Innovative biologics, including cell therapeutics, VLPs, exosomes, recombinant proteins, peptides etc. seem to substitute monoclonal antibodies as the main therapeutic entities in manufacturing over the next decades. This molecular variety causes a growing need for a general change of methods as well as mindset in the process development stage as there are no platform processes available like for mabs.
Moreover, market competitiveness demands hyper-intensified processes, including accelerated decisions toward batch- or continuous operation of dedicated modular plant concepts. This indicates gaps in process comprehension, when operation windows need to be run at the edges of optimization.
In this trainings course potential methods are demonstrated for possible solutions throughout the workflow from process development over piloting towards manufacturing operation from process engineering point of view and experience. Especially, the state-of-art for modelling in biologics manufacturing is assessed, clarifying differences and application of statistical, rigorous physical-chemical based models as well as cost modelling. “Digital-twins” are described and efforts vs. benefits for new applications exemplified including the regulatory demanded QbD-(quality by design) and PAT-(process analytical technology)-approaches towards digitalization or industry 4.0 based on advanced process control strategies. Finally, an analysis of obstacles and possible solutions for any successful and efficient industrialization of innovative methods from process development over piloting towards manufacturing, operation, robustness, and analysis results in some recommendations. A central question is exemplified: Under the mindset of QbD and PAT demanded by authorities since 2004, could any biologics manufacturing process be regulatory approved without being modelled by a digital-twin as part of the filing documentation?
Scientists and technicians, involved in process development, should be familiar with the way, how Downstream Processing Sequences are efficiently transferred from preparative into pilot- and production-scale. Profound theoretical and experimental knowledge as well as comprehension of newest design methods will help to meet the time pressure and enormous experimental efforts in daily project work.