Ailing policy

Gro Harlem Bruntland, Director-General of the World Health Organisation, administers a dose of polio vaccine to an infant in Lucknow. An April 2003 photograph.-PAWAN KUMAR/AFP

India has failed to nurture its scientific institutions owing to the lack of a properly articulated health and immunisation policy.

VACCINES and domestic immunisation policy form a critical component of a nations public health care system. This is particularly true in the context of a developing country like India, where the disease burden of vaccine-preventable diseases and mortality due to them, let alone diseases such as malaria, tuberculosis and the acquired immune deficiency syndrome (AIDS), are high given its large population, to which about 26 million newborns are added every year.

Vaccine development is also heavily science-and- technology-driven, especially since the advent of genetic engineering and biotechnology in the 1980s. Although vaccines form only 2 per cent of the $8 billion global pharmaceutical industry, they account for the largest share in the development of biologicals, and the amount spent on worldwide R&D on vaccines is about $2 billion. This area is dominated by multinationals such as GlaxoSmithKline Beecham, Merck, Aventis Pasteur (formerly Pasteur-Merieux Connaught), Chiron Behringer and Hoechst, and given the huge worldwide market, vaccine-related technologies are tightly held by them. Given the high disease burden in developing countries, many of these operate through the global immunisation programmes and initiatives of world bodies such as the World Health Organisation (WHO) and the United Nations Childrens Fund (UNICEF) to gain access to these markets.

The current Indian market for human vaccines is estimated to be around Rs.1,000 crore and is projected to grow at about 25 per cent. Naturally, the multinationals will not part with the technologies for love or money. Moreover, there are diseases such as leprosy, malaria and TB that afflict only developing countries, and the multinationals do not see it profitable to invest in developing vaccines or drugs for these. Indeed, tropical diseases account for a mere 5 per cent of the global health R&D. The role of domestic R&D and technology base in the area of vaccines assume great importance, particularly in the publicly funded institutions, if we wish to keep costs low and make vaccines affordable.

Today India is among the major makers and buyers of vaccines. Concerned about protecting its military from tropical diseases, the British rulers established a scientific and industrial base for vaccines concurrent with its evolution in the industrial West, beginning with the worlds first plague vaccine in 1897 at the Plague Laboratory in Bombay (now Mumbai), which is now known as the Haffkine Institute. India began to produce essential vaccines such as diphtheria-pertussis-tetanus (DPT), which even today form part of the national immunisation programmes, in early 20th century itself. It was during this period that institutions such as the Haffkine Institute, the Kings Institute for Preventive Medicine (where the BCG Vaccine Laboratory, BCGVL, came to be established in 1948) in Chennai (1898), the Central Research Institute (CRI) in Kasauli (1905), and the Pasteur Institute of India (PII) in Coonoor (1907) were all turned into government units with the Haffkine Institute becoming a state-funded institution.

But as Y. Madhavi of the National Institute for Science, Technology and Development Studies (NISTADS), who has done extensive research in vaccine policy and commerce in India, has pointed out in her 2005 paper in the journal PLoS Medicine, since the British did not hand down the scientific legacy to the Indians, the science of vaccines was lost and the production infrastructure came to be chiefly utilised to meet the needs of routine immunisation. Thus, post-Independence India essentially lost the advantage of its early entry into the field. Over the years, lack of sufficient scientific expertise in vaccinology meant that R&D in the field took a back seat, and it was left way behind world developments in the field. The government has failed to infuse resources into these institutions and foster continued R&D in the field. As a result, vaccines resulting from R&D elsewhere began to enter the country after a lag of five to 10 years.

A properly articulated health and immunisation policy, in conjunction with a science and technology policy, could have contributed to the nurture of these institutions. But, despite espousal of technological self-reliance in word by the government, the state of affairs in vaccine development and production became one of dependency, as indeed it was in other areas of technology as well. Indias policy on immunisation only came with the WHOs famous declaration of Health for All by 2000 at Alma Ata in 1978, and India launched its Expanded Programme of Immunisation (EPI) in that year to protect children from six vaccine-preventable diseases that included diphtheria, pertussis (whooping cough), tetanus, polio, childhood TB and typhoid. The public sector units began to develop and produce these primary vaccines, namely, the DPT group of vaccines, the Sabin oral polio vaccine (OPV), the Bacillus Calmette-Guerin (BCG) vaccine and the heat-phenolised whole-cell typhoid vaccine, to meet the demand of a nationwide immunisation programme. In 1985, the programme aimed to achieve universal immunisation of the countrys children, called the Universal Immunisation Programme (UIP), dropped typhoid from its ambit and included measles instead.

