: Whole blood and/or APH plasma units were collected at 3 European blood centers. Three-unit pools (~600 mL) of WB plasma were prepared. APH plasma (~600 mL) was collected using Autopheresis C (Baxter) or MCS+(Haemonetics) devices. Blood bank personnel processed a total of 60 WB 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 III (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 and stored at ≤−70°C. Retention of activity is expressed as the proportion (%) of pre-treatment (baseline) activity remaining after PCT. Results: Retention of coagulation factor activity in WB 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 (Table). Retention of activity in I-FFP prepared with the commercial PCT system was similar to that of I-FFP prepared with the clinical prototype. Conclusion: The PCT system intended for commercialization provides multiple I-FFP doses with a single PCT process. Retention of coagulation factor activity in WB and APH plasma processed with the commercial PCT system was similar to that of I-FFP used in Phase 3 trials to effectively support patients with congenital and acquired coagulopathies or TTP. Retention of Coagulation Factor Activity in I-FFP