New devices can be tested in Indian territory, without permission/NOC from DCGI



… India is an acknowledged clinical trial destination for drugs and building on this reputation, the country has been garnering its fair share of medical device trials as well. But there are some speed breakers preventing the latter from achieving its full potential. Sachin Jagdale analyses the ‘trials’ and ‘errors’ plaguing this sector in India.

The growth of the medical devices market in India has seen a corresponding surge in the number of clinical trials conducted for such devices. Till a few decades back India was almost completely dependent on imports to meet the need for medical technology. However, over the years, as the Indian population swelled from millions to billion, so did its healthcare requirements. Sensing the huge potential and profits that the Indian market offers, many medical device manufacturers started their operations in India.

The growing medical device trial market in India is perhaps one of the most promising developments in this sector. However, decades of dominance by global players, especially those from Europe, underlines the fact that this segment of the clinical trial industry is still very nascent in India.

Market size
“Indian medical device industry is pegged to be around $3 billion and its growth rate will remain between 12-16 per cent over the next five years.”

Jayesh Chaudhary
Mng. Director, ClinACE Contract Research

According to Jayesh Chaudhary, Managing Director, ClinACE Contract Research, India’s medical device industry is pegged to be around $3 billion, with a projected growth rate of 12-16 per cent over the next five years. Imported products represent more than 70 per cent of the market while only 30 per cent is represented by domestic players. His company has forayed into clinical research of medical devices in February, and has started work on a CE (European Conformity) mark registration trial for a coronary stent device.

Dhirendra Singh, Managing Director, Genelife Clinical Research says, “Newer advancements in medical devices are looked as a major opportunity for medical devices clinical trials in today’s scenario. New oncology, cardiology, critical care, urology, neurology, rehabilitation and respiratory devices, even if they are not regulated, are conducting trials to build their data for various regulatory submissions.”

Regulatory woes

The need for regulations for medical devices, most often used to treat cardiovascular and neurological diseases, was underscored in 2008, when the US FDA received more reports of adverse events stemming from these devices than from pharmaceuticals.

Regulatory pathways for device trials differ from country to country and trials naturally gravitated to locations with less stringent regulations. For instance, Europe was considered less stringent than the US, so new medical devices would come to market first in Europe, followed by the US and then markets like Japan, where regulations were the most stringent.

Eastern Europe, and emerging markets like India, China or Korea had almost no regulation on medical device trials and were consequently considered more attractive. Length of regulatory pathway is directly proportional to cost, with some industry reports mentioning that a medical device trial costing between $5-$10 million in the US or Western Europe, and more in Japan could cost only a tenth of this in emerging nations.

But this is no longer the case, at least not in India. In fact, going by industry complaints, one would feel that the regulator has over compensated.

India’s nodal agency, the Central Drug Standard Control Organisation (CDSCO), which lays down the standards of drugs, cosmetics, diagnostics and devices, and also regulates clinical research in India, seems to have realised way back in August 2010, that medical device trials would flood the country. CDSCO’s medical device division had then circulated draft guidelines laying out the requirements for conducting clinical trials of medical devices which could change the way clinical trials will be conducted in India.

Industry experts, today, unanimously endorse the view that the country’s current regulatory system is the biggest hurdle in the growth of the medical device clinical trial market in India. They allege that it is one area where European countries have an edge over their Indian counterparts.
“Newer advancements in medical devices are looked as a major opportunity for medical devices clinical trials in today’s scenario.”

Dhirendra Singh
Mng. Director,
Genelife Clinical Research

Opining on the biggest regulatory constraint for medical device related clinical trials in India, Singh explains, “As there is an insufficient definition for medical devices and their risks in Indian regulation, the Drugs and Cosmetics Act, there is a very small compulsion for medical device companies to prove safety and clinical efficacy, the widest potential scope of trials. Additionally, this delays the decision making process at the Drug Controller General (India)’s (DCGI) end and hence indefinite postponement of trials also precludes many opportunities before they reach India.

Giving an example of a disparity, he points out, “Many new devices can be tested in Indian territory, without permission/NOC from DCGI. Several companies avail this opportunity and conduct clinical trials. The devices which fall under the category of regulated devices usually face indefinite postponement of their trial.”

The second major constraint is the latest pricing strategy adopted by the Central Government Health Scheme (CGHS) for stents. This medical device currently accounts for a majority of medical device trials in India, especially Drug Eluting Stents (DES). An addition of at least two-three new products in the market provides opportunity to the medical device clinical trial. As CGHS has limited the pricing of FDA approved stents to Rs 65,000, CE approved stent to Rs 55, 000 and Indian (only DCGI approved) stent to Rs 45,000, the potential fund, that is generated for clinical trials is eliminated.”

Chaudhary echoes Singh’s views. Like Singh, he also describes unclear regulation as the culprit. “Due to unclear regulations there are not many clinical trials that are being conducted in India, so in a way the regulations are much to be blamed for the slow growth rate of this sector,” criticises Chaudhary. He adds, “With no clear guidance from the regulators this industry was on a down slide fall until 2005. Several MNCs have downsized their operations in India due to the regulatory issues faced by these companies.”

