(627a) On the Performance of Centrifuge-Free Primary Recovery of Monoclonal Antibodies

Primary recovery of therapeutic proteins from mammalian cell
culture remains one of the most challenging steps in downstream processing due
to ever increasing advances in upstream technology, leading to higher titers,
but also higher cell density and, oftentimes, lower viability.  One of the most
common techniques used to clarify cell culture is centrifugation followed by
depth filtration.  However, because of the large capital expenditure a
centrifuge requires, a disposable depth filtration train capable of handling
cell culture directly is an attractive alternative under some circumstances.  In
this work, the performance of depth filtration of mammalian cell culture
without centrifugation was evaluated.  Two different style depth filter trains
were used - a coarse train with a large pore size distribution for
non-centrifuged material, and a fine train with a smaller pore size
distribution for centrifuged material.  The different trains were evaluated
over numerous mammalian cell culture harvests of various monoclonal antibodies
(mAbs) for capacity and clarification of the feed stream.  As expected, the
direct filtration of mammalian cell culture resulted in lower capacity, as well
as greater sensitivity to variations in the cell culture.  However, centrifugation
itself was seen to have a clear impact on the filterability of the product
stream.  The selection of appropriate filter types to address these variations
will be discussed.