The last three years saw a drop in clinical research being done in India on account of regulatory uncertainty, judicial and social activism and some media sensationalism. This made the clinical research fraternity apprehensive and concerned over how this would translate into delayed access to new therapies for Indian patients. Over the last year and a half, the Ministry of Health and Family Welfare has taken steps to address the challenges posed by regulatory uncertainty and take on board concerns voiced by stakeholder. Regulations were amended and further guidance was given on existing ones. These were significant movements forward and a reiteration of the regulator’s commitment to clinical research in the country.
The changes that began in 2014 now need to be sustained. The inclusive approach adopted by Indian regulators in which multi-stakeholder feedback has been actively sought and acted upon in many cases, must continue. We need to build on an emerging regulatory system that is balanced, aligned with global trends and one that addresses our uniqueness as a country and society. These developments send out a strong signal to the global clinical research community that we are committed to a robust regulatory environment with a focus on collaboration, transparency and, most importantly, patient safety and protection.
Here we would like to flag a few noteworthy measures taken by the regulators that give us confidence that we are moving forward on the right track:
Amendments to Compensation Guidelines:
In December 2014, amendments were made to earlier contentious clauses of Rule 122 DAB of the Drugs and Cosmetics Act (released in January, 2013) on compensation, making the regulation less prone to misuse and litigation. The revised guidelines rationalised compensation and medical management for injuries caused during and because of the participation in clinical research, bringing in a balance between the interests of patients and innovators, and at the same time giving us more clarity in the process. What is also important to note is that for the first time in the world, formulae have been introduced by the regulators for calculating the financial compensation based on the ‘no fault’ principle. This provides ease of implementation and consistency and helps the sponsor of the trial understand the maximum possible liability and to plan appropriately to protect patient well-being.
Predictable approval timelines with the expansion of the Subject Expert Committees
The Ministry of Health and Family Welfare, Government of India has created 25 panels of experts for various therapeutic areas to be known as Subject Expert Committees (SECs). They evaluate the various categories of applications received for clinical trials, new drugs and new medical devices. In strengthening the SECs, the Ministry has addressed an industry concern that the SECs were not run as efficiently as envisaged because of an inadequate representation of subject matter expertise and the lack of availability of members for meetings. Feedback from the industry is that this has resulted in reduced approval timelines which are averaging six to seven months from submission to final approval as compared to 18 months earlier.
Governance over clinical research conduct at sites
The mandated registration of Ethics Committees (EC) with the CDSCO has been another important step towards providing EC oversight at trial sites. The inspection drive by the CDSCO has led to a clear indication that there is intent to improve quality and vigilance. Though the purpose, process and the outcome reporting of these inspection drives has been much discussed and debated, from 2014 onwards most companies and clinical trial sites have recognised the fact that there needs to be a culture of “inspection readiness at all times”, which certainly is a step in bolstering stakeholder confidence.
Clearly the value of clinical research in India is being appreciated more but its full potential has yet to be realised. Several limitations still exist that either delay clinical research or curb its scope. One of our greatest challenges is to instil confidence and trust amongst global stakeholders about the evolving and more scientific regulatory environment in India and the fact that there is now a more conducive environment for clinical research in the country.
There is a need for investment by the regulators in capacity building and infrastructure to ensure better governance and management of clinical research in the country. We also hope that the proposed accreditation of Clinical Research Sites, Investigators and Ethics Committees will come into place soon and the cap limit for investigator initiated trials lifted vesting the final decision with the Ethics Committees.
At ISCR, an association that aims to facilitate the growth of clinical research in the country, we hope that Indian authorities will continue to play a proactive role in encouraging local research and innovation. We have made good progress and should continue this momentum. Millions of patients are waiting in the hope of better and more effective treatment. If we have to find better and more cost effective cures for existing and new diseases, we need to make clinical trials work in our country.
Source: Article by Ms. Suneela Thatte, President, Indian Society for Clinical Research (ISCR), sourced from Financial Express. (link for article)
The Union health ministry has banned the manufacture and sale of the controversial fixed dose combination (FDC) of Flupenthixol and Melitracen for human use with immediate effect in the country. The combination of Flupenthixol and Melitracen is an anti-depressant drug, sold as deanxit in India.
Now, therefore, on the basis of the recommendations of the Drugs Technical Advisory Board and in exercise of the powers conferred by Section 26A of the Drugs and Cosmetic Act, 1940 (23 of 1940), the Central Government hereby prohibits the manufacture for sale, sale and distribution of the following drug with immediate effect “Fixed dose combination of Flupenthixol and Melitracen for human use”, the ministry in its notification, G.S.R. 498(E), said.
This is the second time the government is banning this drug. Earlier on June 18 last year, the health ministry had banned ‘deanxit’ in the country along with two other drugs–anti-diabetic drug pioglitazone and pain-killer drug analgin.
