The INTERCEPT Blood System for Plasma: Process Validation Studies of Coagulation Factor Activity and Yield in Two European Blood Centers.

Introduction: INTERCEPT Plasma (I-FFP) is prepared as FFP for transfusion using photochemical treatment (PCT) with amotosalen HCl (S-59, 150 μM) and UVA light (3J/cm²) to inactivate a broad spectrum of blood-borne pathogens. Phase 3 clinical trials, supported with an inventory of > 19,000 I-FFP units processed in 200 mL/unit with a prototype set, demonstrated retention of coagulation factor activities and hemostatic function in I-FFP for support of patients with congenital and acquired coagulopathies or TTP. For commercial introduction, the clinical prototype I-FFP system has been improved to treat up to 650 mL of plasma in a single, less time-consuming, PCT process yielding up to three 200 mL I-FFP doses per PCT process. The effects of this modified process on coagulation factor activity and yield were evaluated in two European blood centers under routine operating conditions.

Methods: A total of 60 plasma units (approximately 600 mL/unit) were collected using the Autopheresis C device (Baxter-Fenwall) at Haukeland University Hospital and the Institute of Immunology and Transfusion Medicine, University of Lübeck. I-FFP units were prepared at each center by blood bank personnel using the improved set. Baseline and I-FFP samples were collected, frozen (<−60 °C) and sent to Cerus for assay of: Fibrinogen (F I), and Factors II, V, VII, VIII, IX, X, XI, XIII, proteins C (PC) and S (PS), and antithrombin (AT).α-2 antiplasmin (AP) was assayed in a reference laboratory.

Results: Fibrinogen (mg/dL) and coagulation factor activities (IU/dL) are expressed as the mean ±SD (Table). The post-PCT yield for each coagulation factor activity in I-FFP units prepared with the improved set (Improved) is expressed as a proportion (%) of total pre-treatment coagulation factor activity per FFP unit (Baseline). Comparative yield data for I-FFP used in Phase 3 studies (Prototype) were obtained by testing 275 plasma units randomly selected from 19,000 units prepared for use in clinical trials with the protype set at 6 U. S. blood centers.

Conclusions: I-FFP prepared with the improved system retained 78–79% of baseline Fibrinogen and FVIII activity, and 82%–95% of baseline Factors II, V, VII, IX, X, XI, XIII, PC, PS, AT, and AP. Clinical trials have shown that I-FFP provided sufficient levels of coagulation factor activities for treatment of congenital and acquired coagulopathies and for therapeutic plasma exchange of TTP. The improved set, intended for commercialization, provides multiple I-FFP doses with a single PCT process. Using the improved processing set, coagulation factor activities and yields were similar to those for I-FFP used in Phase 3 clinical trials.