Periodic Reporting for period 1 - CODOBIO (Continuous Downstream Processing of Bioproducts)
Reporting period: 2019-02-01 to 2021-01-31
A major challenge for the bio-industry is to accelerate process development and reduce manufacturing costs, in particular for downstream processing (DSP), the purification of biomolecules, in order to speed up time to market. Especially for biopharmaceuticals, the path to market release is lengthy due to extended development times and the need for clinical studies. Moreover, for biopharmaceuticals a shorter time to market and lowered cost relates to a great health benefit for patients without medication either due to general unavailability or in less privileged countries.
Continuous manufacturing in the bio-industry offers new opportunities to increase productivity, reduce the environmental footprint, improve product quality and consistency and to drastically reduce the manufacturing costs to enable accessibility of biologics to a much wider population. The transfer to continuous manufacturing is crucial for cheap accessible biopharmaceuticals, but is still not state of the art in the industry, both to a lack of knowledge and implementation as well as lack of trained personnel capable of developing and implementing continuous manufacturing.
State-of-the-art and related challenges:
A manufacturing process in the bio-industry consists of upstream processing (cultivation of the cells in the bioreactor) and downstream processing (recovery of the product). Products usually undergo several purification steps, like chromatography steps, ultrafiltration / diafiltration and other conditioning steps. All these steps are performed in a batch-wise manner most often in a fixed time mode, with no or minimal digitalization or automation. Real-time in-process control is limited to control of pressure or flow rate or composition of buffers, but product quality or quantity are not analysed. In the last decade the regulatory framework has provided very clear guidelines that process characterization is ultimately governed by a “Quality by Design” (QbD) principle
This requires enhanced process understanding, scale-down tools, Process Analytical Technology (PAT) tools, multivariate data analysis, machine learning algorithms and control strategies to enable a shift from operating fixed processes to adjustable processes within a design space based on desired product quality and performance – this approach is a necessity for continuous processing and is novel in this industrial sector.
The main objective of the CODOBIO proposal is to deliver a new generation of creative, entrepreneurial, highly-skilled and innovative ESRs that are able to face the future transition challenges and to greatly contribute to the knowledge-based economy and digitized environment in manufacturing and society in general. In the proposed research programme, the most urgent questions in continuous downstream processing will be addressed:
- Process control and modelling of continuous downstream processes
- Miniaturization, scale-up and scale-down of continuous downstream processes
- Process design and development of integrated continuous downstream processes
Fulfillment of the first goals and respective deliverables of the project include the quantification of power input and energy dissipation in miniaturized systems as well as following an active dissemination and communication strategy through journal contributions, conference presentations and social media presenting the most important findings during the reporting period including Advanced control strategies for bioprocess chromatography, Miniaturization of Analytics in Continuous Bioprocessing, Fibrous Adsorbents as well as Extraction for Continuous Manufacturing, Characterization of the Residence Time Distribution in Continuous Systems, Trends for Biodegradable Plastics, Microfluidic Chromatography and other Microfluidic Devices including Miniaturized Sensors.
These excellent results will translate to future goals and objectives of the project for a fully characterized continuous integrated biomanufacturing with an emphasis on Process control and Modelling, Miniaturization, Scale-up and Scale-down and Process Design and Development.
Once training is complete, CODOBIO will provide excellently trained and experienced highly skilled researchers that are familiar with the manufacturing of biologics in general, and with continuous manufacturing in both scientific aspects as well as regulatory aspects and entrepreneurship and IP-management.
With the provision of technologies as well as providing the next generation of engineers in the field of continuous downstream processing, we expect strengthen the European innovation capacity both in industrial and academic institutions in Europe.