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Continuous Downstream Processing of Bioproducts

Periodic Reporting for period 1 - CODOBIO (Continuous Downstream Processing of Bioproducts)

Reporting period: 2019-02-01 to 2021-01-31

Bio-industry is defined as an “industry that makes use of biotechnology and other advanced life science methodologies in the creation or alteration of life forms or processes” with the aim to produce bioproducts for various applications, such as pharmaceuticals, nutraceuticals, cosmeceuticals, industrial enzymes or similar. The bio-industry is a major source of growth for Europe and a major employer.
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
CODOBIO is training the next generation of researchers for biotechnology and advanced life science for bioproducts and various applications in pharmaceuticals, nutraceuticals, cosmeceuticals, industrial enzymes or similar. Early stage researchers in the project participated in extensive training sessions on the Basics of Bioprocess Engineering, Unit Operations for Continuous Downstream Processing and their Mathematical Modelling as well as Process Control and Monitoring for Continuous Processes. Those trainings were accompanied by soft skill trainings for Scientific Communication, Scientific Ethics and Scientific Writing as well as trainings on Project Management and Entrepreneurship. Training in both scientific and accompanying soft skills will enable the next generation of researchers to be successful in their academic or industrial careers and CODOBIO provides highly competent research personnel.
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.
CODOBIO already provided new methodologies with a potential to transform the market of continuously produced biologics, with the development and presentation of new technologies, like fiber based continuous purification, alternative purification strategies using precipitation or extraction. These new technologies are accompanied by already published new methodologies for process decisions based on economic and environmental modelling as well as model characterization of chromatography, and the modelling and simulation of complete integrated processes and model description of upscale and downscaling. The work done currently on microfluidic devices, will provide methodologies to accelerate process development in industry and academia significantly.
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.