However, as Madhavi has pointed out, the Indian public sector, without a worthwhile R&D base, failed to keep pace with the technological developments in the field. For instance, the first vaccine technology to be imported after Independence was that of BCG and Tuberculins from the Statens Serum Institute (SSI) of Denmark in 1948 through the WHO, with which the Chennai laboratory began functioning. Even though earlier-generation DPT technology was developed here in the 1920s, the next-generation ones had to be imported after their introduction elsewhere. Similarly, the anti-rabies vaccine was first developed by David Semple at the CRI, Kasauli, in 1911 but the present tissue-culture- based vaccine is being produced only in the private sector, while both the CRI and the PII continue to produce the earlier-generation inactivated sheep brain vaccine.

The story of the OPV is an interesting one and is indicative of how the government has undermined even the marginal developments and efforts of the PSUs. During 1967-1977, the PII indigenously produced OPV from the seed virus procured from no less than A.B. Sabin himself, who had developed the vaccine through the good offices of the WHO. The PII produced six batches of the vaccine, which were found to be of world standards. But the seventh batch was alleged to be virulent and the production was stopped. This in itself would seem strange and defy logic as quality control of biological products can go awry and companies usually reject those batches and begin fresh production. In this case, however, the story is stranger.

A test later by the WHOs reputed scientist, S. Archetti, of a sample from the batch found the vaccine to be of excellent quality and no different from the earlier batches. It was later found that the toxicology test done by the National Institute of Communicable Diseases (NICD), a government laboratory, was wrong. But by then, for some reason, OPV production was not revived. The Haffkine Institute later took the seed but did not succeed in producing quality vaccines. The production of OPV was thus altogether suspended in the country and no one knows what happened to the seed. Today, in the highly competitive vaccine business world, the situation is vastly different. The WHO would not part with the seed even if we wanted to start afresh. As a result, since 1978 interestingly, the timing coincides with the launch of the EPI when the demand for OPV rose India has been importing OPV, essentially importing bulk vaccine and packaging it to be sold in the domestic as well as in the world market.

Today OPV is being bottled entirely by the private sector. But in the interim, two important developments took place in the area of polio vaccines in the Indian public sector, which need to be highlighted. In 1987, the Department of Biotechnology (DBT) established a modern vaccine production unit, Bharat Biologicals and Immunologicals Corporation Ltd. (BIBCOL) in Bulandshahar in Uttar Pradesh, a polio endemic area, to meet the WHOs good manufacturing practices (GMP) norms. The unit received technology for OPV from the Institute of Poliomyelitis and Viral Encephalitis, Moscow. It began by packaging bulk obtained from Moscow and intended to produce indigenously within five years from the seed that was to be transferred from Russia. However, until 2000 BIBCOL produced OPV and even supplied 70 million doses to UNICEF; it even made profits. But it was discontinued abruptly because the Moscow bulk was not WHO-pre-qualified and, as WHO regulations were now strictly enforced by importers, the product was rejected by international agencies.

But that does not explain why it could not continue to supply OPV for the UIP. As a result, with no worthwhile long-term strategy for the unit, it was declared sick and was revived only recently on the basis of the restructuring recommended by the Board for Industrial & Financial Reconstruction (BIFR). Now private companies import WHO pre-qualified bulk from BT Bipharma, Bandung, Indonesia, and Chiron, Italy, and repackage them for domestic consumption as well as for export. The irony is that although BIBCOL is in the OPV business, it is merely repackaging bulk from the same source as the private players, BT Pharma. It is also planning to enter into the business of bottling DPT vaccine by importing bulk from Russia, an area where India achieved self-sufficiency years ago, but failed to keep pace with the rising demand owing to faulty government policies. The unit is still awaiting WHO-certification as, according to M.K. Bhan, Secretary, DBT, polio is no longer a priority for the WHO.

A related episode concerns the inactivated polio vaccine (IPV) developed by Jonas Salk, which is an injectable vaccine. In 1989, the DBT established another state-of-the-art unit called Indian Vaccine Corporation Ltd. (IVCOL) in Gurgaon for the purpose of producing vero-cell-based IPV and measles vaccines using technology to be transferred by the French public sector unit, Institut Merieux, under the Indo-French S&T Cooperation Agreement. But, in spite of paying part of the fees for technology transfer, the project fell through because, in the meanwhile, the French government sold the company to the Canadian firm Connaught.

