Vaccines are important preventive medicines for primary health care and are a critical component of a nation's health security. India is among the major buyers and makers of vaccines, locally as well as globally, and has traditionally aimed at self-reliance in vaccine technologies and production. By 2016, India's vaccine production sector is likely to expand dramatically to  $871 million. Whereas in 2011-12, it was estimated to be $350 million.

India is poised to play a leading role in the global vaccine market even as Asia is emerging as the vaccine hub of the world. Relatively lower costs in manufacturing and research and development, the ability to produce and develop high quality vaccines, the lower costs of clinical trials, a large pool of scientists and increasing local demand are  speeding India into a favourite hub for vaccine development and manufacturing. While forging its way into the vaccine production, India has found itself descending into the clutches of its private sector. In 2008, closing down of government-owned vaccine manufacturing facilities has unintentionally provided a foothold for private companies to sweep in and provide doses for the nation's basic immunization programme.

Vaccine R&D status in India
Ideally, a vaccine should have high protective efficiency with no or negligible side effects and affordable prices. Research is always ongoing in various institutions to develop a still better vaccine against diseases such as cholera, TB, Hepatitis A, Hepatitis E, Hepatitis B, rotaviral diarrhoea, cervical cancer, pneumococcal infections, acquired immune deficiency syndrome, influenza, meningitis, filarial, rabies, typhoid, malaria, dengue, japanese encephalitis, leprosy, etc.

Efforts are on to use the modern tools of science and technology such as tissue culture, genetic engineering, construction of peptide/carbohydrate subunits and also unconventional delivery systems such as edible vaccines, nasal sprays, thermo-stable, slow release etc., basically to obtain the most purified uncontaminated antigens that can elicit high immune response, with minor side effects.

As of today there are around 28 vaccine R&D institutions in India that are actively engaged in research and development of vaccines. Their institutional structures are based on the innovation model where R&D and production co-exist under the same roof. This was basically to facilitate research that would lead to vaccine development against a particular disease and transfer of technology to the production division. This model facilitated better and faster co-ordination between R&D and production divisions, for scaling up technology and other improvements and technological up-gradation. Rest of the research institutions that were set up after independence are dedicated to research and development of vaccines.

Vaccine manufacturing capabilities of India
In India , vaccines are traditionally produced by public sector companies and by state sponsored organizations like in many parts of the world. However, globally there is a radical transformation of the industry and now significant vaccine business is in the private sector, which is growing at rapid rate. Now, Indian market accounts for two per cent of total global pharmaceutical industry. As vaccine market is considered to be a significant profit- making business in the global pharmaceutical industry, several new companies are now highly involved in vaccine business.

Vaccine development has several trends. Until recently, most vaccines were aimed at infants and children, but adolescents and adults are increasingly being targeted. Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world. New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.

Vaccines are being designed to stimulate innate immune responses, as well as adaptive. Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease. Vaccines are being developed to defend against bioterrorist attacks such as anthrax, plague, and smallpox. Appreciation for sex and pregnancy differences in vaccine responses "might change the strategies used by public health officials".

Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders. For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure. Factors that have impact on the trends of vaccine development include progress in translatory medicine, demographics, regulatory science, political, cultural, and social responses.

The challenges posed by vaccine development and manufacture are similar to those faced in the production of other biopharmaceuticals, including escalating demands for increased speed in the transition from research and development (R&D) to clinical trials, increased cost-effectiveness of manufacturing processes and reduced time-to-market.

Small biotechnology companies may present challenges to multinational vaccine manufacturers by improving aspects of vaccine development, such as improved delivery systems. More often, however, the high cost of vaccine development requires partnership between these small firms and the major manufacturers, further cementing their central role in the US and international vaccine landscape.

It takes around five to six months for the first supplies of approved vaccine to become available once a new strain of influenza virus with pandemic potential is identified and isolated. These months are required as the process of producing a new vaccine involves many sequential steps, and each of these steps require a certain amount of time to complete. In an hawkish scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time period. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly two billion courses would be required. If China pursued this goal as well, more than three billion courses would be required to serve these populations.

Challenges for Indian manufacturers
As the Indian vaccine industry is evolving, it is faced with a number of challenges both at the micro unit level and at the macro level. The challenges posed by vaccine development and manufacture are similar to those faced in the production of other biopharmaceuticals, including escalating demands for increased speed in the transition from R&D to clinical trials, increased cost-effectiveness of manufacturing processes and reduced time-to-market.

The vision for the field of vaccine manufacturing is protecting and improving the public health globally and facilitating the development, approval and access to safe and effective products and promising new technologies.

The large size of the Indian market offers scope for bringing higher scales of operations to enable low cost manufacture. The danger here is the risk of lower margins. With costs moving up, the rupee gaining strength and regulatory compliance costs going up, it will be difficult for Indian vaccine manufacturers to play the "high volume low cost" game. Vaccine manufacture is a high overhead, low variable cost driven manufacture. Therefore, the challenge is to keep manufacturing as lean and cost -effective as possible, especially on overheads, fine tuning processes for better yields, adopting industry best practices, reduction of wastage in production and testing.

The road to reliability
Vaccines is a volume game with profits in numbers, i.e  where there are lesser margins there is volumes. So, all the vaccine manufacturers aim to get their vaccine listed as part of the immunization plan to leverage the volume play.

Vaccine business is attractive as the domestic biopharmaceutical segment contributes to 75 per cent of the total biotechnology market, wherein, vaccines alone contribute 47 per cent of it.

India is unable to cope with the growing gap in the demand and supply of universal immunization programme (UIP) vaccines. Therefore, the country must evolve its own national strategies to meet its vaccination needs within its budgetary constraints. There should be decisive intervention of the Indian government to meet the shortfall in the UIP vaccines. This may be done either by strengthening the public sector wherever possible, or by taking suitable measures to encourage the indigenous private sector on a case-by-case basis to make safe and effective vaccines at affordable prices.

What the future holds
The vaccines market will witness a boom in the coming years with support from government agencies and a number of funding opportunities. For instance, the Technology Development Board (TDB) is the first organization to encourage commercial enterprises to take up technology driven projects. It offers soft loans to enterprises for commercializing innovative indigenous technologies and adapting imported technologies to Indian conditions.

There is tremendous market opportunity in the private retail market for vaccines for regional diseases and in the expansion of the limited product range. This however needs innovation ability to be developed and sustained in terms of the requisite scientific talent and the right research infrastructure, apart from funding the new investments.