But immediately after the ministry’s notification, two writ petitions were filed in the Karnataka High Court by Bengaluru-based Lundbeck India and New Delhi-based Mankind Pharma. The petitioners contended that the studies made on the drug has proved its safety, efficacy and benefits.
However, the government contended before the court that melitracen is reported as not efficacious as a single agent in depression and use of flupenthixol is associated with potentially serious neurological side effects. Besides, the government contended that the combination drug is not permitted in USA, UK, Denmark, Canada, Japan and Australia.
After hearing both the parties, the court in its order dated August 14, 2013, quashed the ministry’s notification, and remanded the matter back to reconsider afresh by the government and take a decision one way or other in accordance with the law.
The ministry then asked the Drugs Technical Advisory Board (DTAB, a statutory body under the Drugs and Cosmetics Act, 1940, to examine the issue of suspension of manufacture and sale of the drug. After detailed examination in its 65th meeting on 25th November, 2013, the DTAB, highest authority in the union health ministry on technical matters, recommended that the use of the drug should be discontinued in the country.
On the recommendation of the DTAB, the health ministry has once again banned the controversial drug as “the Central Government was satisfied that the use of the drug ‘fixed dose combination of Flupenthixol and Melitracen’ for human use was likely to involve risk to human beings and whereas safer alternatives to the said drug are available’.
The Central government has to come out with appropriate strategy to overcome the trade barriers put up by the Vietnam government against Indian pharmaceutical exports in recent months. The regulatory authorities in Vietnam have been frequently finding fault with the quality of Indian pharmaceutical exports without much justification, according to some leading exporters.
This hostile attitude of the Vietnamese drug regulatory authority is resulting in issuing letters and blacklisting some Indian exporters citing compliance and quality issues. While the industry appreciated the pro activeness of the Indian government in reaching out to Vietnamese counterparts, the industry insisted that the government should take measures in interacting with the stakeholders as well to understand the ground realities.
Nipun Jain, chief executive officer, of Pharmachem stressed that Vietnam being a major export destination is an important market for the industry and thus pre-emptive measures should be taken to address the issue. To safeguard the interest of the Indian exporters, while maintaining a strong relation with the Vietnamese government, Jain who is also in the SME panel of Pharmexcil suggested that India and Vietnam should work together to collaborate on setting up a joint drug testing lab in Vietnam, which would ease up the tension and build the confidence among both the parties.
He also suggested that if not that the Vietnamese government can try to outsource the drug testing to a third party like SGS. If not that they can try adopting pre-shipment testing through a third party as being done for exports to Nigeria, where samples of drugs to be exported to the Nigerian market is tested through a third party testing laboratory in India itself before being exported.
“These are some of the practical solutions that can be adopted to address the issue. These steps will ease the exporters tension and uncertainity while exporting to Vietnam and will also help the Vietnamese authority in addressing their fears on quality issues, without affecting the exports,” Jain pointed out.
A highly placed source from the industry claimed that contrary to the claims made by the Vietnamese government, the fault does not lie with exporters alone, as the regulatory system in the country is equally to be blamed. On condition of anonymity a source revealed that there is a huge lacunae in the drug testing and regulatory system in Vietnam which is the main cause of concern for many. In fact, the source pointed that the testing labs and other facilities are not even updated and latest as per the internationally accepted guidelines.
“The ongoing situation cannot be sorted out without taking into cognizance of the deplorable state of the drug regulatory system in Vietnam, as well rather than playing the blame game they should take some constructive steps towards modernising their drug testing labs. May be then they will find out that the problem is not with the Indian drugs but is with their incapability in properly testing the products,” a source stressed.
The Drugs Controller General of India (DCGI) has constituted an Independent Expert Committee on Oncology for examination of reports of serious adverse events (SAEs) of deaths occurred during clinical trials in the country. Dr Arun Agarwal, Professor of ENT, Maulana Azad Medical College, New Delhi is the chairman of the expert committee.
The committee will function under the provisions as specified in Appendix XII of the Schedule Y of the Drugs & Cosmetics Rules.
The chairman of the committee will receive reports of serious adverse events of death from investigators, sponsors or his representatives whosoever had obtained permission from the DCGI for conducting the clinical trial and the ethics committee. The committee will examine the reports of serious adverse events of death, to determine the cause of death and if the cause is due to reasons which are considered as clinical trial related death , then it will give its recommendation to the DCGI.
The committee will examine whether the death has been happened due to adverse effect of investigational products; due to violation of the approved protocol, scientific misconduct or negligence by the sponsor or his representative or the investigator; whether it is due to the failure of investigational product to provide intended therapeutic effect; due to use of placebo in a placebo-controlled trial; due to adverse effects due to concomitant medication excluding standard care, necessitated as part of approved protocol; for injury to a child in-utero because of the participation of parent in clinical trial; and due to any clinical trial procedures involved in the study.
