Comparative analysis of GMO regulatory requirements for AAV vectors in the EU and Japan focusing on the shedding data and containment measures

References

• Dunbar CE, High KA, Joung JK, et al. Gene therapy comes of age. Science. [2018 Jan 12];359(6372). doi: 10.1126/science.aan4672
   PubMed Web of Science ®Google Scholar
• Blaese RM, Culver KW, Miller AD, et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science. [1995 Oct 20];270(5235):475–480. doi: 10.1126/science.270.5235.475
   PubMed Web of Science ®Google Scholar
• The Journal of Gene Medicine. Gene therapy clinical trials worldwide. [cited 2023 Jul 6]. Available from: https://a873679.fmphost.com/fmi/webd/GTCT
   Google Scholar
• National Institute of Health Sciences. Approved gene therapy products (in Japanese). [cited 2024 Mar 22]. Available from: https://www.nihs.go.jp/mtgt/pdf/section1-1.pdf
   Google Scholar
• Alliance for Regenerative Medicine. Available products: a comprehensive list of current cell and gene therapy products available in different markets across the world. [cited 2024 Mar 22]. Available from: https://alliancerm.org/available-products/
   Google Scholar
• Nguengang Wakap S, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020 Feb;28(2):165–173. doi: 10.1038/s41431-019-0508-0
   PubMed Web of Science ®Google Scholar
• Pogue RE, Cavalcanti DP, Shanker S, et al. Rare genetic diseases: update on diagnosis, treatment and online resources. Drug Discov Today. 2018 Jan;23(1):187–195. doi: 10.1016/j.drudis.2017.11.002
   PubMed Web of Science ®Google Scholar
• Julkowska D, Austin CP, Cutillo CM, et al. The importance of international collaboration for rare diseases research: a European perspective. Gene Ther. 2017 Sep;24(9):562–571. doi: 10.1038/gt.2017.29
   PubMed Web of Science ®Google Scholar
• Mizoguchi H, Yamanaka T, Kano S. Research and drug development activities in rare diseases: differences between Japan and Europe regarding influence of prevalence. Drug Discov Today. 2016 Oct;21(10):1681–1689. doi: 10.1016/j.drudis.2016.06.014
   PubMed Web of Science ®Google Scholar
• International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH harmonized guideline general principles for planning and design of multi-regional clinical trials E17. [cited 2023 Jul 6]. Available from: https://database.ich.org/sites/default/files/E17EWG_Step4_2017_1116.pdf
   Google Scholar
• Marks P. Enhancing gene therapy regulatory interactions. Expert Opin Biol Ther. 2022 Sep;22(9):1073–1074. doi: 10.1080/14712598.2022.2060736
   PubMed Web of Science ®Google Scholar
• Convention on Biological Diversity. The Cartagena Protocol on Biosafety. [cited 2023 Jul 6]. Available from: https://bch.cbd.int/protocol/
   Google Scholar
• Beattie S. Alliance for Regenerative Medicine, European Federation of Pharmaceutical Industries Associations, European Association for Bioindustries. Call for more effective regulation of clinical trials with advanced therapy medicinal products consisting of or containing genetically modified organisms in the European union. Hum Gene Ther. 2021 Oct;32(19–20):997–1003. doi: 10.1089/hum.2021.058
   PubMed Web of Science ®Google Scholar
• Tajima G, Huh S, Schmidt NA, et al. Impact of genetically modified organism requirements on gene therapy development in the EU, Japan, and the US. Mol Ther Methods Clin Dev. 2022 Sep 8;26:74–83. doi: 10.1016/j.omtm.2022.05.012
   PubMed Web of Science ®Google Scholar
• APACRM Working Group 3. Points to consider for regulations on clinical trials for AAV-based gene therapies in 6 Asia Countries. In: The 6th Asia Partnership Conference of Regenerative Medicine; Tokyo, Japan; [2023 Apr 20].
