Future Downstream Processing
Technologies that will increase overall process efficiency and enable fewer process steps to ultimately reduce cost and project timelines will have the largest impact on the industry. Many agree that the downstream-processing bottleneck will not be overcome by gradual improvement, but via disruptive innovation.
There are many new technologies being explored in the industry, but it is unclear which ones will stand out. “Candidates include optimization of aqueous two-phase systems/crystallization; adoption of alternative chromatographic separations (expanded bed, simulated moving bed, nonaffinity, nonprotein A ligands); and further integration of nonconventional continuous matrix supports (monoliths or membrane absorbers),” Dr. Lias from Eden Biodesign said.
Over the past two years, Cobra has been performing feasibility programs for the integration of disposable technologies into existing in-house platform processes, the cGMP facility, and the quality systems, so that it is ready to meet the ever increasing needs of its customers.
“The introduction of completely disposable flow paths fitted to operational control hardware (i.e., bioreactors, pumping systems, filtration, and chromatography systems) will reduce the requirement for cleaning and validation activities and should, as such, confer an increased safety assurance level to the industry,” Smith said.
“The implementation of new technologies in manufacturing is mainly driven by economic aspects,” according to Dr. Brecht. “Therefore, relevant technologies that make processes more efficient and/or reduce process steps will be implemented in manufacturing, for instance, mixed-mode resins, high-capacity materials for purification, and disposables.”
It is essential that these new technologies have been established in process development, Dr. Brecht noted. “All manufacturing operations have to be established already during process development and be scaled up for production. We are addressing this challenge by having a tight cooperation between our process-development and manufacturing team.”
Disposable membranes may play an increasing role in purification. Laureate Pharma has already made disposable membrane filters for flow-through steps such as ion-exchange, part of its standard process for downstream antibody purification.
“The use of disposable membrane filters avoids the need to pack and qualify columns, speeding turn-around time. The flow properties of the membranes also allow faster processing than columns,” said Dr. Ultee.
“These large disposable membrane columns increase speed, as well as flow rate,” Prof. Wagner added. “To improve downstream performance, many manufacturers are increasingly focusing on improvements to reliability and consistency of their production.
“Many of these changes will be initiated in the process-development area rather than in commercial production. There are a number of Protein A column alternatives in development that promise to perform better, use higher pH, are more durable and cleanable, yet have similar efficiency and better binding capacity. These factors will be critical in the future.”