India’s public health environment has recently become a one-sided discourse on how vaccination against the human papilloma virus (HPV) prevents cervical cancer and death. Interestingly, it cannot be proven that HPV causes cervical cancer, as only a few of the 200 strains that infect humans are also ‘associated’ with ‘precancerous lesions’. Most women who die from cervical cancer are HPV-positive, but most HPV-positive men and women do not get cancer caused by the virus, let alone die from it.
India’s Population-Based Cancer Registry (PBCR) and the International Agency for Research on Cancer (IARC) have recognized a declining trend in cervical cancer prevalence in India and the world, regardless of vaccine coverage or efficacy. Therefore, the time of the overzealous push for the ‘universal’ vaccination of girls against HPV is seriously unfair to the ‘selective’ vaccination that is more applicable to high-risk groups, considering sexual transmission, unlike diseases transmitted by air, water or contagious. . The western assumption that is so important for targeting pre-puberty girls for this vaccine is that adolescent girls who engage in indecent physical relations and become carriers of the virus are a major risk factor for the entire adult population. This is a huge moral conundrum in Indian society and even patriarchy, because men can also be carriers.
Vaccine production line
But this article focuses on the questionable timing, promotion and pricing of the indigenous HPV vaccine, 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 worth asking why an ‘indigenous’ vaccine took nearly two decades after the introduction of the patented HPV vaccine in the United States, Australia and elsewhere in the Global North. Cervavac uses a similar technique, distributing virus-like particles (VLPs) produced using recombinant deoxyribose nucleic acid (rDNA) techniques to generate an immune response to HPV infection. The vaccine against cervical cancer is only the second rDNA vaccine in the world using the technique of the early 1970s, the first being the vaccine against Hepatitis-B.
Prior to the development of the rDNA method, vaccine manufacturers were generally charitable or public sector companies with universal strains/techniques shared and little or no room for vaccine patents. The entire scenario changed with the amendment of the US Patent Act in the 1980s that allowed the patenting of genetically modified organisms (GMOs) and life processes, and the introduction of the Bayh-Dole Act to legalize publicly funded scientists who created companies. With the globalization of US patent law through the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) since 1995, vaccine development and innovation has changed drastically.
Vaccine innovation has undergone significant changes in terms of organization, patent strategy and even distribution practices in academia and industry. An important element of this ‘value addition’ is the legalization of the conversion of public ‘research’ into private ‘development’ and monopolization through patents. This led to a change of hands in the development and production of vaccines from the public to the private sector around the world, helped by the politics of liberalization and globalization. This is explained 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, entitled- title Immunization and the State: The Politics of Vaccine Making, which includes the Indian scenario. Developed under this new state of innovation is the first vaccine for cervical cancer marketed as Gardasil by Merck and Cervarix by Glaxo Smithkline, globally.
Impact on India
These developments have impacted the Indian pharmaceutical and biotech industry in general and vaccine development in particular. Earlier, the Indian Patents Act (1970) de-patented products and allowed only processes, which also excluded agricultural and biological patents. This allowed the growth of the domestic industry to become a worldwide pharmacy in two decades. They make cheap generic drugs and vaccines, often within a few years of their release in the global north. The first rDNA vaccine produced in India for hepatitis-B not only entered the market within five years of the process patent but also reduced its price to a lower price than in the global north.
On the other hand, under the current product patent regime, a locally produced DNA vaccine for cervical cancer will have to wait twenty years for the product patent to expire before an indigenous ‘generic’ version is available. The main patent expiration of the HPV vaccine was recently reported by the World Health Organization and an article cited in Nature Biotechnology.
While multinational patent monopolies largely explain the delay in developing a local vaccine, what remains unexplained is Cervavac’s current high market price. Before domestically produced vaccines, two famous multinational vaccines (Gardasil and Cervarix) were sold in India for ₹4,000 per dose. Even at half that price, domestically produced vaccines in the private market remain unaffordable, preventing them from reaching a large portion of the target population. More worrisome is the unreasonable pricing strategy, as the price does not reflect the cost of production. First, Indian industry is well equipped with the infrastructure to manufacture rDNA products at scale, especially vaccines. Second, the development of Cervavac is heavily funded, including nearly $7 million by the Bill & Melinda Gates Foundation (BMGF) in the Grand Challenges Fund. Third, the infrastructure used to produce Cervavac is also part of the production facility for the Covishield vaccine, built with significant support from the Indian government’s Department of Biotechnology.
Such use of resources should reduce actual input costs to enable more affordable prices, thus casting doubt on SII’s pricing strategy. It seems designed to capitalize on high margins even at low trading volumes, instead of using economies of scale and low margin prices to boost trading volumes. This is important for public health, as high population coverage is essential for the success of any vaccine.
Less competitive vaccines
Another serious concern is the non-availability of other competing vaccines from domestic players, which could put downward pressure on the current price of Cervavac. This is surprising given that there are at least four different vaccine candidates since 2010 from other domestic players. Hyderabad-based Shantha Biotechnics, which produces a cheaper Hepatitis-B rDNA vaccine, promises to bring an affordable HPV vaccine to market by 2015, after securing licenses from the National Institutes of Health and Johns Hopkins University in the US. collapsed after Shanta was bought by Sanofi Pasteur, Paris, which is associated with Merck’s Gardasil in some ways. However, Shantha Biotechnics, Indian Immunologicals, and Bharat Biotech, Hyderabad, and Zydus Cadila, Ahmedabad have all announced HPV vaccines in the pipeline at the same time. Not being available even with earlier patent hurdle expirations is a problem.
The Cervavac vaccine is now universally recommended under the government’s vaccination program for girls between the ages of nine and 26 at ₹500 for two doses, which is expensive even for the government. For the millions left out of government coverage, the retail price of Cervavac will rise fourfold to ₹ 2,000, in a country with low insurance penetration and extraordinarily high healthcare costs. Therefore, although the need for universal HPV vaccination to prevent cervical cancer remains an unresolved doubt, the lack of competition and unclear pricing should be investigated for the greater public interest.
P. Omkar Nadh is a Researcher at the University of Queensland, Australia. Y. Madhavi is former Chief Scientist, Council of Scientific and Industrial Research-National Institute of Communication Sciences and Information Resources (CSIR-NISCAIR), New Delhi. The opinions expressed are personal