MEDICAL BIOTECHNOLOGY / Biotherapeutic Products
Development of biotherapeutic products.
Description of Research
The Biotechnology Development Unit (BDU) focuses on the development of technologies for the production of biotherapeutic products. The aim is to increase the know-how and capabilities of the pharmaceutical industries in ICGEB Member States by transferring technologies for the production and quality control of biopharmaceuticals from lab to pilot scale for Erythropoietin (EPO), Interferon alpha 2a and 2b (IFN alpha 2), Interferon beta 1b, Granulocyte Colony Stimulating Factor (G-CSF), Insulin, Growth Hormone. The Group has also developed PEGylation technologies for IFN, GCSF and EPO as well as fatty acids-protein conjugation technologies for long-lasting insulins. The availability of such scientific support represents a significant incentive for the development of biosimilars locally and internationally, and for accelerating the biopharma ecosystems in emerging markets.
The lab’s procedures can be adapted to the conditions existing in Member States with a financial investment necessary to set-up the production facilities. The transfer of these technologies involves the training of scientists from pharmaceutical companies for periods of four to five weeks. During this time, they learn the manipulation of recombinant strains, practice the downstream process and perform quality control procedures in accordance with the guidelines of the European Pharmacopoeia.
Over the past few years, the Group has trained more than 100 scientists from 19 different ICGEB Member States. Most of these companies are now producing biosimilars using our technologies. Not only are these products sold on the local markets, they successfully compete on the international market.
Current research in the Group focuses on process development for production of GLP-1 receptor agonist Liraglutide, soluble TNF receptor fusion protein Etanercept and antibody fragment Certolizumab pegol.
Finally, we have set up a research project aimed to study miRNAs able to enhance production of recombinant proteins of pharmaceutical interest in CHO cells.
During 2021, in order to meet the growing demand for distance learning, the BDU designed online training modules that cover the entire production process, from the cell to the purified product. This rich video-based platform can deliver training effectively everywhere, as an alternative to standard in-house training. The BDU signed several technical assistance agreements for the production of insulin, based on this video training. In the course of 2021, the ICGEB has created a new pharma-compliant facility for the development of biosimilars. The BDU is now intensively developing the structure and documentation for a Good Manufacturing Practice (GMP)-certified Quality Control laboratory, including the implementation of an Electronic Lab Notebook for easy lab data management in a GLP/GMP-compliant manner. The new facility will help to continue supporting the global harmonization of quality specifications for biologics. This expansion will also allow the development of similar antibody- based therapeutics. A key focus is the development of technologies for the production of the monoclonal antibodies trastuzumab and tocilizumab, for the treatment of breast cancer and arthritis, respectively. Furthermore, in response to the coronavirus pandemic, the BDU has prepared stably transfected CHO cell lines for the production of the spike protein, as well as a SIP recombinant antibody for serology testing SARS-CoV-2.
Sreejith Rajasekharan, Rafaela Milan Bonotto, Yvette Kazungu, Lais Nascimento Alves, Monica Poggianella, Pamela Martinez Orellana, Natasa Skoko, Sulena Polez, Alessandro Marcello (2020) “Repurposing of Miglustat to inhibit the coronavirus Severe Acquired Respiratory Syndrome SARS-CoV-2”, preprint from Biorxiv, doi: https://doi.org/10.1101/2020.05.18.101691.
Erik Laurini, Suzana Aulic, Natasa Skoko, Domenico Marson, Maurizio Fermeglia, Sabrina Pricl (2020) “ITC for characterization of self-assembly process of cationic dendrons for siRNA delivery”, accepted for publishing as a book chapter of the book manuscript entitled “siRNA delivery”, Methods in Molecular Biology by Springer Nature.
Rehman M, Vodret S, Braga L, Guarnaccia C, Celsi F, Rossetti G, Martinelli V, Battini T, Long C, Vukusic K, Kocijan T, Collesi C, Ring N, Skoko N, Giacca M, Del Sal G, Confalonieri M, Raspa M, Marcello A, Myers MP, Crovella S, Carloni P, Zacchigna S. (2019) “High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation”, JCI Insight, 4(8), doi.org/10.1172/jci.insight.123987
Polez S., Origi D., Zahariev S., Guarnaccia C., Tisminetzky S. G., Skoko N., Baralle M. (2016) “A simplifiedand efficient process for insulin production in Pichia pastoris”, PLos One, 11(12), doi: 10.1371/journal.pone.0167207
Zampieri D, Mamolo MG, Vio L, Romano M, Skoko N, Baralle M, Pau V, De Logu A. (2016) “Antimycobacterial activity of new N1-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives”, Bioorganic & Medicinal Chemistry Letters, 26(14):3287-90, doi: 10.1016/j.bmcl.2016.05.053
Skoko N., Baralle M. and Baralle FE. (2016) “Absence of TDP-43 is difficult to digest”, The EMBO Journal, News &Views, 35 (2): 115-117, doi: 10.15252/embj.201593603