Late-Stage R&D and Bioproduction Unit

In the context of the EU-funded project DiViNe, the Late-Stage R&D and Bioproduction Team developed a bioprocess for gram-scale production of high-quality ligands/therapeutics.

Our work included the optimized production and purification of nanofitin-based ligands up to 30 L, focused on optimized feeding strategy, high-cell density culture and high-volumetric productivity. This approach yielded the gram-scale production of our ligand with high quality and purity. This work was developed in partnership with Affilogic (Chevrel et al., 2022).

Within the R&D projects in collaboration with Repligen (USA) and Cytiva (Sweden), iBET has implemented (i) a continuous integrated production, harvest, and clarification platform of AAVs using mammalian (HEK293) cells and transient transfection, and (ii) a continuous chromatography capture process for AAV.

The two applications developed hold the potential to further intensify (e.g. via high cell density cultures and continuous processing) the biomanufacturing of this relevant product for gene therapy applications (Mendes et al. Frontiers in Biotechnol Bioeng, 2022, Mendes et al. Pharmaceuticals, 2022).

iBET successfully scaled its rAAV manufacturing process to 50 L while maintaining efficiency and robustness.

Key improvements included an optimized clarification step and the addition of a polishing step, resulting in preparations with over 80% full rAAV particles. The process is broadly applicable to other rAAV serotypes, requiring only minor serotype-specific adjustments, and consistently meets regulatory standards with minimal impurities and high full capsid percentages (Nascimento et al. J Biotechnol, 2025).

iBET successfully developed and implemented GMP-compatible bioprocesses for two distinct products: an oncolytic virus and a new malaria vaccine candidate.

For the oncolytic virus program, our team completed upstream and downstream process development, with an increase in cell specific and volumetric productivity. The optimized manufacturing protocol was then scaled up and seamlessly transferred to GMP production, ensuring readiness for clinical manufacturing.

For the malaria vaccine program, we developed a robust, scalable and GMP-compliant process for manufacturing a new malaria vaccine candidate (recombinant PfRipr5 protein) and transferred the technology to GenIbet – ReciBioPharm for GMP production. This project was supported by the Japanese GHIT Fund, in which we partnered with the European Vaccine Initiative e.V. (Germany), Sumitomo Pharma Co., Ltd. (Japan) and Ehime University (Japan).