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expert speak
“What man has made of man?” n Anay Shukla & Dr. Milind Antani,
“stem cell clinics” have mushroomed in
Nishith Desai Associates
cosmopolitan cities of India over the past few years.
I
n April 2014, after a four yearlong investigation
therapy has the potential to grant a new
into stem cell therapy
lease of life to many patients. However,
provided by an
there are some valid concerns associated
organization called
with use of stem cells at present in form
Stamina Foundation in Italy, the public
of therapy. According to The Indian
prosecutor concluded that the
Council of Medical Research (ICMR),
organization was “a criminal
these concerns are: (i) Stem cells have
organization that has defrauded about a
the capacity for unlimited proliferation
thousand patients since 2006 by
or tumorigenicity; (ii) risk of rejection
administering a dangerous and
of the new stem cells as “foreign body”
unapproved treatment in exchange for
by the recipient’s own immune system,
money”. The report identified a series of
and (iii) and risk of contamination
problem with the treatment, for
and/or alteration in the properties of
instance, that the cells handled,
cells.
processed and injected in non-sterile
Whether stem cell therapy is regulated
were turned into guinea pigs”.
so that a person is assured of its safety
India has turned out to be a popular
93 B, Mittal Court,Nariman Point, Mumbai 400 021, India Tel +91 - 22 - 6669 5000 Fax +91 - 22 - 6669 5001 Email
[email protected]
50 | Lex WITNESS | August 2014
Such concerns beget the question:
conditions. It also stated that “patients
hub for stem cell therapy, arguably
NISHITH DESAI ASSOCIATES
It is undisputable that stem cell
and efficacy? The fact of the matter is that the
because of the lax regulations. In fact,
science of stem cells is still in its
some of the medical practitioners in
nascent stage, and both basic and
India have heavily capitalized on the
translational research is ongoing. There
promise of stem cell therapy, and to
is not enough evidentiary proof
some extent the desperation of patients,
available to conclusively establish that
and are offering stem cell therapy for a
stem cell therapy is safe and efficacious
range of diseases and conditions. New
to be used on humans in the form of
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expert speak standard therapy, except in cases of
safety of process and end-product to be
hematopoietic disorders (i.e. disorders of
met by stem cells before they can be
the blood connected to bone marrow). The
administered into patients? How should
Indian Council of Medical Research has
the study design of the clinical trial be?
categorically denounced stem cell therapy
What is the format for the clinical trial
in as many words as follows:
protocol?)
“every use of stem cells in patients
In order to monitor those involved in the
outside an approved clinical trial shall be
field of research, the ICMR has mandated
considered as malpractice. It is hoped that
establishment of an institutional
this clear definition will serve to curb the
committee called Institutional Committee
malpractice of stem cell “therapy” being
for Stem Cell Research (IC-SCR) in each
offered as a new tool for curing untreatable
institution involved in stem cell research.
diseases”
The methodology of monitoring is
The scientific and medical community is
described in the next paragraph. The
in need of clinical (i.e. patient) data
composition of IC-SCR includes members of
through clinical trials (i.e. tests on real
the institution and experts from the field
patients) so that safety and efficacy of
of law, ethics and social-sciences, all of
stem cell therapy may be established. As
whom have no conflict of interest. The
stepping stones towards that end, the ICMR
ICMR has also pushed for and established
has notified certain standards and
the National Apex Council for Stem Cell
limitations which must be observed by
Research (NAC-SCR). The NAC-SCR has
researchers and practitioners who are
representation of all the government
conducting basic and translational
departments which deal with the subject of
research. The key areas ICMR has identified
public health, notably the Drugs Controller
for regulation are:
General of India (Or DCGI, the executive
1. ProcuremeNT
body that controls standards and quality of
(i.e. Which biological material may be
medicines in Indian market), the Medical
procured as a source of stem cells? What is
Council of India (which regulates
the process to be followed?);
professional and ethical standards in
2. BANkiNg AND DiSTriBuTioN
practice of medicine) and the Department
(i.e. What are the requirements for starting a cell bank or tissue bank? What is the process to be followed for obtaining
of Biotechnology. All IC-SCRs have to be registered with NAC-SCRs. Most of the research in the area of stem
and storing stem cell lines? What are the
cells is self-regulated. Interested persons
conditions to be satisfied before
in all institutions have to take permission
distribution of stem cells lines?);
of the IC-SCR of their respective institution
3. reSeArcH
before commencing any significant activity
(i.e. Whether the research falls into the
in any of the areas outlined earlier. The
category of permitted research, restricted
role of IC-SCR before permitting any
research or prohibited research); and
research activity is to ensure that such
4. uSe
activity falls within the bounds set out by
(i.e What is the standard in terms of
A Lex Witness Privileged Partners Initiative
Anay Shukla is a member of Pharmaceutical and Healthcare Team at NDA. He focuses on pharma and life sciences laws, intellectual property laws, litigation and dispute resolution. He has been regularly advising on regulatory issues surrounding the pharmaceutical and life- science sector.
