Focusing just on the manufacturing element, the ideal approach would be to have stockpiles of product (a good example in the
pandemic is Tamiflu), but in reality, unless we have a clearly identified threat, it is difficult to stockpile. For a generalized
response, therefore, we are looking at two options:
1. Modular deployable manufacturing units. This assumes that we can quickly mobilize and send these to the areas where manufacturing
is needed most. This approach may be flawed on two counts, however. First, to run any form of biomanufacturing operation requires
skilled people, and in such a situation they would not be readily available. Second, there are likely to be restrictions on
movement between countries during a pandemic.
2. Strategic manufacturing locations. By having established operations strategically located, it should be possible to respond
effectively to an emergency once the manufacturing process has been defined.
The ability to establish strategic manufacturing capacity and redeploy it for use by the government is not new. What is new is the potential offered by disposables technologies to make this much easier. To understand why, let's consider some
of the issues that make it difficult to reconfigure a traditional facility:
- integrated pipework and building
- clean-in-place (CIP) and steam-in-place (SIP) systems
- associated utility infrastructure
Several of these issues are linked. For example, reusable equipment requires cleaning, sanitization, and sterilization between
uses, and this requires a lot of piping and infrastructure, which then requires automation. CIP drives the requirement for
high quality water (up to 80% of water for injection is used for cleaning).5 The promise of disposable manufacturing is that by making the processing equipment and flow paths single-use, a lot of the
complexity disappears because the building is effectively decoupled from the process. The implications of this are significant:
- Processes can be built up from stand-alone modules that can be reconfigured easily.
- Processes are physically independent of the buildings in which they take place, thereby allowing the deployment of a process
within any simple building structure.
- A process can be upgraded and potentially scaled up with little disruption. For example, if you were using a 1,000-L bioreactor
and you wanted to upgrade to 2,000 L, the larger bioreactor could be tested and validated off line and quickly moved in when
Such a setup allows for a facility to be reconfigured for a new manufacturing process quickly—within 2 to 3 months. In addition,
a facility can be designed to include cheap "fallow" space that could be quickly configured to provide new cleanrooms for
a disposable manufacturing system (in 6 to 9 months) This then would allow a staged response to any emergency.
We are now in a fortunate situation where a number of suppliers are committed to establishing a disposable manufacturing line
that could support the idea of rapid response manufacturing. Listed below are some of the leading companies who are active
in this area, along with their main product line that would aid rapid response:
Figure 1. An artist rendering of Xcellerex's modular FlexFactory system.
- GE Healthcare, ReadyToProcess
- Millipore, Mobius
- Xcellerex, FlexFactory.
The companies' approaches vary. For example, Xcellerex provides each piece of equipment within its own process environment
(Figure 1), thereby offering the potential of running a process in controlled-not-classified space. GE Healthcare and Millipore,
in turn, offer solutions built around modules (Figure 2) that sit in a cleanroom environment.
Figure 2. Millipore Mobius manufacturing modules.
The issues with these approaches are maturity and scale, although now with the advent of the 2,000-L disposable bioreactor,
there is the option to use multiple bioreactors to achieve the desired capacity. The benefits of this approach are significant
in terms of flexibility, speed of response, and cost. Xcellerex, for example, says that a greenfield site can be established
in 12 to 18 months from start to operation and it would cost 50% less than a reusable facility.6