Summary
India and China have been identified by pharmaceutical companies as the future markets that would support drug research and development in a cost efficient manner. This has become necessary as resources to conduct clinical studies dwindle, coupled with the fact that pharmaceutical industries are under pressure to deliver quality medicine, on time, to the public. Exploring and examining India and China’s potential in a stepwise fashion provides the opportunity to dissect the good, the bad and the ugly of globalization in a comparative approach. This paper will cover areas like ethics in the conduct of studies, good clinical practice (GCP), economic realities, ICH influence, intellectual property security and the role of government in global clinical trial.
Excerpt
Table Of Contents
5
The Comparative Impact of Globalization of Clinical Trials
in India and China
Increasingly, resources for conducting clinical trials continue to dwindle following
pressure from other economic competing priorities. To this end, pharmaceutical industries look
for more innovative ways of delivering medicinal products to the door steps of end users who are
in need of quality medicines for their health. In addition, pharmaceutical industries are also faced
with the challenge of a more cost efficient way of doing business which culminates to balancing
quality, time and cost (Phillips, 2005). The outcome of this development is the exploration of
off-shore drug research and development. This is also referred to as outsourcing of clinical trials,
as well as globalization of clinical studies.
India and China have been identified as potential hubs and are currently being explored
by large and medium scale pharmaceutical/biotechnology companies as future markets. These
two countries hold great potentials, considering the abundance of humans in need of quality
medicine, the labor workforce with Western education to support clinical studies at a reduced
cost, upcoming infrastructures that are of internationally recognized standards, a mixture of
relaxed and complex regulatory pathways and drug naïve subjects that are ready to enroll in
trials. These two emerging markets are also in the process of aligning their regulatory guidelines
and laws with that of the Western world. As rosy as this appears, there are still hurdles to
overcome in these countries being explored by pharmaceutical industries.
Some large pharma industries, in trying to make the best of these opportunities, have entered into
strategic alliances, collaboration and partnership with local industries and other multi-national
CROs with the ability to navigate complex drug regulatory pathway to fast track business
6
development and to conduct research (EMERGING MARKETS). However, this also comes with
its attendant challenging risk of losing intellectual property, quality standard compromise and
recruiting patients without consent (EMERGING MARKETS).
The speeds at which pharmaceutical industries are exploring these offshore terrains vary
because of the competitive advantage of one region over the other or rather the way these
countries are repositioning themselves to attract the capital market of the industry. This paper
will explore and examine the good, the bad and the ugly in a comparative manner that has
resulted following globalization of clinical trials. As the paper examines the impact of
globalization, it will compare a broad range of globalization impacts on regulatory climates;
ethics in the conduct of clinical trials; ICH influences (good clinical practice (GCP) and global
acceptance including adaptation; intellectual property security; and the role of government in
global clinical trials; economic realities.
7
Indian drug regulatory body versus the Chinese system
The increasing outsourcing of clinical trials to India stems from the fact that large
pharmaceutical companies are pressured to deliver quality medicines to meet unmet needs in the
society. In addition, dwindling research funds calls for more effective ways of doing business
across the globe.
Not only that, companies are also interested in repositioning themselves to capture emerging
markets as projection have shown that these markets hold great potentials for global clinical
trials. The Indian pharmaceutical market capitalization was projected to grow to 2 billion US
dollars as of 2010 (Chatterjee, 2008). India is now one of the emerging hubs for clinical trials as
it boasts of technically competent and young workforce (More than 500,000 trained in the US
and in the UK), low cost of drug development, availability of treatment naïve population,
concentration of large population in urban cities, presence of major diseases, use of English as a
means of communication, supportive infrastructure, population diversity, highest number of
FDA-approved labs as well as friendly drug control systems (Chatterjee, 2008; Mukesh, 2009;
Jankosky, Jiang,& Farwell, 2007 and China).
As companies try to take advantage of the potential gains presented by the outsourcing of
clinical trials to emerging markets, their actions and inactions have impacted both positively and
negatively in the evolutions of drug regulatory system, including uncovering gaps that have
exposed patients to harm during trial conducts. Before now, India has demonstrated expertise in
conducting research in generic medicines while hosting only 1% of US sponsored investigational
new drug research (Mukesh, 2009). However, with increased outsourcing of clinical trials, and
expected rise of FDA regulated drug research, India conducted 10% of FDA regulated studies
8
back in 2010 and 15% in 2011 respectively (Jankosky,Jiang,& Farwell, 2007; Deepakmb, 2011 ).
