RG3: Process Engineering for Biopharmaceuticals

RG3 integrates upstream and downstream processes using physico- and biomathematical tools to design processes for novel biopharmaceuticals. Simplicity, feasibility, transferability and economics are essential for such processes to translate to industrialization. RG3 bridges post-translational modified therapeutic proteins (eg. with Novartis) to vaccines (eg. with GSK) and viral vectors for gene therapy (eg. with Sanofi). Activities comprise the optimization of mammalian and insect cell expression systems, application of scale-down models for high-throughput screening, design of novel up- and down-stream integrated continuous bioprocesses, deployment of systems biology for increased process understanding, modelling towards biological and chemical process control, and scale-up for pre-clinical applications.

RG3 focuses on broaden and deepen bioprocess understanding to improve translational feasibility for biopharmaceuticals testing and production. In particular, i) knowledge systematization into mechanistic and hybrid models for different steps (cell growth, production, purification); ii) design and implementation of optimization strategies at the genetic, metabolic and process levels; iii) implementing systems for full bioprocess integration, monitoring and control of the different unit operations, from cloning to purified product.

One of the latest RG3 major contributions was creating new analytics for supporting bioprocess development: from thermal, structural and chemical stability of proteins to identifying individual viral proteins (hemagglutinins) in multivalent virus-like particles (VLP) influenza vaccines. New processes require ever more complex analytical tools for characterisation of the biopharmaceuticals produced in a data rich environment, essential to support robust translational implementation to the clinic.

RG3 supports activities in the TL2: Cardio-Metabolic Disorders and TL3: Cancer.

Keywords: Bioprocess understanding and engineering; Integrated continuous biomanufacturing; Vaccines; Gene therapy

Latest Publications

Charlton Hume HK, Vidigal J, Carrondo MJT, Middelberg APJ, Roldão A, Lua LHL (2019) Synthetic biology for bioengineering virus-like particle vaccines. Biotechnology and Bioengineering 116(4):919-935

Moleirinho MG, Silva RJS, Carrondo MJT, Alves PM, Peixoto C (2019) Exosome-based therapeutics: Purification using semi-continuous multi-column chromatography. Separation and Purification Technology 224:515-523

Carvalho SB, Silva RJS, Moreira AS, Cunha B, Clemente JJ, Alves PM, Carrondo MJT, Xenopoulos A, Peixoto C (2019) Efficient filtration strategies for the clarification of influenza virus-like particles derived from insect cells. Separation and Purification Technology 218:81-88

Carvalho SB, Silva RJS, Moleirinho MG, Cunha B, Moreira AS, Xenopoulos A, Alves PM, Carrondo MJT, Peixoto C (2019) Membrane-based approach for the downstream processing of influenza virus-like particles. Biotechnology Journal (in press)

Carvalho SB, Fortuna AR, Wolff M, Peixoto C, Alves PM, Reichl U, Carrondo MJT (2018) Purification of influenza virus-like particles using sulfated cellulose membrane adsorbers. Journal of Chemical Technology and Biotechnology 93(7):1988-1996