(15c) Excipients Removal by Capto S Chromatography and UF/DF Process Development for High-Concentration Drug Substance Production

The scope of this work is two-fold: 1)  excipients removal from formulated  mAb drug substance by Capto S chromatography and 2) UF/DF process development to make high-concentration drug substance (DS)  for subcutaneous injection.  During process scale-up, the project team decided to make a high-concentration  mAb drug substance for subcutaneous injection and change the formulation. Since the pilot plants were not available for large-scale campaigns, a creative alternative was needed to produce 2 kg of antibody from formulated DS for these studies.  Fortunately, a sufficient supply of  formulated DS was available for reprocessing.  A Capto S column  was chosen over Protein A chromatography to remove excipients from formulated drug substance because of  its higher binding capacity.  In addition, Capto S has lower resin costs, takes less time to process, and uses milder elution conditions.   Analysis showed that the Capto S run removed the excipients with yields of  ≥ 96%.  During the UF/DF process,  the antibody was initially concentrated  to 90 g/L , diafiltered, and concentrated to ≥ 180 g/L, then the retentate was collected.    After the  retentate was collected, a minimal volume  of buffer was added for the UF rinse.  Most of the rinse was combined with the retentate to hit the target protein concentration.  UF/DF  yields of  92% have been obtained.    This  method enabled  > 90 % overall recovery of  unformulated DS at ≥ 150 g/L.