"By 2016, six out of ten of the blockbusters will be monoclonal-antibody-based therapeutics. With patent protection ending on many of these blockbusters by 2020 and this market estimated to be worth $100 billion a year, it is clear why developing biosimilars is attractive,” stated Stuart Melville, purification team leader at Eden Biodesign.
Speaking at the recent “Future Technologies in Downstream Processing” conference at the Stevenage Bioscience Catalyst, Melville added, “Biosimilars also have a shorter development cycle. To develop an innovative biologic, it costs in the region of $800 million and can take around 10 years, whereas for biosimilars it costs around $100–150 million and takes approximately eight years because you can bypass the Phase II dosing range studies.
“However, it is a very competitive marketplace, and Teva and Lonza have already halted their rituximab biosimilar development, so looking at areas such as cost reductions in manufacturing and ways to differentiate your biosimilar other than on price is imperative.”
The difficulty with manufacturing a mAb therapeutic is that the molecule has huge complexity with over 100 million variations of the IgG, and finding the most effective clone that can generate antibodies cost-effectively is challenging.
To reduce manufacturing costs, during upstream processing the focus is on optimizing clone selection and bioprocess conditions, but there is also a need to look at how to maximize antibody yield from the clarification, purification, and polishing steps in the downstream processing phase of production.
New technologies are being used in the initial stage of the downstream process to help overcome process bottlenecks and drive down cost-of-goods (COG) of mAb therapeutics.
Aloke Dey-Chowdhury, senior technical specialist at Pall Life Sciences, discussed the Cadence™ single pass tangential flow filtration (TFF) system, which showed that by using a Cadence module with a flow path equivalent to six TFF cassettes in series, 100 L of bioprocess liquid containing a mAb could be concentrated in-line, reducing the overall step processing time from 18 to 11 hours.
“Eliminating the requirement for recirculation associated with conventional batch TFF allows for continuous in-line concentration and is how we can achieve six hours process time savings,” Dey-Chowdhury explained. “With single pass TFF the concentration process is a function of the flow path and not of time, and so depends on how many cassettes are in the flow path.