Friday, January 13, 2012

India as a Growing Vaccine Hub

Science & Technology feature by  Richa Dubey*    

Albert Einstein defined insanity as doing the same thing over and over again and expecting different results. I would extrapolate a bit: it is also possible to do the same thing differently – we call this innovation. 
The meaning of innovation differs: to some, it means idea generation; for some others, it is a process by which an idea or invention is translated into a good or service for which people will pay. In the context of life-sciences, product innovation has great complexity because of the need for regulatory and ethical rigour in developing and testing new drugs, vaccines or devices, and in ensuring that they are affordable and relevant to public health.
Vaccines are an interesting case study of India’s growing experience and role in affordable product innovation. They are also hugely important to the world because we have the means to carry them to every child: rich or poor, rural or urban. They prevent disease – an important consideration – because treatment in remote locations is difficult.
In terms of achievements, the vaccine industry has not lacked for laurels. In fact, right from the basic science required in the initial stage of research up to affordable, bulk manufacture of high-quality products, the Indian vaccine industry has established a firm hold over the entire chain of vaccine development.
Indian vaccines are known for world-class manufacturing and have been stamped with one of the surest seals of quality in any health product: the WHO “pre-qualified” tag for production. India has also emerged as a key bulk vaccine manufacturer in recent times and already produces 60 percent of the world’s vaccines. Viewed another way, one in every 3 doses of vaccines used in the world are produced in India. Indian firms are big suppliers to the UN agencies, accounting for between 60% and 80% of the vaccines it buys every year. Besides mass-manufacture of vaccines, we have also been successful in creating or modifying a whole new range of vaccines indigenously.
Vaccine development is an arduous and lengthy process, however, speedy development has been a hallmark of the new vaccine industry in India, where both: response to a crisis (as in response to Japanese Encephalitis and H1N1 flu – with the latter taking just a couple of years to develop) as well as regular development of vaccines have been speeded up to the extent that a matter of a decade or so has been compressed into a few years. The H1N1 flu vaccine in fact, just took a couple of years to develop.
Development of vaccines is an essential stage of the process but by no means the ultimate one. Vaccine candidates need to be rigorously tested with every possible safeguard in place for clinical trial volunteers. This again, has seen a remarkable improvement. The rotavirus (which combats childhood diarrhoea) Phase III clinical trial supported by the Department of Biotechnology(DBT), Ministry of Science and technology, has been a model of an ethical and patient-friendly trial. Full insurance for the family of trial participants as well as coverage of all hospital treatment costs, if required was provided.
Similarly, an expensive vaccine has little meaning in the public health sector, particularly in a country like ours where the bulk of our population: millions of people cannot afford expensive health-care. India has proved to be a low-cost product manufacturer and service provider and benefits in many industries. It is far tougher to do so in scientific product development.  But we have achieved this by dint of pure innovation.
India’s growing capacity in this field also augurs well for the fulfilment of the needs of the developing world.  This capacity has been acknowledged by UNICEF through the very fact of India being its major supplier of vaccines. We are today preparing to take on the larger mantle of scientific development to fulfil the health needs of the developing world. In accordance with Gandhiji’s commandment to practice science with humanism, we must now learn to deliver vaccines to the 24 million children born every year in India and to millions born in other developing countries.  India already produces 60 percent of the world’s vaccines. 
This is evident from the rapid development and commercialization of several influenza vaccines as a response to influenza pandemic, new combination vaccines and development of low cost Meningococcal B Vaccine for Africa, by our researchers and industry. India is a destination for affordable products for the entire developing world now.  The key drivers of the emergence of India as a vaccine hub are a large pool of scientific talent, relatively lower costs in manufacturing, research and development capacity, availability of GMP requirements on par with all international standards, lower costs of clinical trials and a high potential for contract services by vaccine manufacturers.
The current Indian vaccine market is estimated to be around $ 900 million (in 2011).  It is poised to grow at the rate of 23% during 2011-2012 and by 10-13% CAGR over the next five years registering revenues and around $2 billion in 2011-2012, $4.6 billion by 2017.   With a number of important vaccines in the pipeline, the market is expected to explode globally in future with vaccines expected to grow faster than any other therapy area at around 13 percent during 2009-12.
India has been building capacity in the area of human resources by investments in science and education – both qualitative and quantitative. The figures speak for themselves. In 1981, more than 95 percent of Thomson Reuters-indexed papers from India named authors exclusively at India-based institutions. By 2007, however, the percentage of such papers had fallen to 80 percent, indicating that the nation is gradually participating more in internationally collaborative research. Further, between 1985 and 2007, publications co-authored by scientists in India have more than doubled in volume—and those papers were in general more heavily cited than in previous years. Not only has the volume of India’s scientific output risen, so has its quality. In fact, a recent media report indicated that placement of India’s top universities on the H-index, which measures citation impact, has gone up significantly in the past two years. Better funding has certainly helped. A recent report indicates that the only significant percentage increase in spending on Science and Engineering Research and development between 1996 and 2007 has come from the Asia Pacific region, led by India, China and other developing countries. The prime driver for this has been increased capacity for research.
Additionally, there have been a number of scientists who have returned to our shores or are in the process of doing so, thanks in no small part to government efforts like the Ramalingaswami Fellowships announced by the Department of Biotechnology which are 5-year fellowships for re-entries.
