There is an increasing trend in the biopharmaceutical industry towards high protein concentration in commercial mAb formulations to achieve clinical efficacy and reduced drug volume for subcutaneous injection. The charge density of the solution increases as the protein is concentrated, which can create an offset in excipient levels and pH between the retentate protein solution and the permeate across a tangential flow membrane in an ultrafiltration/diafiltration process, a phenomenon which is known as the Donnan effect.  Donnan effect behavior was observed when performing UFDF step development using two different diafiltration buffers. Based on the observed shift in protein pool pH and excipient concentration, the compositions of buffers were adjusted to compensate for the Donnan Effect. Studies were performed using both the control process buffers and the modified buffers at challenge conditions. This study indicated that the modified buffers can compensate for the Donnan effect and ensure that the final pool pH and excipient concentration are reliably within their target ranges.<br/>

Evaluation of the donnan effect and a mitigation strategy in UFDF process development

2019 Spring National Meeting

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