A cellulose adsorbent has been designed to operate in a rapid cycling chromatography mode, with each unit being cycled &gt;100 times in a single working shift. The result is a unit that can be sized such that its lifetime (in terms of cycles) can be exhausted over the batch, with the aim of making single-use operation economically feasible. This gives rise to a new high productivity industrial chromatography technology that can purify 100’s g/L/h mAb, using Protein A and IEX chromatography units that scale directly from process development (PD) to production.<br/><br/>The case study presented covers early stage process development of a three step purification isolating an industrially relevant mAb from CCCF. High throughput PD scale screening was carried out, where process conditions are evaluated. The value that sub second residence times impart upon building process understanding within a matter of hours is demonstrated; with full DoE runs carried out on ProA capture and IEX steps. The 2 min cycle time allows for repeat runs to give confidence in the data. Finally, cycling and process stability data for the chosen performance conditions is transferred to large scale devices to demonstrate direct scalability. Product quality at both scales is analyzed in terms of purity, yield & titre and shown to meet the expected requirements e.g. 3 log reduction in HCP, &lt;10 ppm ProA leaching.<br/><br/>The units can be used at clinical scale in a cost-efficient manner with full utilization of the chromatographic lifetime with a high degree of process robustness having completed scalable PD studies in a fraction of the usual time. Additionally they can be scaled such that production feed material can be processed in a significantly shorter amount of time, this flexibility enables the end-user to choose a processing strategy that best fits their specific needs, or the changing needs of the product throughout its lifecycle. The ability to handle different processing flowrates without affecting the product quality offers a potential for integrated continuous processing with the coupling of independent unit operations.

Implementation of directly scalable single-use protein A chromatography for rapid processing from bench to industrial processing

255th National Meeting (2018)

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