However, while the base may come from the focus on education and retaining our best brains, it is true that vaccinology is a specialised science and without a focus on infectious diseases, it is not possible to build a robust talent pool or infrastructure. Developed countries which have largely eradicated infectious diseases are understandably less interested in focussing on them, and prefer to focus on chronic diseases. India by virtue of its unique position as an emerging economy with the disease burden of a developing country needs to tackle the problem of infectious diseases internally. We have managed to focus on our own solutions to our problems with a high level of success, particularly in terms of developing the scientific community in this regard. It is no exaggeration to say that some of the best brains in the infectious disease space come from India today.
Brains and talent, crucial as they are, cannot deliver outside of a nurturing and enabling environment. There are several elements this environment, not least of which is funding. Vaccine development is a risky venture, particularly in terms of financing it. We are dealing with the fear of the unknown and the ever-present risk of failure. Few private companies want to take that kind of risk without assured success. This is where the balance between the public and private sector comes into play. The government undertakes the high-risk funding role and guides the private sector, which in turn, builds and utilises capacity for product development. The Indian private companies in the vaccine field have been remarkably open to innovation and it is this combination that has contributed largely to our success in vaccine development.
Collaboration is another element of this environment. It enables healthy knowledge and experience sharing in a mutually beneficial manner, while building and strengthening linkages across geo-political divides. Both North-South and South-South country-to-country collaborations have had a significant role to play in this success story. Multilateral partners too, have provided significant aid. The systematisation of demand and procurement of vaccines through UNICEF provided a crucial safety net for vaccine development. Similarly the knowledge-sharing achieved through collaborations like Indo-South Africa and organisations like the International AIDS Vaccine initiative is headed towards a promising turning point.
Moving up the chain, what is done with a vaccine once it is ready? Or, looking at it another way, will this entire process actually take place if there is no demand for it? Vaccine innovation, like everything else in a market economy, requires a spur to kick-start it. That spur is demand and demand generation is the crucial spark. It was the demand put forth by the Bill and Melinda Gates Foundation that resulted in the successful development of an inexpensive Rotavirus vaccine. Similarly the crisis engendered by H1N1 flu and Japanese Encephalitis created a demand pressure to develop these vaccines. However, there is a clear difference between the two. The former was a proactive demand whereas the latter was a reactive one.  Obviously, the need is to create demand for sustainable and positive vaccine development for the greater good.
Therefore it is important to sustain efforts in the field, particularly those directed at difficult-to-make vaccines for major killers like HIV, dengue, malaria etc. The stakes are higher here because it is not possible to predict a definite positive outcome by a definite date due to the nature of the disease we are battling. Therefore it becomes even more important for the government to play an anchoring role here.
In the case of dengue, Indian players have licensed live dengue virus-based vaccine technologies from different US developers. In accordance with the WHO and Dengue Vaccine Initiative directive, the International Center for Genetic Engineering and Biotechnology (ICGEB, New Delhi) is currently developing a non-infectious dengue vaccine based on the well-established Hepatitis B vaccine technology. The Hepatitis B vaccine strategy will not only maximize potency, but will also minimize cost.
The malaria vaccine candidate, after one unsuccessful attempt, is being tested after modifications (a combination of Plasmodium Vivax and Falciparum) in a Phase I trial for safety evaluation in Pune.
For HIV/AIDS, the DBT has set up a joint laboratory with IAVI: the THSTI (Translational Health Science and Technology Institute) which will both, speed up the process of assaying HIV vaccine candidates, as well as boost the research on antibodies that neutralize the HIV virus.
There are several lessons to be learnt from the vaccine success story however, I would like to focus on two of them as key innovation enablers. It is crucial to develop the entire value chain. An innovation system means a chain linking all the way from idea to customer service and this means ensuring that the entire system, from the capacity – be it human resource, funding or physical infrastructure – to the relevant regulatory policies and subsequent distribution is in place. It is only with the balanced development of the entire value chain, right from procurement of samples to robust cold chains that we can achieve success.
It is also essential to ensure that demand generation continues apace. No form of innovation can occur without an impetus in the form of demand. Necessity may be the mother of invention, but demand is the mother of innovation. If there is no demand for it, no innovation can happen. Demand generation for the greater public good is something that needs to be undertaken by the government and the private sector alike.
We do have challenges in the case of the vaccine industry and indeed, every industry that thrives on innovation. The vaccine story in India is hardly a fairy tale. Despite its phenomenal success, the industry faces tremendous challenges not the least of which is the openness of society. It is a truism that there is little resistance to any technological improvement for the benefit of the individual – mobile phones are a case in point. However, when it comes to the greater good, where benefits to the more vulnerable sections of society, like children, are seen, there is little eagerness to implement these improvements.
Vaccines have seen an improvement in this direction, particularly with the NRHM network of ASHAs, but a lot more needs to be done – both in terms of shifting to a positive mindset as well as following up on it by reaching high-quality, low-cost vaccines to everyone who needs them. We must remember that the numerous new health benefits that are available to the economically advantaged classes don’t necessarily reach the masses. Public policy needs to even this gap.
In the case of vaccines, we require political will and public funding; prioritisation of public health; a robust regulatory system; a strong private sector focus on public goods; public-private partnerships and social venture capital; capacity to innovate and deliver at scale; participation of all stakeholders; and the strengthening of systems through product introduction.
With the government declaring 2010-2020 as the “Decade of Innovation” and the establishment of the National Innovation Council in 2010, India is certainly receiving a strong top down impetus for innovation. Now we need to see how that can translate into tangible benefits for the country’s public and economic health. 
Table detailing vaccine development currently underway in the country

