S61: Biosimilar MAb Production in Stainless Steel and Single-Use Bioreactors

Single-use bioreactors are gaining widespread acceptance in cGMP biologics manufacturing. Wave bioreactors are displacing older technology in seed train applications, and disposable stirred tank bioreactors of up to 2000L working volume are being used in pilot plants and manufacturing facilities. In this work, a Chinese hamster ovary (CHO) fed-batch process for production of a biosimilar monoclonal antibody (mAb) was transferred from conventional stainless steel (SS) at the 110L scale to a disposable stirred tank bioreactor (HyClone SUB) at the 250L scale. Cell growth kinetics, metabolite profiles, product titer, and product quality attributes (including mAb purity and glycoforms) were evaluated and compared for the two production bioreactors. Dynamic oxygen mass transfer (kLa) measurements were performed on the SUB to inform tech transfer and bioreactor scale-up. Although the bioreactors have different aspect ratios, impeller types, sparger designs and dissolved oxygen control strategies, our results demonstrate that with appropriate selection of engineering parameters single-use bioreactors can yield mAb product that is comparable in quantity and quality to product from conventional stainless steel bioreactors.  The resulting cell culture process, however, will not be equivalent in detail when executed in a SUB versus a conventional SS bioreactor.