The high cost of Protein A affinity resins has been an object of discussion for many years. The contribution to cost of goods in regular production, where resins are typically used for over one hundred cycles, is generally accepted because it only adds up to a small fraction of the manufacturing cost. However in clinical production, where resins are typically used for only a few cycles, the high resin cost becomes very significant. One way to address this would be to use a less expensive resin for early clinical production and switch to an alkaline stable Protein A when (if) the drug candidate is entering Phase III and regular production.<br/>Looking at the purification performance of Protein A resins, differences are mainly a function of the type of base matrix or immobilization chemistry used, rather than the type of Protein A. In this study we have compared native Protein A (rSPA), with a Protein A modified for improved alkaline stability. Both Protein A ligands have been immobilized to the same type of agarose matrix. The idea was to design an inexpensive efficient resin for early clinical manufacturing where columns are rarely used for more than 10 cycles and where the inherent alkaline stability of rSPA is sufficient for efficient cleaning and sanitization using 0.1-0.5 M NaOH for up to 20 cycles. The second, alkaline stable Protein A resin, is designed for regular manufacturing and will withstand use for several hundreds of purification cycles.<br/>The achieved dynamic binding capacities range from 40-60 mg hIgG/ml resin at residence times of 4-6 minutes. Purification data such as host cell protein content, DNA levels, and Protein A has been assayed to compare the agarose based, Protein A resins.<br/>In addition application data from novel Protein A prototype resins with capacities over 90 g/l will be shown and discussed.<br/>

Bringing down the cost of MAb purification with novel resin designs

253rd National Meeting (2017)

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