ICMR. The IC-SCR has the power to carry
Dr. Milind Antani is Partner in charge of Pharma-Life Sciences and Healthcare Practice at Nishisth Desai Associates.Dr. Antani represents clients in matters including corporate mergers and acquisitions, investments, regulatory and transactional matters, intellectual property prosecution and litigation, joint ventures and formation of new companies.
August 2014 | Lex WITNESS | 51
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expert speak Any person who wishes to collect, process and store SCCP for the purpose of test and analysis must obtain a license. To obtain the license, the applicant must ensure that the research facility complies with the Good Manufacturing Practices norms under Part X D of Schedule F of the Drugs and Cosmetics Rules, 1945.
l
Any person who wishes to collect, process and store SCCP for the purpose of test and analysis must obtain a license (Category 1 License). To obtain the license, the applicant must ensure that the research facility complies with the Good Manufacturing Practices norms under Part X D of Schedule F of the Drugs and Cosmetics Rules, 1945 (D&C Rules). Further, all clinical and
out periodic inspections of research being
of each MCI and DCGI has been given a
cell storage areas must conform to the
carried out at the respective institution.
permanent position in NAC-SCR with the
requirements laid down in Schedule L
The role of NAC-SCR comes to light when
intention of improving co-ordination
of the D&C Rules.
a sensitive research activity such as
amongst the government institutions.
genetic modification (major
l
To conduct a clinical trial, a separate license will be required (Category 2
The regulatory framework published by
manipulation) of stem cells is proposed.
ICMR suffers from another serious
License). Category 2 license will be
In these cases, the researchers have to
limitation. It does not extend to
issued only to those institutions which
take permission of NAC-SCR. Where
commercial use of stem cells because the
have a Category 1 License.
research is focused on commercial
mandate of ICMR is limited to regulation
marketing of stem cell in future, the
of research. In fact, there is no regulatory
require another license (Category 3
permission of DCGI is generally required.
guidance at all available at present for
License), which will be issued to those
commercialization of stem cells.
institutions which have Category 1 and
It will come as a surprise to many that ICMR has not laid down any punishment
l
Import or manufacture of SCCP will
2 Licenses. The license will be granted
Perhaps, to fill this void, the Central
for violation of the regulatory framework
Drugs Standards Control Organization
after satisfaction of quality controls;
drawn by it. The reason for this is that
(CDSCO), the parent organization of DCGI
establishment of characterization, cell
the ICMR has not been bestowed by the
and apex drug standard control body in
identity, purity, impurity and potency;
legislature with a power to punish those
India, has recently published draft
stability testing; proof of adequate
who default. At present, the enforcement
guidelines for regulatory approval of
container and closure systems; proper
of the standards set by ICMR is done
commercial use of stem cell and cell
labeling and product tracking and few
indirectly. For example, if a medical
based products (SCCPs). In effect, the
other requirements.
practitioner is found administering stem
draft guidelines propose to regulate all
cell in form of therapy, it would not be
practices related to the use of stem cells
level will also require a license
ICMR who will punish the medical
as well as other cells for therapeutic
(Category 4 License). A Category 4
practitioner, but the Medical Council of
purposes in India. They require that all
license applicant must have already
India (or appropriate State Medical
SCCPs and all activities related to their
received all the previous Category
Council) who will initiate action against
usage i.e. manufacture/isolation/
licenses.
