The biopharmaceutical industry represents over a $200 billion market globally. With the global market expected to double over the next 10 years, the expansion rate of biopharmaceutical manufacturing capabilities and capacities represents an inevitable bottleneck both for clinical development and commercial production. To eliminate this bottleneck, innovative technologies must emerge and evolve in step with the increasing demand for biopharmaceutical products.
But the biopharmaceutical upstream and downstream processing has remained largely unchanged for decades, as industry leaders have adopted similar manufacturing processes, irrespective of cost, to enable speed to market, to capitalize on industry knowledge of equipment and processes, and to ensure regulatory compliance.
This stagnation is predominantly due to:
The establishment of large, capital-intensive manufacturing plants
The reliance on conventional industry knowledge and technology
The inability to adopt disruptive change amidst regulatory guidelines and R&D inertia
Traditionally, the innovation in large biopharma has been defined solely as the ability to modify existing equipment or processes to make incremental advances toward cost reduction, higher purity, and increased throughput. In efforts to spur innovation in biopharmaceutical manufacturing, the FDA has been urging a gradual transition from batch to continuous manufacturing capabilities for biologics through establishing the Emerging Technology Program to promote technology innovation and industry modernization.
While continuous manufacturing affords smaller process equipment, a more streamlined and controllable process, and an overall cost decrease in terms of both CapEx and OpEx; in practice, large biopharma companies are again trying to capitalize on their existing infrastructure through making modifications to existing equipment and processes (e.g. column switching purifications) to achieve semi-continuous processing.
Single-Use technologies do not solve the problem
The predominant current strategy to enable cost reduction in biopharmaceutical manufacturing is to transition toward single-use technologies. The current thinking is that single-use technologies, in combination with semi-continuous processing, will offer a means of cost reduction, however, adopting these technologies for such a large global market will ultimately have a profound negative impact on the environment whilst only yielding marginal cost reduction.
To move the needle on cost and ultimately realize the benefits of continuous manufacturing, there is an urgent need to innovate upstream and downstream processing technologies to support the emerging trends and evolving demands of the biologics and biosimilar industry.
Design Limitations of
Current Plants Lead to Uncertainty
High initial capital outlays amidst regulatory uncertainty leads to prohibitively expensive projects
Variable parameters for a typical conventional manufacturing facility
$500 – 1,000 MM
Cost to construct a conventional state-of-the-art manufacturing facility
3 – 5 years
Time to construct a conventional state-of-the-art manufacturing facility
These economic decisions are confounded by the fact that investment decisions must be made fairly early in product development when there are still significant technical, clinical, and regulatory risks associated with drug development, and the probability of the product successfully reaching the market is still low.
If too much in-house capacity is built, the company will be left with an underutilized asset and suffer the consequences of the high opportunity costs of resources that could have been better utilized elsewhere
If insufficient capacity is available when needed, the company may experience delays in advancing a product candidate through clinic trials or lose substantial revenue due to the inability to meet market demand