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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

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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.

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