Labile Biologics - Stable Aqueous Formulation of Recombinant Factor VIII

Challenge

All marketed Factor VIII products are lyophilised preparations produced by either recombinant technology or purified from pooled plasma. The preparations are typically stabilised by addition of sugars. Administration of the lyophilised product is a very complex procedure involving a number of steps to reconstitute the product and maintain the sterility of the formulation. Administration is initially conducted in haemophilia centres, but once patients are capable of self-administration, and where practical considerations allow, the patient will self-administer at home.





 

 

Therefore, a strong need exists to provide an easy-to-use formulation of Factor VIII that does not rely upon reconstitution. A stable aqueous formulation of Factor VIII would allow the development of a convenient patient-ready pre-filled syringe, replacing the current powder formulations. The objective of this study was to demonstrate that a stable liquid formulation of Factor VIII can be developed using the ArestatT technology

ArestatT solution

Factor VIII was reformulated into a new liquid formulation, based on the principles of the ArestatT technology, using a reconstituted lyophilised Factor VIII product as the starting material. All key formulation parameters, such as osmolality, pH and surfactant were comparable in both formulations. The components of the stabilised formulation were selected to ensure a minimal rate of proton exchange at the protein surface and to control the interactions between the protein and metal ions. Factor VIII showed considerably improved retention of potency in the ArestatT formulation following storage at 25C and 2-8C compared with the formulation of the currently marketed product. Potency was measured by an APTT coagulation method and by a chromogenic assay.

Effect of ArestatT formulation on stability of aqueous Factor VIII during storage. Coagulation activity of FVIII was measured following incubation at 25C.

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