Country reports
Index:
1) China (A.R, A.E, S.S, X.Z & Y.S)
2) India (C.H & P.K.P)
3) Japan (M.S.F & P.K.P)
4) South Korea (C.K.C)
5) Taiwan (H-C.C)
6) Thailand (N.C)
1) China (A.R, A.E, S.S, X.Z & Y.S)
Introduction
This report contains of two parts, and three appendices. PART I provides an overview of the current
funding landscape for stem cell research in China. It introduces, furthermore, some of the keyprojects that have been funded by the Chinese government in recent years, and key-priority areas in
the regenerative stem cell field in the recent past, the present and future. PART II provides an
overview of the regulatory situation for stem cell research. We have listed (1) regulations for basic
research, (2) the regulations for clinical research on human subjects in China (these regulations do
not explicitly address clinical stem cell research, but they constitute a set of horizontal regulations
that affect experimentations with stem cell-based applications indirectly). Thereafter (3) the
regulatory approach for clinical research and applications with stem cells will be explored. An
overview will be provided of the currently existing regulatory steps and documents, and some
commentary on implementation is provided, if possible. The final appendix provides information on:
(1) Key state institutions that affect stem cell research in China. (2) Key research institutes and stem
cell biobanks in China. (3) A list of clinics that offer experimental stem cell therapies in China.
PART I: The funding landscape: a provisional sketch
During the last three decades, the promotion of innovation processes in science and technology has
been defined as a key driver for economic development in China. China has surpassed Japan as the
second largest investor of R&D expenditures in 2006 (US NSF 2012). Drug discovery and regenerative
medicine, as has been re-emphasized by premier Wen Jiabao in January 2012, form two keystrategic areas of investment (Qiu 2012).
According to the Cure Report – a 2009 report from the UK Medical Research Council on Sino-UK
research collaborations in biomedicine and the biosciences – the Chinese government has between
2005 and 2010 spent between RMB 500 million (USD 63m) and RMB 2 billion (USD 250m) into the
development of SC research. The UK in contrast, invested in the two-year period 2006-2007 GBP 30
million (ca. USD 43m) (Cure 2009).
Since the Ninth Five-Year Plan (1997-2001) stem cell research has been endorsed by several
governments departments. The largest part of funding has been provided by the National Science
Program of the Ministry of Science and Technology, with the "863" program targeting the promotion
of high technology research, and the "973" program focusing on the promotion of basic research (in
all fields of science) (Cure 2009).
However, grants for stem cell research were also allocated through the Chinese Academy of the
Sciences, the National Natural Science Foundation Committee, and other government related
departments and organizations (Cure 2009). In the Eleventh Five Five-Year Plan (2007-2011) the
“863” program included a funding section for “Stem Cells and Tissue Engineering”, within a wider
program that aimed to the development of biological and pharmaceutical technology (China
National Center for Biotechnology Development 2011a). This program finished in 2011, with the
following PIs having been awarded major grants: ZHOU Qi, WANG Changyong, MA Yue, WU Fang,
WANG Yan, LI Lingsong, WANG Ren (ibid.).
In the context of the Twelfth Five-Year Plan (2012-2016), the "stem cell therapy clinical translational
and applied research program” has been initiated, with money allocated through the “863” program
(MOST 2013).
Another important measure for the promotion of stem cell research, has been the formation of the
National Stem Cell Advisory Committee (国家干细胞研究指导协调委员会), by the Ministry of
Science and Technology in October 2011 (Wang 2011). Through this committee, the ministry aims to:
1. Further coordinate stem cell research, to make strategic funding decisions (to increase
efficiency of the use of national funding resources)
2. To further create a favourable environment for innovation, to promote high-level training
3. To strengthen international collaborations, and exchanges, so as to stimulate research into
major scientific issues, and major technical breakthroughs
A closely related initiative, also funded by MOST, is the formation of biobanks, which has been set as
a key-target in the Twelfth Five Year Plan (2012-2016) (China National Center for Biotechnology
Development 2011b).
More specifically, the plan emphasizes the construction of biobanks as repositories for genetic
clinical specimen, to:
- develop drug research / pharmaceuticals and for purposes of development biomedical
engineering products, as well as for biological breeding.
A standardized clinical information database and biological specimen database shall be established
in this respect in Beijing, administered under the Beijing Municipal Science and Technology
Commission. The bio-bank shall be hosted by the Capital Medical University. It shall form a
repository that contains samples of major disease transmitters (hope have understood this correctly),
clinical data and other biological samples (China National Center for Biotechnology Development
2011b).
Furthermore, four national level stem cell banks have been founded under the Chinese Academy of
the Sciences (ibid.):
(1) Beijing Municipality Stem Cell Bank
(2) Southern Stem Cell Bank, in Guangzhou
(3) Stem cell bank of the Chinese Academy of the Sciences, Shanghai
(4) East China Stem Cell Bank (also in) Shanghai
One of the authors of this report was in 2008 reported, furthermore, that a five-year government
grant was provided for the foundation of five human embryonic stem cell banks. One of these five
banks, in Changsha, should be specialized in the banking of disease-specific stem cells lines. The
current status and exact functions of these banks would have to be explored in further research.
An open question is at this moment also what the role (a) of provincial and municipal governments is
in funding stem cell research. Unclear is furthermore, the role of (b) foundations and (c) private
investors and companies, in the financiering of translational stem cell research and/ or experimental
for-profit clinical applications. Regarding the latter group, private investors and companies, active
investment activity can be expected, since the application of (non-systematically proven or
completely unproven) experimental stem cell therapies, constitute important market opportunities
in China.
PART II: Regulatory Situation
I. Basic Research
The following regulations have been issued in China, to govern basic research with stem cells. Both
of these regulations focus on human embryonic stem cell research only. The first concerns the
sourcing of human embryos and ova in the context of IVF clinics. The second addresses the specific
conditions under which human embryos can be produced and used for research. No regulation exists
currently that addresses (a) somatic cell nuclear transfer techniques for research purposes (i.e.
“therapeutic cloning”), (b) basic or preclinical research with iPS cells, and (c) research with humananimal hybrids.
(1) 2001-2003, MOH: The Ethics Guiding Principles for Assisted Reproductive Technology
This regulation addresses stem cell research, by stipulating that all ART institutions must set up
ethics committees, and that these committees must approve applications of human embryos to be
donated for research (Hu, Min and Wei 2011; Cure 2009). The regulation affects the supply of
embryos, ova and fetal tissue for research also in the following ways: (i) by stating that the buying
and selling of human eggs, embryos or fetal tissues is prohibited, (ii) by restricting the use of
embryos for research to super-numerous embryos in the context of an IVF treatment, and by
explicitly prohibiting the creation of IVF embryos for research only, (iii) by specifying that embryos
and gametes must be voluntarily donated, on the basis of informed consent, and (iv) by forbidding
hormonal super-stimulation, to harvest more eggs. This regulation is backed up by punitive
measures: IVF clinics or ART centers can loose their license if they violate these guidelines (Cure
2009).
(2) 2003, MOH/MOST: The Ethics Guiding Principles for hESC research
《人胚胎干细胞研究伦理指导原则》
Human embryonic stem cell (hESC) research is regulated with these principles at a national level,
through ministerial guidelines. The core aspects of this regulation are that: (i) embryos are not
allowed to be used for hESC after 14 days post conception, (ii) embryos used for research can not be
implanted in human beings (prohibition of human reproductive cloning). The principles demand,
furthermore, that institutions that are involved in hESC form an ethics committee that details
regulatory rules and exact conditions under which research can be conducted.
Criticism of existing basic research regulation from the National Ethics Committee of the MOH
These principles have been criticized by the National Ethics Committee of the MOH in China because
(a) they do not introduce a registration or licensing system of research institutes or clinics that
conduct hESC research, (b) because they are not backed up by law, and (c) no clear control pathways
for the principles are provided. Plans and efforts to revise this regulation, from the side of the MOH
National Ethics Committee, are ongoing (Zhai 2007).
II. Clinical Research
It follows now an overview of the regulations, laws and institutions, that play a role (or are foreseen
to play a role) for clinical stem cell research. This process is still evolving. Before briefly discussing
this regulatory approach, I will introduce however an overview of the regulations and laws that
govern research on human subjects in China, of which some do – indirectly – also impact on
experimental clinical research and applications.
II.a. Regulations for human subject research (affects clinical SC research horizontally)
The following provides an overview of existing regulations for human subject research. These
regulations are not designed for clinical trials with stem cells, but they affect clinical research that
involves stem cell-based applications indirectly (i.e. as horizontal regulations).
(1) Review of clinical research and review by Ethics Committees / hospital-internal IRBs
(a) Foundation of a national-level ethics committee
The MOH ‘Ethics Committee on Biomedical research involving human subjects’ was founded in 1998,
and renamed in 2000 as ‘Medical Ethics Expert Committee’. The committee comprises since a
reform in 2007 – 17 members from multi-disciplinary background.
(b) The 2007 ‘Regulation on ethical review of biomedical research involving human subjects’ 《涉
及人的生物医学研究伦理审查办法（试行）》
A draft regulation on Ethical Review of Medical Research involving human subjects was drafted in
1998, but was due to controversies failed to be endorsed (Hu, Min and Wei 2011). It was issued by
the MOH only in 2007. According to this regulation – all – research on human subjects has to occur
under review of ethics committees at the level of research institutes and hospitals. It specifies details
for how informed consent procedures have to be structured. This regulation is of fundamental
importance to clinical stem cell research and applications, because it requires mandatory EC
approval at the level of medical institutions that engage in these activities.
(2) The 1994 Regulation on the Government of Medical Institutions
This regulation has been passed by the state council in 1994. It clarifies that informed consent is
required for performance of surgical operations, special investigations, and special (experimental)
treatments. It sets out, furthermore, a number of rules for medical institutions, such as for instance,
that approval documents for treatments, can not be ‘inherited’, if the owner, or name of a hospital
changes. This regulation is of some relevancy for clinical SC research, in particular institutes that
offer for-profit therapies. The Jilin Silicon Valley Hospital, for instance, was criticized by the media on
the basis of this regulation. Reason: the hospital had changed its name and proprietor, but the same
approval license was used (issued by a local and a provincial health bureau) to attract patients
(approval documents were publicly displayed on the internet).
(3) The 1999 Drug Clinical Trial Regulations Law on Practicing Doctors
This regulation protects patients by stating that doctors who violate a patient’s privacy or conduct
experimental interventions without informed consent, will be legally persecuted. I have not yet
heard of cases where this regulation was applied, in the context of SC based for experimental
treatments. In theory, however, this regulation applies to doctors who fail to sufficiently inform
patients, or who violate a patient’s privacy (Cure 2009). In other words, patients could sue doctors
who offered experimental stem cell treatments based on fraudulent claims, on the basis of this
regulation.
(4) The 2001/2001 Drug Administration Law / Regulations for implementation of the drug
This law has been passed by the National People’s Congress. It covers the use of pharmaceutical
products in research as well as practice. It clarifies that GCP and GMP standards must be followed.
(Cure 2009).
This regulation (if I understand it correctly – need for verification by CIs in China) is of relevancy to
hospitals that conduct clinical trials with SC in the context of an SFDA monitored IND application.
These hospitals would, according to this regulation require GCP certification, obtained through the
procedures set out above. Other clinical trials or forms of experimentation – that are conducted
outside of the jurisdiction of the SFDA do – not require to be carried out in GCP accredited hospitals,
and the regulation is for these hospitals redundant.
(5) The 1999-2003 SFDA good clinical practice standards (药物临床试验质量管理规范)
These SFDA GCP standards were issued in a first version in 1999, and in a second more complete
version in 2003. Both were issued by the SFDA. The SFDA GCP standards specify procedures for the
accreditation of medical institutions, to take part in drug trials. They require that each hospital in
human subject research acquire GCP certification (Cure 2009). An interesting feature is that GCP
certification is based on examinations of high-level clinical staff (heads of department). They
emphasize strict informed consent and strict review by ethics committees, and include provisions on
how IRBs should be composed and be organized. The Chinese GCP standards, draw actively on the
now internationally handled ICH GCP standards. (Cure 2009). These SFDA GCP standards are of
relevancy to hospitals that conduct clinical trials with SC in the context of an SFDA registered IND
application.
II. b. The evolving regulatory approach for clinical SC research
It follows now an overview of the evolving regulatory approach for clinical SC research and
applications in China. Three regulatory documents shall be discussed: (1) The 2009 May 1
Regulation; (2) a 2010 draft regulation; (3) the January 6 2012 notification for clinical stem cell
research and application.
1. The ‘May 1 2009 regulation’ and its impact
On May 1 2009 the MOH promulgated the “Management Measures for the Clinical Use of Medical
Technologies” [医疗技术临床应用管理办法], a regulation that classified a range of new medical
technologies and procedures into three categories. Stem cell transplant technology was grouped
into category III, which included technologies considered as risky, ethically controversial and in need
of clinical verification (Chen 2009). To implement the regulation the MOH assigned five institutions
(ibid.: 271), among them the Chinese Medical Association, the Chinese Hospital Association and the
Chinese Doctors Association. According to an associate of the MOH in Beijing, clinics that used SC
transplantation technology were summoned to register at these institutions. These organizations in
turn were assigned to grant licenses on the basis of newly formed assessment criteria and review
and inspection committees. In practice, this regulation has not yet been implemented for SC
transplantation technologies. As stated by a senior SC scientist, who as a member of the Chinese
Doctors Association was involved in the formulation of review criteria, there were widespread
disagreements among experts of the assigned five institutions, over the precise characteristics of
these criteria, over feasible implementation pathways, as well as the extent to which the situation
should be controlled.
