Quantitative Risk assessment of product disulfide bond reduction in a recombinant protein manufacturing

Abstract

Disulfide bond reduction occurred now and then during a recombinant\nprotein manufacturing. Their reduction often led in the loss of batches.\nVarious prevention measures were developed. Their implementation in a\nmanufacturing inevitably increases its operation complexity and even\nmight impact its product qualities and process performances. It is\nhighly desirable to apply a reduction measure only if necessary and to\napply no strong measure if a moderate one works. The reduction\noccurrence is determined both by the reduction sensitivity of a\nrecombinant molecule and by the reduction power of harvested cell\nculture fluids. The reduction power of harvested cell culture fluids\nvaries largely and depends on cells, lysis level, growth stage, and\nculture conditions. The method of the quantitative risk assessment of\ndisulfide bond reduction was reported here. The quantitative assessment\nis realized by comparing the reduction sensitivity of a recombinant\nmolecule with the reduction power of its harvested cell culture fluid.