Last February BiosanaPharma received approval from the Australian Bellberry Human Research Ethics Committee to begin a Phase I clinical trial for a biosimilar version of omalizumab, the first monoclonal antibody (mAb) produced with a fully continuous biomanufacturing process. The trial consists of a bioequivalence double-blind, randomized, two-parallel-group study of a humanized anti-immunoglobulin E monoclonal antibody (BP001) as lyophilized powder formulation compared with the standard omalizumab lyophilized powder formulation, which has been marketed as Xolair® since 2006 by Roche/Genentech and Novartis, in healthy male volunteers.

Xolair, delivered via subcutaneous injection, is used to treat moderate to severe allergic asthma and chronic idiopathic urticaria in patients aged 12 years and above in the United States and the EU. Additionally, it is approved for pediatric patients aged 6–11 years in the EU. Meanwhile, the last patient has been dosed in this clinical trial; the full end report is expected Q1 2020.

During the recent Bioprocess International Conference in Boston, Maarten Pennings, CTO at BiosanaPharma, gave a presentation entitled: “Integrated Continuous Bioprocessing: A Small Company Approach for a Phase I Clinical Trial Material Manufacturing Case Study.” Pennings said the company chose this mAb because the molecule has a validated biomarker and because competition for this biosimilar molecule was still low.

Regarding why the company decided to go the continuous biomanufacturing route Pennings replied that BiosanaPharma wants to make antibodies more accessible as therapeutics. Lowering cost of goods by using continuous manufacturing is an essential part of the route to reach this goal, especially in the biosimilars area where price will become a distinguishing factor in the near future.

“Therapeutic mAbs have been on the market for over 20 years [rituximab became the first mAb approved for cancer therapy in November 1997].  This business is ready to go into a maturation phase where the cost of goods must come down,” Pennings explained. “If you look at other industries, the maturation level has several indicators. One is energy consumption per kilogram of product. There is also water consumption as well as chemical, labor, and wastage. Right now, the antibody industry is very inefficient.”

In general, he noted, continuous manufacturing is a great contributor to bringing down all of these costs so there was a natural fit for the technology to be brought into the manufacture of biosimilars.

“Our choice of manufacturing technology was not specifically based on omalizumab but for antibodies in general. Biosimilar mAbs are the most logical group to choose from because of expected price competition. We wanted to develop a production platform for antibodies and then go look for products that fit to validate the platform,” he said.

According to Pennings, the company’s 3C biomanufacturing platform offers high productivity, flexibility, and a small footprint (50m2) and is capable of making 1 kg of drug substance antibody per week at a 50 L bioreactor scale. Batch processing is made continuous with multicycle counter current operation.

The upstream process is based on high cell density continuous perfusion culturing with alternating bioreactor use (the company’s own IP) and the downstream process is based on simulated moving bed chromatography combined with flow-through adsorption. The process has GMP status. All steps run in parallel while compliant control and data acquisition is in place, pointed out Pennings.

“The main advantage is that it is one integrated, continuous process that has been designed to run for two months. Rather than having to start a process, go to some endpoint, and then harvest, we run everything continuously, so the daily routine becomes a totally different picture,” said Pennings. “We will be looking at indicators that show the quality of the process and the product. Our goal is to have an approach to biotech manufacturing that goes beyond the traditional process.”

“Smaller scale parallel processes running for longer can reduce the scaling costs associated with traditional operations,” notes Peter Levison, executive director, business development, Pall Biotech. “These really look to be the future for cost efficient commercial biomanufacturing.”

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