2. The 2010 Draft Regulation
In 2008 the Science and Education unit of the MOH authorized an expert committee of medical
ethics chaired by Prof Chingli Hu, to develop a comprehensive draft regulation for clinical research
and applications with human SC in China. After a two-year consultation and preparation process, a
draft was submitted to the MOH in October 2010. This proposal has subsequently been under
internal consideration, and is expected to form the foundation of a finalized version that is expected
soon.1
A central premise of this draft is the promotion of standardized and rigorous scientific forms of
clinical SC research (Hu 2010: 27). It asks for methodical preclinical studies and the generation of
reliable safety data, as well as standardized clinical trials that precede clinical applications (27).
These trials shall be subject to approval and review procedures under the MOH and the SFDA (which
since 2008 has been a subunit of the MOH). Only qualified and licensed hospitals would be able to
provide approved clinical applications (37). Furthermore, the draft stipulates that the quality and
safety of used cells must be subjected to reliable controls and documentation (32). Medical
institutions that violate these principles will be forced to stop SC-based clinical trials or applications
for a period of five years (37).
The draft specifies approval and review procedures for three central forms of clinical research and
applications with SC. First is approval of clinical trials and applications of stem cell based drug
products, i.e. standardized batch products based on amplification of cells from one or multiple
donors. Responsibilities for evaluation and market approval of these ‘off-the-shelf’ SC products
(commonly regarded as the most risky treatment form with SC) shall be handled by the SFDA, and be
based on systematic preclinical studies and closely reviewed Phase I-III clinical trials (36). Second is
approval of clinical trials and applications of modified SC from a single donor to single recipient. With
reference to the 2009 regulation these treatment forms were defined as medical technology.
Regulatory distinctions are made in this respect between autologous/allogeneic SC, and
minimally/extensively manipulated SC. Approval of minimally processed autologous SC, which are
seen as the least risky group of cells, shall occur through the MOH Bureau of Medical Administration.
More extensively manipulated cells, particularly from allogeneic sources, shall be approved by the
MOH Bureau of Science and Education. Application and review procedures shall be handled by the
thirty-one province-level sub-branches of the MOH, with the MOH in Beijing as the central
supervising agency. Third is approval of experimental therapeutic approaches with SC. Experimental
for-profit applications shall be strictly delimited. In accordance with article 35 of Helsinki Declaration
1
This information is based on a presentation of this draft regulation, generously provided by Prof Chingli Hu and his team
in Shanghai, on January 21, 2011.
first-in-human experimental treatments with SC shall be allowed, but in a low number of patients,
and according to clear approval criteria. Applications and oversight shall occur through specialized
ethics committees, at the provincial MOH branches.
With this draft regulation, a clear step toward international harmonization has been set into motion.
In regulating medical procedures with SC proportionate to risk, for example, the Chinese draft
regulation follows essentially the approach that is also taken in the EU (Faulkner 2009: 641).
Differences exist, however, with respect to terminology and the allocation of responsibilities. In the
EU, all experimental medical procedures with SC (including autologous SC for non-homologous use)
have since 2007 been classified as advanced therapy medicinal products. These are regulated under
the centralized auspice of the European Medicines Agency (EMA) (ibid. 2009; EMA 2012). The 2010
draft regulation for China, on the other hand, follows a slightly different strategy. For one thing,
approval procedures are divided between the categories ‘medical products’ and ‘medical
technologies. For the other thing, responsibilities are not done by a centralized drug regulatory
agency, but split across three administrational units of the MOH, each with its own subsidiary branch
organizations at a provincial level. Since the draft regulation is likely to still undergo significant
revisions, it is too early to say what the implications of these differences for processes of regulatory
harmonization and international collaborations will be. Further research into these directions,
together with a focus on local implementation, will be of interest.
4. The January 2012 notification
On January 6 2012, the MOH issued a regulatory document called ‘Notification on Self-Evaluation
and Self-Correction Work regarding the Development of Clinical Stem Cell Clinical Research and
Applications’ [关于开展干细胞临床研究和应用自查自纠工作的通知].2 With this document an
initial one-year phase of a more comprehensive regulatory approach has been initiated, whose
precise details have not yet been publicized. In the January 2012 document, four subsequent stages
of this forthcoming approach have been announced: self-evaluation (zicha), self-correction (zijiu), recertification (chongxin renzheng), and standardized management (guifan guanli).
The initial one-year phase that is set out in the 2012 document, however, addresses only the first
two of these stages: self-evaluation and self-correction. Self-evaluation of the hospitals that carry
out SC-based clinical research and applications shall occur in the following way. First, clinics are
required to fill in the ‘Self-Evaluation Form for Inquiry into Conditions of Stem Cell Clinical Research
and Applications’.3 In this form, clinics are asked to report truthfully on previously and currently
developed kinds of clinical research and applications with stem cells. Information is requested on (1)
types of cells and forms of cell-processing, (2) the disease types for which cells have been used, (3)
forms of ethics and regulatory approval mechanisms, (4) informed consent procedures, (5)
information on risks and experienced problems, (6) sources of funding and patient fees, (7) number
of patients experimentally treated, and (8) publications or summarizing reports from clinical trials or
other types of clinical studies. Second, this information is evaluated by province-level MOH
workgroups, which are coordinated by the ‘Stem Cell Clinical Research and Application
Standardization and Rectification Work and Leadership Group’, co-founded by the MOH and SFDA in
Beijing (paragraph 2). The task of these province-level workgroups is to appraise the incoming data,
to produce summarizing reports to Beijing (paragraph 4), and during later stages, to play an active
role in the implementation and enforcement of the regulation (paragraph 2).
2
http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohkjjys/s3582/201201/53890.htm
This document has been put on the MOH website.
http://61.49.18.65/publicfiles///business/cmsresources/mohkjjys/cmsrsdocument/doc13829.docx
Translations of these two documents can be requested from the author of this article per email.
3
Self-correction means that all institutes that have not yet received approval, either by the MOH or
the SFDA, must stop clinical stem cell research or application activities until approval has been
obtained. Institutes that continue to carry out unauthorized clinical research or applications have
been announced to be targeted as focal points for rectification (paragraph 2). On the other hand,
clinical trials for stem cell products that have obtained approval by the SFDA are expected to act in
strict accordance with the requirements set out by the SFDA, and in compliance with the Chinese
GCP standards (paragraph 2). The document has announced that no registration applications will be
accepted by the MOH or the SFDA until July 1 2012 (paragraph 2). Information on how applications
for registration will be handled, however, has not been provided in the text. Uncertainty also
remains as to how non-compliance will be dealt with, and which role the MOH and its province-level
workgroups will play in this. It is not clear, furthermore, whether military hospitals (that operate
under the command of the Health Department of the Army General Logistics Department), will be
subjected to the same review and approval procedures as state hospitals, or whether a different
regulatory approach shall apply.
5. The March 2013 announcement of three inter-related draft regulations
On March 7 2013, the MOH has published on its website, three documents that summarize, and
introduce to the public, the basic structure and central regulatory instruments of three inter-related
draft regulations, that have been developed by the MOH for the regulation of clinical stem cell
research and applications, in recent months. In contrast to initial media coverage (Zornoza 2013),
these documents do not constitute the regulatory draft documents themselves, but they provide
comprehensive summaries of the three draft regulations, that introduce the underlying rationale of
the forthcoming regulatory framework, its purposes, central regulatory premises, and
implementation structure. From these documents it becomes clear, that each of the three draft
regulations, consists of ca 35 to 40 articles, that address different aspects of the review and approval
procedures, for clinical stem cell research and applications (details will follow below).
The summaries of the draft regulations have been published on the website of the MOH for the
purpose of public feedback and commentary. The public dissemination of the introductory
summaries of the three draft regulations, constitutes the first publicly visibly step toward regulatory
intervention of clinical stem cell research and applications in China, since the above-mentioned
January 6 2012 notification. The announcement and summary of the three draft regulations,
represent the first move toward realization of the third and the fourth of the four regulatory phases
that were announced by the MOH in the ‘January 6 2012 notification’ (above): “re-certification”
[chongxin renzheng] and “standardized management” [guifan guanli] (following from phases one
and two: “self-evaluation” [zicha] and “self-correction” [zijiu], which were initiated in the course of
2012.
The titles of the three draft regulations are as follows:
1.
Stem cell clinical trial research management methods [ganxibao linchuang shiyan yanjiu
guanli banfa]
2.
Stem cell clinical trial research basic management methods [ganxibao linchuang shiyan
yanjiu jidi guanli banfa]
3.
Guidance principles for stem cell preparation, quality control and preclinical research
[ganxibao zhiji zhiliang kongzhi he linchuangqian yanjiu zhidao yuanze]
The most important points in these three documents are as follows:
(1)
Approval of stem cell based therapeutic applications must be based on phase I, II and III
clinical trials
(2)
In the context of these trials it will not be allowed to charge patients for money
(3)
Clinical trials must be approved by ethics committees, and designed specifically
administrational units, that involve review by expert committees, as formed by provincial and
national level units of the MOH, and the SFDA
(4)
Clinical stem cell trials must be based on, and will be approved on the basis of, solid
preclinical evidence, that established the safety and therapeutic potential of a candidate application
(5)
Stem cell clinical trials must be conducted in line with the SFDA’s ‘Good Clinical Practice
Standards’ (药物临床试验质量管理规范), and related regulatory documents
a.
This means that hospitals and/ or departments that conduct stem cell trials, must be
qualified as GCP hospitals, by the SFDA (will require verification)
(6)
Stem cell clinical trials must be conducted in accordance with ethical norms, as laid down in
the ‘2007 Interim Regulation on the Ethical Review of Biomedical Research involving Human Subjects’
(涉及人的生物医学研究伦理审查办法（试行）), and the Ethics Guiding Principles for hESC
research （人胚胎干细胞研究伦理指导原则）
(7)
Stem cell collection, separation, purification, amplification, certification, packaging, storage
and transport of stem cells that are used for clinical trials, must occur in accordance with GMP
standards.
a.
Staff must be trained in these procedures, and GMP compliance of laboratories and related
technologies and equipment must be certified
(8)
The regulation applies to all types of stem cell research and regulations, with the exception
of hematopoetic stem cells, and related products
(9)
Application and review procedures for stem cell clinical trials
a.
Medical institutions must apply at specifically designed report units
b.
The report units distribute the application to the province level branches of the MOH and
SFDA for formal examination and review
c.
The province level review is followed by a national-level review procedure, through the
‘Stem Cell Clinical Research and Application Regulation Management Work and Leadership Group’,
which is co-founded by the MOH and SFDA and situated in Beijing (this group is also designated in
the document as “the office”)
d.
In The Office the application is reviewed by expert committees, and experts brings site visits
to clinics, as part of the review process
e.
Following this, applications are accepted, or rejected.
(10)
Clinical trials must be conducted in phase I-III format, if there are indicated of serious
adverse events, these must be reported to Ethics Committees and The Office, and the trials must be
immediately stopped
(11)
Progress reports of the trials must be submitted to The Office on a 12 months basis
(12)
Punishment procedures are specified, that hold institutions and personnel that violate
regulatory provisions, directly responsible. Legal persecution will occur under the existing drug
management law.
Appendix:
I. Key state institutions that affect stem cell research in China
(1) Ministry of Science and Technology (MOST) / China
(2) The China Centre for Biotechnology Development
Has been established under MOST in 1983, to promote innovation processes in biotech, and
related commercialization.
Helps to oversee and handle administrative tasks for MOST, especially in the context of the
863 and 973 funding programs.
The office for Human Genetic Materials Management is also housed by the China Centre for
Biotechnology Development.
(3) The Chinese Academy of the Sciences (manages several national key-institutes in basic science,
among which biology, with a key focus also on disease research and drug development)
(4) The Ministry of Health
Oversees and funds all forms of clinical research /clinical translation processes, as well as
clinical applications
Medicine research and applications are regulated through three various subunits of the
MOH
- The SFDA
- Bureau of Science and Education (Kejiao Si)
- Bureau of Medical Administration (Yizheng Si)
- Since 2009 there is also a new office for the monitoring and registration of serious adverse
events after approval, which also operates under the supervision of the MOH
(5) The Chinese Medical Association (CMA)
Plays a leading role in medical education, training and professional exchanges
Oversees 82 specialty societies
Publishes over 70 medical journals
Is also occasionally involved in regulatory processes
Comment: The CMA is to our knowledge currently not involved in the regulation or oversight of stem
cell-based clinical research.
2. Research institutes and stem cell biobanks
Four national level stem cell banks under the Chinese Academy of the sciences:
(1) Beijing Municipality Stem Cell Bank
(2) Southern Stem Cell Bank, in Guangzhou
(3) Stem cell bank of the Chinese Academy of the Sciences, Shanghai
(4) East China Stem Cell Bank (also in) Shanghai
Clinics that offer experimental for-profit therapies
-
Beijing cell permeable rehabilitation center
Qingdao SC therapy and rehabilitation center
Chongqing stem cell therapy center
Beike Biotech
Jilin Silicon Valley Hospital
Tiantan Puhua Hospital
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(accessed August 11 2011): http://wenku.baidu.com/view/f52fd4886529647d27285223.html (note:
this URL is no longer active).
