High purity oritavancin and method of producing same

A method for preparing an oritavancin drug substance preparation, comprising:

• a) growing a culture of a chloroeremomycin-producing microorganism under fermentative conditions in a medium free of animal-sourced material (ASM) and under conditions promoting biosynthesis of chloroeremomycin by the culture,
• b) recovering chloroeremomycin from fermentation broth produced in a) using a polymeric exchange resin,
• c) decolorizing the chloroeremomycin recovered in b) using a polymeric adsorbent resin, chromatographically separating the decolorized chloroeremomycin using a hydrophobic polymeric resin column, and precipitating the separated chloroeremomycin using an organic solvent,
• d) preparing a solution of the precipitated chloroeremomycin of c) and a copper salt in an organic solvent, reacting the solution with 4-chloro-4′-biphenyl carboxaldehyde, and precipitating oritavancin-copper complex from the solution using acetonitrile,
• e) de-complexing copper from the oritavancin-copper complex of d) by adding an aqueous acid and separating the de-complexed oritavancin using a polymeric hydrophobic resin, wherein the adding and separating are performed concurrently or sequentially,
• f) eluting oritavancin from the polymeric hydrophobic resin of e),
• g) concentrating oritavancin eluted from the resin in f),
• h) precipitating oritavancin from the concentrate of g) in aqueous ethanol, and
• i) drying the precipitated oritavancin, thereby preparing an oritavancin drug sub stance preparation,
• wherein the oritavancin drug substance preparation has a maximum impurity level of not more than 3.0% by peak area of impurity 1 and impurity 7, defined by peak A of FIG. 1 and peak G of FIG. 2, respectively;
• or
• wherein the oritavancin drug substance preparation has about 85% purity or greater by peak area relative to impurities 1-16, defined by peak A of FIG. 1 and peaks B-P of FIG. 2, respectively.