Quantitative Risk assessment of product disulfide bond reduction in a
recombinant protein manufacturing
Abstract
Disulfide bond reduction occurred now and then during a recombinant
protein manufacturing. Their reduction often led in the loss of batches.
Various prevention measures were developed. Their implementation in a
manufacturing inevitably increases its operation complexity and even
might impact its product qualities and process performances. For
monoclonal antibody, a decrease in main peak and an increase in acidic
peak were observed when air sparging, a reduction prevention measure,
was applied during a harvested cell culture fluid (HCCF) hold in the
literature (Mun et al., 2015) and in our lab and at-scale manufacturing.
The change in the filterability of HCCF was noticed as well in our lab
and at-scale manufacturing when air sparging or air overlay was applied.
It is highly desirable to apply a reduction measure only if necessary
and to apply no strong measure if a moderate one works. The reduction
occurrence is determined both by the reduction sensitivity of a
recombinant molecule and by the reduction power of HCCF. The reduction
power of HCCF varies largely and depends on cells, lysis level, growth
stage, and culture conditions. The method of the quantitative risk
assessment of disulfide bond reduction was reported here. The
quantitative assessment is realized by comparing the reduction
sensitivity of a recombinant molecule with the reduction power of its
HCCF.