MOST (2013) The domain of "stem cell therapy technology and clinical translation and applied
research", of the 12th Five year Plan's "863" Program for biology and medical technology, (“十二
五”863 计划生物和医药技术领域“干细胞治疗技术临床转化及应用研究” ), February 16 2013,
MOST, URL: http://www.most.gov.cn/kjbgz/201302/t20130208_99717.htm, (accessed April 1, 2013).
Wang, J. (2011) ‘Establishing of national stem cell leadership and coordination committee’ (国家干
细 胞 研 究 指 导 协 调 委 员 会 成 立 ), ScienceNet.cn, October 21, 2011; URL:
http://news.sciencenet.cn/htmlnews/2011/10/254182.shtm, accessed April 1, 2013.
Zhai, X.M. (2007) ‘Challenges & Governance / Regulatory Responses in China’, conference paper,
BIONET workshop: October 2007; Shanghai.
Zornoza, L. (2013) ‘China proposes stem cell clinical trial rules’, Website of Regulatory Focus, URL:
http://www.raps.org/focus-online/news/news-article-view/article/2983/china-proposes-stem-cellclinical-trial-rules.aspx, (accessed April 2, 2013)
2) India (C.H & P.P)
Contextual sketch:
The two main centres for both commercial and public research in the area of stem cells are the cities
of Bangalore and Mumbai (referred to as ‘bioclusters’). Bangalore has several of the most respected
scientific institutes working in the area of stem cell research including the following:
 the National Centre for Biological Sciences (NCBS) which has recently begun an institute
dedicated primarily to stem cell research (the Institute for Stem Cell Biology and
Regenerative Medecine, or inSTEM);
 the Jawaharlal Nehru Centre for Advanced Scientific Research (JNC) in which one of the
scientists, Dr. Maneesha Inamdar developed the first human embryonic stem cell line in
India which is now also available in the UK Stem Cell Bank;4
 the Indian Institute of Science (IISC) where basic research is also being conducted in the area
of embryonic stem cell research and scientists there have developed an embryonic stem cell
line from mice.
In addition, a number of biotech companies working in the area of stem cell research and therapy
have also sprung up in Bangalore in the last decade. Most notable of these is Stempeutics which has
labs in Bangalore, Manipal (also in the state of Karnataka) and Kuala Lumpur, Malaysia. According to
most reports, they are not engaged in therapy but only conducting clinical trials at the moment,
although some people that CH has spoken to have alluded to the fact that they also have ‘patients’.
There are a number of other companies that provide stem cell treatment to patients, although will
not admit to doing so openly and rather emphasise the research and biobanking elements of their
work. These include companies such as Advanced Neuro-Science Allies (ANSA), International Stem
Cell Services Ltd. and Stem Cell and Tissue Engineering Research Private Ltd.
In Mumbai, the largest and most advanced commercial enterprise in the field of stem cell research
(and therapy?) is Reliance Life Sciences (RLS), part of the Reliance corporation. As mentioned, they
claim to have developed their own human embryonic stem cell line and are currently conducting
clinical trials for specific stem cell ‘products’. Many smaller ventures also exist, mostly providing
experimental stem cell treatment to patients who are willing to pay exorbitant sums of money (a
few of these include Dr. Rajput’s Orthopaedic and Stem Cell Research Center, Elixir Hospitals which
uses technology from Cytori, Emprocell). One middle-sized company, Kasiak Research, is supposedly
conducting clinical trials and is headed by the former CEO of Stempeutics, Dr. Satish Totey.
In addition, numerous small clinics and companies have recently been established through the major
cities in the country including Delhi, Hyderabad, Pune, Calcutta and Cochin.
In 2002, the Indian Council of Medical Research, institutionally located under the health ministry,
announced a policy that permitted therapeutic cloning and encouraged stem cell research. But, the
previous year the Department of Biotechnology (DBT), under the science ministry, had also issued
guidelines, and some clinics had exploited the difference between the two sets of guidelines,
starting clinical treatments (Jayaraman 2005).5 With an increasing number of funding applications to
the ICMR and the DBT, media reporting of unethical practices in biomedical research, and India’s
growing thrust on stem cell research, the DBT and ICMR in 2005 decided to jointly devise guidelines,
4
Reliance Life Sciences (RLS) had developed an embryonic stem cell line prior to Dr. Inamdar but has neither made it
available to the public nor published the details and, as such, cannot be confirmed.
5 Jayaraman, K.S. (2005) ‘Moving too fast: the All India Institute of Medical Sciences is already using stem cells to treat
stroke’, Nature, Vol. 434, 17 March, p. 259.
which were released as the Guidelines for Stem Cell Research and Therapy in November 2007 (DBTICMR 2007).6 The guidelines permit research pertaining to adult and umbilical cord blood stem cells
if approved by Institutional Committees.
The guidelines are not free from shortcomings, expressed in the comments by the legal critic, Basu:
‘The extent of ambiguity and subjectivity prevalent in the Draft ICMR Guidelines can be gauged from
the phrase’ ”Any violation of guidelines would be strictly dealt with” (Basu 2006).7 In its current form,
the guideline is a mere soft law, presently awaiting approval by the government before it can
become law. Though the central guidelines (DBT-ICMR 2007) permit basic, translational and clinical
research on stem cell science under certain conditions, the X and Y Hospital hubs provide service
facilities for therapies in various stages of development indiscriminately as experimental therapy or
clinical trials. The DBT-ICMR clearly stipulates that all institutions and investigators engaged in
human stem cell research, both public and private, should be registered (Clause 4.1) and require
prior approval and ethical clearance at multi-level authorities both at the institutional level as well as
at the national level (Clause 4.5).
A revised version of the draft guidelines were issued on March 30, 2012. The title of the draft
guidelines has changed so that it no longer includes the word ‘therapy’ (they are now known as the
‘National Guidelines for Stem Cell Research’). The revised guidelines have been updated to include
iPSC and clinical trials.
Prior to then, the ICMR conducted a series of public consultations beginning in February 2010 in the
cities of Bangalore, Delhi, Calcutta and Dibrugarh and invited researchers, members of the
pharmaceutical and biotech industries, patient groups, clinicians, ethicists, members of legal and
religious bodies and the general public to give feedback on how the guidelines should be revised. In
drafting the revisions of the guidelines, they also included members of commercial companies
working in the area along with scientists, clinicians and members of the ICMR and DBT. These were
organised according to different themes:
1)
Product and development;
2)
Pre-clinical and clinical trials;
3)
Biobanking in stem cells; and
4)
Standard Operating Procedures (SOPs), Quality Assurance and Control, informed consent.
The regulation at present is very much centred on ‘self-regulation’. Companies must register with
the Indian Clinical Trials Registry (http://ctri.nic.in/Clinicaltrials/login.php) to be granted official
permission to conduct clinical trials. In addition, hospitals are officially required to form their own
institutional ethics committees that will oversee clinical trials and ensure that they are being
conducted according to protocols. A National Apex Committee on Stem Cell Research and Therapy
(NAC-SCRT) which has been charged to ‘oversee and monitor the activities in the field of Stem Cell
Research’ although how often the committee meets and how involved they are in implementing
policy. In addition, all bodies involved in stem cell research are required to register with the ICMR. At
present, CH was told that they have received approximately 25 applications and they have started
‘scrutinising’ these. In addition, CH was told that the ICMR only registers these bodies, it does not
provide accredidation.
6
DBT-ICMR (2007). Guidelines for stem cell research and therapy. Published by the Director General, Indian Council of
Medical Research, New Delhi. Available at: http://www.icmr.nic.in/stem_cell/stem_cell_guidelines.pdf
7 Basu (2006). Ibid.
Relevant documents:
ICMR-DBT Guidelines for Stem Cell Research 2012
Website: http://icmr.nic.in/stem_cell_guidelines.pdf
Constitution of National Apex Committee for Stem Cell
Website: http://www.icmr.nic.in/icmrnews/constitution_nac_stem.pdf
Clinical Trials Registry - India (CTRI)
Website: http://www.ctri.nic.in/Share
Embryo creation and use in research
A good summary of the regulations on embryo creation and use in research in India (according to
the 2007 Guidelines for Stem Cell Research and Therapy produced by the Indian Council of Medical
Research and the Department of Biotechnology) can be found in the Witherspoon Report (2012,
Appendix E ‘Overview of International Human Embryonic Stem Cell Lines’):8
‘The [2007] Guidelines divide research on human stem cells into three areas: permissible, restricted,
and prohibited. Permissible research includes in vitro studies on previously established cell lines
from any cell type (including ES cells), in vivo studies in animals with established cell lines from any
type of stem cells (including ES cells), the establishment of new ES cell lines from “spare” IVF
embryos, and clinical trials with minimally manipulated cells. The Guidelines restrict the creation of
human embryos by IVF or SCNT for the purpose of deriving an ES cell line: If researchers seek to
create ES cell lines specifically for research purposes, they must provide explicit justification for the
procedure, establishing that the creation of the embryo is essential for their research. The
Guidelines also restrict clinical trials using cells that have undergone major manipulations such as
genetic alteration (which would seem to include many iPS cells and ANT-derived stem cells). And the
Guidelines restrict various forms of chimera research, such as the introduction of human ES cells into
embryonic animals. The Guidelines prohibit germ-line engineering and human cloning for
reproductive purposes, the growing of embryos in vitro for longer than fourteen days, transferring
SCNT embryos into a uterus, and the breeding of animals that have received human ES cells.’
Specific language in the guidelines on the area of embryo creation and research includes:
Permissible areas of research (p. 4):
6.1.4
Establishment of new hES cell lines from spare, supernumerary embryos with prior approval of the
IC-SCRT and IEC provided appropriate consent is obtained from the donor as per guidelines given
below. Once the cell line is established, it shall be registered with the IC-SCRT and NAC-SCRT.
Restricted areas of research (p. 4-5):
6.2.1
Creation of a human zygote by IVF, SCNT or any other method with the specific aim of deriving a hES
cell line for any purpose.
•
Specific justification would be required to consider the request for approval by the NAC-SCRT
8
While much of the rest of the report is quite politically charged, this overview of the regulations in India is relatively
comprehensive (http://www.thenewatlantis.com/publications/appendix-e-overview-of-international-human-embryonicstem-cell-laws).
through IC-SCRT /IEC.
•
It would be required to establish that creation of zygote is critical and essential for the
proposed research
•
Informed consent procedure for donation of ova, sperm, somatic cell or other cell types as
detailed in these guidelines would need to be followed.
The 2012 updated guidelines expand on these points but maintain the same conclusions:
2012 Guidelines:
7.1 Permissible areas of research (p. 12-13)
7.1.4 Establishment of new hES cell lines from embryos left unutilized in IVF programme, or iPS cell
lines with prior approval of the IC-SCR and IEC provided appropriate consent is obtained from the
donor as per guidelines given below. Once the cell line is established, it shall be registered with the
IC-SCR and NAC-SCR and deposited in a cell bank for use by others.
Restricted areas of research (p. 14):
7.2.1. Creation of human zygote by IVF, SCNT or any other method with the specific aim of deriving a
hES-cell line for any purpose. This requires the following:
a.
Specific justification would be required to consider the request for approval by the NAC-SCR
through IEC and IC-SCR.
b.
It would be required to establish that creation of zygote [sic] is critical and essential for the
proposed research, and no other alternative will serve the purpose.
c.
Informed consent procedure for donation of ova, sperm, somatic cell or other as detailed in
these guidelines would need to be followed.
Prohibited areas of research (p. 15-16):
7.3.2 Any in-vitro culture of intact human embryo, or any organized cellular structures that have
the potential of developing into human organs and tissues, regardless of the method of its derivation,
beyond 14 days or formation of primitive streak, whichever is earlier.
7.3.4. Any research involving implantation of human embryo into uterus after in-vitro
manipulation, at any stage of development, in humans or primates.
Storage and research use of human tissue
Aside from sections of the draft guidelines stating that cord blood stem cell banking is permissible
but must be registered with the DCGI (11.1, p. 28), there are no other specific provisions addressing
the storage and research use of human tissues. Under the scope of the National Apex-Committee for
Stem Cell Research and Therapy, it states on p. 41, section 1.1.8 that:
‘NAC-SCRT will set up standards for safety and quality, quality control, procedures for collection and
its schedule, processing or preparation, expansion, differentiation, preservation for storage, removal
for storage to assure quality and/or sterility of human tissue, prevention of infectious contamination
or cross contamination during processing, carcinogenicity, xenotransplantation.’
As far as I can tell, the NAC-SCRT has not made this set of standards public as of yet.
Low risk clinical use (e.g. autologous therapies)
Not allowed, only research and clinical trials are permissible (hence the title of the draft guidelines
from 2007 [‘Guidelines for Stem Cell Research and Therapy] has been amended to ‘Guidelines for
Stem Cell Research’ in the 2012 revised draft.
3) Japan (M.S.F & P.K.P)
This country report contains a section on policy-background (I) and regulation (II). As the regulatory
situation in Japan is changing radically this year, this report will be out-dated soon. The last part (III)
sketches the expected regulatory changes in 2013/4.
