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

Recombinant viral-based gene therapy products, such as those incorporating adeno-associated viruses (AAVs), fall under the category of genetically modified organisms (GMOs). The European Union (EU) countries and Japan must obtain environmental risk assessment (ERA) approval for the use of GMOs before starting any clinical trials. It has been reported that the development of GMO-containing products in these two regions encounters several regulatory obstacles due to the longer regulatory procedures and document preparation for ERA. In this article, we comparatively analyzed the ERA document requirements in the EU and Japan for AAV-based recombinant medicinal products to highlight the differences in the context of potential future attempts of convergence. Additionally, we analyzed non-clinical and clinical shedding data requirements, which are key components of ERA reviews in the EU and Japan. Lastly, we compared the containment measures to minimize the spread of GMOs in the environment in the EU and Japan. Based on our comparative analysis, we present several policy recommendations of standardizing and simplifying the application materials and procedures for the ERA regulations on GMOs in the EU and Japan in the mid-, and long-term timeframe to achieve global regulatory convergence.

以腺相关病毒（adeno-associated viruses, AAVs）为载体的重组病毒类基因治疗产品，属于转基因生物（genetically modified organisms, GMOs）范畴。欧盟（European Union, EU）成员国与日本在启动任何临床试验前，均需就转基因生物的使用获得环境风险评估（environmental risk assessment, ERA）审批。据报道，由于环境风险评估的审批流程更长、文件编制要求更为繁琐，这两大地区的含转基因生物产品研发面临诸多监管障碍。本文针对基于AAV的重组医药产品，对比分析了欧盟与日本的环境风险评估文件要求，以凸显二者在未来潜在监管趋同背景下的差异。此外，本文还分析了非临床与临床病毒脱落数据要求——此类数据是欧盟与日本环境风险评估审评的核心组成部分。最后，本文对比了欧盟与日本为最大限度降低转基因生物向环境扩散而制定的管控措施。基于本次对比分析，本文针对欧盟与日本的转基因生物环境风险评估法规，提出了中长期内标准化、简化申报材料与流程的多项政策建议，以期实现全球监管趋同。