Thinking about ways in which to improve the output of the manufacture of biologics has often led the pharma industry to look to other industries. The continuous process that was developed in the car manufacturing industry, as an example, provided a model where production could be streamlined through the use of automation and the harnessing of technological developments.
For the pharma industry, elements of this process were possible – with perfusion bioreactors able to be used for continuous cell culture and production formation. However, true continuous bioprocessing has proved difficult to achieve.
State backed development
The US National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) is aiming to address this through Project Call 5.2. The latest part of this strategy sees funding of $15.8m (€15.81m) provided into 14 projects looking to improve on technology and workforce developments, with the stated goal of “addressing key opportunities for innovation.”
Of those technology projects, three of the nine are focused on developing continuous and automated solutions for bioprocessing. This followed similar efforts by the organization in 2021, when it concentrated on COVID-19-related projects but also provided funding to work on continuous bioprocessing.
The latest projects include the University of Massachusetts working alongside Whirlcell, Yokogawa Corporation of America, and Pfizer to develop and validate a mammalian cell culture system with an integrated continuous upstream processing platform. Another proposal sees Rutgers University combining with the University of Delaware, Agilent, Endress + Hauser Optical Analysis to create an online sampling processes analytical technology (PAT) to enable continuous monoclonal antibody (mAb) manufacturing processes.
The push by the US for progress to be made on continuous manufacture was also strengthened last year when US Congress approved the “National Centers of Excellence in Advanced and Continuous Pharmaceutical Manufacturing Act of 2021.”
This Act was passed with the intention to set up centers for excellence in continuous manufacturing at universities across the country. The US government provided $100m to support the effort and called on the Food and Drug Administration (FDA) “to craft a national framework for advanced and continuous pharmaceutical manufacturing, including workforce development, standardization, and collaboration with manufacturers.”
Why the push?
There are numerous benefits to adopting continuous processes, which is why the technology has been talked about for years within the context of the pharma industry. One report stated that manufacturing costs could be lowered by 60%, reduction in buffer use of 30-50% could be achieved, and facility footprints could be brought down by 50-70%.
One of the major reservations has been the cost of setup and integrating continuous approaches into existing systems. However, recent research from the University College London and the Centre for Process Innovation concluded that single-use continuous bioprocessing would have cost advantage over stainless steel batch plants. This same analysis found the major cost advantage was found at smaller scales, which fits into the overall trend seen across the industry where bioreactor sizes are dropping and production is occurring often at smaller scales.