Part I
The Japanese government has taken the initiative to lead RM in Japan: In 2007, the Council for
Science and Technology Policy (CSTP), a scientific advisory board reporting to the Prime Minister, set
up a policy for generating scientific achievements that would benefit the society. The policy set out a
strategy to launch government-led projects, and one of the areas selected for this initiative was
regenerative medicine. The Ministry of Education, Culture, Sports, Science and Technology (MEXT),
the Ministry of Economy, Trade and Industry (METI) and the Ministry of Health, Labour and Welfare
(MHLW) are responsible for the development of regenerative medicine R&D and its clinical
application in Japan. Fundamentally, MEXT is responsible for basic research, METI is responsible for
bringing basic research to clinical research and commercialisation, and MHLW is responsible for the
research close to clinical application. They have implemented various strategic initiatives and
continuously made significant investments into stem cell and regenerative medicine research (The
British Embassy 2011).9
Below is a timeline of major incentives and government measures which are relevant to the
Japanese biotech sector:10
1998: Legislation to promote technology licensing from universities to the private sector was
enacted, and about 40 technology licensing organisations were established by 2004.
1999: The Japanese equivalent of the Bayh-Dole Act, a US law related to intellectual property rights
for academic-industry collaborations, was enacted.
1999: A subcommittee of the cabinet Council on Science and Technology (CST) presented the Prime
Minister with a report on techniques that would potentially enable human reproductive cloning.
Based on this subcommittee’sr ecommendations, the National Diet (Japan’s parliamentary body)
enacted the ‘‘Law concerning regulation of human cloning techniques and other similar techniques’’
in 2001 (National Diet, 2001, see Part II, Regulation), one of the first laws in any country to expressly
prohibit human reproductive cloning in any country.
2000: Legislation to strengthen industrial technologies was enacted.
2001: The Ministry of Economy, Trade and Industry [METI] unveiled a plan to increase the number of
university spin-outs to 1,000 for three years from 2002 to 2004. It was one of the government’s 15
proposals to create new markets and employment amid the economic recession.
2002: The committee on Biotechnology Strategy headed by the Prime Minister was created and
issued the Biotechnology Strategy Guidelines. With 200 action plans, it aims to grow the biotech
9
Life Sciences Team Science and Innovation Section The British Embassy, Tokyo (2011) Brief of Regenerative Medicine in
Japan, July 2011.
10 Ichiko Fuyuno & Kaoru Kambe (2009) 2009 Biotechnology Industry in Japan Life Sciences Team, Science and Innovation
Section, The British Embassy, Tokyo. April 2009.
market to 25 trillion yen (£185 billion) by 2010 from 1.3 trillion yen in 2001, and produce 1 million
new jobs in the biotechnology sector by 2015. An interim report, released in 2008, said 70% of them
were completed or almost completed by the end of 2007.
2003: National universities were given administrative authorities (independent administrative
institutes).
2006: The government issued ‘Innovation 25,’ a forward-look strategy to realise sustainable society
in 2025.
2006: In August guidelines were published focusing on the maintenance of safety and determination
of efficacy, ethical conduct, informed consent for donors and patients, quality assurance,
transparency, and protection of privacy (MHLW, 2006, see Part II, regulation).
2007: The Ministry for Education, Sports, Culture, Science and Technology [MEXT] reacted to
Yamanaka Shinya’s announcement of the discovery of the iPS factors in humans. On December 22,
2007, that is, about a month after his announcement, the Ministry published a document ‘The
General Strategy to Promote iPS Cell Research [iPS Saibou (Jinkou-Tanousei Kansaibou) Kenkyu nado
no kasokuni muketa Sougou Senryaku] (see Part II, regulation). In this document, MEXT described
Yamanaka’s success as ‘a national accomplishment of which we are proud’ and listed plans for
further support ‘to win the international competition’ in this field.
On December 25, 2007, the JST organized a symposium titled ‘The Impact of
Induced Pluripotent Stem Cells - the Future of iPS Cell Research Research - [Jinkou-Tanousei
Kansaibou no Inpakuto - iPS saibou kenkyu no kongo -].’ In this symposium, Yamanaka argued that
‘all researchers in this field should assemble and form Team Japan,’ and revealed MEXT’s plan to
establish a consortium for iPS cell research as a platform for the researchers ‘to share the latest
research results and materials’ (JST 2008, see regulation).
June 2008: The government announced a plan to create ‘Innovation Creation Organisation,’ a 50-50
funding corporation jointly set up by the government and the private sector.
Dec 2008: The government’s committee compiled an interim report of “Drastic Reform with
Effective and Agile Movements for BT innovation in Japan (DREAM BT Japan).”
2008: The expert committee under the Cabinet’s Office published recommendations for lifting the
moratorium on somatic cell nuclear transfer in 2008, after more than 3 years of discussion.
2009: In the spring of 2009, the Tokyo Stock Exchange and the London Stock Exchange plan to
launch ‘Tokyo AIM,’ which targets professional investors in Asia and will be the Japanese equivalent
of the UK’s Alternative Investment Market (AIM).
2009: MEXT launched the iPS cell research 10-year roadmap, to effectively and holistically promote
research for the early translation of research achievements into clinical practice.
2011: MEXT and the Ministry of Health, Labour and Welfare [MHLW] launched the program of the
Highway for Realization of Regenerative Medicine, which selected a few non-iPS cell projects along
with others focusing on iPS cells.
In January 2011, the government announced the establishment of the Office of Medical Innovation
in the Cabinet Secretariat.
2012: Yamanaka announces that he wants to build a bank of iPS stem cells for therapeutic use. The
iPS Cell Stock project received permission from MoHWL to allow the creation of cell lines from the
thousands of samples of fetal UCblood held around the country.
2012: Scandal occurs in stem cell therapy clinic in Kyoto (Bethesda Clinic), where a South Korean
patient receives therapy and dies after returning to South Korea. The clinic is closed, but its owner
sets up anew in Fukuoka.
2013: Takahashi Masayo announces the application to the MEXT for the clinical application of RPE
stem cells for macular degeneration.
2013: In 2013, under Shinzo Abe’s LDP government, science is a big winner, received a 10.3 trillion
Yen economic stimulus package, approved by the cabinet on 15 January. The biggest beneficiary of
the stimulus is stem-cell research, especially that geared towards clinical applications. The science
ministry alone has earmarked 21.4 billion Yen for research on stem cells.
Part II Regulation
Human embryonic stem cell research/ therapeutic cloning
Since the first hES cell line was reported in 1998,11 many countries convened public discussions to
shape policies surrounding hES cell research. With a pro-science government and without major
objections from religious or other groups, Japan was recognized as one of the world's permissive
countries. In principle, Japanese policies and guidelines (see Regulation for the derivisation and
utilisation of hESC lines, 2001 below) are moderate and similar to many other countries. For
example, hES cell lines can be derived using surplus embryos from fertility clinics. Even somatic cell
nuclear transfer (SCNT) seems to be allowed under very strict oversight and regulation, although the
government guidelines are not yet finalized. (Norio Nakatsuji 2007). In practice, however, it turned
out to be nearly impossible to get access to human embryonic stem cell lines or permission to create
them.
Soon after reports of the cloning of mammals such as sheep and mice from somatic cells, Japan
began to develop policies to address the possibility of performing SCNT with human cells or genetic
material. In 1999, a subcommittee of the cabinet Council on Science and Technology (CST) presented
the Prime Minister with a report on techniques that would potentially enable human reproductive
cloning. Based on this subcommittee’s recommendations, the National Diet (Japan’s parliamentary
body) enacted the ‘‘Law concerning regulation of human cloning techniques and other similar
techniques’’ in 2001 (National Diet, 2001, see Regulation), one of the first laws in any country to
expressly prohibit human reproductive cloning in any country. The new law did not, however,
address legal issues surrounding the generation of research-use human embryos by somatic cell
nuclear transfer. Only in 2008, the guidelines allowed a simplified form of using hES lines, but a twostep application for permission to create hESC lines was still required.
Somatic Stem Cells and Clinical Research
Although hematopoietic stem cells have been used in clinical applications for decades, for much of
this time there were no specific governmental regulations on clinical research with somatic stem
11
Thomson, J.A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).
cells, leading to concerns that this may have made it possible for inappropriate experimental or nonefficacious clinical protocols to be implemented. In response to the demands of this rapidly evolving
field, the Ministry of Health, Labor, and Welfare (MHLW) organized an expert committee on clinical
research with human stem cells in 2001. Its discussion focused on three key questions: the limits of
clinical application, systems for evaluating clinical research with somatic stem cells, and issues
surrounding the harvesting, processing, transplantation, and monitoring of stem cells and their
derivatives. After these deliberations, guidelines focused on the maintenance of safety and
determination of efficacy, ethical conduct, informed consent for donors and patients, quality
assurance, transparency, and protection of privacy were published in 2006 (MHLW, 2006, see
Regulation). These guidelines also call for a two-tiered review system, by the institutional review
board and governmental committee. As of February 2010, 36 research applications had been
submitted, 24 of which were approved. Here again, the process from convening of the expert
committee to the publication of the guidelines required 5 years (Kawakami et al 2010).
Toward clinical application and innovation:
In 2009, the Japan Science and Technology Agency (JST) indicated that Japan was lacking vision and
an overall strategy to promote the translation of laboratory-based research into clinical applications.
It therefore introduced the following initiatives:12
a. iPS cell research 10-year roadmap
In 2009, MEXT launched the iPS cell research 10-year roadmap, to effectively and holistically
promote research for the early translation of research achievements into clinical practice. Four
major objectives are as follow:
 Identification of iPS initialising mechanisms (basic/fundamental research)
 Creation and distribution of standardised iPS cells (standardisation)
 Creation and verification of patient-derived iPS cells for drug discovery and clinical research,
and the establishment of the iPS cell bank
 Regenerative medicine (pre-clinical and clinical research for treatment technologies using
cells, tissues, tissue transplants differentiated from iPS cells).
b. Project for realisation of regenerative medicine
The national project funded by MEXT to promote regenerative medicine was initiated in 2003 based
on a ten-year plan and currently in its second phase (2008-2013). The project was led by three
flagship universities and one research institute (namely, Kyoto, Tokyo and Keio Universities and
RIKEN Center for Developmental Biology) in collaboration with major academic, industrial and
government bodies.
c. ‘Regenerative medicine research highway’ initiative
In order to advance and accelerate the development of stem cell research and bring them through
to clinical application, a new scheme called ‘Regenerative medicine research highway’ initiative was
implemented in 2011 as part of MEXT’s project for realisation of regenerative medicine.
d ‘Life Innovation’ and Office of Medical Innovation
New Growth Strategies released by the government in June 2010 emphasise that ‘life innovation’
and ‘green innovation’ were to be the drivers of the country’s future growth and prosperity. ‘Life
Innovation’ aims to advance health, medical and nursing-care industries including fields such as
12
Life Sciences Team Science and Innovation Section The British Embassy, Tokyo (2011) Brief of Regenerative Medicine in
Japan, July 2011.
regenerative medicine and drug discovery.
Websites for regulation:
Cabinet Office (CAO) (1995) The Science and Technology Basic Law (in English), unofficial translation:
http://www8.cao.go.jp/cstp/english/law/7Law-1995.pdf
Ministry of Health and Welfare (1999) Saibou Sosiki wo riyoushita Iryouyougu mataha Iyakuhin no
Hinshitsu oyobi Anzensei no kakuho nitsuite (Iyaku-hatsu dai 906 gou) [the Notification on Quality
and Safety Assurance of Cell/Tissue-derived Medical Devices and Pharmaceuticals (Notification
No.906)]:
http://www.pmda.go.jp/operations/shonin/info/report/saibousosikisinsei/file/906goutuuti.pdf
Ministry of Education, Culture, Sports, Science and Technology (MEXT) (2001) Guidelines for the
derivation and utilization of human embryonic stem cells (Hito-ES saibou no jyuritsu oyobi siyou ni
kansuru sisin). Enacted September 25, 2001. http://www.lifescience. mext.go.jp/files/pdf/32_88.pdf
[in Japanese], http://www.lifescience.mext.go.jp/files/pdf/32_ 90.pdf [in English].
National Diet, Japan. (2001). Law concerning regulation of human cloning techniques and other
similar techniques (Hito ni kansuru clone gijyutu-tou no kisei ni kansuru houritsu). Enacted June 6,
2001. http://www.lifescience.mext.go.jp/files/pdf/1_3.pdf
[in Japanese], http://www.cas.go.jp/jp/seisaku/hourei/data/ htc.pdf [in English].
Council for Science and Technology Policy (CSTP), Cabinet Office, Japan. (2004). Basic concepts in the
handling of human embryos (Hito-hai no toriatsukai ni kansuru kihonteki kangae-kata) Published July
23, 2004. http://www.lifescience.mext.go.jp/files/pdf/6_28.pdf [in Japanese].
Ministry of Health, Labour, and Welfare (MHLW), Japan. (2006). Guidelines for clinical research using
human stem cells (Hito-Kansaibou wo mochiiru rinsyou-kenkyu ni kansuru sisin).
http://www.mhlw.go.jp/bunya/kenkou/
Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. (2007). Guidelines for
the derivation and utilization of human embryonic stem cells (Hito-ES saibou no jyuritsu oyobi siyou
ni
kansuru
sisin).
Amendment
August
1
2007.