In case of clinical trial related death, the committee will also give recommendation to the DCGI the quantum of compensation to be paid by the sponsor or his representative.
Dr YK Gupta of AIIMS New Delhi; Dr Renuka Kulkarni-Munshi of TN Medical College and BLY Nair Charitable Hospital, Mumbai; Dr Hemant Malhotra of SMS Medical College, Rajasthan; Dr SD Banavali of Tata Memorial Hospital, Mumbai; Dr TN Sagar of Cancer Institute, Adayar, Chennai; Dr Kishore Singh of Maulana Azad Medical College, New Delhi; and Dr S Kataria of Safdarjung Hospital are the other members of the 8-member expert committee.
There was mixed reaction to the budget presented yesterday by Union finance minister Arun Jaitley.
Biocon chairman and managing director Kiran Mazumdar-Shaw said she is disappointed as the Union Budget 2014-15 has no takeaways for the biotech and pharma industry. “This Budget is positive but largely directional and aspirational. I was expecting bolder reforms for boosting investor sentiments. The long-pending GST issue needed a stronger messaging with a commitment to time-bound implementation, however the FM has only assured to arrive at a decision by end of the year,” she noted.
The finance minister has given the necessary directives to the respective ministries for action and implementation, and it now needs to translate into tangible outcomes. The reluctance of the FM to articulate Big Bang reforms received an initial thumbs down from the markets, but the smart rally later signals a resounding acceptance of Budget 2014. The pronouncements on the retrospective tax issue, easier FDI rules, jobs creation in manufacturing sector and improving predictability in India‘s tax regime will improve the investment sentiment in the country. As will measures for addressing the funding needs of small entrepreneurs. Also welcome are the proposals to shift to e-governance, which is expected to improve efficiency and stem administrative leakages. Disappointingly, however, Budget 2014 did not have much for the pharma & biotech sector. We welcome the intent to establish more biotech clusters but most of the proposals are tokenism at best. Implementation timeline for GST and abolition of MAT for SEZs could have been positive moves for our sector, which has been long ignored. I expected more. I would rate the Budget between 6.5- 7 out of 10, stated the Biocon chief.
Sujay Shetty, leader pharma and life sciences, PwC India pointed out that some good initiatives were announced in the budget across capacity and infrastructure building. The main one is hike in insurance investment limit to 49 per cent. This will help both the patients and the pharma industry. Free drugs and free diagnostics for all, sounds potentially promising for patients. We will have to see more details on this.”
Dr Rana Mehta, Leader- Healthcare, PwC India said that this budget provisions to enhance both financial and physical access of healthcare for the country. Through broadband in rural area, telemedicine will increase the accessibility of qualified doctors and specialist into rural area and increased FDI in health insurance to 49 per cent will help increase financial accessibility of population. Opening up of 4 additional AIIMS and 12 government medical colleges will ensure improvement in quality of medical education and a step towards covering the shortage of one million doctor in India. It will also enhance access to tertiary care for patients who need to travel from far flung areas to reach AIIMS in Delhi.
According to Charu Sehgal, senior director, Deloitte India on Life Science and Healthcare, “The almost negligible focus on healthcare in this budget was disappointing. There was hope of the government increasing Health Expenditure closer to the 2.5 per cent of GDP as well as of announcing initiatives that would encourage private investments aimed at improving healthcare availability in underserved areas.
While the setting up of twelve new government medical colleges is welcome, given that we have a shortage of one million doctors currently, there was a need for a major thrust to enable and facilitate private investment in Medical education to bridge the huge gap. The setting up of fifteen Model Rural Health Research Centres sounds interesting and has potential, although the exact framework of its operations needs to be examined. It will be excellent if it can provide the much needed impetus and support to collaborative innovations aimed at increasing access and affordable healthcare for the poor. Although the decision to set up several more AIIMS will provide high quality tertiary care in these towns, the more urgent need is for the government to tackle primary and secondary care so that the pressure on tertiary and quaternary facilities can be reduced,” said Seghal.
According to Dr PM Murali, president, Association of Biotechnology Led Enterprises (ABLE), overall, the budget seems to have delivered in line with market expectations, with adequate focus on infrastructure and measures to boost financial savings. Though, more clarity on the roadmap to GST would have been welcome. ABLE welcomes the focus on strengthening of institutions as Technical Research Centres as this will strengthen the skill gaps and boost productivity. The emphasis given to start-ups, entrepreneurship, innovation and incubation is also a welcome initiative to boost technology and product innovation. It is also heartening to see the focus on the agriculture and biotechnology sector. The scaling up of agri-biotech clusters will help enhance competitiveness and innovation capacity.
