Design of a filter train for precipitate removal in monoclonal antibody downstream processing.
Protein A chromatography has become widely established for the preparative purification of mAbs (monoclonal antibodies). Low pH elution from Protein A columns followed by neutralization can often lead to precipitation of impurities in the product stream, leading to a visually turbid solution. Pretreatment of the cell culture harvest stream with an increased surface area of the depth filter was found to reduce the magnitude of this problem through exploitation of the adsorptive properties of harvest depth filters. However, this was not a complete solution. Clarification of this turbid product stream prior to the polishing chromatographic steps in the downstream process posed significant filtration challenges. Development of a staged filtration process with the use of low plugging glass fibre depth filters as the first stage prior to membrane filtration through an absolute pore size membrane is described. Finally, a cost calculation is used to drive the selection of the final filter train for this application. The results presented here are expected to have wide applicability in mAb downstream processing as well as for other turbid solutions encountered in the downstream processing of other biomolecules.
Kandula
Sunitha
S
Manufacturing Sciences, Bristol-Myers Squibb Co., Syracuse, NY 13221, USA.
Babu
Sudha
S
Jin
Mi
M
Shukla
Abhinav A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification* / Q000378:metabolism; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D011232:Chemical Precipitation; D002846:Chromatography, Affinity / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D005374:Filtration / Q000191:economics / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D013205:Staphylococcal Protein A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D013205:Staphylococcal Protein A