Available
at:
http://
www.lifescience.mext.go.jp/files/pdf/32_165.pdf [in Japanese].
Ministry of Education, Culture, Sports, Science and Technology (MEXT) (2007) iPS Saibou (JinkouTanousei Kansaibou) Kenkyu nado no kasokuni muketa Sougou (The General Strategy to Promote iPS
Cell Research Senryaku):
http://www.lifescience.mext.go.jp/download/news/ips_senryaku.pdf.
Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. (2008). On germ cell
differentiation from human pluripotent stem cells and usage. (Hito-ES-saibou tou kara no seisyoku
saibou
no
sakusei/riyou
ni
tsuite.).
December
19,
2008.
http://www.lifescience.mext.go.jp/download/rinri/es63/es63- 02.pdf [in Japanese].
Japan Science and Technology Agency (JST) (2008) Tanousei Kansaibou Kenkyu no Inpakuto –iPS
saibou kenkyu no kongo- Houkokusyo [Report on the Impact of Pluripotent Stem Cell Research –the
future of iPS cell research-]: http://www.jst.go.jp/report/2007/071225 ips symporeport.pdf
Part III
A law is under construction concerning stem cell ministration and treatment institutions: its culture
and utilization will have a 2-stem system for permission. The notification of the MoHWL and IRB
permission required are often violated, as the regulation has little clout as there is no fine or
punishment. For this reason, it was not possible to investigate the death of a man after stem cell
treatment at Bethesda, while a monthly 500 Korean patients are treated in the Xinjuku clinic.
MoHWL says it is drafting a law proposal applying to both research and treatment, where high-risk
treatment requires licence/notification. Accidents need to be prevented as society has high
expectations of RM.13
Another law will appear to the effect that it will make the support of RM obligatory.
13
Mainichi Shimbun, 23 Dec 2012再生医療:幹細胞投与に罰則も
培養と使用規制の新法検討.
4) South Korea (C.K.C)
Policy Context
The South Korean government’s policy on stem cell research
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

Bio & health industry is one of the country’s three key industries (alongside with cultural
industry and SoC(System on Chip) that is expected to create jobs and Korea has potential to
“dominate” the global [biomedicine/health] market
Key policy strategies include: “constructing a success model of tailored [personalized]
biomedicine” and “developing ‘IT hospitals’ as an export industry”
Government funding of biomedical research to be increased: stem cell research funding to
be tripled by 2015 (120 billon Korean won = to £7 billon).
Buzzwords in the S. Korean bio-health policy/publicity documents: globalisation,
international collaborations
The Global Regenerative Medicine Initiative launched in October 2011 by the Ministry of
Health and Welfare (MOHW) in order to promote the practicalization of the nation’s
regenerative medicine research and to strengthen the competitiveness of related
technologies and Global Stem Cell and Regenerative Medicine Accelerating Center (GSRAC)
appointed accordingly in December 2011. (source: press release by MOHW)
A strong government support to drive medical tourism industry (with the full assistance of
the Korea Tourism Organization)
National Stem Cell R & D Investment: The South Korean health ministry announced last
month that research into stem cells and regenerative medicine will receive a funding boost
of 33 billion won (US$29 million) in 2012, four times that given in 2011. Overall, six different
ministries will invest 100 billion won in stem-cell research this year. (“South Korea steps up
stem-cell work”, Nature News, 1 May 2012)
Bio-vision 2016 (2007-2016)14
This stipulates the second national framework plan for biotechnology promotion.
Targets include:




World 7th place in scientific publication (from 13th in 2005)
World 7th place in patent treated (from 14th in 2005)
Increase of human resources from 9600 in 2005 to 17300
Increase of market size from US$ 2.9 billion in 2005 to US$ 65 billion [by 2016]
Strategies
The
restructuring
national
Tasks
innovative (i) Increasing strategic, efficient investment in biotechnology system
of
the (ii) Improving coordination between governmental departments
biotech (iii) Improving the biotechnology policy analysis and evaluation
14 Ministry of Science and Technology, Ministry of Commerce, Industry, and Energy, and the Ministry of Health and
Welfare. et al. (2006) Bio-Vision 2016: The 2nd Framework Plan for Biotechnology Promotion.
promotion system
system
Expanding infrastructure (i) Advancing the basic capability of national biotechnology
for upgrading R&D
(ii) Training excellent biotechnology personnel to respond the
rapidly changed environment
(iii) Improving the quality of international joint research and
international cooperation
(iv) Upgrading the infrastructure for biotechnology R&D
Achieving globalization of (i) Acceleration of R&D investment for biotechnology
bio-industries
industrialization
(ii) Improvement of the global competitiveness of bio-companies
(iii) Expanding the biotechnology infrastructure
(iv) Activation of technology transfer and improve support systems
for bio-industries
The regulatory and legal (i) Cultivating sound biotechnology research ethics
overhaul
and
the (ii) Improving the laws and regulations on bioethics and bio-safety
enhancement of public (iii) Raising awareness among the general public and spread the
acceptance
relevant culture
Regulation
South Korea has only recently established national legislative regulatory frameworks and set up
institutions govern the use of stem cells. Therefore relevant regulations have been amended and
added in the last decade to keep up with technological progress and consequent clinical and
commercial applications. Furthermore, it is quite clear from regulatory documents that the national
regulatory authorities aim to push deregulation (regulation in some cases) in order to promote
national bioindustry.
Historical Overview of Stem Cell Research Regulations in S. Korea
Ministry
in Title
Aims and contents
charge & Year
MOHWFA 1987
Guidelines
for To protect human subjects of clinical drug trials; to be
Good
Clinical directed at research institutions and pharmaceutical
Practice
companies; Made binding in 1995 and amended in
2000.
MOHW 1997
Guidelines
on
Recombinant DNA
Experiment
KMA 1999
Guidelines
on Initiated by the KMA’s Investigative Committee that
Research
on was set up to investigate the allegation of human
Cloning Lives
cloning at the Kyunghee Fertility Clinic; prohibits
research on human embryos for cloning purposes,
implantation of cloned embryos into a woman’s
uterus, and experimentation on embryos after 14 days
post-fertilisation (Article 4); prohibits the trading of
sperm, eggs or somatic cells (Article 8)
KHIDI 2001
Guidelines
on
KMA 2001
SCRC 2003
Human Stem Cell
Research
and
Supervision
Guidelines
of Non statutory professional rules enforced by the KMA;
Ethics for the to act ethically and secure consent to treatment
Medical
(Article 23); to refrain from trading in human eggs
Professional
(Article 55); to limit cloning research to curing and
preventing specific diseases (Article 68); to establish
ethics committees in hospitals and research
institutions (Article 74-75).
Guidelines
for Apply to any research which the SCRC funds; require
Review
of stem cell research be supported by surplus IVF
Research
embryos, and prohibit the production of human
Proposals
embryos for stem cell research.
Amendment Bill of the Bioethics and Safety Act/The New Bioethics and Biosafety Amendment Bill
(Draft 17-8353)







To be enforced from the 2nd of Feb 2013 and public hearing took place in June 2012
New clauses added on genetic discrimination; gene therapy; and gene test.
A conservative interpretation of government’s policy since it leaves certain interpretive
space and makes exceptions [but ‘for whose benefits?’ remains as a question]
Demonstrates that Korean regulative authority attempts to close existing loopholes and deal
with regulative vacuum
On the importance of international collaborations:
“In order to secure bioethics and safety, one should seek after necessary international
(research) collaborations and should make efforts to accept universal international
standards.”
The amended bill has faced resistance from the medical professionals since, for being
‘unrealistic’
Regulation on Review and Authorization of Biological Products (KFDA Notification No. 2010-50,
Amended on June 29, 2010; Established on May 23, 2003; Seoul: KFDA, 2010)

“For autologous cartilage and skin cell therapy products, the therapeutic confirmatory
clinical study data may be submitted after the product is marketed. In this case, if the
product has the same indications as those previously authorized (where authorization
conditions regarding therapeutic confirmatory clinical study are removed) or if it is intended
to include the indications similar to those of the previously authorized products in light of
their causes, progress, and outcomes, information and data on clinical pharmacological
study and therapeutic exploratory clinical study may not be required.”

This regulation defines "orphan drug" as “a medicinal product that is intended to treat a rare
disease or condition, and requires immediate introduction, since appropriate alternative
medicinal products are not available” and this could include stem cell drugs. According to
this regulation, “Orphan drugs are designated by the Commissioner of the Korea Food and
Drug Administration. For orphan drugs, the single dose toxicity data and short-term repeat
dose toxicity data (1-3 months) (including target organ toxicity data) may be provided as the
toxicological data, while the effectiveness study data or clinical study data may be submitted

as the pharmacological data. Especially, for orphan drug used for treatment of a rare lifethreatening disease or in emergency cases, exploratory study may be substituted for
confirmatory study on the conditional submission of confirmatory study after authorization.
KFDA has eased its regulation on autologous cell therapy products in last couple of years by
granting exemption from submission requirements & exemption from phase I trial when the
data have been published in professional journals (Notification 2011-225, 2011). KFDA also
amended its act to specify the definition of gene therapeutics (Notification 2012-3, 2012).
Recent new development in stem cell regulations

A South Korean Parliament member (Seung-Jo Yang) proposed a new law for the
management and transplantation of stem cells (1 Aug. 2012) and the National Health and
Welfare Committee referred the bill to the Conference for review (17 Sep. 2012) which is
still pending.15

The proposed law suggests that the harvesting and preservation of stem cells must be
controlled by national regulation, specifically a management system for stem cell harvesting,
storage and implantation. The bill under consideration proposes that physicians can use
their own stem cells to treat conditions under their discretion if those stem cells are
properly expanded, managed, handled and provided to clinicians for them at or above the
proposed standards, which is the best news patients with incurable diseases for which no
existing cure is available by current medicine have had in a long time. (cf. The current Korean
policy requires stem cell programs - regardless of whether there are available therapies for
patients with any particular condition - to complete clinical trial phase III for market
approval.)

Other recent developments worth mentioning:
The National Stem Cell Bank of Korea has launched in October 2012 as part of efforts to promote
research into advanced medical treatment. According to press release issued by the Ministry of
Health and Welfare, the bank will be supervised by the Korea National Institute of Health (KNIH)
under the Ministry of Health and Welfare and plans to establish a network between foreign and local
researchers and play an active role in managing research resources. It will acquire, preserve, and
manage domestic stem cell lines as well as cooperate with overseas banks to receive research
15
The Korea Federation of Organizations of the Disabled, the largest Korean patient’s group, publicly expressed their
support for this bill by issuing a statement (8 Feb. 2013) as well as petitioned the presidential transition committee
government for a special law that exempts phase III study of autologous stem cell drugs (06 Feb. 2013). In interviews with
me, RNL Bio personnel also expressed their strong support for this bill. In their press release on the proposed bill, RNL
argues:
‘When the bill is passed, high standards will be established and the better methods will immediately be made
obvious to both government and patients. Through this the stem cell community expects a leap in industrial growth, and a
leap in the ethical adherence of physicians to do no harm to patients and to provide remedies where possible for the aid of
their patients. The Korean medical community also expects not only to see an influx of domestic patients but also many
patients from other nations that lack standards for the growth of patients' own stem cells. South Korea, many economists
predict, could become the Mecca for stem cell therapeutics’.
(“South Korean lawmakers one step from rigorous new system for stem cell Advancement: scientists, physicians and
patients applaud, urge lawmakers to complete The Job”, PRNewswire, 19 Sep. 2012, http://www.prnewswire.com/newsreleases/south-korean-lawmakers-one-step-from-rigorous-new-system-for-stem-cell-advancement-scientists-physiciansand-patients-applaud-urge-lawmakers-to-complete-the-job-170377556.html)
information on stem cells to support local scientists. The bank will act as the core part of a
“regenerative center” which will be established in 2015.16
Key Korean bioventures in stem cell research & therapy: based on sources of SC
Division of labour among Korean biotech firms?
Adipose-derived SC
(Autologus)
Mesenchymal stem cell
[RNL BIO] [Antrogen] [Cha Bio]
Umbirical Cord Blood
Adult Stem Cell
Stem Cell Med
Neural SC [Cha Bio]
(Allogeneic)
[Medipost] [Cha Bio]
Embryonic Stem Cell
Hematopoietic SC
[Cha Bio]
[Parmicell] [Cha Bio]
Fetal Stem Cell
[Cha Bio]
Umbirical/Placental
[Cha Bio]
IPS
Table 1 KFDA-Approved Stem Cell Drugs*
(*as of 29 Aug. 2012; 3 in total)(Source: KFDA & other)
Name
Company
Date
FCB
Pharmicell
Hearticellgr
am-AMI
2011.07.01
Target
Note
mesenchymal
stem
cells
cultured from a
patient's own
bone marrow
(that
are
injected into the
coronary artery
the first licensed stem cell
treatments that use bone marrow–
or cord blood–derived stem cells to
treat diseases outside of the blood
and immune systems;
Traditional transplants of bloodforming stem cells from bone
marrow and peripheral blood are
A 59-person trial with
Hearticellgram-AMI
found
that people who received
the stem cell product could
eject around 6% more blood
out of their left ventricles at
the end of the six-month
study, compared with just
16
“We expect the stem cell bank to help commercialize the induced pluripotent stem cell technology that the Nobel Prize
winner in physiology or medicine discovered this year and provide human embryonic stem cells,” a spokesman of the stem
cell bank said. “Moreover, the opening of the bank is significant in that the government is directly providing support for
research on stem cells and regenerative treatment which will be applied to curing intractable diseases.”
