The IBET ACT Unit’s know-how in terms of biopharmaceuticals spans from the initial expression vector design and cell line establishment through all stages of process development and scale-up.
On the upstream bioprocessing, the ACT Unit is focused on devising strategies to control and optimize final product titer and quality. An array of different culture systems/platforms (mammalian, insect, transient and stable) is available, providing a landscape of possibilities for specific targets, challenges and product requirements. On the downstream bioprocessing, the ACT Unit is focused on innovative solutions, reducing manufacturing costs, increasing productivity, safety and efficacy.
The bioprocess cycle is finalized with extended expertise in (i) bioprocess monitoring tools and modelling approaches (e.g. mathematical models and 2D-fluorometry), (ii) functional genomic tools (e.g. transcriptomics, metabolomics and fluxomics), and (iii) analytical tools for product/cell characterization and quality control/assurance (e.g. mass spectrometry, tunable resistive pulse sensing and analytical size-exclusion chromatography) that can be performed at iBET’s GMP certified Analytical Services Unit and Mass Spectrometry Unit. Process scale-up can be performed from lab (250 mL to 5 L) to pre-clinical scales (2 L to 70 L scale), the latter performed at iBET’s Pilot Plant (2000 m2), an infrastructure that routinely supplies pre-clinical grade biopharmaceutical products (e.g. vaccines, mAbs and VLPs).
A crucial infrastructure of added value to Prometeus is the Protein Production Platform (PPP). The PPP main activities are recombinant protein production in several expression systems (e.g. E. coli, yeast, baculovirus-insect and mammalian cells), bioprocess development, scale-up, analytics for quality control/assurance, formulation and delivery.
IBET’s ACT Unit has been dedicating substantial effort in the development of new in vitro models for pre-clinical research (incl. toxicological assessment), the reason being the lack of efficient and cost-effective in vitro tools to predict pharmacokinetics and toxic reactions of new compounds at early stage of drug discovery. Biotransformation occurs mainly in the liver, after which hepatocyte-end products are transported to other organs, such as the brain.
ACT Unit has been working on new tools, with higher predictive power in terms of xenobiotic biotransformation than the currently available ones, using primary cultures of hepatocytes (rat and human origin) and differentiating human embryonic stem cells into functional hepatocyte-like cells. Training at ACTU and collaboration with Prometeus partners on specific/selected protein targets will be key to ensure ESRs and ERs have at the end of Prometeus project the needed skill set for membrane protein based drug design.