Continuous mode production will come to dominate monoclonal antibody (mAb) drug manufacturing as the approach becomes a “platform” and more firms realize the cost benefits, says Suzanne Farid, PhD, professor of bioprocess systems engineering at University College London (UCL).
Biopharmaceutical industry use of continuous production processes is increasing thanks to both technology advances—notably automation—and continued regulatory support. The FDA, for example, has made continuous processing the center piece of its efforts to encourage industry to modernize, describing the switch from batch mode as “a challenging but worthwhile transition.”
For companies thinking of changing from batch to continuous mode one of the challenges is determining if the benefits outweigh the costs, says Farid.
“Companies need to consider when deciding whether to implement a continuous process establishing if there is a business case for it,” she says. “So, from a manufacturing perspective, are the investment, cost of goods (COGs), and facility footprint savings enough of a game-changer to justify the switch?”
It is also critical to consider the complete product lifecycle, according to Farid, who adds that firms should ask “do any cost of goods savings with continuous bioprocessing outweigh the higher upfront cost of development that comes with implementing new technologies?”
Farid and colleagues modeled the benefits and costs of continuous processes in a paper last month, revealing that technology choices depend on the nature and volume of the product being made.
“On the manufacturing cost front, we found that hybrid and end-to-end continuous facilities offer COG savings when at smaller commercial demands where single USP and DSP trains are required,” she tells GEN. “This is driven by the higher productivities and reduced facility footprints. At larger scales above one ton per year, the cost effectiveness of continuous manufacturing is reduced when parallel continuous trains are implemented, and the cost of media dominates the COG.
“We ran an array of scenarios representing different company situations in terms of scales of production, perfusion rate, volumetric productivity, and media costs and we illustrate how these impact the potential cost of goods savings and hence ranking of continuous versus batch processes.
“We used the analysis to identify the critical thresholds required to achieve a desired level of cost of goods savings and the jumps required to reach these targets. These can be used to prioritize process development efforts.”
The team also explored how the cost-benefit profile of continuous manufacturing is likely to change over time as the biopharmaceutical industry becomes more familiar with the approach.
“When continuous processes are considered new technologies, the analysis indicated that end‐to‐end continuous facilities may struggle to compete on development costs,” says Farid.
Yet, when taking the longer outlook across the project lifecycle, they can become more cost effective than stainless steel batch facilities when considering the total out‐of‐pocket cost across both drug development and commercial activities.
“Once platform continuous processes are established, we predicted that this would make continuous facilities more attractive than batch processes in scenarios where they currently cannot compete in terms of CMC development costs,” notes Farid.