Abstract:

Continuous integrated manufacturing of monoclonal antibodies is a new paradigm that is being considered not only to decrease capital and operating costs but mainly to improve product quality and facilitate regulatory issues. With reference to a specific commercial mAb, we analyze a few steady state runs where all steps (perfusion, capture and polishing) are integrated and operated as a single unit. The use of simulation models to keep the various units within specifications while reducing production costs is discussed.

We show that, as expected, the final protein quality is different compared to state-of-the-art batch processing. The lower residence time in the bioreactor and the higher loading in the multi-column capture step lead to post-Protein A pools with more uniform product quality. Hence the performance of subsequent polishing steps is improved. Additionally, it is shown that continuous process polishing with the MCSGP technology overcomes the purity-yield tradeoff of classical batch chromatography. All these aspects contribute to make integrated continuous manufacturing more efficient in terms of productivity, yield and product quality then the current batch technologies. This conclusion is discussed quantitatively by comparing product quality (i.e. glycoforms, charge isoforms, aggregates and fragments) in continuous integrated and classical batch production units, measured, in both cases, after the bioreactor, the capture and the polishing steps.

Biography:

Massimo Morbidelli received his Laurea in Chemical Engineering at the Politecnico di Milano in 1977, and his PhD in Chemical Engineering at the University of Notre Dame in 1986. After his first appointments as professor at the University of Cagliari (Italy) and then at the Politecnico di Milano, he is, since 1997, Professor of Chemical Reaction Engineering at the Institute for Chemical and Bioengineering at ETH Zurich (Switzerland).

His main research interests are in chemical reaction engineering, with particular emphasis on polymer reactions and colloidal engineering. This has evolved over the years in developing new processes for the production of polymer particles, ranging from the micro to the nano scale, exhibiting various types of functionalities and physico-chemical characteristics, including bio compatibility and degradation kinetics. Applications in various areas are considered including drug delivery, composite materials and treatment of oil reservoirs. Massimo Morbidelli is co-author of more than 600 papers, 11 international patents and four books. He serves as an associate editor of the ACS journal of Industrial & Engineering Chemistry Research, and is a member of the scientific board of several international scientific journals. He is the recipient of the 2005 R.H. Wilhelm Award in Chemical Reaction Engineering of the American Institute of Chemical Engineers and of the 2014 Gerhard Damköhler-Medaille of DECHEMA.and VDI-GVC.

Massimo Morbidelli is a cofounder of ChromaCon Ltd., a spin-off company from his research group. Since 2007, ChromaCon Ltd. brings new chromatographic processes (MCSGP-technology) for the purification of proteins and peptides to the market.