2021年12月27日,国家发改委和商务部发布了新版的《外商投资准入特别管理措施(负面清单)(2021年版)》和《自由贸易试验区外商投资准入特别管理措施(负面清单)(2021年版)》(以下简称“《2021版负面清单》”),并于2022年1月1日生效。《2021版负面清单》禁止外商投资人体干细胞、基因诊断与治疗技术开发和应用,引起了业内人士的高度关注。在此之前,2021年12月24日,中国证监会公布《国务院关于境内企业境外发行证券和上市的管理规定(草案征求意见稿)》(以下简称“《管理规定》”)和《境内企业境外发行证券和上市备案管理办法(征求意见稿)》(以下简称“《备案办法》”) ,向社会公开征求意见(上述规范性文件合称“新规”)。
《2021版负面清单》最大的修改亮点在于增加了从事负面清单禁止投资领域业务的境内企业到境外上市的相关规定。与《管理规定》及《备案办法》相结合,将对被列入负面清单禁止投资领域的人体干细胞及基因诊疗行业境外上市产生较大的影响。本文旨在结合新规的修订,对人体干细胞及基因诊疗行业境外上市相关问题进行探析。
一、哪些细分领域属于人体干细胞及基因诊断与治疗行业
(一)基本介绍
1. 干细胞
根据国家药品监督管理局药品审评中心于2020年8月发布的《人源性干细胞及其衍生细胞治疗产品临床试验技术指导原则(征求意见稿)》的相关规定,干细胞是指一类具有自我更新、多向分化潜能的细胞,在再生医学领域有广阔的应用前景。人源性干细胞及其衍生细胞治疗产品作为重要的再生医学产品,可能应用到几乎涉及人体所有重要组织器官的修复及研究人类面临的许多医学难题,在细胞替代、组织修复、疾病治疗等方面具有巨大潜力。
2. 基因诊断
基因诊断是利用现代分子生物学和分子遗传学的技术方法,直接检测患者体内基因结构及其表达水平是否正常,从而对疾病做出诊断或辅助诊断。基因诊断的前提是已明确疾病表型与基因的关系。目前基因诊断的基本方法主要是建立在核酸分子杂交、聚合酶链式反应(PCR)和DNA序列分析技术或几种技术的联合的基础上。
3. 基因治疗
根据国家药品监督管理局于2021年6月发布的《基因治疗产品长期随访临床研究技术指导原则(征求意见稿)》,基因治疗是指通过修饰或操纵基因的表达或改变活细胞的生物学特性以达到治疗目的的治疗手段。
(二)产业链
1. 干细胞产业链
干细胞产业链可分为上中下游三个领域,包括上游干细胞存储、中游干细胞技术与产品研发、下游干细胞治疗等。
2. 基因测序及诊疗产业链
基因诊疗是基于基因测序等相关技术,同时依赖于基因测序相关产品。基因测序及诊疗产业链包括上游的基因测序产品供应、中游的测序技术服务、下游的终端应用等。
值得注意的是,并非所有干细胞及基因诊疗产业链相关的版块均被纳入负面清单禁止投资范围之内,例如高通量基因测序系统制造属于外商投资鼓励类。究竟如何定义“基因诊断与治疗技术的开发和应用”,法律法规并无明确的规定,行业内也尚未形成共识。
二、人体干细胞及基因诊断与治疗行业能否境外上市
(一)境外上市的前置审批及条件要求
《2021版负面清单》规定从事外资准入负面清单禁止投资领域业务的境内企业到境外发行股份并上市交易的,应当首先经过国家有关主管部门审核同意,审核同意的,也应满足两个条件,包括:
l 境外投资者不得参与企业经营管理
l 持股比例参照境外投资者境内证券投资管理有关规定执行
根据上述新规,人体干细胞及基因诊疗行业即使被纳入了负面清单禁止投资领域范围之内,但其赴境外上市并非“一刀切”地被完全否定。在取得相关主管部门同意不适用负面清单的禁止性规定的前提下,人体干细胞及基因诊疗企业境外上市存在法律上的可行性。从新规来看,其具体审批程序及前提条件如下:
1. 通过两类审批
《备案办法》规定发行人应当向中国证监会提交的备案材料包括但不限于:
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