In the past 5 years, European investigators have played a major role in the development of clinical gene therapy. The provision of substantial funds by some individual member states to construct GMP facilities makes it an opportune time to network available gene therapy GMP facilities at an EU level. The integrated coordination of GMP production facilities and human skills for advanced gene and genetically-modified (GM) cell therapy, can dramatically enhance academic-led “First-in-man” gene therapy trials. Once proof of efficacy is gathered, technology can be transferred to the private sector which will take over further development taking advantage of knowledge and know-how. Complex technical challenges require existing production facilities to adapt to emerging technologies in a coordinated manner. These include a mandatory requirement for the highest quality of production translating gene-transfer technologies with pharmaceutical-grade GMP processes to the clinic. A consensus has emerged on the directions and priorities to adopt, applying to advanced technologies with improved efficacy and safety profiles, in particular AAV, lentivirus-based and oncolytic vectors. Translating cutting-edge research into “First-in-man” trials require that pre-normative research is conducted which aims to develop standard assays, processes and candidate reference materials. This research will help harmonise practices and quality in the production of GMP vector lots and GM-cells. In gathering critical expertise in Europe and establish conditions for interoperability, the PEVI infrastructure will contribute to the demands of the advanced therapy medicinal products* regulation and to both health and quality of life of EU-citizens.
Keywords: Clinical grade GMP production, gene therapy and gene-modified cells, first-in-man trials, pre-normative research and reference methods, interoperability and regulatory harmonization, lentivirus-based and oncolytic vectors, X-SCIDs, adrenoleukodystrophy, ADAdeficiency, Leber's congenital amaurosis, self-inactivating lentiviral (LV), retroviral vectors (RV), adeno associated virus (AAV), PEVI, GLP, GCP, ATMP, ERA, ERIC, ESFRI, EATRIS, ECRIN, CAT2, GTWP, EDQM, hemoglobinopathies, Fanconi's anaemia, CEN-Star, AAV8 standard, CliniGene-NoE, Insertagene, Baculogenes, Persist, Consert, Giant, EVGN, PolExGene, PCO-SMEs, Clonality assays, Immunotoxicology, RCR, &, RCL-assays, RCAAV, CAT, ICH, PCC, PCO