The Indian regulatory framework is repositioning itself and as well aligning its practices and
organization to measure up to that of the West in order to make it competitive among emerging
markets.
The Drug Controller General India (DCGI) has being restructured to serves as the Indian
equivalent of Food and Drug Administration of the US and European Medicine agency in
Europe. It is the Federal body regulating all pharmaceutical related issues in India as described
in the drug and cosmetic rule of 2005 (Mukesh, 2009). The DCGI is equivalent to the FDA
commissioner, while clinical trial is regulated per schedule Y of the drug and cosmetic rule,
synonymous with the investigational new drug regulation described in 21 CFR 312 of the United
States (Mukesh, 2009). This resemblance on the surface is attractive to Western countries as it
makes India a favorable hub for clinical trials. The FDA is subdivided into various offices that
address issues regarding new chemical entities, biologics and medical devices with designate
leads. This is not the case with the DCGI, making regulatory approval cumbersome and
complex. Drug approval in India could take as long as six months. Trial documents with queries
may stay longer including trials considered as sensitive. Indian drug regulatory system was
realigned to capture lead drug markets in 2006 by categorizing application in A&B. Category A
are trials that have received approval in major markets (US, UK, Germany, South Africa,
Canada, Australia and New Zealand including Europe) following the rigor and expertise of
regulatory system in these countries. Proposal and protocol documents submitted under category
A are given preference and reviewed within 2 - 4 weeks. The category B research is reviewed
within 5 - 6 months (Mukesh, 2009). Before 2005, retesting of foreign drugs is required and in
addition, the Indian regulatory system requires all research to be conducted in India to lag by one
9
phase from the country outsourcing the trials (Deepakmb, 2011). However this has changed as
parallel studies are now allowed making Indian suitable to participate in multinational trials.
As good and appealing as these prospects to clinical trial conduct, continual outsourcing
of clinical studies to India has revealed that the gains of global clinical trial is that of a slow yet
consistent improvement. The human resource for health needs of DCGI is yet to be addressed as
the DCGI is only one person supported by a deputy that reviews research proposal documents
submitted for research conduct. This has further lengthened research approval process to 6 - 8
weeks. There are still gaps in the tracking system for submitted files making it difficult for
sponsor companies to accurately predict the position of submitted files and their status. In
additions, global outsourcing to India is yet to address formal meetings with regulatory bodies
before submission of files making it challenging in putting documents together to meet
regulatory requirements (Mukesh, 2009).
China as an emerging market in Asia Pacific and as well a potential hub for the
conduct of clinical trial across the globe features some unique advantages that make it
attractive to lead markets in the pharmaceutical industries. Some of the potential it shares
with India and beyond include; having the largest urban treatment naïve population,
supportive and motivated workforce (18,000 hospitals, 1.5 million physicians, 2 million
physician assistance, and 1.6 million nurses), significantly reduced cost of research
conduct, abound and unique disease resources, a huge market, GCP compliant database
and certified GCP public hospitals for research conduct. (Jankosky, Jiang, & Farwell,
2007; How to conduct clinical trials in china). To this end, it is expected that china will
be the 3
rd
largest pharmaceutical market by 2020. Global clinical trials have impacted
positively on the Chinese drug regulatory process to support clinical trials in this region.
10
China has already developed traditional research and development processes and
systems. However, the quest for modern pharmaceutical remains obvious following the shifting
dynamics of the Chinese population as well as the rapid urbanization of rural China (Emerging
Market; Faiz & Eric, 2007). Beyond having a traditional medicine system, the Chinese
government in a bid to reposition itself to become attractive to Western countries introduced her
GCP in 1998. This version of the GCP was revised in 2003 by the Chinese State Food and Drug
Administration- an equivalent of the US FDA created in 2000. A new drug administration law
was also introduced in 2001 coupled with a new drug registration procedure in 2002 (How to
conduct clinical trial in China) .Another impact seen with globalization of clinical studies in the
Chinese system was the adoption of the World Trade Organization recommendation on patent
law protection and intellectual property right in 2002. To make her shores competitive and
attractive for innovative drug investigation, the regulatory system has extended patent law and
intellectual property rights to 20 years.
