title: The European Regulatory Environment of RNA-Based Vaccines.
abstract: A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.
authors.affiliation: Section for Therapeutic Vaccines, Division for Immunology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Germany. thomas.hinz@pei.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hinz
authors.affiliation: Kallen Consulting, Köln/Frechen, Germany.
authors.forename: Kajo
authors.initials: K
authors.lastname: Kallen
authors.affiliation: R&D Oncology, Glaxo Smith Kline, Stevenage, UK.
authors.forename: Cedrik M
authors.initials: CM
authors.lastname: Britten
authors.affiliation: URPhyM, NARILIS, University of Namur, Namur, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Flamion
authors.affiliation: Granzer, Regulatory Consulting & Services, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Granzer
authors.affiliation: Glaxo Smith Kline, Collegeville, PA, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
authors.affiliation: Association for Cancer Immunotherapy, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.affiliation: GHSU Cancer Center, Augusta, GA, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Khleif
authors.affiliation: Association for Cancer Immunotherapy, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreiter
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.|German Cancer Consortium, DKFZ Partner Site, Tübingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: TRON - Translational Oncology at the University Medical Center, Johannes Gutenberg University, Mainz, Germany.|Biopharmaceutical New Technologies (BioNTech) Corporation, Mainz, Germany.|Research Center for Immunotherapy (FZI), Mainz, Germany.
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
authors.affiliation: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Singh-Jasuja
authors.affiliation: CI3, Cluster for individualized Immune Intervention, Mainz, Germany.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Türeci
authors.affiliation: Institute for Experimental Infection Research, Twincore, Centre for Experimental and Clinical Infection Research a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Feodor-Lynen-Str. 7-9, 30625, Hannover, Germany. ulrich.kalinke@twincore.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005060:Europe; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D012333:RNA, Messenger / Q000276:immunology*
chemical_list: D000941:Antigens; D019496:Cancer Vaccines; D012333:RNA, Messenger
keywords: Advanced therapy medicinal products (ATMP); Anticancer vaccination; Genetically modified medicinal products; Preventive and therapeutic approaches; Regulatory framework in the EU; Vaccination against infectious disease; Vaccines; mRNA