   Google Scholar
• Official Journal of the European Communities. Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing council directive 90/220/EEC. [cited 2023 Jul 6]. : Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:L:2001:106:FULL&from=EN
   Google Scholar
• Official Journal of the European Union. Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms (Recast). [cited 2023 Jul 6]. Available from: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:125:0075:0097:EN:PDF
   Google Scholar
• Bachtarzi H, Farries T. The genetically modified organism medicinal framework in Europe, United States, and Japan: Underlying scientific principles and considerations toward the development of gene therapy and genetically modified cell-based products. Hum Gene Ther Clin Dev. 2019 Sep;30(3):114–128. doi: 10.1089/humc.2019.042
   PubMed Web of Science ®Google Scholar
• Anne Schmidt JGN, MacLachlan TK, Dandapat S, et al. Current global regulatory landscape for biodistribution & shedding assessment of rAAV gene therapies & recommendations of the IMI ARDAT consortium on future directions. Cell Gene Ther Insights. 2022;8(3):377–394. doi: 10.18609/cgti.2022.056
   Google Scholar
• Official Journal of the European Union. Regulation (EU) 2020/1043 of the European Parliament and of the Council of 15 July 2020 on the conduct of clinical trials with and supply of medicinal products for human use containing or consisting of genetically modified organisms intended to treat or prevent coronavirus disease (COVID-19). [cited 2023 Jul 6]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R1043
   Google Scholar
• European Commision. Communication from the Commission to the European Parliament, the European Council, the Council and the European Investment Bank EU Strategy for COVID-19 Vaccines. [cited 2023 Jul 6]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:52020DC0245&from=EN
   Google Scholar
• Act on the conservation and sustainable use of biological diversity through regulations on the use of living modified organisms. [cited 2023 Jul 10]. Available from: https://www.japaneselawtranslation.go.jp/en/laws/view/3252
   Google Scholar
• Alliance for Regenerative Medicine. Clinical trials in Europe: recent trends in ATMP Development. [cited 2023 Jul 6]. Available from: https://alliancerm.org/wp-content/uploads/2019/10/Trends-in-Clinical-Trials-2019-Final_Digital.pdf
   Google Scholar
• National Institute of Health Sciences. Major gene therapy products under clinical development in Japan (in Japanese). [cited 2023 Jul 6]. Available from: https://www.nihs.go.jp/mtgt/pdf/section1-2.pdf
   Google Scholar
• Ruehle S, Omnes P, Parsley K, et al. Evolution of GMO requirements for innovative investigational medicinal products upon transition to the EU CTR. Regul Rapporteur. 2023 May 18;20:(5). Available from: https://www.regulatoryrapporteur.org/pharmaceuticals/evolution-of-gmo-requirements-for-innovative-investigational-medicinal-products-upon-transition-to-the-eu-ctr/274
   Google Scholar
• European Commission. Genetically Modified Organism (GMO) aspects for investigational medicinal products. [cited 2023 Aug 2]. Available from: https://health.ec.europa.eu/medicinal-products/advanced-therapies/genetically-modified-organism-gmo-aspects-investigational-medicinal-products_en
   Google Scholar
• European Commission. Proposal for a Regulation of the European Parliament and of the Council laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006. [cited 2023 Jul 6]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A52023PC0193
   Google Scholar
• Alliance for Regenerative Medicine. ARM releases statement on European commission’s proposal to Revise EU Pharmaceuticals Legislation. [cited 2023 Jul 6]. Available from: https://alliancerm.org/press-release/arm-releases-statement-on-recent-draft-eu-pharmaceuticals-legislation/
   Google Scholar
• European Commission. Common application form for investigational medicinal products for human use that contain or consist of AAV vectors. [cited 2023 Jul 17]. Available from: https://health.ec.europa.eu/system/files/2022-01/aavs_caf_en.pdf
   Google Scholar
• European Commission. Common application form for viral vectors contained in investigational medicinal products for human use. [cited 2023 Jul 17]. Available from: https://health.ec.europa.eu/system/files/2022-01/vvs_caf_en.pdf
   Google Scholar
