Rising to the challenge in biotechnology, 3M explains more

Mark Kelly, business development manager for the Separation and Purification Sciences division at 3M Ireland, reflects on some of the challenges facing the biotechnology industry, and explains how the science-based technology company is rising to them.

The biopharmaceutical industry is always striving to make process improvements, which come in many forms. Recent improvements in the upstream process have led to higher product concentrations, which are associated with higher cell densities.

All of this is positive news. However, it also means higher levels of soluble impurities within the harvested cell culture fluid. As a result, this leads to challenges in the downstream process, particularly the primary capture and polishing steps.

Mammalian cell culture

Mammalian cell culture is typically clarified in one of two main ways to enable further downstream purification.

The first is clarification based on density, methods of which include centrifugation, which employs centrifugal force to reduce the time taken for particles, such as cells and cellular debris, to settle out of the cell culture fluid. The second is tortuous path traversal, or depth filtration, which results in particles being retained within the filter media as they flow through a tortuous path.

Neither approach has much impact on reducing soluble impurities. Therefore, 3M developed an alternative technology, which uses charge to clarify the cell culture fluid, the 3M Emphaze AEX Hybrid Purifier.

Chromatographic clarification

The single-use chromatographic clarification product consists of a quaternary amine functional nonwoven, which provides a high anion exchange capacity, as well as a mechanical sieving of large debris, and a fine particle and bioburden reduction membrane. As a result, the hybrid purifier removes negatively-charged soluble impurities, such as host cell DNA and negatively-charged host cell proteins, early on in the purification process. This, in turn, can help address turbidity problems at various points in the downstream process.

Removing these soluble impurities at this stage in the process may also enhance the purification performance of the Protein A affinity chromatography step, which, in turn, may assist in the downsizing of anion exchange polishing steps.

To further investigate the product’s potential, the National Institute for Bioprocessing Research and Training (NIBRT) was commissioned to conduct in-depth research into the hybrid purifier.

Collaborative project

The collaborative project involves two studies, each being performed independently by NIBRT at its global centre of excellence for training and research in bioprocessing in Dublin, Ireland.

The first study began in January and is on track for completion later this year, examining the effect of chromatographic clarification on host cell DNA and the specific type and quantity of host cell proteins removed prior to downstream processing. The second study will run later in 2017. It will investigate gains in performance from optimising the load conditions for the product.

This research is aimed at qualifying and quantifying the impact that the 3M Emphaze AEX Hybrid Purifier will have on the downstream process, in terms of complexity and cost. The results are expected to be published early next year.