The vaccine manufacturing industry in India, which contributes a significant share to the country's biopharmaceutical segment, is poised to take the leadership in generating low cost, effective and easy-to-deliver vaccines in the global vaccine markets.
The country houses some of the leading vaccine manufacturers in the world, including Serum Institute, Shantha Biotechnics, Bharat Biotech and Indian Immunologicals. It supplies more than 60 per cent of the world's requirements of basic vaccines procured by UNICEF. It is because the Indian firms are able to produce quality vaccines at reasonable rates, making it affordable for many developing nations. Industry experts observe that India would become a hub for vaccine production in the near future.
According to the available reports, the Indian vaccine market is estimated at Rs 1,800 crore in 2005-06. The volume of the business is growing with the newer vaccines coming in and companies increasing their production capacities. The spurt in vaccine market was mainly due to the entry of new players and new vaccines.
The vaccine research in the country is being conducted either by scientists located in academic or research institutes or by scientists located in the R&D units of biopharmaceuticals or biotechnology companies. Some of the key vaccine programmes, which are of national importance, are being carried out at academic institutes with financial support from government agencies like DBT, DST ICMR and CSIR. Most of the existing vaccines included in the extended immunization programmes of government of India have been produced through the conventional approaches. However, the impetus today is on using modern biotechnological tools to develop recombinant and chimeric vaccines.
"The newer vaccines are being developed to control rabies, Japanese Encephalitis (JE), HIV/AIDS, tuberculosis, rota virus, malaria infection, cholera infection, typhoid infection and human papilloma virus (HPV) infection. The country has earlier developed an anti-fertility vaccine, which has undergone phase-II clinical trials couple of years ago," said, Rajesh Jain, managing director, Panacea Biotec. "An anti-leprosy vaccine has also under gone ten years long phase- III clinical trails. Efforts are being made to develop certain therapeutic vaccines, especially for some of the cancers. In the industry set up, in addition to developing appropriate newer vaccine, improvements in the process development and yield of vaccines are some of the focused areas. Research is also being conducted to develop single shot multivalent vaccines that can be delivered through pain less route," he added.
On going researches for developing safe and effective vaccines against major diseases like malaria, HIV and rotavirus would be helpful for the global community to combat these diseases at affordable cost, said, Union Health Minister Dr Anbumani Ramadoss. He also highlighted the need for developing newer and more effective vaccines.
"Vaccine research in India is mainly directed towards development of newer combination vaccines, novel routes of vaccine delivery, utilization of the recombinant DNA technology and development of vaccines for the emerging infectious diseases. Vaccine R& D labs in India works in collaboration with various global agencies to develop newer vaccines with an objective to launch these vaccines globally," said, Varaprasad Reddy, managing director, Shantha Biotechnics.
Commenting on the advantages of combination vaccines, Reddy said, "WHO and various national immunization guidelines across the world advocates vaccination of every child against a number of life threatening diseases. As per the recommendations, a child would have to be given around 20 injections till reaching 1 year old, if all the vaccines were to be given separately. These vaccines have immense implications for the child, parents and public health in general. Combination vaccines are a methodology under which various component vaccines are developed as a single formulation so as to decrease the cost of the vaccine, minimize the trauma to the child and at the same time maintaining the effectiveness of each individual component in the combination. Combination vaccines will guarantee the compliance of immunization schedule.
Shantha Biotechnics Limited's pentavalent vaccine, which combines diphtheria, pertussis, tetanus, hepatitis B and hib, is an example of such a combination vaccine. Globally, hexavalent and heptavalent vaccines are at various stages of development.
As per industry sources, the Indian companies are investing heavily in R&D. Bharat Biotech has tied up with International Centre for Genetic Engineering and Biotech for a malaria vaccine, besides partnerships with Centre for Disease Control, Atlanta, National Institutes of Health, Washington D.C, Institute of Genomics and Integrative Biology, New Delhi, and National Institute of Virology, Pune. Shantha Biotechnology has collaborated with ICMR and National Institute of Health for developing a HIV vaccine. Serum Institute is developing an aerosol measles vaccine. It is also developing a quadravalent vaccine (combination of Hep B, diphtheria, Pertussis and tetanus). However, pipeline products of most of the companies are similar, which may lead to destructive price war among the Indian firms.
