"Oxygen carrier OXY-0301", our leading drug candidate, is categorized as "Blood derivatives" which are manufactured from donated blood. "Blood derivatives" is specified in biological product in the drug regulation and had a lot of problems that should have been cleared on our development process. We have made further improvements in its manufacturing process of OXY-0301 after much trial and error. Establishment of our liposome technology, which enables to encapsulate macromolecular substance, such as proteins, into liposome in high concentrations, has succeeded and it is quite unique compared to conventional liposome technology. We are convinced of great contribution through developing new medicine to society with this one and only liposome technology in the near future. GMP(Good Manufacturing Practice) facility has been constructed in Kyoto Research Center to manufacture OXY-0301 for upcoming clinical trials. As the center is the "Center" of our liposome technology, it is called our "Motherland". As for GMP facility itself, it is capable of manufacturing other protein-based liposomal drugs from our pipeline according to our business strategy. Hereafter, the outline of our manufacturing process will be explained as an example of the manufacturing process of "OXY-0301". [ process 1 ] Purification Purification of hemoglobin from RBC and virus removal The process starts washing Red Blood Cells from expired donated blood using physiological saline. Then, it goes to initial virus inactivation process, heat treatment. Our original know-how has been condensed to this washing method and virus inactivating technique including preparation of carbon monoxided hemoglobin(Hb) owing to protein protection from the heating step. Afterwards, the inactivated virus is removed with the nano filtration. These two steps, virus inactivation and its removal, will bring much higher safety on this developing product. After we enhanced technology, now it is capable of completing the process in a short time and purifying a large amount of hemoglobin efficiently. process 1 Purification of hemoglobin [ process 2 ] Manufacture of empty liposome Manufacturing of "Envelope" which will cover Hb Producing empty liposome, a covering portion of the component, is the next process. process 2 Manufacturing of empty liposome [ process 3 ] Hydration Encapsulation hemoglobin into liposome Liposome encapsulated hemoglobin is formed by stirring empty liposome and hemoglobin purified in process 1 in a proper way. process 3 Stirring process of hemoglobin with empty liposome [ process 4 ] Extrusion Size adjustment Size of this particle is prepared in its best and even way by extruder. This process used to be time consuming process and our bottle neck. We have achieved original know-how and skills, therefore we are now and ready to mass production. process 4 Extrusion [ process 5 ] Gas (carbon monoxide and oxygen) control Original technology for long term storage It is a process of removing the carbon monoxide bonded with the hemoglobin in process 1 for heat-treatment, and removing oxygen to prevent oxidation during storage. The processes hereafter are the most difficult and cutting-edged in the manufacturing of "OXY-0301". All steps has to be controlled under no oxygen condition. These technologies are the only one. process 5 Gas control [process 6 ] Filling and sealing Filling and sealing under extremely low oxygen condition After nitrogen is blown in isolator, this environment can be nearly oxygen-free condition. Finally it is filled into a bottle and packed as a final product. process 6 Filling and packing under the oxygen-free condition