The goal of the bank is to act as a national repository for stem cells and will provide them to private researchers to
invigorate research on regenerative treatment.
The use of embryonic stem cells and induced pluripotent stem cells are quite similar for regeneration. Until now the
technology for general use has not been developed and only clinical trials to cure retinal damage have been conducted on
patients. For other conditions such as liver damage, domestic technology is still at the animal experimentation stage. “We
expect the stem cells to be used in a greater variety of experiments for various purposes. We hope that they can be used to
cure incurable diseases,” said an official from the KNIH (Yun Suh-young, “State stem cell bank opens today”, Korea Times,
16 October 2012)
Medipost
Cartistem
2012.1.18
Anterogen’
s
Cupistem
2012.1.18
to
improve regulated under separate terms
heart function)
from other human cell and tissue
products in many countries, and so
uses
banked Hearticellgram is the first stem cell
umbilical cord 'product' approved by a regulatory
blood stem cells authority anywhere in the world.
to
help (The second approval came just
regenerate knee four months later when the US
cartilage (ICRS Food and Drug Administration
grade IV) for legalized its first stem cell product,
a cord blood stem cell–based
people
therapy called Hemacord, from the
undergoing
non-profit New York Blood Center.)
orthopedic
Nature Medicine 18, 329 (2012)
surgery
an injection of
fat stem cells
derived from a
patient's own
abdomen
or
thigh that is
intended to help
people
with
Crohn's disease
who suffer from
painful
anal
fistulas
2% improvements in people
who
received
standard
medical therapy.
“In an 89-person Korean
clinical trial, 26% more
people who received the
Medipost
treatment
experienced
an
improvement
in
knee
function on a widely used
cartilage repair assessment
scale compared with those
who underwent knee surgery
alone.
KFDA-Approved Clinical Trial for Stem Cell Treatment
Table 2 Summary
Number of Autologous
or
Derived from
Current status
companies allogeneic
Autologo Allogene Bone
Umbilica Adipose Com In
us
ic
marrow
l
cord plete Clinical
derived
blood
derived d
Trials
mesenchyma stem
stem
l stem cells
cells
cells
7
13
9
6
6
10
13
9
* As of 29 Aug. 2012; 22 in total (The clinical trials using stem cell induced cells are excluded in the
total number) (Source: KFDA)
Table 3 The List of Clinical Trials in South Korea
1
Company
Name
of
Type
product
Medipost
카티스템
Allog
eneic
Source of SC
Target
Clinical
Status
The date
of
approval
제대혈유래
간엽줄기세포
무릎연골결
손
Phase
1/2
2005.04.0
1.
2
FC Pharmicell
FC Pharmicell
3
FC Pharmicell
4
5
6
RNL BIO
Medipost
7
RNL BIO
8
Medipost
9
호미오세라
피
10 Anterogen
11 Anterogen
12
알앤엘생명
과학
Anterogen
13
Anterogen
14
Autol
ogou
s
Autol
MSC2
ogou
s
Cerecellgra Autol
mogou
spine
s
Autol
바스코스템 ogou
s
골수유래
중간엽줄기세포
급성 뇌경색
Phase 3
2005.06.0
3.
골수유래
중간엽줄기세포
급성
심근경색
Phase
2/3
2006.04.1
7.
골수유래
중간엽줄기세포
만성
척수손상
Phase
2/3
2007.12.1
0.
지방유래줄기세포
버거씨병
Phase
1/2
2007.12.1
8.
Allog
프로모스템
eneic
제대혈유래
간엽줄기세포
비혈연조혈
모세포
이식보조
Phase
1/2
2008.03.0
5.
지방유래줄기세포
퇴행성관절
염
Phase
1/2
2008.05.1
3.
제대혈유래
간엽줄기세포
무릎연골결
손
Phase 3
2008.07.2
3.
골수유래줄기세포
GVHD
Phase
1/2
2008.09.2
2.
지방유래줄기세포
치루
Phase 1
2008.11.0
6.
지방유래줄기세포
변실금
Phase 1
2009.04.2
9.
지방유래줄기세포
척수손상
Phase 1
2009.04.2
9.
지방유래줄기세포
크론병성
치루
Phase 2
2009.11.1
3.
지방유래줄기세포
크론병성치
루
(연장임상)
Phase 2
2010.03.1
6.
지방유래줄기세포
복잡성 치루
Phase 2
2010.06.1
0.
제대혈유래
간엽줄기세포
미숙아
기관지폐
이형성증
Phase 1
2010.07.2
7.
골수유래줄기세포
이식편대숙
주질환
Phase 1
2010.08.3
0.
MSC1
Autol
알앤엘ogou
조인트스템
s
Allog
카티스템
eneic
이식편대숙 Allog
eneic
주
질환치료제
Autol
아디포플러
ogou
스주
s
Autol
ANT-SM
ogou
s
Autol
알앤엘아스트로스 ogou
s
템
Autol
아디포플러
ogou
스주
s
Autol
아디포플러 ogou
스주
s
Anterogen
15
ANTG-ASC
16 Medipost
17
호미오세라
피
뉴모스템
Homeo-GH
Autol
ogou
s
Allog
eneic
Allog
eneic
18 Anterogen
ANTG-ASC
Autol
ogou
s
지방유래줄기세포
복잡성치루
(연장임상)
Phase 2
2010.09.0
1.
19 Medipost
뉴로스템
Allog
eneic
제대혈유래
간엽줄기세포
알츠하이머
형 치매
Phase 1
2010.10.2
9.
골수유래줄기세포
근위축성측
삭경화증
Phase
1/2
2010.12.2
7.
지방유래줄기세포
크론성누공
Phase 1
2011.05.1
1
제대혈유래간엽줄
기세포
하지허혈증
Phase 1
2011.05.2
0
Autol
20 CORESTEM
HYNR-CS 주 ogou
s
Allog
21 Anterogen
ALLO-ASC
eneic
Adult
Stem
Allog
Cell Research 제대혈유래 eneic
22 Center
간엽줄기세
(funded
by 포치료제
Seoul City)
Stem Cell Cosmetics
(Source: A press release from the Korean Intellectual Property Office, 23 Sep. 2012)
Table 1 Stem Cell Cosmetics Patents by year (2005-2011)
Year
Number
patents
of
2005
2006
2007
2008
2009
2010
2011
Total
1
2
3
6
15
7
3
37
Table 4 Stem Cell Cosmetics Patents by Sources of SC (2005-2011)
Source
Adult Stem Cell Derived Adult Stem Cell Derived Plant Stem Cell Derived Total
Number
%
24
43.4
3
4.8
10
17.9
37
100
Table 5 The List of Stem Cell Cosmetics (worldwide)*
Company
or
Name of Product
Research Group
Source of Stem Cell
Voss Laboratories
Amatokin
Expanded Adipose Stem Cell
Dermaheal
StemC'rum
Expanded Adipose Stem Cell
CHA Bio & Diostech
Evercell
Embryonic Stem Cell
LG Household
Health Care
OHUI The Fisrst
Embryonic Stem Cell
17
&
Note
Co-developed
by
CHA Bio & Diostech17
http://www.lgcare.com/english/news/news_view.jsp?flash_num=610&bid=101&searchnm=&pageNum=3
LG Household
Health Care
&
Isaknox Te'rvina
Placenta Stem Cell
Co-developed
by
CHA Bio & Diostech
Christian Dior
Capture R60/80
-
Contains ingredients
stimulating
stem
cells
RNL Bio
Dr. Jucre
Expanded Adipose Stem Cell
Amore Pacific
IOPE Stem Polio
Plant Stem Cell
Prostemics
AAPE Stem
Cream
Expanded Adipose Stem Cell
Cell
herbal stem cell from
Ajuga reptans
Expanded
Adipose/Bone
Marrow Stem Cell
*Products developed by South Korean firms are highlighted
Parmicell
BeuCell
Also, it seems worth taking a note on the recent changes in regulating cosmetic ingredients since
most stem cell biotech companies produce stem cell cosmetics products (see the table below)
KFDA proposed partial amendment to “Regulation on Designating Cosmetic Ingredients” in its
Cosmatics Act (KFDA Notification 2009-287, 18 November 2009).18 In March 2009, KFDA prohibited the
use of human-derived biological materials which include human stem cell and culture fluid of human
stem cell. However, this amendment was overturned by November in the same year by allowing the
use of human stem cell in cosmetic products.
18
This proposed amendment is to add and amend the cosmetic ingredients in Annex 3 (list of ingredients restricted for use in
cosmetics) and Annex 4 (list of ingredients prohibited for use in cosmetics).
5) Taiwan (H-C.C)
Taiwan Contextual Sketch
Government policy and organisation
The activities relating to stem cells in Taiwan are ruled by Taiwan Food and Drug Administration
(TFDA), which was set up in 2010 with the government reorganization. Somatic cell therapy is
categorized now as an investigational new drug (IND). The Medical Ethics Committee in the
Department of Health published the ethical regulation of stem cell research in 2002 and regulated
the cell sources that stem cell research can use from. This committee is composed of 17 members
from different areas to give advices and guidelines about medical ethics. Each of the medical centre
in Taiwan has its own medical ethic committee, which focuses on clinical ethics and clinical trials.
The biotechnology industry has been was a key industry promoted by the government. The
government aimed to develop Taiwan into “Biomedtech Island,” and this industry was included in
the “Two Trillion and Twin Star Development Program” announced by the Ministry of Economic
Affairs (MOEA) in 2002. The twin stars means biotechnology industry and digital industry, which the
government planed to investigate in Taiwan. The Ministry of Economic Affairs aimed to produce NTD
one trillion of output value from each of them. The Biotechnology and Pharmaceutical Industry
Promotion Office in MOEA19 has the function to assist government to produce industry strategies
and promote the investment and international cooperation in health industry. The biotechnology
industry is now the only industry in Taiwan that benefits from tax reduction20. In 2009, Executive
Yuan announced another action plan21 to promote biotechnology industry. These policies mentioned
above shows the government plays a vey supportive role for the development of biotechnology
industry. For example, Gwoxi is one of the companies that the government supports to set up and
especially focuses on stem cell technology and medicine.
The Taiwan Stem Cell Bank (TSCB) is one of the first publicly funded cell repositories in the East Asia
region that is dedicated to the high-quality banking of human embryonic stem cells (hESC), induced
pluripotent stem cells (iPS cells) and various types of somatic stem cells. The TSCB has in 2010
finished the construction of one general laboratory and three good laboratory practice (GLP)compliant stem cell processing rooms, and it has adopted the pre-master/ master /working bank
method that is also used by the UK Stem Cell Bank, so as to minimize chances ofcontamination and
genetic change. In addition, it has established a back-up bank, for the case of unforeseen disasters
caused by weather or accidents. The bank has fully characterized and quality controlled eight hESC
lines that have been derived in Taiwan between 2002 and 2009. Five additional hESC and seven iPS
cell lines are currently subjected to the bank’s quality assessment and characterization program, and
shall be included in the bank’s catalogue soon. The first eight approved hESC cells have been given
free for public distribution in January 2011. The total available stock shall be expanded to 20 human
embryonic- and 20 iPS cells in 2015, and be opened for the inclusion of somatic stem cells at about
the same time.
19
It is established in the Ministry of Economic Affairs (MOEA) in 1996.
According to the Biotech and New Pharmaceutical Development Act (生技新藥產業發展條例) announced by the
Executive Yuan in 2007.
21 Biotechnology Industry Taking Off Action Plan (台灣生技起飛鑽石行動方案) The action plan has four main strategies: a.
strengthen value chain; b. establish funds for the establishment and investment of biotechnology industry; c. promote the
mechanism of educational integration; d. set up the TFDA.
20
Furthermore, Taiwan and China government signed the “Economic Cooperation Framework
Agreement (ECFA)” in 2010. It is anticipated that ECFA will promote the development of stem cell
industry.
Funding Agencies and Key persons
National Science Council (NSC) and National Health Research Institutes (NHRI) distribute the funds to
support stem cell research in public and private institutions. NHRI also conducts research in its
research divisions. The Institute for Biotechnology and Medicine Industry (國家生技醫療產業策進
會) plays an networking role among the government, research, and industry.
According to Liu (2011), a major force of regulation development was John Yu, the head of Academia
Sinica’s Stem Cell Program, and a member of the International Society for Stem Cell Research’s
(ISSCR) International Human Embryonic Stem Cell Guidelines Task Force. The resultant regulations
were “Policy Instructions on the Ethics of Human Embryo and Embryonic Stem Cell Research,” which
were approved in 2007.
Research and Education
Taiwan Society for Stem Cell Research was established in 2005 to facilitate the research and
interactions among researchers in Taiwan and with other international stem cell societies and
networks. According to the Taiwan Society for Stem Cell Research, the stem cell research group in
Taiwan is composed of 12 research centres collaborating with hospitals. The major stem cell
research centers include Academia Sinica (Stem Cell Program of Genomics Research Center),
National Health Research Institute (Institute of Cellular and Systems Medicine), National Taiwan
University (Teaching Resource Center for Stem Cell and Tissue Engineering), and National Yang-Ming
University (Stem Cell Research Center).