Government has adopted international standards for clinical research on vaccines. But, as far as R&D of vaccines is concerned it would go a long way in establishing India as the hub of vaccine technology. To boost this segment, the government needs to provide funding to the private players for research in the field of vaccine delivery methods. This area is the only one, where Indian companies are lagging behind in comparison to the world players, Reddy noted. Another essential area where the government has still not shown initiative is the non-inclusion of hepatitis B vaccine in the national immunization schedule. This has deprived the Indian children of a vaccine that is beneficial to all children in the world. Major vaccines produced in India include DPT, DT, BCG, tetanus toxoid, oral polio, measles, mumps, rubella, hepatitis B, rabies (tissue culture-based) and an injectable typhoid vaccine. Serum Institute of India (Pune) is the largest global exporter of vaccines and immunobiologicals in India. The company's flagship products are measles and DPT group vaccines. Serum is now working on a quadravalent vaccine that will reduce the number of injections for infants to just one. It has established a marketing alliance with Serono in Switzerland.
The Hyderabad-based Shantha Biotechnology markets recombinant hepatitis B vaccine and streptokinase. The company has so far exported hepatitis-B vaccines to various countries through UNICEF and PAHO and also directly to more than 20 countries. During the last financial year, the company recorded an export sale of Rs.95 crores, an 86 per cent of its turnover in the year. The company has various vaccines in different stages of development. The company is expected to launch haemophilus influenza (Hib) based pentavalent vaccine containing diphtheria (D), tetanus (T), pertussis (P), hepatitis B (HB) and hib, tetravalent DPT and hib and hib monovalent vaccines. Other vaccines in development are rotavirus, cholera, typhoid, measles, mumps, rubella combination (MMR) and vacricella.
Bharat Biotech with its revac-B, a recombinant vaccine for hepatitis B using its HIMAX technology, is active in the vaccines business. The technology used eliminates ultra centrifugation and the use of toxic metals, while increasing the recovery of antigenic proteins. Revac-B thus became the world's first recombinant hepatitis B vaccine to be manufactured without the use of cesium chloride. The company also markets streptokinase and is developing a rotavirus vaccine.
Panacea Biotech, yet another important player in this segment, has received WHO-GMP certification for oral polio vaccine. The company's anthrax vaccine is in phase I trials. Panacea Biotech has entered into joint ventures with Chiron Vaccines (Emeryville, CA) and Cambridge Biostability (Cambridge, U.K.) for vaccine manufacturing and thermostable vaccine production, respectively. Panacea Biotech is also negotiating collaboration with ApoLife (Detroit) for using ApoLife's yeast-based technology for the production of therapeutic humanized antibodies.
Many Indian companies with multimillion-dollar revenues in chemical, enzyme and pharmaceutical fields have also invested heavily in the biotechnology subsidiaries. These include, Biocon, Nicholas-Piramal India (Bombay), Panacea Biotech (New Delhi), Reliance, Ranbaxy and Reddy Laboratories. Apart, Nicholas-Piramal has entered into exclusive licensing and co-marketing agreements with global giants like Biogen Idec, Gilead Sciences and Genzyme.
Vaccine manufacturers may have only a limited product range, but their capabilities in reverse engineered vaccines are highly developed. Many of the plants possess WHO pre-qualification and manufacture as per US Food and Drug Administration specifications. At the international level also things are in favour of the Indian firms, as the multinationals are not showing interest in the developing markets. However, the Indian manufacturers are yet to make the expected leap into the big league. It is mainly because the Indian manufacturers are restricted to the low-end segments of the market.
"Vaccine manufacturing plants need to be upgraded almost every three years, though it is a costly affair," said, Cyrus Poonawalla, managing director, Serum International. As demand projections are given in advance, the firms are not in a position to charge high price. It is a disadvantage of the Indian firms. Whereas the MNCs, who are more focused on the self-pay segment, are immune to such pricing pressures.
Referring to the hurdles faced by the industry, Rajesh Jain, said, "Lack of concerted efforts by multi disciplinary teams of scientists and medical personnel, appropriate facilities for translational research as related to vaccine discipline, poor understanding of regulatory requirements, especially those relating to molecular vaccines, and non availability of GMP facility to produce candidate vaccines for proof of concept are major hurdles for the growth of vaccine industry.
Apart, lack of co-ordination between the academia involved in vaccine and vaccine industry outfits, upgradation of infrastructure, more qualified and well trained manpower with exposure to global regulatory needs, revisit existing regulatory norms needed at NRA and NCA and paucity of available qualified and trained manpower also act as stumbling blocks for the industry.
Moreover, the Indian firms have failed to enter into lucrative markets in the developed world. Indian manufacturers have no products in the categories that drive growth in these markets, like flu and travel vaccines. Hence, the Indian manufacturers are yet to tap the European and US markets.