TransBIB scaling workshop: From the lab to the market - challenges and opportunities in bioprocess scale-up

The scaling of biotechnological processes is a key success factor for the bioeconomy - but in Germany it is associated with numerous hurdles. As part of a workshop organised by CLIB and BioCampus Straubing, challenges, solutions and future visions for a more efficient infrastructure were discussed. The current situation in Germany was analysed and ways for more effective scaling and better infrastructures were outlined.

Scaling up biotechnological processes in Germany poses considerable logistical and technical challenges. One key difficulty is that there is no universally applicable plant. In practice, transport steps are therefore often required between the process stages, for example between fermentation and downstream processing (DSP). Although smaller product streams in particular can be transported easily, their shelf life must be taken into account. Such transport routes often lead to a lower informative value, as they only reflect the subsequent commercial process to a limited extent. While laboratory and pilot processes usually run in a batch process with a separate DSP, large-scale commercial processes are usually continuous and integrated. Therefore, the scaling process should - ideally - also be continuous and integrated, but this is rarely feasible in reality.

Another important aspect is the customer's objective. Before scaling begins, it must be clear whether the aim is to produce samples or to collect reliable engineering data. This decision determines the required scope of work, the operation (e.g. 24/7 continuous operation) and the necessary process and system analyses. In addition, the planning of a production plant requires careful consideration of costs, technological maturity, market situation and competitive situation. There are also differences in the providers: Academic institutions and commercial contract manufacturing organisations (CMOs) offer different services, which is why the choice of the right partner depends heavily on the project objectives.

Special requirements also apply to different product groups. Greater modularisation and standardisation in early process development can also make scaling easier. However, although the use of automation and AI reduces labour requirements, it limits the flexibility of the systems and therefore makes it more difficult to scale a variety of processes. Start-ups in the field of proteins and food have a particularly high demand, but encounter few offers and high costs. Due to their low market price, polymers require large-scale production plants, for which specialised, specially developed demo plants are recommended. Similar requirements apply to commodities and fine chemicals, which require both chemical and biotechnological expertise. In the area of crop protection products, legal and safety aspects make co-operation with external suppliers difficult, so that in-house development of plants often appears to be the most sensible approach here too.

In Germany, there are currently various challenges in scaling up biotechnological processes. A gap in the supply of specialised engineering consulting is particularly evident. While start-ups often place too little value on reliable engineering data, a lot of knowledge is being lost at the same time as experienced scaling experts are leaving the labour market. This makes it more difficult to reliably plan and further develop processes. There are also limits at a technical level: standard processes can be scaled well in external systems, while special processes or products can usually only be realised in systems developed specifically for this purpose. In addition, the industry shows little willingness to share plants, as this is perceived as a loss of flexibility. New business models are therefore necessary in order to better utilise unused potential.

Various visions have been developed to overcome these deficits. For example, the targeted promotion of engineering consulting should start at the early development stages of bioprocesses. A personalised, company-independent pool of expertise could help to secure knowledge in the long term and make it available. It is equally important to consider scalability at an early stage of process development. This is where TransBIB wants to start in future with its own pool of expertise and the one-stop shop.

So-called multipurpose plants offer certain advantages when it comes to scaling up biotechnological processes, but their capacity utilisation and economic operation harbour risks. A promising approach could therefore be the spin-off of pilot plants that continue to be operated as contract development organisations (CDMO) after primary use by companies. Other options for future infrastructures could include maker spaces with basic equipment for start-ups. In addition, a knowledge hub would be conceivable, in which experienced plant personnel are combined with modular process units to support young companies in scaling up and at the same time avoid high investments in diverse plants.

In order for these ideas to be realised, a political course also needs to be set. Firstly, clear guidelines are needed on the areas in which German industry should play a part in global competition. Instead of a purely trend-driven development, a long-term political orientation would be helpful. Customised business ideas also require targeted start-up funding so that scaling infrastructures and networks can be created and become self-sustaining in the long term. The BMWE's current calls for proposals are already moving in a good direction here.

The financing of demonstration projects must also be made easier, as these are particularly costly. Reliable framework conditions are also crucial: a secure supply of biomass and the removal of regulatory hurdles would make the successful scaling of processes much easier.