Kim F Pearce1, Martin Hildebrandt2, Hildegard Greinix3, Stefan Scheding4, Ulrike Koehl5, Nina Worel3, Jane Apperley6, Matthius Edinger7, Andrea Hauser7, Eva Mischak-Weissinger8, Anne M Dickinson1, Mark W Lowdell9. 1. Haematological Sciences, Institute of Cellular Medicine, Medical School, University of Newcastle upon Tyne, United Kingdom. 2. TUMCells Interdisciplinary Centre for Cellular Therapies, Technical University Munich, Faculty of Medicine, Munich, Germany. 3. Medical University of Vienna, Austria. 4. Lund University, Stem Cell Center, Lund, Sweden. 5. Institute of Cellular Therapeutics, IFB-Tx, Hannover Medical School (MHH), Hannover, Germany. 6. Department of Haematology, Imperial College London, United Kingdom. 7. University Hospital, Regensburg, Germany. 8. Hannover Medical School, Hannover, Germany. 9. Department of Haematology, Royal Free Hospital & University College London, United Kingdom. Electronic address: m.lowdell@ucl.ac.uk.
Abstract
BACKGROUND AIMS: Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. METHODS: European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. RESULTS: Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. CONCLUSIONS: GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field.
BACKGROUND AIMS: Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. METHODS: European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. RESULTS: Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. CONCLUSIONS: GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field.
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