2013 Volume 25 Issue 145 Pages 179-198
Since its inception in 1975, primary focus of JCR was the isolation and purification of proteins from natural sources, e.g. human urine, blood and milk. JCR succeeded in industrial production of highly purified human-derived bioactive substances such as urokinase which to date are sold commercially in Japan. In the 80s, although R&D efforts resulted in the several new drug application (NDA) filings, all of them were rejected due to concerns about “unknown infectious agents” in human-origin proteins or use of animal-derived ingredients by the influence of the report concerning CJD or other infectious diseases. In such circumstances, we redirected our R&D strategy to recombinant DNA technology. Combination of our experience in protein purification and directions to eliminate risk associated with the use of human/animal derivatives to research for intensive and patient screening of master cells with high-productivity of recombinant human erythropoietin (EPO) which grow in suspension without animal serum led to the successful establishment of our current platform “serum-free” technology and development of without the use of animal-derived ingredients. Most important effort was to find out the master cell producing the extreme similar EPO with similar carbohydrate chain structure and similar biological activity among the above cells. After evaluating our EPO (JR-013) through CMC and non-clinical comparative studies with the innovator products, epoetin α and β which to be find highly similar with each other, we conducted clinical studies, including comparative PK study against epoetin α, pivotal double-blind comparative study against epoetin α and long-term study of one year. Once the similarities were confirmed, we filed NDA. It was only after our filing that the Japanese guidelines for biosimilar were released. Because the contents of these guidelines encompassed all the studies which we had conducted for JR-013 development, we received the marketing approval of epoetin kappa (INN) as a biosimilar product in January, 2010.