• European Commission. Common application form for clinical research with human cells genetically modified. [cited 2023 Jul 17]. Available from: https://health.ec.europa.eu/system/files/2021-11/gmcells_caf_en_0.pdf
   Google Scholar
• Pharmaceuticals and Medical Devices Agency. Applications related to Cartagena Act (in Japanese). [cited 2023 Jul 6]. Available from: https://www.pmda.go.jp/review-services/drug-reviews/cartagena-act/0003.html
   Google Scholar
• Pharmaceuticals and Medical Devices Agency. Regulations regarding living modified organisms (genetically modified organisms). [cited 2023 Jul 6]. Available from: https://www.pmda.go.jp/english/review-services/reviews/cartagena-act/0001.html
   Google Scholar
• Ministry of the Environment in Japan. Japan biosafety clearing-house (in Japanese). [cited 2023 Jul 6]. Available from: https://www.biodic.go.jp/bch/lmo.html
   Google Scholar
• Fleischmann T. Assessing the environmental fate of rAAV in activated sludge and water: Implications for environmental risk assessments and GMO regulatory frameworks. J Environ Manage. 2023 Nov;345:118754. doi: 10.1016/j.jenvman.2023.118754
   PubMed Web of Science ®Google Scholar
• National Center for Child Health and Development. National center of neurology and psychiatry. Cartagena act type 1 use regulations response manual – appropriate use of living modified organisms in medical facilities (in Japanese). [cited 2024 Apr 5]. Available from: https://www.childneuro.jp/uploads/files/about/AAVCartagena20240301/AAVCartagena20240301.pdf
   Google Scholar
• European Medicines Agency. Guideline on the non-clinical studies required before first clinical use of gene therapy medicinal products. [cited 2023 Jul 6]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-non-clinical-studies-required-first-clinical-use-gene-therapy-medicinal-products_en.pdf
   Google Scholar
• International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH considerations: general principles to address virus and vector shedding. [cited 2024 Apr 9]. Available from: https://admin.ich.org/sites/default/files/2019-04/ICH_Considerations_Viral-Vector_Shedding_.pdf
   Google Scholar
• Pharmaceuticals and Medical Devices Agency. Supplemental explanation for points to consider for writing biodiversity risk assessment report of Type 1 use application (in Japanese). [cited 2023 Jul 6]. Available from: https://www.pmda.go.jp/files/000239087.pdf
   Google Scholar
• World Health Organization. Laboratory biosafety manual.4th edition. [cited 2023 Jul 6]. Available from: https://www.who.int/publications/i/item/9789240011311
   Google Scholar
• Vulto AG, Stoner N, Balásová H, et al. European association of hospital pharmacists (EAHP) guidance on the pharmacy handling of gene medicines. EJHP Pract. 2007 May;13:29–39.
   Google Scholar
• Schöning T. Leitlinie zum Umgang mit Gen-Therapeutika in der Apotheke (in German). Krankenhauspharmazie. 2009;30(2):49–56.
   Google Scholar
• Official Journal of the European Union. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. [cited 2023 Aug 3]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32014R0536
   Google Scholar
• European Medicines Agency. Guideline on the principles of regulatory acceptance of 3Rs (replacement, reduction, refinement) testing approaches. [cited 2024 Apr 5]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-principles-regulatory-acceptance-3rs-replacement-reduction-refinement-testing-approaches_en.pdf
   Google Scholar
• Sakurai A, Kanzaki S, Honda F. Japanese pharmaceutical regulations of engineered viral vectors for medical use compared with those in the United States and the European union. Clin Pharmacol Ther. 2023 May;113(5):960–962. doi: 10.1002/cpt.2788
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration. Determining the need for and content of environmental assessments for gene therapies, vectored vaccines, and related recombinant viral or microbial products guidance for industry. [cited 2023 Jul 6]. Available from: https://www.fda.gov/media/91425/download
   Google Scholar
• Iglesias-Lopez C, Obach M, Vallano A, et al. Hurdles of environmental risk assessment procedures for advanced therapy medicinal products: comparison between the European Union and the United States. Crit Rev Toxicol. 2019 Aug;49(7):580–596. doi: 10.1080/10408444.2019.1689380
   PubMed Web of Science ®Google Scholar