In education, the ministry of education framed the "Advanced Biotechnology Education
Programme22" and established "Biotechnology Education Centres of Advanced Biotechnology23" to
assist the policy of "Challenge 2008-Council for Economic Planning and Development" from
Executive Yuan in 2002. The education centres were set up to integrate the technology, manpower,
and material resources of colleges, universities, research institutes, and industrial circles. The
education centres that join this programme included National Taiwan University, National Tsing Hua
University, National Chung Hsing University, National Cheng Kung University, Tzu-chi University, and
China Medical University
The Chinese Medical Association-Taipei (中華醫學會-台北) included a session of “Cross-Strait
Symposium on Current Advances in Cell Therapy” in the annual meeting in 2012, which shows the
significant role that cell therapy play recently.
Commercial Services
Cord blood banking is popular in Taiwan. Each year 8-10% newborns’ cord blood is stored, compared
to that 2.6% and 0.6% storage rate in the USA and Europe. The main strategy that family cord blood
banks use is to construct cord blood banking as a form of biological insurance (Rei 2010).
22尖端生物技術科技人才培育計畫
23尖端生物技術教學資源中心
Although stem cell therapy is not approved in Taiwan, advertisements from some cosmetic medicine
clinics that use stem cells in their rejuvenation medicine are visible on the street.
Regulations in Taiwan
Taiwan regulations focus on the embryonic stem cell (ESC) research, but lack regulations for adult
stem cell research. Most of the regulations in Taiwan can be viewed as soft-regulation because they
have not been approved by the Legislative Yuan, except the “Artificial Reproduction Act (人工生殖
法)”. Promulgated in 2006, it regulates the collection and storage of embryo cells. Another
regulation relating to the collection of stem cell is the “Guidelines for Cord Blood Collection and
Process (臍帶血收集及處理作業規範)”, which was published in 2002. It regulates the standard
procedure of cord blood collection, process, and storage, including collection, testing, transportation,
storage, cell usage, personnel, infrastructure, and quality control.
The storage of human tissues are regulated by the Regulations for Administration on Human Organ
Bank (人體器官保存庫管理辦法) (promulgated on 2 February 2009) and Human Biobank
Management Act (人體生物資料庫管理條例) (Announced on 3 February 2010).
Regulations for Research
The cell sources for stem cell research are regulated by the DOH Medical Ethics Committee since
2002. The Article 1 of the ‘ethical codes of embryonic stem cell research (胚胎幹細胞研究的倫理規
範)” says that embryos that are used for hESC research are limited to the following sources: 1. the
embryonic tissues from spontaneous abortion; 2. the embryonic tissues from artificial abortion that
meets the regulation of Genetic Health Law; 3. the remaining embryos from the artificial
reproduction that were to be destroyed, limiting to the embryos that are less than fourteen days
after fertilization. Article 6 approved clinical trials for the purpose of treatment and condition
improvement. The DOH further promulgated the “Policy Instructions on the Ethics of Human Embryo
and Embryonic Stem Cell Research (人類胚胎及胚胎幹細胞研究倫理政策指引)” on 9 August 2007.
The main regulatory document for stem cell research can be the Human Embryo and Embryonic
Stem Cell Research Act Draft (人類胚胎及胚胎幹細胞研究條例草案), which was approved by the
Executive Yuan on 24 July 2008. It is a more comprehensive regulation, including the regulation of
the obtaining of cells, the rights of the tissue donors, the ethics review process, tissue preservation
and destruction, and punishment. This Act added that the cells for research can be made from
somatic cell nuclear transfer (SCNT).
Regulations for Clinical Trials
An early regulation relating to stem cell clinical trial is the “Application and Operational Guidelines
for Somatic Cell Therapy Human Clinical Trial (體細胞治療人體試驗申請與操作規範)”, which was
published by the DOH in 2003. The Taiwan Food and Drag Administration (TFDA) was set up in 2010
and became the regulator for medical products in Taiwan. This move is to faclitate the development
of biomedical industry in Taiwan. Stem cell therapy is not approved by the DOH in Taiwan yet. The
relating therapy used to follow the Article 8 of the Medical Care Act. In 22 February 2011, TFDA
announced drafts of two regulations: “the standard draft of the clinical trials of somatic cell therapy
(體細胞治療臨床試驗基準(草案)) ,” and “the operational regulation draft for the application and
evaluation of somatic cell therapy and gene therapy clinical trial (體細胞治療及基因治療臨床試驗
計畫申請與審查作業規範(草案))”. Somatic cell therapy and gene therapy are categorized as
investigational new drug (IND) and administered by TFDA. However, compared with somatic cell
therapy, stem cell therapy contains the mix of differentiated and undifferentiated cells, which
require specific regulation. The Act on Human Subjects Research (人體研究法), published on 28
December 2011, was the first step in establishing a statutory system to regulate research involving
humans, as well as human tissues.
These processes should obey relating regulation, such as the Good Tissue Practice (GTP) (人體細胞
組織優良操作規範), the Good Clinical Practice (GCP) (藥品優良臨床試驗規範), which is a guideline
to ensure the quality of drug clinical trials, and the Guide to Good Manufacturing Practice（GMP）
(藥品優良製造規範) for Medical Products.
6) Thailand (N.C)
National policy and funding for stem cell research
Like in many countries, stem cell is a currently ‘hot’ topic amongst Thai researchers, medical
practitioners and the general public. Successes by Thai research teams, particularly on the
international scene, are reported with pride in the media, often making headline news. However,
while individual research teams have found success, for example, in having their research results
published in peer-reviewed journals, Thailand is reported to still be lacking a clear policy direction
and investment into its public R & D system24. It could therefore be said that Thailand still lags
behind other countries in Asia, such as China, India, Japan, South Korea and Singapore, as far as
infrastructure development and investment into stem cell research are concerned.
The National Research Council of Thailand (NRCT)25 is the organisation that oversees all research
activities in the country. Although the NRCT strategic plan of 2008-2010 suggested that health
biotechnology was a research area that was in need of development, the Eighth National Research
Policy and Strategy of 2012-2016 does not give a clear research policy direction. In general, it is
reported that26, rather than a centralised or top-down approach, research projects in universities
and medical schools are often initiated by individual researchers or research teams, focusing on their
areas of interest and expertise.
In terms of funding, the NRCT receives approximately 10 billion baht in government budget, the
majority of which is allocated to research on agriculture27. Approximately 60 – 100 million baht (1 – 2
million GBP) goes towards stem cell research28. Apart from the NRCT, researchers may also apply for
funding from the National Science and Technology Development Agency (NSTDA)29, the Thailand
Research Fund (TRF)30 and the Ministry of Public Health. Some research projects are also funded by
private donations. It is reported31, however, that the NSTDA does not always have the capability to
provide grants for large-scale clinical trials.
Stem cell research, both basic and clinical, is generally carried out in state medical schools and their
associated hospitals. There is sometimes confusion as to whether private hospitals can carry out
clinical research32. According to my interview with the former President of the Thai Medical Council,
Dr. Somsak Lohlekha, the legislation for private hospitals does not state clearly that private hospitals
can carry out clinical research, as legislation for state hospitals does, but it does not expressly forbid
it, either. Nevertheless, my interviews with individuals in private hospitals suggest that most private
hospitals do not have the infrastructure and resources to carry out clinical research.
24
Heath Intervention and Technology Assessment Program (HITAP), Report on Advanced Health Biotechnologies in
Thailand, 2012
25 สำนักงำนคณะกรรมกำรวิจย
ั แห่งชำติ (วช)www.nrct.go.th
26 Heath Intervention and Technology Assessment Program (HITAP), Report on Advanced Health Biotechnologies in
Thailand, 2012
27 http://www.nationmultimedia.com/national/Show-scientists-the-road-30192788.html
28 ibid
29 สำนักงำนพัฒนำวิทยำศำสตร์ และเทคโนโลยีแห่งช่ติ (สวทช)www.nstda.or.th
30 สำนักงำนกองทุนสนับสนุนกำรวิจย
ั (.สกว)www.trf.or.th
31 Heath Intervention and Technology Assessment Program (HITAP), Report on Advanced Health Biotechnologies in
Thailand, 2012
32 กรุ งเทพธุรกิจ [ศบุภเวลิมวิญำส แสวง.รร. ] www.bangkokbiznews.com 9 February 2010
Research Institutes
Mahidol Unviersity and its medical schools
Mahidol University hosted the first medical school in Thailand, Siriraj Medical School, which was
established in 1888. It was then reorganised as University of Medical Sciences in 1943 and renamed
as Mahidol University in 1969. Because of its history, Mahidol University is often regarded as one of
the top universities for medical sciences. At Mahidol University, there is the Salaya Stem Cell R&D
Project33, established in 2010, and funded by a private source. The project built its facility to comply
with Good Manufacturing Practice (GMP) and the project had ambitious objectives, including a plan
to develop and produce clinical grade human autologous stem cells for various cell therapies. When I
spoke to a researcher from the project in 2012, I learned, however, that the project suffered
unexpected delays due to the unstable political situation in Thailand and the severe flood of 2011.
As a result, funding to the project had been cut and its future is more uncertain. Apart from the
Salaya Stem Cell R&D Project, there was also a research group that worked on the use of stem cells
for heart and epiglottis diseases but the research had since been terminated.
Mahidol University has two medical schools, the Faculty of Medicine Siriraj Hospital and the Faculty
of Medicine Ramathibodi Hospital. In October 2012, a research team at the faculty of medicine of
Siriraj Hospital, led by Dr. Tassanee Permthai, announced that they had devised a novel method to
isolate stem cells from amniotic fluid34. The research findings were published in BMC Cell Biology in
2010 (11, 79)35. The announcement was reported in national media and made front page news on
several national newspapers. There is now a plan to establish a stem cell bank at Siriraj, with stem
cells from umbilical cord, amniotic fluid and placenta. The Faculty of Medicin Ramathibodi Hospital is
particularly well known for their expertise in treating patients using haematopoietic stem cell
transplantations. There is also a research group that is investigating the use of adult stem cell in
arthritis treatment.
Chulalongkorn University
Chulalongkorn University was founded in 1917 and is often regarded as one of the top universities in
Thailand. There are a number of research teams working on stem cells: one research team focusing
on human embryonic stem cells, one on iPS and another on clinical application of mesenchymal
stem cells. In June 2012, a research team at the Faculty of Medicine, led by Assoc. Prof. Kamthorn
Pruksananonda, announced that Chulalongkorn University had established the first human
embryonic stem cell bank in Thailand36. According to news reports, the University first developed its
embryonic stem cell line five years ago and has since developed five embryonic stem cell lines, all of
which are registered with the European Human Embryonic Stem Cell Registry. (The lines are
Chula1.hES, Chula2.hES, Chula3.hES, Chula4.hES and Chula5.hES. Only lines 2, 4 and 5 are reported
to be stable, however.) The embryonic stem cell line was developed from the inner cell mass of
leftover embryos at 5-7 days after fertilisation, donated by couples who had successfully undergone
IVF treatment at Chulalongkorn Hospital.
Police General Hospital
33
http://salaya-stem-cell.mahidol.ac.th/
http://www.nationmultimedia.com/national/Mahidol-team-achieves-stem-cell-success-30192636.html
35 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973936/
36 http://www.thairath.co.th/content/edu/268074
34
A research team, led by Dr. Thana Turajane, is conducting a clinical trial using stem cells derived
from patients’ blood to treat arthritis. The study involves 60 arthritis patients, aged between 45 and
60, and is expected to be completed in 2013.
Lerdsin Hospital
Dr Krissanapong Manodham and his research team have been conducting research into the use of
stem cells to treat patients with HIV.
There are also researchers who had recently returned to Thailand after studying their PhD and/or
working as a postdoc abroad. Dr. Nopporn Jongkamonwiwat, for example, is currently at
Srinakharinwirot University. He worked in collaboration with researchers from Sheffield University
on a new stem cell treatment for hearing loss, tested on gerbils, which was published in Nature in
October 201237.
Private Sector
Stem cell companies
The Israeli stem cell company TheraVitae38 came to Thailand in 2005 and formed partnerships with a
number of private hospitals to offer stem cell treatments for heart conditions. In this procedure,
blood is drawn from the patients, sent to be processed in laboratories in Israel and then transported
back to be injected into the patients, cared for by Thai medical staff in private hospitals. In 2006, the
Thai Board of Investment (BOI) featured the company prominently in its brochure on investment
opportunities in biotechnology in Thailand39. Prior to the Medical Council’s regulation (see below),
the treatment was offered to “hundreds” of both domestic patients and ‘medical tourists’ from
abroad40, though the treatment was still being investigated in clinical trials in the USA. However,
after the regulation, private hospitals stopped offering the treatment to patients (at least openly). In
an email correspondence, TheraVitae said that they now offer the treatment in Israel, Lebanon and
the Dominican Republic.
Another Bangkok-based company, SiriCell Technologies Inc41, was founded in January 2008 (in
Vanuatu and therefore presumably an offshore company). It established a joint venture with Beike
Biotech in November 2008. Subsidiary companies for SiriCell-Beike JV were established in Bangkok in
January 2009, Kuala Lumpur in November 2009 and Manila in May 2010. SiriCell then signed MOU
agreement with Bangkok Dusit Medical Services Plc (Bangkok Hospital Group) regarding a strategic
partnership to introduce and integrate stem cell therapies and regenerative practices in March 2010.
