With this month's column, we are introducing a new regular section dealing with the latest developments in disposable technology and, in particular, feedback from users about these developments. In putting this together, I will be helped by my colleague Miriam Monge, a well-known figure in the disposables business; she is also European chair of ISPE's Community of Practice for Disposable technologies.
CHANGING MABS MARKET MAKES DISPOSABLES USE MORE FEASIBLE
Much of the current clinical pipeline is geared toward monoclonal antibodies (MAbs) and the current trend is for smaller market-volume requirements for MAbs. When linked with increasing product titers, this trend puts many new manufacturing facilities well within the reach of disposable technologies. Johannes Roebers made this point in a recent talk, noting that annual product requirements of about 500 kg/year will become the norm.
1 As disposables become more and more integrated in our manufacturing facilities, it is interesting to assess the implications for both design and project management.
Implications for Facility Design and Project Management
If we consider a typical bulk MAb facility, designed to produce 500 kg/year with a titer of around 3 g/L and product recovery to bulk of about 60%, around 8,000 L of bioreactor capacity is needed.2 If processed as one batch, about 63,000 L of solutions are required for processing. At this scale, this facility is well within the comfort zone for using disposable technologies. Today, we would consider disposables for various unit operations in a plant, such as: production bioreactors (4 by 2,000 L or 8 by 1,000 L); depth filters for harvest; membrane chromatography for flow-through columns; process mixing; and product, media, and buffer hold and preparation.
So, what are the implications for facility design? One clue is given by the amount of water used for cleaning a stainless-steel facility, in which much of the complexity of facility design is driven by pipework for steam-in-place (SIP) and clean-in-place (CIP). For example, if our model 500 kg bulk MAb plant were a stainless-steel facility, 155,000 L of solutions would be required annually for cleaning. In a disposable facility, on the other hand, we can:
- remove most CIP systems, restricting their use to packaged equipment
- remove all CIP and SIP infrastructure
- remove the autoclave and wash-up areas
- remove process pipework between the unit operations by replacing it with physical movement and disposable tubing.
Figure 1 shows a development of these design concepts, published in 2004.3 The result of this level of integration is a building containing cleanrooms but little process infrastructure. The process is configured by setting up process operations in designated serviced work stations minimally equipped with power, data links, and gases. In this way, the operational space becomes flexible and easily reconfigurable. This kind of facility design has more in common with traditional manufacturing operations, focusing on optimizing material and people flows and giving serious consideration to lean approaches (e.g., reducing changeover times, inventories, and waste). In the building project, there is less emphasis on the process that will take place in it, because we have now effectively separated the process from the building. Against this backdrop, below are the key considerations when undertaking this type of a design project.
Figure 1. A disposable concept facility