There are numerous challenges facing the biopharmaceutical industry that will require a combination of innovation, creativity and objective consideration to overcome within the next 5–10 years. The cost of existing and new biologic drugs continues to escalate, which is arguably reducing the market size because many payers either cannot or will not fund these increasingly expensive treatments. The cost:benefit calculation, in terms of life expectancy, is a harsh reality in first world markets — and it’s even more brutal in poorer countries.
To reduce the cost of biologics, such as monoclonal antibodies (mAbs) and other protein-based drugs, biopharma, including CDMOs, are looking to develop and adopt both upstream and downstream continuous manufacturing processes, thereby increasing yields through a combination of longer production run times, more stable and higher secreting cell lines and increased downstream yields at each stage of the purification processes.
The advanced — cell and gene — therapy industry, by comparison, is in its infancy and is facing similar price pressures to deliver powerful therapies while also dealing with a raft of different technical challenges to deliver treatments that are commercially viable. Although the production of viral vectors and allogeneic therapies bear a number of process similarities to “traditional” biologics manufacture, the challenge of consistently producing large quantities of GMP-grade vector remains problematic, whereas the technical issues associated with the development of allogeneic cell banks that result in high density and high viability cells upon thaw and expansion for each treatment, pose different but equally complex technical challenges.
Autologous therapy manufacturers face a new and entirely different set of challenges, as each treatment is unique. In the short- to mid-term at least, each patient donor will have been subjected to different treatment regimes, they will be suffering from different clinical diseases and they will be at differing stages of disease progression; and, as with all other treatments, each patient responds to treatment in a unique way.
For all cell-based therapies, the costs of the growth factors, cytokines and other essential media components necessary to isolate, engineer, expand and maintain the engineered cells in the required differentiated state are extremely high because these components are typically added as a bolus; there are currently no technologies to enable their addition “on demand” at different stages of the process.
New process control and analytical technologies, or “repurposed” existing technologies, need to be employed to help deliver these drugs and treatments at commercially viable price points. Like the treatments themselves, the answers are almost certainly going to lie in a combination of innovative thinking and the application of existing technologies for different applications from their original purpose. There is an undoubted need for real-time adaptive control — for both upstream and downstream processes — to enable the genuine, continuous production of biologics.
Adaptive control will be essential if we are to develop a robust and consistent platform process for the manufacture of autologous therapies at commercial scale; that is, adaptive control will be essential for the development of the autologous therapy closed system “Magic Box”.
One of the new technologies that has been demonstrated to enable rapid optimisation and ongoing adaptive control of the upstream nutrient feed for bioreactor processes is Stratophase’s Ranger. Ranger has the capability to provide dynamic adaptive control of either single or multiple nutrient feeds for bioreactor cultures based on the metabolic activity of the cells in the bioreactor, and it has the potential to provide the dynamic adaptive control necessary to establish a platform process for autologous therapy manufacture.
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