Although it is a cliché to describe an industry as having reached a turning point or a crossroads, the description is very apt in the context of biomanufacturing. We are literally poised on the brink of revolutionary change, driven by the current limitations of downstream processing combined with the twin demand for low costs and high productivity, and in an economic climate where many companies are considering transferring their manufacturing overseas.
It is also clear that downstream processing technology needs to adapt to both the increasing diversity of upstream production platforms (e.g., not only microbes and mammalian cells but also plant cells, leaves, seeds, milk, hens’ eggs), and the changing economic landscape as the industry matures and more biopharmaceuticals come off patent.
The age of generic biopharmaceuticals is already upon us and manufacturing technologies will need to adapt to this new paradigm. Furthermore, providing generic biopharmaceuticals in developing countries will require manufacturing on a scale never envisaged before, which will make downstream processing an even greater challenge.
In the past, success was based on capacity, and the ability either to invest in new pilot facilities or to outsource the manufacturing to contract manufacturing organizations. In the future, success will be based on flexibility, as more products are approved, some in response to a huge demand (particularly in developing countries) and some for niche markets. Companies that can develop and deploy innovative upstream and downstream processes, and that can switch from product to product rapidly, will rise to the top level of the industry in the decades to come.
For this reason, disposable manufacturing using processes assembled from ready-made and prevalidated modules is going to be an important industry driver in the coming years. Disposable modules provide an excellent example of a truly disruptive technology.
First appearing in niche markets such as syringe filters and spin columns used in the laboratory, the idea of “going disposable” has crept stealthily toward the production plant, first through the introduction of filter modules containing stacked filter pads in a sealed plastic housing, then disposable media and buffer bags, and more recently disposable bioreactors and membrane adsorbers for chromatography.
Although arguably more expensive in terms of operational costs over a product lifetime, disposable modules save a fortune in up-front investment costs and also have a much smaller footprint than their fixed, stainless steel counterparts, therefore reducing the space needed for buffer storage and preparation.
Disposables also save a biomanufacturing resource that is potentially even more important than raw costs, i.e., time. With prevalidated modules there is no cleaning or steaming, no validation of cleaning routines, and no process downtime while the equipment is cleaned in place.
Production can be scaled up simply by swapping to a larger module, exhausted modules can be replaced quickly without interrupting the rest of the process, and switching to a new product no longer requires extensive cleaning and validation to prevent carryover.
Perhaps most importantly, a cleanroom environment can be quickly adapted to suit any process by assembling the necessary modules in the correct order, and process development can be accelerated by testing different components in a plug-and-play approach.
Last but not least, the ability to build processing infrastructure from prevalidated components makes one of our greatest dreams possible—the construction of inexpensive processing facilities in developing countries allowing the production of good-quality pharmaceuticals in the region for the region, thus improving the health and economic welfare of the world’s poorest people.
In my vision of the future of biopharmaceutical processing, I see this as the greatest potential achievement of all.