(427d) Development of a Continuous Crystallization Platform for Monoclonal Antibody (mAb) Purification

Monoclonal antibodies (mAbs) have emerged as powerful therapeutic agents with effective and targeted treatments in recent years. The downstream processing of mAbs traditionally relies on protein A chromatography followed by ion exchange or hydrophobic interaction chromatography for purification. Despite the high purification efficiency of protein A chromatography, additional steps are needed to meet biopharmaceutical standards such as stability and bioactivity. However, the growing demand for mAbs production coupled with the high cost of chromatography columns requires the exploration of more cost-effective and sustainable alternatives. Batch-to-continuous transition of biopharmaceuticals production is increasingly being developed and applied during the last decade to improve product quality attributes at a low manufacturing cost. This study focuses on the development of a continuous crystallization platform as a promising solution to address these challenges. The primary objective is to enhance purification efficiency while reducing operational costs and facility size. By leveraging continuous crystallization experiments, the research aims to optimize purification capabilities, improve yield, purity, and maintain biological activity.

Crystallization conditions will be presented for distinct mAbs across varying scales, ranging from microliters to five milliliters. This approach aims to fine-tune the crystallization process, ensuring optimal yields and purity of the target mAbs. Moreover, to comprehensively assess the quality and efficacy of the purified mAbs, analytical and biological characterization techniques has been established. These techniques play a critical role in evaluating critical quality attributes such as structural integrity, biological activity, and purity, thus guaranteeing compliance with regulatory standards for the final product. Furthermore, the implementation of continuous operation in the crystallization process holds significant promise. By utilizing the inherent slow kinetics of mAb crystallization, continuous operation offers notable advantages over traditional batch methods. By maintaining a consistent flow and reaction environment, continuous operation enhances productivity and efficiency, thereby streamlining the purification process and ultimately reducing operational costs.

The study also aims to achieve high yields of purified mAbs with minimal residual host cell proteins and DNA, while also seeking to mitigate the formation of mAb aggregates. Overall, this research holds promise in developing efficient and economically viable downstream processing strategies for mAbs, which are highly relevant to the biopharmaceutical market.