First rotavirus vaccine 116E developed in India at All India Institute of Medical Sciences (AIIMS), New Delhi in collaboration with Centres for Disease Control and Prevention (CDC), USA
Rotavirus vaccine 116E is undergoing phase III clinical trial at three sites: Society for Applied Studies (SAS), Delhi; Christian Medical College (CMC), Vellore; KEM Hospital Pune.
Live oral cholera vaccine candidate VA1.4 developed at Institute of Microbial Technology (MTECH), Chandigarh & National Institute of Cholera & Enteric Diseases (NICED), Kolkata
The candidate vaccine strain VA1.4 will be undergoing Phase II Studies
Malaria vaccine candidates JAIVAC-1 forP.falciparum & PvDBPII for P.vivaxdeveloped at International Centre for Genetic Engineering & Biotechnology (ICGEB), N. Delhi
JAIVAC-1 vaccine for P.falciparumhave been developed and transferred to Bharat Biotech India Ltd (BBIL), Hyderabad.  Phase I clinical trials completed
A vi-conjugate typhoid vaccine developed at AIIMS , N. Delhi
Technology has been transferred to USV Ltd. Mumbai
Dengue vaccine candidate being developed at ICGEB N. Delhi
Efforts on the possibility of developing safe, efficacious and inexpensive tetravalent dengue vaccine candidate are underway.
Collaborative efforts are underway between University of Delhi South Campus (UDSC) & Vaccine and Infectious Disease Research Centre (VIDRC) of Translational Health Science and Technology Institute (THSTI): and autonomous institution of DBT, for the development of recombinant BCG.
Several candidates for tuberculosis have been developed at DUSC with promising results in animal models, (rBCG85c) is being developed as an effective vaccine for tuberculosis.
Vaccine development support given to Panacea Biotec Ltd. New Delhi under Biotechnology Industry Partnership Programme (BIPP)
The Project has been successfully completed by Panacea Biotec Ltd. Leading to the development ofPandyflu TM (H1N1 vaccine)
Vaccine development support given toTergene Biotech Pvt Ltd Hyderabad under BIPP
Efforts for Development of an Affordable, Asia specific 15 valentPneumococcal polysaccharide-CRM 197 Protein co
Translational Health Science and Technology Institute (THSTI): an autonomous institution of DBT and International AIDS Vaccine Initiative (IAVI) have forged a partnership to develop “Next Generation” HIV vaccine candidates
Efforts are underway towards design of candidate vaccines to elicit neutralizing antibodies against HIV.
Development of HPV Vaccine by Serum Institute of India Ltd. Pune; is being supported under BIPP
Efforts are underway towards design of an affordable vaccine.
Vero cell derived inactivated JEV vaccine developed at National Institute of Immunology (NII), N. Delhi.

Development of JE Vaccine by Biological E Ltd., Hyderabad

Disclaimer: The writer is a freelance journalist and the views expressed by the author in this feature are entirely his own and do not necessarily reflect the views of PIB. 
*Freelance journalist

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