India’s public health sphere was subject recently to a one-sided discourse on how vaccination against the human papilloma virus (HPV) prevents cervical cancer and consequent death. Interestingly, it is not proven beyond doubt that HPV causes cervical cancer, as only a couple of strains out of 200 strains that infect humans are somehow ‘associated’ with ‘precancerous lesions’. Most of the women who die of cervical cancer are HPV positive, but most of the men and women who are HPV positive do not get virus-induced cancer, let alone die due to it.
The Population Based Cancer Registries (PBCR) of India and the International Agency for Research on Cancer (IARC) have acknowledged the declining trends of cervical cancer prevalence in India and the globe, regardless of vaccine coverage or efficacy. Therefore, the timing of the overzealous push for ‘universal’ vaccination of girls against HPV does serious injustice to the more justifiable ‘selective’ vaccination of high-risk groups, considering its sexual transmission, unlike air-borne, water-borne or contagious diseases. An extremely important western assumption behind targeting pre-puberty girls for this vaccine is that teenage girls indulging in promiscuous physical relations and becoming carriers of the virus are a huge risk factor for the entire adult population. This is a huge moral conundrum in Indian society and even reeks of patriarchy, as men can be carriers too.
The path of vaccine manufacture
But this article focuses on the questionable timing, promotion and pricing of indigenous HPV vaccines, assuming some high-risk populations need it. The Serum Institute of India (SII) developed ‘Cervavac’ and promoted it as an indigenous and affordable vaccine. It is pertinent to ask why it took nearly two decades for the ‘indigenous’vaccine after the introduction of a patented HPV vaccine in the United States, Australia and elsewhere in the Global North. Cervavac uses similar techniques, deploying virus-like particles (VLPs) produced using recombinant deoxyribose nucleic acid (rDNA) techniques to generate an immune response against HPV infections. The vaccine against cervical cancer is only the second rDNA vaccine in the world using the techniques of the early 1970s, the first being the vaccine against Hepatitis-B.
Prior to the development of rDNA methods, vaccine manufacture was largely a charitable or public sector enterprise with universal sharing of strains/techniques and little or no place for patenting of vaccines. The whole scenario changed with the amendment of the U.S. Patent Act in the 1980s allowing the patenting of genetically modified organisms (GMOs) and life processes, and the introduction of Bayh-Dole Act to legalise publicly funded scientists setting up companies. With the eventual globalisation of U.S. patent laws through the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) since 1995, vaccine development and innovation changed drastically.
Vaccine innovation underwent significant changes in terms of its organisation, patenting strategies and even distribution practices in academia and industry. An important element of this ‘value addition’ is legalisation of the conversion of public ‘research’ into private ‘development’ and its monopolisation by patenting. This facilitated the change of hands in vaccine development and production from the public to private sector the world over, aided by the politics of liberalisation and globalisation. This was elaborated by William Muraskin in his book, The Politics of International Health: The Children’s Vaccine Initiative and the Struggle to Develop Vaccines for the Third World, and, more recently, in a collection edited by Stuart Blume and Baptiste Baylac-Paouly, titled Immunization and States: The Politics of Making Vaccine, that included the Indian scenario. Developed under these new innovation conditions was the first vaccine for cervical cancer marketed as Gardasil by Merck and Cervarix by Glaxo Smithkline, globally.
Impact on India
These developments impacted the Indian pharmaceutical and biotech industry in general and vaccine development in particular. Earlier, the Indian Patent Act (1970) abolished patenting products and allowed only processes, that too excluding agricultural and biological patents. This enabled the growth of domestic industries to become the pharmacy of the world within two decades. They manufactured low-cost generic drugs and vaccines, often within a couple of years after they were introduced in the global north. The first rDNA vaccine produced in India for hepatitis-B not only entered the market within five years under the process patent but also dropped the price to an order of magnitude cheaper than in the global north.
On the other hand, under the current product patent regime, a locally made DNA vaccine against cervical cancer had to wait for two decades till the expiry of the product patents before its indigenous ‘generic’ version was made available. The expiry of key patents of the HPV vaccine was recently reported by the World Health Organization and a highly cited article published in Nature Biotechnology.
While multinational patent monopolies largely explain the delay in developing a local vaccine, what still remains unexplained is the exorbitant current market price of Cervavac. Prior to the domestically manufactured vaccine, two prominent multinational vaccines (Gardasil and Cervarix) were sold in India for ₹4,000 a dose. Even at about half that price, a domestically manufactured vaccine in the private market remains largely unaffordable, keeping the vaccine out of reach for a large section of the target population. What is even more worrisome is the unreasonable pricing strategy itself, as the price does not truly reflect the production costs. First, Indian industry is well equipped infrastructurally to make rDNA products at scale, particularly vaccines. Second, Cervavac development was funded heavily, which included nearly $7 million by the Bill & Melinda Gates Foundation (BMGF) under its Grand Challenges Fund. Third, the infrastructure used in producing Cervavac was also a part of the production facility for the Covishield vaccine, built with significant support from the Indian government’s Department of Biotechnology.
Such a shared use of resources must have reduced the actual input costs to enable more affordable pricing, thus raising doubts on the pricing strategy of the SII. It seems to be designed to capitalise on high-margins even at low trade volumes, rather than using economies of scale and low margin pricing to boost volume trade. This is essential for public health, as high population coverage is crucial for the success of any vaccine.
Competing vaccines are scant
Another serious concern is the unavailability of other competing vaccines from domestic players, which could have put downward pressure on the current price of Cervavac. This is surprising given the fact that at least four different vaccine candidates were in the pipeline since 2010 from other domestic players. Shantha Biotechnics, Hyderabad, which produced a rDNA Hepatitis-B vaccine at a cheaper price pledged to bring an affordable HPV vaccine to the market by 2015, after it acquired licences from the National Institutes of Health and Johns Hopkins University in the U.S. This may have collapsed after Shanta was acquired by Sanofi Pasteur, Paris, which itself was associated with Merck’s Gardasil in several ways. Nonetheless, Shantha Biotechnics, Indian Immunologicals, and Bharat Biotech, Hyderabad, and Zydus Cadila, Ahmedabad have all announced their HPV vaccines in the pipeline around the same period. Their unavailability despite the expiry of the earlier patent barrier is a matter of concern.
The Cervavac vaccine is currently recommended universally under the government vaccination programme for girls between the ages of nine to 26 at a price of ₹500 for two doses, which is expensive even for the government. For those millions who are left out of the government coverage, the retail price of Cervavac will shoot up four-fold to ₹2,000, in a country that has low insurance penetration and catastrophically huge out-of-pocket health expenditures. Therefore, even as the need for universal HPV vaccination to prevent cervical cancer remains an unresolved doubt, the lack of competition and opaque pricing merits investigation in the larger public interest.
P. Omkar Nadh is a Research Fellow at the University of Queensland, Australia. Y. Madhavi is former Chief Scientist, Council of Scientific and Industrial Research-National Institute of Science Communication and Information Resources (CSIR-NISCAIR), New Delhi. The views expressed are personal