Union budget for the financial year 2014-15 has shown encouraging signs for the growth of healthcare entrepreneurs in India, hailed Gopi Gopalakrishnan, president of World Health Partners (WHP) which is an international non-profit organization that provides health and reproductive health services in developing countries across the world. The NGO has hailed the Indian budget as an encouraging sign for the growth of healthcare entrepreneurs in the country.
This year’s budget has been a deviation from the trend, where healthcare has been mentioned quite often, and in a positive framework. The finance minister, although walking a tight rope on the fiscal front, has initiated a substantial amount of measures which directly or indirectly affect the healthcare of the citizen, said Zahabiya Khorakiwala, managing director, Wockhardt Hospitals Ltd.
Right from macro issues of sanitation, malnutrition and safe drinking water, to the caring of differently abled and the ageing, he has tried to touch the long standing sore health issues of India. The mention of free drug service and free diagnostic service for the poor are sentiments in the right direction, although they carry the risk of execution, given the federal structure of the country, she added.
For healthcare delivery industry, the setting up of 12 more medical colleges, and 4 AIIMS would be a welcome move as it would augment the very critical medical manpower in the country which is in very short supply. REIT’s entry in the real estate space may indirectly ease the woes of hospital industry, and e-visas would be a hassle-free tool for medical value travel. While saying this, there have not been mentions of any SOPs for the healthcare industry, or under National Health Assurance Mission. Government could also have promoted health insurance coverage for citizens by bringing it in the negative list for Service Tax. We still have to analyse if the healthcare spends suggested in this budget have achieved a desirable level of percentage of GDP. The healthcare industry would also have been overjoyed, if it was included in the list of Infrastructure sector, as it would have then availed several pushes designed in this budget, added Khorakiwala.
Dr Pavan Kumar, consultant cardiac surgeon at Lilavati Hospital & Head of Cardiac Surgery Department and Telemedicine Center at Nanavati Hospital in Mumbai said the Union Budget of 2014 is totally uninspiring and pedestrian. A lot was expected from the Namo Budget, but after the budget was announced, no difference can be seen between the current and the earlier government. There are no new reforms for the health or pharma sector, he said.
Amol Naikawadi, joint managing director, Indus Health Plus says, “Overall, the health market players may not be too happy since there aren’t any major reforms announced for the entire health industry. We have again failed to make government realize that it is importance to address the increasing health issues. Various non-communicable and communicable diseases are taking toll which affects the nation’s health and overall growth.”
“The free diagnosis services under Health for All will encourage more people to undergo healthcare checkups which will further help in early diagnosis and treatment of diseases. The opening of AIIMS and 12 medical colleges will ensure better medical facilities, tertiary care and trained medical professionals but this however may solve sectorial problem only. Nationally the concern for health can’t be addressed with this number. Increased GDP allocation on healthcare will make good healthcare services almost affordable to the lower income groups. This would also include spending more on public health services and making health insurance available to all. The tax benefit offered in general will be of a great help for the disposable income earners to invest in preventive healthcare” says Amol Naikawadi.
The budget lays a lot of emphasis on spurring growth in the manufacturing sector. The investment allowance linked to the new investments in plant and machinery are likely to benefit pharma companies also. The Government has hinted at supporting SEZs. Pharma companies setting up export units should be enthused by this intent, although the devil lies in the details, said Anand Mehta, Partner (pharmaceutical and healthcare sector group), Khaitan & Co., a law firm based in Mumbai on the pharmaceutical and healthcare sector.
The budget as proposed will encourage R&D. The Government has proposed to strengthen biotech clusters. Innovator companies are also likely to benefit from the proposed provision for refund of customs duty on the import of scientific and technical instruments. Investigators in clinical trial programmes may now be subjected to service tax with the exemption proposed to be withdrawn. These had been included in the negative list of exempted services. This will make clinical trials more expensive, he said.
“With regard to the healthcare sector, the government appears to have recognised the need to address critical shortages of qualified doctors and medical staff and announced setup of more AIIMS, government medical colleges and institute for higher dental studies as well as establishment of model rural health research centres for undertaking local health research. We expect that the commitment to providing Smart Cities and digitising India through broadband connectivity at village level could result in a boost for models such as telemedicine, which can provide significant impetus to healthcare delivery in rural areas”, said Gagandeep Bakshi, Associate Director – Investment Banking, Intellecap.
However, we are disappointed with the absence of targeted incentives such as infrastructure status to hospitals and increasing tax exemption for setting up hospitals which would have provided access to affordable and quality healthcare in Tier II and Tier cities. This should be addressed by the government in the near future to enable rapid health infrastructure growth,” he added.