“We don’t have enough trained principal investigators, support staff and our doctors are overloaded with patient care. Conducting a clinical trial on a medical device is much more involving, time consuming and volunteers are hard to find.”

Sandeep Saxena
CEO, Acton Biotech

“We don’t have enough trained principal investigators, support staff and our doctors are overloaded with patient care. Conducting a clinical trial on a medical device is much more involving, time consuming and volunteers are hard to find,” opines Sandeep Saxena, Chief Executive Officer, Acton Biotech, a Pune-based biotechnology company. Lack of distinct regulations between drugs and devices confuses medical device manufacturers who see the opportunity in India but are wary of tapping it due to these factors.

“Lack of a dedicated center in the country to oversee certification, approval or monitoring of medical devices etc. has created a problem. Due to this, registration of foreign manufactured medical devices takes sometimes up to one year.”

Ajit Mahadevan
Partner – Life Sciences, Ernst & Young

Ajit Mahadevan, Partner – Life Sciences, Ernst & Young, explains the scenario. He says, “Currently, medical devices are regulated as drugs under Drugs & Cosmetics Act by DCGI of CDSCO, the central governing body of the country. Lack of a dedicated centre in the country to oversee certification, approval or monitoring of medical devices etc has contributed to the cause. Due to this, registration of foreign manufactured medical devices take sometimes up to one year.”

Ruchi Malhotra, Manager and Mohit Jain, Consultant, Ernst & Young, feel that lack of CROs with medical device development capabilities is also an issue. They say, “Very few Indian CROs have specialised capability in terms of a medical device trials track record, regulatory know-how, site infrastructure, and experienced investigators to conduct medical device trials in India.” According to them, since India has hosted a very limited set of medical device trials, primarily in big cosmopolitan sites and hospitals, there is a lack of well developed and qualified medical device sites and institutions that can scale up to the expanding need of medical device research. Most current medical device research sites are small private clinics.

Drug versus device trials

The underlying principles for conduct of medical device clinical trials remain the same as for drug trials but the processes are completely different. In India a drug trial has very specific regulations. The type of data required for a new drug or an existing drug are very clear. The trials and trial applications submitted to DCGI’s office are evaluated in a highly organised way.

Medical device trials, in contrast, according to Singh, find limited mention in Indian regulation. Singh says, “Apart from stents, DES and other regulated devices which hardly require clinical trials, medical devices in India are not mentioned in regulation. The devices in India hence can start clinical trial with their own right, with probably permission from ethics committee approvals.”

While clarifying that processes for clinical trials for drugs and medical devices are completely different, Chaudhary provides details of how the process of clinical trial for medical devices starts.

“The first aspect is to have a clear indication of which class the device belongs to and what is the final objective of conducting the trial (objectives can be CE marking or a 510(k) filing etc),” opines Chaudhary.

He adds, “In India, the regulators have issued a list of devices which are classified as drugs and for such devices the same process as a drug is followed. (The Ministry of Health and Family Welfare, under Gazette notification S.O.1468(E) dated 06th Oct 2005 declared the following sterile devices as drugs under section # (b) (iv) of the Act-cardiac stents, DES, catheters, IOL, I.V. canulae, bone cements, heart valves, scalp vein sets, orthopaedic implants, internal prosthetic replacements etc. The 2009 notification has added other new devices which are classified as drugs. One of the main differences in the data to be submitted is biocompatibility data (which is not submitted for drugs) body contact, contact duration, submission of protocol and study report of the biocompatibility study.”

Chaudhary explains, “Schedule M-III outlines the requirements for manufacture, import and sale of medical devices. The clinical trials for devices should aim at verifying that the device conforms to the ‘Essential Requirements’ mentioned in Annex I of Schedule M III. They should also comply with ISO 14155 standards.”

Positive steps

The regulator seems to have taken note of industry’s distress. The DCGI’s office announced last November that from December 1, they would pre screen registration applications for medical devices and pharmacy products. The announcement was clearly a move to expedite device and drug registration applications, by allowing regulatory reviewers to notify applicants in a quicker manner if any required documentation is missing or insufficient. It is going to be interesting to see whether this move has the desired effect and whether it would help attract more medical device trials to India. While Singh asserts that this move will have no impact as this announcement refers only to the 25 medical devices that need regulatory approvals, Chaudhary is more willing to hope for a positive turn. He insists, “Yes, this will definitely help in getting more clinical trials conducted in India but provided the regulators are able to keep up with the number of applications and the approvals are received in an appropriate time.”

Future on ‘trial’

It takes a long time to build a reputation and the same is true for the clinical trial industry. It took time for India to make a niche for itself as a destination for drug trials and medical device trials is going through a similar learning curve right now, with the last few years showing promising growth.

According to Chaudhary, medical device clinical trials are expected to grow at the rate of approximately 20 per cent for the next five years. “Even if there are not many pilot/pivotal studies and First in Man (FIM) studies taking place currently, we see wider prospects in the near future and scope for medical device clinical research in India,” says Singh signing off on a positive note…(read more: http://bit.ly/wYdEHE)

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