In-Vitro Stability of B-Domain Deleted Recombinant Factor VIII in Syringe-Based Continuous Infusion Devices.

Continuous infusion (CI) factor VIII (FVIII) replacement is commonly used for serious bleeds in patients with FVIII deficiency. Clinicians lack stability information for Refacto®, a B-domain deleted recombinant FVIII (BDDrFVIII), when it is diluted or stored in CI devices for extended time periods. We studied BDDrFVIII to determine its concentration- and time-dependent stability and sterility when stored (reconstituted; reconstituted then diluted with normal saline) at ambient temperature in syringe-based CI devices (CADD-Micro^TM; Baxter Colleague^TM). Three replicates of BDDrFVIII 125unit/mL and 25unit/mL admixtures were admixed aseptically then placed in CI devices that operated continuously for 48 hours. Samples (0.5ml) were obtained from control solutions (stored in the manufacturer’s glass vial) or expressed from the distal end of tubing at Hour −0.25 (priming volume), 0, 1, 2, 4, 8, 12, 24 and 48. Samples were stored at −70C until assayed for Factor VIII activity using a 1-stage automated assay and Refacto® [chromogenic equivalent] Standard. Results of FVIII assays for each trio of replicates were averaged. BDDrFVIII admixtures were considered stable if they retained ≥80% baseline (control) FVIII values. Recoveries for BDDrFVIII 125unit/mL admixtures remained stable and sterile for 48 hours when stored in the manufacturer’s glass vial, Baxter Colleague^TM or CADD Micro^TM devices, sufficient for clinical use (Table). BDDrFVIII, when diluted to 25unit/mL, remained sterile but not stable when stored in Baxter Colleague^TM or CADD Micro^TM devices, and is not recommended for CI in clinical settings. Loss of FVIII activity in BDDrFVIII 25unit/mL admixtures is thought to be due to binding of BDDrFVIII to device components.

%FVIII Activity of BDDrFVIII Stored in Infusion Devices