Monoclonal Antibodies Production Platforms: An Opportunity Study of a Non‐Protein‐A Chromatographic Platform Based on Process Economics

Abstract

Monoclonal antibodies currently dominate the biopharmaceutical market with growing sales having reached 80 billion USD in 2016. As most top-selling mAbs are approaching the end of their patent life, biopharmaceutical companies compete fiercely in the biosimilars market. These two factors present a strong motivation for alternative process strategies and process optimization. In this work a novel purification strategy for monoclonal antibodies comprising phenylboronic acid multimodal chromatography for capture followed by polishing by ion-exchange monolithic chromatography and packed bed hydrophobic interaction chromatography is presented and compared to the traditional protein-A-based process. Although the capital investment is similar for both processes, the operation cost is 20% lower for the novel strategy. This study shows that the new process is worthwhile investing in and could present a viable alternative to the platform process used by most industrial players.

Economic Analysis of Batch and Continuous Biopharmaceutical Antibody Production: a Review

“…Instead of converting the traditional batch downstream process operations to continuous process operations, some other researches invest their research on alternative batch operations. For example, Grilo et al [69] suggested a novel downstream purification processing that uses phenylboronate multimodal chromatography followed by monolithic AEX chromatography and packed bed HIC. The researchers built two integrated mAb production line with the same perfusion upstream and two different downstream processes by using SuperPro Designer software.…”

Optimization of Vapor Diffusion Conditions for Anti-CD20 Crystallization and Scale-Up to Meso Batch

“…It is mostly used in autoimmune diseases therapy and it is effective against CD20-expressing non-Hodgkin's lymphoma, although it is not curative [18]. Similarly to other antibodies, the high production costs of anti-CD20 ($4000/g) [21] are mainly due to the usage of traditional purification methods such as protein-A chromatography, which is very effective in mAb recovery but very expensive due to the high cost of protein-A [22,23]. Conversely, crystallization is more cost-effective because it does not require expensive chemicals, while keeping the same purity level of chromatography [24].…”

Optimizing the Performance of Chromatographic Separations Using Microfluidics: Multiplexed and Quantitative Screening of Ligands and Target Molecules

“…The drawbacks of these bioaffinity ligands (e.g., protein A, G, or L) have been widely discussed and are due to their intrinsic economical and performance limitations. In this context, novel synthetic ligands have been receiving increasing attention as cost‐effective alternatives to be integrated into the downstream processing of mAbs or other biopharmaceuticals …”