Far above the introduction of drug regulatory process and new procedures for the
registration of drugs in the early 2000, China lately streamlined its drug regulatory processes
coordinated by the Chinese State Food and Drug Administration (SFDA). Some of these changes
include the conduct of clinical trials by only GCP-certified sites, the presence of US FDA offices
in China, strict monitoring of sites where trials are ongoing, shortening of drug approval
processes making (90 working days in 2007), the centralization of the drug regulatory processes
and harmonization of multicenter clinical trial conduct in 2007 including the inclusion of
international trials in Chinese regulation for the first time
(How to conduct clinical trials in China; Jurij &Petrin). The Chinese population dynamic shift
that contributes to China's competitive advantage in clinical trial conduct is uncovering the
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participation of increasing number of aged population in clinical studies. This is a grey area
which increasing outsourcing of clinical studies to China will explore. Global outsourcing in this
region will address research in elderly including the care of aged population across the globe.
This is likely going to be one of the impacts of and revelations of global clinical trial
outsourcing.
12
Ethics in Indian drug development versus Chinese; global clinical trial
impact
The need for good and improved medicines stands out as one of the compelling reasons
for the move of clinical trials to emerging markets. Testing drug in human before approval is a
pre-requisite, however this requires extreme care as these markets offer a large population of
treatment naïve and vulnerable patients with diversity of diseases and gene variability, to support
drug studies (Deepakmb, 2011). In addition, weak and poorly constituted ethic committee in
emerging markets has provided the platform for exploiting vulnerable populations.
Following outsourcing of clinical trials in India, havoc, horror, and harm have been
witnessed and recorded during clinical trial conducts. Ethic committees in India are saddled with
clinical trial document (Protocol, informed consent form, protocol amendment risk assessment
etcetera) review and as well support the DCGI when consulted to review submitted document by
foreign sponsors (Deepakmb, 2011). These ethic committees however are not under the control
of the DCGI nor accountable to any public authority.
There is also no formal registration of the ethic review committees in India. The number of
existing ethic committee cannot be estimated nor registration with regulatory body required
before they commence operation. In addition, private medical centers conduct research involving
human without adequate consultations with regulatory bodies (Mukesh, 2009). Most of these
ethic committees are staffed with physicians working in institutions where the research is being
conducted (Mukesh, 2009). Fewer than 40 ethic committees in Indian are well constituted,
making safety of Indian subjects of great concern (Mukesh, 2009; Deepakmb, 2011 ; Clinical
trial ethics in Indian one step forward two steps backwards) The resultant effect is the loss of
13
focus of her (ethic committee) core responsibility of protecting human subjects of research. The
ultimate effect is comprises in research document review (informed consent document, risk
benefit analysis and research protocol), poor monitoring of ongoing trial and lack of
accountability in the form of progress notes. The delinking of the DCGI as the legal regulator
from the ethical regulators (ethic committees) has demonstrated the inefficiency in the system.
These gaps have introduced questionable and unethical research practices.
Reports of recent misconduct in public and private health sector in India on mentally
challenged persons over a period of 2 years (2008-2010) put to question the functionality of the
ethic committees in these institutions including their understanding of the principles of respect
for person, beneficence and justice (Clinical trial ethics in Indian one step forward two steps
backwards). In the past three years (2010-2013), 1,542 deaths have been recorded in India
resulting from participation in research. 668 occurred in 2010 with drug companies admitting
that only 22 are directly related to their trials (Serious adverse events). 438 and 436 occurred in
2011 respectively. 211 were admitted to be drug related injury in 2012.
The fact that compensation is yet to be paid to more than 85% of families of subjects affected in
line with GCP requirements continue to buttress the gaps in ethical regulation of Indian clinical
trials. (The Tribune, February 23, 2013).
With increasing outsourcing of clinical studies, the Indian regulatory system is also
undergoing critical reforms to forestall human subject injuries during research proceedings. One
such reform is the push for the centralization of drug regulatory systems. In 2008, the Indian
counsel of medical research and reputable journals have also called for the mandatory clinical
trial registration in the Indian clinical trial registry (Deepakmb, 2011). This process is aimed at
Details
- Pages
- Type of Edition
- Erstausgabe
- Publication Year
- 2014
- ISBN (eBook)
- 9783954897650
- ISBN (Softcover)
- 9783954892655
- File size
- 282 KB
- Language
- English
- Publication date
- 2014 (April)
- Keywords
- rsm2