the medical practitioner for “professional
collection, storage and transplantation
misconduct”. This long-arm approach has
into patients must be done only under a
however, seem to be extremely
been criticized for being ineffective.
license or permission that would be
controversial and bereft from the
However, the government is hopeful of
granted by the DCGI. Some of the
commercial realities of the day. The “tying-
stringent enforcement as from the
highlights of the draft guidelines are as
in” of licenses means that the research
beginning of December 2013, a nominee
follows:
institution has to necessarily conduct
52 | Lex WITNESS | August 2014
l
Sale of SCCPs at whole sale or retail
The draft guidelines by themselves,
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expert speak clinical trials, establish a commercial scale
development requires substantial capital
its investment. While the less ethical
manufacturing facility and eventually set
investment and continuous financial
have started administering stem cells as
up a retail outlet from where stem cells
support. The cost of developing a viable
therapy, a lot of institutions are
may be sold. There is no scope for market
SCCP must also include cost of research
generating revenue by supporting clinical
players to don roles of just a manufacturer
that failed. Hence, the institutions
trials by supplying clinical grade stem
or just a retailer. The draft guidelines also
involved in research and development are
cells for use in trials or conducting
completely negate the possibility of setting
almost always looking out for cash-rich
clinical trials themselves. Many patients
up commercial cell repositories in remote
investors/partners. At present, there is
are willing to enroll in clinical trials to
areas of the country because a commercial
little clarity on regulatory framework for
take a chance with stem cell therapy and
repository would not be able to obtain
commercialization of stem cells. If a SCCP,
are ready to pay. However, acceptance of
Category 1, 2 and 3 licenses required for
or for that matter a product of any
money for enrolment in clinical trials is
end consumer sale.
research, does not get commercialized
unethical and prohibited by Indian Good
within reasonable time, those who were
Clinical Practices. Realizing this, many
will be ineffective without supporting
involved in doing research and those who
such institutions have devised innovative
amendments to the Drugs and Cosmetics
financially supported it end up making a
ways to plough in some revenues in order
Act, 1940 and Rules, 1945. It is expected
loss. Hence, it is natural that investors
to off-set the cost of research.
that such amendments will be introduced
are hesitant to commit a substantial sum
soon.
for research and development of SCCPs.
surprise inspection that state-level drug
The draft guidelines, even if finalized,
The absence of a clear regulatory
The Industry is also upset with the
Institutions then are left with no option
regulatory authorities conduct on
pathway to commercialization of stem
but self-financing through loans or
research and development facilities. The
cell therapy in the present day has done
diverting profits from its portfolio.
Drugs and Cosmetics Act, 1940 and Rules,
a lot of harm to the industry. While the
However, there is a limit up to which
1945 regulate manufacturing carried out
less ethical minority has profiteered from
they can support themselves after which
for sale or distribution only. Thus, if an
the absence of enforcement, the majority
there is no option left but to discontinue
institution is engaged in research and
feels it has “burnt holes” in its pockets
the effort.
development of stem cells is processing
by investing in the science. This
In light of the above, most research
stem cells for that purpose, it is not
sentiment of the majority has to be
and development institutions are
carrying out illegal activity and any state
understood in a context. Research and
understandably eager to get returns on
drug regulatory authority is not legally equipped to take any adverse action
The absence of a clear regulatory pathway to commercialization of stem cell therapy in the present day has done a lot of harm to the industry. While the less ethical minority has profiteered from the absence of enforcement, the majority feels it has “burnt holes” in its pockets by investing in the science. This sentiment of the majority has to be understood in a context. Research and development requires substantial capital investment and continuous financial support.
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against such institutions for said activity. One can only hope that an effective regulatory framework for commercialization is introduced soon which is able to balance the regulators’ apprehensions and the industry’s commercial interest in a way that provides maximum benefit to the public! The need of the hour is to have sensible regulations which may be enforced, in absence of which patients will continue to be victims, not being able to benefit from a potentially curative therapy.
w
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