Wednesday, November 11, 2009 - 9:00 AM
S33

Large scale saline fermentation process for providing clinical supply of proteasome inhibitor NPI-0052

Ray Lam, Vice President Microbiology and Industrial Fermentation, Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, CA 92121

Marine microorganisms have become an important source of pharmaceutically active natural products.  The saline fermentation process poses a major challenge in scale-up since the stainless steel fermentors commonly found in manufacturing facilities are not resistant to the saline media, therefore, hindering the development of biologically active natural products produced by marine microorganisms.  NPI-0052 is a novel, potent proteasome inhibitor isolated from the culture broth of marine actinomycete, Salinispora tropica.  It is currently undergoing clinical studies for the treatment of patients with various cancers.  At Nereus Pharmaceuticals, we developed protocols to minimize the corrosive effect of saline media on stainless steel fermentors that resulted in the production titers of NPI-0052 as high as 300 mg/L in commercial production fermentors.  The clinical supply of NPI-0052 is currently manufactured under cGMP through a robust saline fermentation process, which represents the first production of pharmaceutical by a marine microorganism via saline fermentation.