The implementation of a platform purification process for therapeutic monoclonal antibody (MAb) products is highly desirable because it allows for rapid and cost-effective process development. A platform process often includes a viral filtration (VF) unit operation in order to provide sufficient viral clearance by the end of the manufacturing process. Virus filter performance, as characterized by flux and loading density (kg antibody/m<sup>2</sup>), was found to be inconsistent for certain MAbs despite feed material being processed by a similar platform purification process. A subset of therapeutic MAbs in pipeline development suffered from a severe flux decay and low throughput in spite of containing negligible HCP, DNA, and aggregate content.<br/>One root cause could be batch-to-batch variation in cell culture conditions resulting in variable product quality attributes; charge variants, glycosylation patterns, and hydrophobicity. Alternatively, operational parameters such as source and mode of flowrate, pH and conductivity could impact VF performance. A design of experiments (DOE) study was performed to investigate whether pH, ionic strength, protein concentration, and mode of operations could alleviate poor filter performance. Filtration performance outputs such flux decay, product-related impurity and step yield were monitored. Optimization of the various operating conditions led to the development of a robust viral filtration unit operation that fits within the platform purification process to manufacture clinical materials.

Optimization of process parameters for viral filtration of therapeutic monoclonal antibodies

253rd National Meeting (2017)

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