The Indian government also seems not to have pushed its case strongly enough because of the misplaced perception that the national immunisation programme, dictated by the WHO, will not need IPV, and there may not be sufficient market for it. After its privatisation, Institut Merieux became Pasteur Merieux Connaught, and today it has become Aventis Pasteur, a major multinational in the vaccine business. As a result, IVCOL today remains shut down and India has no capacity in IPV especially when introduction of IPV in a couple of years down the line appears imminent. IVCOL infrastructure may be revived as a hospital for clinical studies for the nearby National Brain Research Centre (NBRC) of the DBT.

The inability of the Indian public sector to recover from its mounting failures to achieve self-sufficiency and self-reliance in primary vaccines is also related to liberalisation and globalisation of the Indian economy, wrote Madhavi in her PLoS Medicine paper. It is no longer fashionable to produce vaccines in the public sector in India, let alone try and revive failing public sector units, even if essential vaccines are not available in the private sector, she added. The growing gap between supply and demand in India today with regard to primary vaccines and the need to import even these is because while public sector production is going down, neither the private sector nor the WHOs mechanism of procuring them globally has been able to fill the gap effectively (see Figure 1).

In fact, this is part of the global trend that one has been witnessing in recent years (see Figure 2), as warned by UNICEF in 2003. In its document titled Vaccines for Children: Supply at Risk, UNICEF pointed out how a shortage of primary vaccines had begun to set in the 1990s (see Figure 2).

These shortages, it said, was because more sophisticated and more expensive vaccines were being introduced in industrialised country markets [see separate story]. As long as industrialised and developing countries gave the same vaccines to their children, it was possible for UNICEF to procure vaccines at low prices, because industrialised country markets paid higher prices for those vaccines and passed on a price advantage to developing country markets. With industrialised countries now buying new vaccines, the low prices at which UNICEF had been able to buy traditional vaccines were threatened. Vaccine manufacturers began phasing out the production of the traditional, less expensive vaccines used in developing countries. The overall outcome is that the availability of vaccines to UNICEF has dramatically decreased. Vaccine prices have also increased. Between 2000 and 2001, for example, the cost of vaccines for DPT rose by 15 per cent, BCG by 27 per cent, measles by 10 per cent and TT by 23 per cent; the prices are likely to climb even higher.

It is in this context that it was important to nurture domestic units producing traditional vaccines, but what we are seeing today is the shutting down of three of the five remaining vaccine-producing PSUs. It is the result of this inexorable push from outside. The Ministrys order of January 15 dealt the last blow to whatever remained of an indigenous vaccine production base.

For all practical purposes, the remaining two, namely, the Haffkine Institute and BIBCOL, have been merely rendered bottling and packaging units. Of course, the government might argue that the new vaccine park to be set up by Hindustan Latex Ltd. (HLL) is essentially a public institution. But as Health Minister Anbumani Ramadoss himself admitted, it is likely to go down the same path of bottling and repackaging of imported WHO pre-qualified stock or enter into the infamous public-private partnership (PPP), which recent experience shows is actually a euphemism for privatisation, with global players through the dubious role of international agencies such as the Global Alliance for Vaccines and Immunisation (GAVI) and the International Vaccine Initiative (IVI).

The decline of the CRI and the Pasteur Institute is indeed a sad story, says D. Banerjee, Emeritus Professor of Public Health and Community Medicine at the Jawaharlal Nehru University. The decline of these institutes is part of the general decay of general public health services. The decline of public health has happened since the abolition of the Indian Medical Service soon after Independence. On the other hand, the WHOs credibility has eroded as a public health leader of the world owing to its domination by the United States, he adds.

We have not invested enough in them, says Bhan, Secretary, DBT. One problem with the PSUs is that they have not been able to get WHO-GMP certification easily. But what are the issues that this is owing to? These units cannot give market salary to their scientists, rigid rules prevent hiring. These have to become flexible if we have to meet regulations of international standards. Our standards are not good enough. I have not been able to hire a capable technical person to head BIBCOL; we now have an IAS [Indian Administrative Service officer] there and BIBCOL remains a single-product company, he says.

The question is, do we need them or do we shut them down? The Health Secretary says that he does not want to preserve outdated institutions. I would tend to agree with him if we cannot invest in them and make them vibrant autonomous institutions with good R&D base. But the rigid system does not allow me that. Every time you try to cross the line, the system pulls you back, he adds with concern. In this scenario, we need the public sector only to create competition and keep the costs low. Except for a price strategy, I do not see a greater role for them given the limitations in which these have to function.

But we do have successful and internationally competitive PSUs. To this, Bhans response strikes at the root of the problem that is afflicting all sciences in the country. It is possible in engineering fields because the total availability of human resource in engineering is large and you always find good people to work even with low salaries in PSUs. But in biology we are woefully short of human resource and skilled personnel. Lack of experience with biologicals at a national level is the core issue.