As primary recovery TFF is a partial purification step, it aids in reducing the demand of host cell contaminant removal during
CEX chromatography. These two-step operations provide efficient purification fold. Primary recovery TFF with ~90% or above
process step recovery, along with CEX capture, were comparable to Protein A schemes in overall process recovery.
Assuming the polishing steps are similar for both CEX and affinity schemes, which is the case for HuMAbs, there are more cost
advantages for processing the same amount of HuMAbs for a nonaffinity scheme over a protein A scheme. By developing optimal
process conditions, the binding capacity of current leading cation exchange resins can reach several-fold over Protein A resins
(Table 1). With a much cleaner load on the cation exchange, the resin lifetime is well maintained to easily reach more than
100 cycles. Cation exchange capture also provides hidden advantages if there is a need to change the resin because of longer
schedule interruption during product campaigns or an unforeseen new resin need during storage in large-scale manufacturing.
An ion exchange purification process for HuMAbs provides an alternative approach to traditional Protein A schemes, and is
comparable in terms of process consistency, time, product recovery, and quality.
Capture load conditioning for cation exchange is performed by a TFF operation, which can provide several advantages, such
as batch volume reduction and partial purification. Furthermore, the TFF bulk provides a better environment and builds flexibility
as a process storage intermediate during manufacturing. Different process parameters that seem to influence the concentration
and diafiltraion stages of primary recovery are discussed to design efficient and scalable nonaffinity purification scheme
JUE (MICHELLE) WANG is senior manager, TIMOTHY DIEHL is a scientist, MARK WATKINS-FISCHL is a scientist, DEBORAH PERKINS is a scientist, and DEENA AGUIAR is a scientist, all of Purification Process Development, and ALAHARI ARUNAKUMARI is the senior director of Process Development, all at Medarex, Bloomsbury, NJ, 908.479.2451, firstname.lastname@example.org
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