Over the last fifteen years, monoclonal antibodies (mAbs) have dominated the market but, today, alternative antibody formats are coming through company pipelines, including mAb fragments, single-chain fragment antibodies, and modified antibodies, such as antibody drug conjugates (ADCs), engineered antibodies and bi-specific antibodies.
For conventional mAbs, pharma companies tended to have one platform process for all (or the majority of) products. But these same platforms are not optimized, or simply do not work, for other antibody formats. In short, manufacturers are facing significant challenges. For example, for mAbs production, protein A was used as capture chromatography resin in purification platforms, as it interacts with the FC part of a mAb, but what about antibody fragments? Well, fragments lack the FC part, so there is no interaction with protein A! To capture mAb fragments, there has been a need for innovative chromatographic media, such as Protein L, which binds to a different part. To that end, we launched our protein L resin (Toyopearl AF-rProtein L-650F) to help manufacturers adapt to newer antibody formats coming through pipelines.
Feedback from our customers about our protein L resin has been very positive. For instance, Dr Michael Davids, CEO of Davids Biotechnologie GmbH, said: “Toyopearl AF-rProteinL-650F is an innovative and very useful chromatographic resin in my purification toolbox, as it allows capture of multiple antibody types. It is the resin I’ve been expecting for many years.”
From the data produced in our lab, we know that our protein L resin has the highest dynamic binding capacity and highest alkaline stability compared with other protein L resins on the market. Many of our customers are now scaling up their protein L processes.
Initially, the focus was on antibody fragments, but there is also a growing trend towards ADCs. The hydrophobicity of ADCs is dependent on the number of payload molecules linked to the antibody; hydrophobic interaction chromatography (HIC) allows manufacturers to separate ADCs with different drug to antibody ratios, using those differences in hydrophobicity. Tosoh has historically been very strong in HIC media and so we’ve done a lot of application work in this area. One of our most recent application notes shared tips and tricks on how to separate different drug to antibody ratios using our existing hydrophobic interaction resins (1). We are continuously working on additions to our HIC toolbox, both for resins and analytical columns.
Working together
One of the biggest challenges for everyone in biopharma is that the industry is very slow to change. Developing a new biopharmaceutical takes years, and once completed, companies prefer not to replace it unless there is a very good reason to do so! And this is something we take to heart at Tosoh: we have a very strong commitment to continue producing and supplying established products for a very long time. Our customers don’t want to wake up one morning and realize that Tosoh has suddenly stopped producing a material that is essential to their process and product! For example, the on-going expansion of production capacity by 50 percent is part of this commitment.
In the same way, close cooperation with the biopharma industry is crucial for us when we want to develop new prototypes or products, and we are always talking with companies to find out what innovations they would like to see, both in terms of the near and long term. Current buzzwords in downstream processing are “single-use technology” and “continuous production”. Continuous technologies offer the potential for using smaller volumes of highly efficient resins and getting more productivity out of the resin – a win-win situation.
It’s clear there is an exciting future for the industry; biopharmaceuticals are becoming more advanced, manufacturing methods are improving, and there is also the advent of cell and gene therapy medicines that could completely change how patients are treated. But we need to work on development timelines. It can take in excess of 10 years for a product to go from idea to market. Surely this can be reduced if regulators, manufacturers, resin vendors and other suppliers work together to optimize bioprocessing.
Patrick Endres is Senior Laboratory Specialist at Tosoh Bioscience, Germany.
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