This improvement was achieved mainly through the introduction of products allowing significantly shorter residence time at similar or higher binding capacity than previous generations of chromatography resins (Figure 2). Factors contributing to these improvements have been seen in the media for growth and the production phase, feed composition and strategy, process control and design, and host-cell engineering.ĭuring the same period, purification by chromatography has improved its productivity by a factor of 10–20. At the same time, manufacturers observe new challenges, resulting from the increased generation of antibody aggregates and increased presence of host-cell proteins from the high-producer cells used in such upgraded processes.įigure 1.Twenty years of development in mammalian cell culture have led to significant increases in product titres for monoclonal antibodies (MAbs), as a result of higher expression levels, faster process times, and higher cell densities. Recent reports from industry demonstrate that antibody titres higher than 1g/L are the rule, and 5 g/L readings are already on the horizon for processes currently under development. 1 This review describes a reference downstream process developed at GE Healthcare 2 and discusses technical and updated economical analysis of various process design options found in the literature and conference presentations.Īntibody titres in mammalian cell culture have improved one hundred fold over the last 20 years, mainly through the ability to grow higher cell numbers (~10 fold) and through increasing productivity of those cells (~10 fold) 3 (Figure 1). Major cost reductions have been reported through the use of platform technologies upstream, downstream, and with the portfolio of analytical assays used. Technology to manufacture high-dose therapeutic monoclonal antibodies (MAbs) at scale has evolved in several waves over the last two decades.
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