Team-powered innovation combats Rotavirus where India’s need is greatest
The decades-long development of an Indian pharmaceutical startup’s revolutionary rotavirus vaccine would not have been possible without public-private partnership and robust intellectual property (IP) protections.
Rotavirus infections and associated dehydrating diarrheal diseases pose a serious health challenge for young children, particularly those living in low-income and resource-poor areas. The vast majority of the 215,000 infants and toddlers that die each year from rotavirus infections live in challenging conditions, according to the World Health Organization (WHO). In countries like India, where rotavirus diarrhea leads to as many as 800,000 hospital admissions and two million outpatient visits annually, there is an urgent need for effective, safe, and inexpensive interventions. Bharat Biotech, a Hyderabad-based vaccine manufacturer, has answered the call, developing a low-cost rotavirus vaccine, ROTAVAC, which has been awarded WHO prequalification and license in two countries.
Rotavirus is a highly contagious disease. It causes dehydration, severe diarrhea and vomiting, and fever through fecal-oral transmission. The virus’ ability to survive for long periods of time in standing water and feces means rotavirus infections are generally widespread. They commonly occur through hand-to-hand contact in close, unhygienic settings such as hospitals and daycare centers. With insufficient access to suitable healthcare, poor sanitation and high rates of malnutrition, developing countries bear a disproportionate burden of disease from rotavirus infections. While diarrheal diseases impact most children under the age of five worldwide, 82 percent of all resulting deaths occur in low-resource areas.
Previous attempts to treat and prevent rotavirus infections have fallen well short of what’s needed. Sanitation efforts often fail in developing countries; regular soap is ineffective against rotavirus spread and water quality improvement measures are limited in scale and degree by the resources available. Antibiotics are incapable of treating or preventing infections because they are viral rather than bacterial. Oral rehydration therapy (ORT), a simple fluid replacement using a solution of water, sugar, and salts, has proven effective, inexpensive, and easy to administer in developing countries. However, it is not ideal for large scale use in areas with scarce or unpotable water; it does nothing to reduce the incidence of rotavirus infection in developing countries’ populations over time. Further, ORT is ineffective as a treatment for those suffering from severe vomiting.
ROTAVAC is not the first rotavirus vaccination, but it does represent an unprecedented feat of indigenous innovation and a revolutionary improvement in prevention of the infection in developing countries. While other rotavirus vaccines have been developed by multinational corporations, their price and their questionable efficacy mean they are not viable treatment options. Bharat Biotech’s vaccine is the first in recent history to be developed entirely within India, from the initial isolation of the rotavirus strain over 30 years ago to the development and licensing of today’s product. As such, it is the first of its kind to be clinically tested for efficacy in India, evaluated among the same population it’s intended to treat. Clinical trial results published in The Lancet show that, when given to Indian infants in rural and urban settings, ROTAVAC demonstrates efficacy of 55.1 percent in children under two-years-old. Moreover, the efficacy of doses administered in the child’s second year were only marginally less effective than those before their first birthday.
ROTAVAC’s success is a beacon for the importance of government and market frameworks that embrace and protect innovation. Support and funding from multiple partners including the Government of India’s Department of Biotechnology, PATH, and the Bill & Melinda Gates Foundation have safeguarded Bharat Biotech’s commitment to keep prices below $1 per dose. That means ROTAVAC is a crucial, long-term solution for those in low-income countries who otherwise rely upon short-term subsidies from Gavi, the Vaccine Alliance, to access and afford necessary vaccinations. Bharat Biotech also accelerated the large-scale production and marketing of its vaccine after an $18.5 million grant was awarded by the Gates Foundation in June 2015, intended to support the construction of a WHO-compliant manufacturing facility.
Partnerships have given Bharat Biotech access to the technical knowledge and manufacturing know-how in the public domain in the form of published research findings on previous innovators’ R&D activities. IP laws governing the patent process and the transfer of knowledge have been crucial in fostering innovation in a market where demand for niche expertise can often act as a barrier to entry for new innovators. According to the World Intellectual Property Organization (WIPO), processes and proprietary knowledge not disclosed in patent applications can still be accessed through publications and partnerships between research organizations and vaccine developers. Guided by legal frameworks which protect IP without hiding it from the public, Bharat Biotech capitalized on freely available technological information to build its own unique product. ROTAVAC’s development was distinguishable from its predecessors but drew upon and contributed to the same pool of resources related to manufacturing, disease immunology, and rotavirus antigens. Rather than start from scratch, new players like Bharat Biotech can innovate on what already exists thanks to legally sound information flows regulated by IP protections.
