Manufacturing Friendly Aggregate Clearance in Downstream Processing of Bispecific and Traditional Antibodies Using a Novel POROS Mixed-Mode Chromatography Media

Bispecific antibodies (BisAbs), which can bind to two distinct antigens, are prone to high levels of aggregate (10-30%), challenging traditional platform downstream processes and impacting product yields. Mixed-mode chromatography (MMC) presents a potential improved solution for aggregate control due to enhanced selectivity compared to traditional ion exchange and hydrophobic interaction chromatography resins.

In this webinar, results are shared from the evaluation and preliminary optimization of a MMC unit operation designed for aggregate removal in flow-through mode using a high-throughput POROS resin with immobilized caprylic acid. Monomer recovery and aggregate reduction were measured for various mobile phase conditions using a design of experiments (DoE) approach for two different BisAbs and a traditional monoclonal antibody (mAb), examining the impact of operating pH and arginine concentration. The results demonstrate that this resin offers an efficient, robust, and scalable method for aggregate control, providing a significant advantage over traditional resins.
Key Takeaways:

• High aggregate challenges for various molecular formats can be effectively addressed with the evaluated POROS™ mixed-mode chromatography resin.
• Variations in pH, salt concentration, arginine concentration, and load challenges can be adjusted to optimize yield and purity.
• Run in flow-through mode, Thermo Scientific™ POROS™ Caprylate Mixed-Mode Cation Exchange Chromatography Resin potentially allows for significant process efficiencies over traditional aggregate control methods.