SBIR-STTR Award

Vestar proposes to develop the methods necessary to lyophilize liposome encapsulated hemoglobin (IEH). The methods and equipment utilized will be commensurate with large-scale lyophilization practices common to the pharmaceutical industry in full accordance with Good Manufacturing Practice (GMP) guidelines. Present practice in freeze-drying of liposomes centers on the use of disaccharides as a cryoprotectant. Initial work will focus on selecting the most suitable disaccharide in terms of maintaining the desirable liposomal properties of mean diameter, component chemical stability and hemoglobin encapsulation and suitability for injection in humans. Following, but to some extent in parallel with cryoprotectant selection work will emphasize cycle parameter identification using a shelf type lyophilizer. The controlling parameters of freezing rate, fill height, container selection, primary and secondary drying temperatures and pressures will be evaluated. Analytical comparison of pre-and post-lyophilization IEH will be done to demonstrate the effectiveness of the proposed cycle. Final tests will be done in Vestar's GMP aseptic filling and lyophilization complex utilizing sterile product to demonstrate post process sterility. No in-viva testing of LEH is planned.

Vestar proposes to continue the development work started in Phase I which established the technical feasibility of lyophilizing liposome encapsulated hemoglobin (LEH). This will be done utilizing essentially the same equipment, personnel, and facilities as in Phase I. Work will be centered on establishing acceptable excipient concentration ranges, defining freeze rate effects, selection of final lipid formulation, setting of product specifications, scale up of volume as required for in-vivo tests in small animals, and evaluation of product stability. This development activity will occur under GMP conditions when necessary, but the primary focus will be establishment of a lyophilized product as defined by existing analytical methods and evolving product specifications. Because of limited availability of raw recombinant hemoglobin (rHb), no large increase in experimental run volume is planned. That will be reserved for Phase III.

Keywords:
BLOOD SUBSTITUTE HEMOGLOBIN LIPOSOME LYOPHILIZATION