IP protections have also enabled Bharat Biotech to capitalize upon the commercialization of the ROTAVAC vaccine and invest in future innovation that will help to grow India’s economy and improve its healthcare. Since being granted a patent for its rotavirus vaccine and related administering process in 2013, the company has gained a total of five global patents and pursued licensure in 30 countries. Such protections have given Bharat Biotech control over how its rotavirus vaccine is sold. Differential pricing allows Bharat Biotech to create different levels of price-setting for specific markets; lower in poorer countries, higher in wealthier ones. The positive effect of such price modeling is twofold: Bharat Biotech can sell more vaccines in a greater variety of markets. By expanding its reach, it can also collect enough revenue to fund investments in future research. All this is a result of access to a base of knowledge and the ability to extend it with one’s own contributions (that can also receive patent protection for a limited period of time), the rewards of strong and effective IP rights.
Since its first vaccine, the Indian company has produced numerous other innovations with the assistance of its public and private supporters. Knowledge and experience gained by its team members has informed the growth of current research organizations and the establishment of a virus reference laboratory, the Translational Health Science and Technology Institute. Since ROTAVAC’s licensure by the Drugs Controller of India in 2014, the vaccine has become part of India’s national immunization program. It was prequalified by WHO to improve access for Gavi and UN agencies, and is in the process of being licensed in 30 countries.
The success story of Bharat Biotech and ROTAVAC is a model for innovation in developing countries and reinforces the importance of robust IP laws and diverse partnerships. A shared commitment to protect the legitimacy of the product, ensure its efficacy in local populations, and keep the price low adds up to a commercial success. Further developments that can benefit the patients in need, government partners, private donors, research facilities, and vaccine producers will follow ROTAVAC’s lead.
 World Health Organization (WHO), Immunization, Vaccines and Biologicals: Rotavirus (Geneva: WHO, 2018), https://www.who.int/immunization/diseases/rotavirus/en/.
 Maharaj K Bhan et. al, “Team science and the creation of a novel rotavirus vaccine in India: a new framework for vaccine development”, The Lancet Vol. 383, 9935 (June 2014): 2180–2183, https://doi.org/10.1016/S0140-6736(14)60191-4.
 Amiti Sen, “Bharat Biotech’s diarrhoea vaccine gets WHO nod,” The Hindu Business Line, January 24, 2018, https://www.thehindubusinessline.com/todays-paper/tp-news/bharat-biotechs-diarrhoea-vaccine-gets-who-nod/article10050026.ece.
 Paramita Sengupta, “Rotavirus: The Challenges Ahead,” Indian Journal of Community Medicine: official publication of Indian Association of Preventive & Social Medicine Vol. 34, 4 (2009),:279–82, 10.4103/0970–0218.58382.
 Bhan et. al, “Team science”, 2181.
 Nita Bhandari et. al, “Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life”, ScienceDirect Vol. 32, Supplement 1 (2014),:A110-A116, https://doi.org/10.1016/j.vaccine.2014.04.079.
 “Grant: Bharat Biotech International, Ltd.”, The Bill & Melinda Gates Foundation, June 2015, https://www.gatesfoundation.org/How-We-Work/Quick-Links/Grants-Database/Grants/2015/06/OPP1106905.
 Stevens et al, ”Vaccines: Accelerating Innovation and Access”, World Intellectual Property Organization (WIPO) (2017), https://www.wipo.int/edocs/pubdocs/en/wipo_pub_gc_16.pdf.
 V. K. Srinivas, “Product development and programmatic implementation of TYPBAR TCV® and ROTAVAC® vaccines” in “Vaccine Technology VII”, Amine Kamen, McGill University Tarit Mukhopadhyay, University College London Nathalie Garcon, Bioaster Charles Lutsch, Sanofi Pasteur Eds, ECI Symposium Series, (2018). https://dc.engconfintl.org/vt_vii/102.
 Kate Davidson, “India-made rotavirus vaccine achieves World Health Organization prequalification,” PATH, January 24, 2018, https://www.path.org/media-center/india-made-rotavirus-vaccine-achieves-world-health-organization-prequalification/.