Then according to SiriCell website, SiriCell and Beike ended their Joint Venture in November 2010.
Territory subsidiaries in Thailand, Malaysia and the Philippines were renamed and rebranded as
SiriCell companies during January and March 2011. From SiriCell’s official website:
37
http://www.nhs.uk/news/2012/09September/Pages/Stem-cell-deafness-cure.aspx
www.vescell.com
39 The 2006 document is no longer available online but see:
http://www.boi.go.th/english/download/publication_investment/87/May_08.pdf
40 http://stemcelllist.com/home/hospitals-and-agents/hospitals/bangkok-heart-hospital.html
41 http://www.siricell.com/
38
“SiriCell has established therapeutic product development programs in the areas of spinal cord
injuries, cardiovascular disease, and neurological conditions such as Parkinson’s disease, cerebral
palsy, ataxia and multiple sclerosis. In addition, the Company is planning treatments for multiple
causes of critical limb ischemia, optic nerve pathologies, cell-based immune therapies, and liver
disease. Our research and development of therapeutic cell products and delivery protocols are
anchored by a knowledge transfer during a two-year partnership with a leading Asian biotechnology
company and other select research scientists and medical professionals.”
However, based on fieldwork investigations, SiriCell does not appear to be operating at the moment.
Cord blood banks
Currently less than 1% of babies born in Thailand have their cord blood banked42. Cord blood
banking companies therefore see potential for growth in the Thai market. A cord blood banking
package can cost around 85,000 to 130,000 baht (1700 – 2600 GBP), while a stem cell banking
package from peripheral blood and adipose tissue can cost considerably higher e.g. 300,000 baht
(6000 GBP). There are a number of private cord blood banks in Thailand, including Thai StemLife
(www.thaistemlife.co.th),
Cyroviva
(www.cryoviva.com),
Thai
Health
Baby
(www.thaihealthbaby.com) and Bangkok Stem Cell (www.bangkokstemcell.co.th)
Private clinics
There are private clinics that offer stem cell treatments for cosmetic purposes or as part of
holistic/complementary/alternative medicine e.g.
http://www.absolutehealthplus.com/adipose-stem-cell-therapy-tid67.aspx)
http://www.cellportthailand.com/
http://www.holistic-medical.com/
http://www.patr-life.com/
http://www.villamedicathailand.com/
Regulations
Horizontal regulations
Regulations regarding research in human subjects43
Researchers who plan to conduct research involving human subjects must submit their research
proposals to the IRBs/ECs of their institutions or to the Ethics Committee of the Ministry of Public
Health for approval. Doctors conducting clinical trials must also act according to the Rules of the
Medical Council on the Observance on Medical Ethics44 B.E. 2526 (1983) and its amendments45. For
42
http://m.bangkokpost.com/business/322112
กำรวิจยั ในมนุษย์
44 ข้ อบังคับว่ำร้ วยกำรรั กษำจริ ยธรรมแห่งวิชำชีพเวชกรรม
45 Legal documents can be found on the website of the Office of the Council of State www.krisdika.go.th
43
hospitals directly under the Ministry of Public Health, there is also the Ministry of Public Health’s
Ethical Guidelines for Research in Human Subjects. It is acknowledged46, however, that there are still
gaps in existing regulations, including:
-
The current regulations do not systematically address and protect the rights of participants
The current regulations do not address the consent of those who cannot give informed
consent
The state does not have the mechanism to monitor and protect the rights of participants
There may be variations in the standards and approval processes of different IRBs
Criminal prosecutions may be used inappropriately
Therefore a draft bill ‘Research in Human Subjects Act’47 is in the process of being drafted by the
Ethics Committee of the Ministry of Public Health [Department of Medical Services]48. Based on the
report49, the objectives of the bill are:
-
To clarify and protect the rights of participants
To clarify and certify the legal status of and to clearly state and define the roles and
responsibilities the Ethics Committee of the Ministry of Public Health
To ensure that the approval processes follow similar standards and principles
To ensure that there is a guarantee that participants/research subjects will be compensated
in the case of adverse event
It should be noted that there had been attempts to pass a law regarding research in human subjects
in the past. In 1985, for example, a draft bill was accepted by the Cabinet and sent for consideration
of the Parliament but it was not in session due to a dissolution of the House of Representatives and
the draft bill was therefore automatically dropped.
Thai Food and Drug Administration
Initially there was some confusion as to whether stem cells should be regulated as food or drugs. But
on 27 March 2009, the Thai Food and Drug Administration (TFDA)50 announced that stem cells and
products containing stem cells which aim to have curative and/or preventative effects on diseases or
symptoms are to be regulated as biological drugs. Therefore the importation, production (under
GMP) and development of stem cell products must follow regulations as detailed in the Drug Act B.
E. 2510 (1967) and all other amendments. Clinical trials with stem cell products intended to be
commercialised/marketed have to be approved by the TFDA (as well as IRBs/ECs). There are
currently no stem cell products registered/authorised by the TFDA. However, the TFDA regulatory
framework does not apply to clinical trials involving stem cell products, whether substantially or
minimally manipulated, intended for individual patients in hospitals and not to be marketed. (In such
cases, approval needs to be sought from the Medical Council and IRBs/ECs, as outlined below.)
46
http://www.fercit.org/news.php
ร่ ำงพระรำชบัภภัติกำรวิจยั ในมนุษย์
48 กรมกำรแพทย์ http://www.dms.moph.go.th/dmsweb/dmsweb_v2_/2
49 http://www.adtec.or.th/main/EthicCommittee_web/EthicCommittee/archive.htm
50 http://www.fda.moph.go.th/
47
It is reported51 that the TFDA has reviewed regulations of other countries and attempted to draft
guidelines such as Good Tissue Practice (GTP). There has been no further information on these
possible draft regulations, however. Finally, the TFDA also banned the advertising and sale of
cosmetic products containing stem cells and warned the public against facial treatments involving
stem cells52.
The Medical Registration Division, Department of Health Service Support
The Medical Registration Division in the Department of Health Service Support (DHSS)53, under the
Ministry of Public Health, has an authority to register private medical establishments, supposedly
including private hospitals, clinics and stem cell banks. An informant said, however, that the DHSS’
role is simply to register private hospitals and clinics. It therefore seems that the DHSS’ role is very
limited in controlling activities in private hospitals and clinics. According to my informant,
registration depends upon the private hospitals/clinics having medical doctors with valid medical
licenses.
In regards to stem cell banks, there is currently no regulation on private stem cell banks which only
provide stem cell banking services. These companies, instead, seek accreditation, such as the AABB
accreditation, and ISO 9001 certification to demonstrate standards to potential and existing
customers.
Consumer Case Procedures Act
The Consumer Case Procedures Act, which became effective from 23 August 2008, revises the
former Consumer Protection Act. The new Act may make it easier to file legal actions against doctors
and health service providers for medical malpractice. Prior to the new Act, prosecutions against
medical providers were difficult for certain defendants to maintain due to the burden of proof
resting on the victims or victims' families. Under the current Act, the burden of proof has been
shifted from the complainant to the medical provider. The number of lawsuits against medical
practitioners had increased substantially under the current Act54. The Medical Council had been
working to revise the law and in November 2012 the Medical Council formally submitted a petition
to the House of Representatives to seek amendments to exclude medical practitioners from the
law55. [I need to check if there has been a case involving stem cell treatment under the new Act.]
Use of human embryos in research
There is currently no specific legislation regarding the use of human embryos in research. The
Medical Council, though, has released regulations on Human Cloning in June 2002 (No. 21/2544),
prohibiting reproductive human cloning. As far as I understand, there is currently no central
authority that oversees the use of human embryos in research, nor is there a licensing system.
Rather it is up to individual IRBs/ECs to approve research. Based on interviews, it seems that Thai
51
Heath Intervention and Technology Assessment Program (HITAP), Report on Advanced Health Biotechnologies in
Thailand, 2012
52 http://www.thairath.co.th/content/edu/284897
53 กรมสนับสนุนบริ กำรสุขญำพ http://203.157.7.46/home.jsp
54 http://www.nationmultimedia.com/national/PETITION-SEEKS-EXCLUSION-OF-MEDICS-FROM-CONSUMER-A30194274.html
55 Ibid
researchers generally follow the international guidelines (e.g. not exceeding the 14-day after
fertilisation limit).
Vertical Regulations
The Thai Medical Council
The Medical Council’s Rules on the Observance on Medical Ethics regarding stem cell transplantation
for therapeutic treatment B. E. 2552 (2009)56 was drafted and issued to deal specifically with the
clinical applications of stem cells. The regulation states that the Medical Council draws on the
Medical Professional Act B.E. 2525 (1982) Section 21 (3) (ช) , which states that the Medical Council
has an authority to issue rules concerning the professional and ethical conduct of doctors. Noncompliance may lead to the revocation of medical license.
Dr. Somsak Lolekha, who was President of the Medical Council when the regulation was drafted and
announced, said that the regulation was a response to the criticisms, both at home and abroad, of
the unproven stem cell therapies that were widely advertised and available in private hospitals and
clinics in Thailand. In 2007, there was one widely reported case of a patient with lupus nephritis who
passed away after receiving an autologous stem cell treatment at a clinic in Thailand57. At her
autopsy, lesions were discovered in her kidneys, at sites of injections. At the same time, the
American Medical Association, based on its survey, also categorised Thailand as having deceptive
and exaggerated advertisements for stem cell therapies and treatments58.
The regulation states that stem cell therapies that can be offered as therapeutic treatments must
already have been proved in research, established as standard practice and agreed by the Medical
Council. Effectively, these only include therapies involving haematopoietic stem cell transplantation.
All other stem cell therapies can only be offered to patients as part of clinical studies, which must be
approved by both the IRBs/ECs of the doctors/researchers’ institutions (or the ethics panel of the
Ministry of Public Health) and the scientific and ethic committee of the Medical Council. The
approval process is therefore different to general research involving human subjects, which only
requires approval from IRBs/ECs. Since the regulation became effective, there have been 17
research proposals submitted to the Medical Council, 11 of which have been approved. In general,
the Medical Council’s regulation seems to have been successful to an extent, in that private hospitals
that used to openly advertise and offer experimental stem cell therapy to patients appear to no
longer do so.
Preliminary assessment: gaps and weaknesses
In regards to research, researchers I have spoken to during fieldworks have said that they are
concerned that the regulations are both not strict enough and that they are too strict. There are also
concerns with the issues of transparency and possible conflicts of interest in IRBs and ECs. The gaps
and weaknesses in the current regulations for research in human subjects are as already listed
56
http://www.tmc.or.th/download/stemcell.pdf
http://www.nationmultimedia.com/home/2010/08/02/national/Stem-cell-patient-dies-in-Bangkok-30135005.html;
http://www.nature.com/news/2010/100622/full/465997a.html
58 http://en.thaihealth.or.th/resource-center/reports/health-report/2010
57
above. The Research in Human Subject Act is supposed to address these issues, though it is still in
the drafting process. There is also currently no central authority who oversees the use of human
embryos in research, nor is there a licensing system. The decision making process here rests with
IRBs and ECs.
The Medical Council has been successful, to an extent, in controlling the availability of experimental
stem cell therapy. The former president, Dr. Somsak Lohlekha, said in my interview with him, that
the Thai Medical Council has been quite successful because “for better or for worse, everything in
Thailand is quite centralised and Thailand is much smaller than countries like China and India.” Other
interviewees also suggest that the Medical Council is a powerful institution and that “no one wants
to become an enemy of the Medical Council” because as a professional organisation, the Medical
Council, can give professional and legal assistance should a doctor ever need it. Nevertheless, there
are gaps and weaknesses associated with the Medical Council’s regulation. Firstly, the Medical
Council can only control the conduct of doctors, but not nurses or commercial companies. Secondly,
the Medical Council does not have the authority to police, arrest and prosecute. Therefore, the
quality assurance of medical services in Thailand is passive, in that the Medical Council generally
takes action only after there have been complaints made by patients. In addition, researchers have
also expressed that the Medical Council’s regulation is not an ideal long-term solution. Some have
suggested, for example, that there should be another organisation that oversees regulatory issues
not just for stem cells but for the whole field of advanced health biotechnologies.
In the case of private clinics that offer stem cell treatments for cosmetic purposes or as part of
holistic/complimentary/alternative medicine, it is unclear how these activities are regulated.
According to my informant, the DHSS only registers clinics but does not oversee activities that may
be subsequently offered in the clinics. Doctors who offer live cell therapy or stem cell injections may
be found to be breaching the Medical Council’s regulation, but only if they are reported to the
Medical Council when things go wrong. The Bureau of Complementary and Alternative Medicine59
has a section on Cell Therapy on their website. However, when I spoke to the Bureau, I was told that
the Bureau is currently focusing on research and does not give licenses to practitioners of cell
therapy. It is currently unclear whether stem cells or stem cell products used in such treatments are
under the TFDA rules as they can be seen to be prepared for individual patients and not to be
marketed. I am told that the TFDA will make announcements on this issue soon (maybe February March 2013). Similarly, as noted, there is also currently no specific regulation governing private stem
cell banking. The only information that I have been able to find is that regulatory bodies and
research institutes are encouraged to educate the public so that they can make informed decisions.
59
สำนักกำรแพทย์ทำงเลือก http://www.thaicam.go.th/