Interview Dr Marc Bisschops
Before the pandemic process intensification and continuous processing were already seen as a means to speed up manufacturing in pharma. "The pandemic has shown that we can produce a lot even faster, from proof-of-concept of a vaccine to final commercial production. Thanks to single use and process intensification," says Dr Marc Bisschops Vice President MSAT of Pall Corporation. “A holistic approach is important and not one solution fits all.”
Process intensification is about making the production process as compact as possible. It can contribute in driving down the footprint of biopharmaceutical manufacturing facilities. Single use means that everything that comes into contact with the product does not need to be cleaned and can be discarded after use. This makes the process faster, efficient and more flexible as no cleaning is required and safer because the risk of contamination can be significantly reduced. “However, there is a limit to the size of the batches,” says Bisschops.” In the past, you needed a bioreactor of 10,000 litres for 10 kilograms of protein, which is not realistic for a single use batch. Nowadays, we can make the same amount of product (monoclonal antibody) with much smaller bioreactors because of the improved higher expression levels of (cells that) produce antibodies. Single use devices can be made for that. Therefore process intensification and single use reinforce each other and need each other," says Bisschops.
High water and buffer consumption
"Many people focus on process intensification on the production itself such as the purification steps but lose sight of the fact that a lot of water and buffers are used Bisschops emphasises. A good example are perfusion bioreactors: more material can be produced with a smaller bioreactor. However 1 or 2 bioreactor volumes of growth medium flow through it every day. So after 30 days you need 30 to 60 times as much growth medium It makes sense to include this in the assessment of which solution makes most sense for a manufacturing process. Furthermore direct and indirect reduction in water consumption can contribute to sustainability.”
Extra data
People often do not realise that process intensification involves a lot of extra data. All these data that come out of the process has to be put in a report that has to be reviewed and approved. "For example, AstraZeneca developed the production process for its corona vaccine fairly quickly and set it up in various locations around the world, but the report approval process took a long time in many cases. This slowed down product release considerably and that's where improvements can be made. Continuous production also generates a lot of data. Rather than analysing all the data in a traditional way, we should consider review by exception data, so that we focus at data that doesn’t fall within the expectation pattern."
Scaling up production process
Astra Zeneca's corona vaccine, which was produced with an adenovector, required a large number of bioreactors. They dealt with this by building decentralised production sites in many different locations around the world, where the process was carried out in the same way everywhere. “This is only possible if your process is robust and standardised. Single use made this possible,” says Bisschops. Pall Corporation, together with a consortium of companies, contributed to the development of the production process by making choices that supported implementations across the globe.
Single Use proliferation
"People think: 'Nice and flexible, a single use device, we can have it designed exactly the way we want it'. That's true: nearly everything is possible, hoses and bags in all sizes, but a lot of manual work is involved in the assembly of it. This can create bottlenecks at our production location, resulting in longer delivery times. Standardisation does help to maintain quality and delivery times. So at Pall we try to standardise the supply chain for single use as much as possible."
Dr. Marc Bisschops gave this interview before his lecture at the Single-Use Event 2022