Evaluation of Stability of Sucrose – Formulated, Full-Length Rfviii for Use in Continuous Infusion Therapy

Abstract number: P1235

Uri M, Aaron L, Ilia T, Jacob L

Stability of a FVIII preparation in mini pumps is an important consideration for its use in a continuous infusion manner. Our goal was to evaluate the stability of recombinant FVIII (Kogenate® FS: KOGENATE® bayer) in two commonly used infusion mini pumps with and without anticoagulant additives that may be used in clinical practice to prevent local thrombophlebitis. Kogenate® FS(250 IU/vial and 1000 IU/vial) was reconstituted using aseptic technique according to the manufacturer's instructions with normal water for injection (100 IU/ml and 400 IU/ml, respectively): an additional dilution of 100 IU/ml was made from the 1000 IU/vial size. Reconstituted material with and without addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH: Enoxaparin/clexane) to a final concentration ~5 U/ml, was transferred to reservoirs of 2 mini pumps (Walkmed, Medfusion Inc., Duluth, GA and CADD, Deltec, Inc., St.paul, MN). All bags were stored at room temperature (22°C) for 7 days. Samples were drawn at baseline (immediately post reconstitution), 3 h, 6 h, 12 h, 24 h, and days 2–7, frozen at 30°C, and assayed for FVIII activity by one stage assay. On day 7, the residual volume of the mini pump containers was cultured for bacteria. All samples except one had FVIII activity >90% of baseline. Kogenate® Fs appears to retain excellent stability at room temperature during 7 days in both CADD and Walkmed infusion pumps with and without addition of UFH or LMWFH. No bacterial growth was observed. These results indicate that Kogenate® FS may be suitable for continuous infusion therapy. A study on continuous infusion of Kogenate® FS in surgery will be finalized by May this year.