Continuous Manufacturing for Better Access: A Paradigm Shift in Biologics

Christelle Dagoneau, senior vice president, global biologics business development, Just–Evotec Biologics.

Christelle Dagoneau began by explaining Evotec’s focus on evolutionary technology. The company seeks out innovative and disruptive technologies and assembles teams to support integrated discovery, development, clinical, and commercial programs. The aim is to make decisions at the start of development that will increase clinical success rates. Evotec is headquartered in Hamburg, Germany, with 17 sites across the globe, mainly in Europe and the United States. With a diversified business model, the contract development and manufacturing organization (CDMO) also codevelops programs through pharmaceutical partnerships and investments into small companies. It develops what it calls “bridges” by partnering with academic laboratories to transfer results into commercial technology platforms.

Dagoneau highlighted four key areas in Evotec’s offerings: panomics (integration of complex -omics data sets for deeper analyses of systems biology), the company’s core induced pluripotent stem cell (iPSC) platform for cell therapy development, program integration from research and development (R&D) to manufacturing stages, and implementation of continuous processing. Following some examples about the first three areas, she focused on benefits of continuous processing from discovery to manufacturing and how it can be supported by artificial-intelligence and machine-learning–based platforms.

Evotec’s continuous processing platform supports clients from early- to late-stage clinical, commercial, and manufacturing activities with J.POD facilities: economical, small-footprint, and quickly deployable current good manufacturing practice (CGMP) biomanufacturing plants. They accommodate perfusion, intensified fed-batch, semicontinuous, and end-to-end continuous biomanufacturing processes. The facility can operate at a standard 500-L scale to deliver a few kilograms of drug substance for “first-in-human” (FiH) studies to metric tons of product for large commercial supply

With continuous perfusion cell culture, fresh media are added to the cells every day; spent media are removed, and the antibodies produced are sent directly into downstream steps. Dagoneau pointed out that this process achieves high productivity because the antibodies do not degrade in cell culture and have no opportunity to aggregate.

Operating continuous bioprocessing at a 500–1,000-L scale, the company can large amounts of antibodies, fusion proteins, and multispecifics. With automated processes at that small scale, relatively fewer people are needed to oversee the equipment and conduct the processes. Reducing human errors in the small-scale design also improves success rates along with reducing the carbon footprint of a facility.

Dagoneau’s slides showed case studies of how continuous biomanufacturing outperformed fed-batch processes. She explained how a J.POD facility can (for example) run six trains/bioreactors as separate manufacturing slots, all using the same scales and equipment in the same configuration. So the company has the flexibility to choose whether to manufacture for clinical or commercial scale. She described how manufacturing can be scaled up from one slot/train for a 15-day, 500-L clinical supply, and then how other dedicated lines can be set up to address pressing needs for commercial supply (such as in response to a pandemic).

Because the continuous process is highly automated and productive, requires fewer operators, and is much smaller than a standard 20,000-L stainless-steel facility, it drives both process efficiency and cost reduction. Evotec’s goal is to get to US$50/per gram of protein produced, and despite development issues still to be worked though, the company believes that such a goal is achievable.

Dagoneau explained how the company partners with biopharmaceutical developers to produce material for FiH trials — again, showing how such processes are enhanced by continuous processing. The company uses both proprietary and commercially available cell lines, but it uses its own media, which are engineered for cell growth and productivity.

She concluded by talking about a program still in development for helping companies analyze and resolve unanticipated challenges with addressing cost of goods sold (CoGS), productivity, or high demands for existing commercial products. She described a recent partnership with Sandoz, which is developing a similar facility design.

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