Nowadays the majority of downstream processes (DSP) for biopharmaceuticals are based on chromatographic separation techniques and platform technology. Model-based process understanding and optimization is a sensible and important addition to the exclusive use of platform processes. The integration of mechanistic modeling tools into process development is an essential part of the strategy for the implementation of Quality by Design approach (QbD). In addition, the inclusion of small scale experimental formats and high-throughput techniques is becoming more and more relevant in DSP. Until now these two approaches are used mostly independent of each other: Mechanistic modeling is applied solely in a single scale and high-throughput techniques e.g. in context of DoE. Here we present a systematical comparison of model calibration in ion exchange chromatography, on the basis of data collected from different chromatographic scales. The case study covers a range of experimental systems from commonly used lab scale (CV 16mL) and small scale (CV 1mL) columns, down to robotic high-throughput formats as 600µL RoboColumns (Atoll) and 20.8µL batch adsorption data. This equates to a scaling factor of about 770. We applied the scale invariant model parameters derived from one column scale for the prediction of the elution behavior on the other chromatographic scales. As case study we employed a Poros 50HS cation exchange resin and a monoclonal antibody and its aggregates in a bind-elute mode. The scalability of model parameters among different column scales has great implications for the prediction of production scale chromatography.

Scalability of mechanistic models for ion exchange chromatography

251st National Meeting (2016)

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