Meeting Report For reprint orders, please contact reprints@expert-review s.com TB diagnostics in India: creating an ecosystem for innovation Expert Rev. Mol. Diagn. 12(1), 21–24 (2012) Nora Engel1, John Kenneth2 and Madhukar Pai*3 TB diagnostics in India: from importation and imitation to innovation St. John’s Research Institute, Bangalore, India, 25–26 August 2011 1 Department of Health, Ethics and Society Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 616, NL - 6200 MD, Maastricht, The Netherlands 2 Division of Infectious Diseases, St. Johns Research Institute, St. Johns National Academy of Health Sciences Koramangala Bangalore, India 3 Department of Epidemiology & Biostatistics, McGill University, Montreal, 1020 Pine Ave West, QC, H3A 1A2, Canada *Author for correspondence: Tel.: +3 514 398 5422 Fax: +3 514 398 4503 madhukar.pai@mcgill.ca The ‘TB diagnostics in India: from importation and imitation to innovation’ conference was held in Bangalore, India, on 25–26 August 2011, and was organized by the St. John’s Research Institute, Bangalore, with the support of several partners. This unique conference brought together, for the first time, over 220 representatives from industry, government, donors, academia, civil society and the media to discuss what it takes to innovate in tuberculosis (TB) diagnostics in India. The goal was to engage these stakeholders to stimulate interest and investments in TB innovations. The conference was successful in engaging stakeholders and understanding the challenge of TB innovations from diverse perspectives. Coordination between stakeholders and innovations in delivery systems, partnerships, funding, regulatory and communication mechanisms are among the key challenges ahead. KEYWORDS :฀diagnostics฀•฀India฀•฀innovations฀•฀tuberculosis฀ Unearthing India’s innovation potential Novel and improved diagnostic tests for tuberculosis (TB) are urgently needed to control the epidemic that continues to affect more than 9 million people every year [1] . Existing tests are slow, insensitive or expensive and often require highly specialized facilities [2,3] . The conference in Bangalore [101] was aimed at engaging the various stakeholders, especially in Indian industry, to stimulate interest and investments in TB innovations in India [4] . The conference featured several panel discussions comprised of a mix of different stakeholders who highlighted the challenge of research and development in TB diagnostics from its different angles [101] . There is a lot of hope in the potential of emerging economies such as India and China to develop affordable healthcare technologies [5] . While these countries have a large TB burden, they also have the technical and economic resources to invest in solutions and are capable of addressing the funding gap that exists for poverty-related diseases by infusing more resources into research and development [6] . There is also potential for philanthropic www.expert-reviews.com 10.1586/ERM.11.80 initiatives from high-net worth individuals and companies in these growing economies. With over 2 million new TB cases every year, India has the highest burden of TB in the world [1] . Despite this burden, Indian industry and academics have not developed any new tools (diagnostics, drugs or vaccines) for TB. The innovation potential for TB diagnostics in India [7,8] has been underused, despite a long tradition of TB research [9] . The conference offered an opportunity to discuss why India has failed to innovate in TB research and development, and what it would take to change this reality. Lucica Ditiu, Secretary of the Stop TB Partnership, inaugurated the conference with a clear message on the importance of industry in TB control. She emphasized that the international TB community is looking to India with the hope that India will take the lead in developing new products. “We need your help, not only for India but globally!” she concluded. Nachiket Mor, Director, IKP Centre for Technologies in Public Health, Hyderabad, spoke on essential health system design innovations that are necessary to take advantage of © 2012 Expert Reviews Ltd ISSN 1473-7159 21 Meeting Report Engel, Kenneth & Pai new diagnostic technologies [102] . He emphasized that “clever human resources strategies, advanced point-of-care diagnostics, health management information systems, and expert architectural designs, when combined together in interesting ways, have the potential to dramatically transform the provision of primary healthcare and the integration of care across levels.” Challenges in diagnosing TB in India Kuldeep Singh Sachdeva, of the Revised National TB Control Programme (RNTCP), Government of India, spoke about the burden of TB in India, progress made and the challenges ahead. Despite the scale-up of TB treatment in India through directly observed short-course therapy by the RNTCP, undiagnosed and poorly managed TB continues to fuel the epidemic. Recognizing these challenges, the RNTCP has set an ambitious goal of providing universal access to quality diagnosis and treatment for all TB patients [10] . Innovative tools and delivery systems in both the public and private sectors are critical for reaching this goal. What the RNTCP needs most, he said, were a new point-of-care test for active TB that is simple, easy, cheap and can be performed with minimal training at primary healthcare level; as well as an indigenous, economical, simple, automated (battery operated) or manual molecular test to detect drug resistance that can be performed in a peripheral laboratory with minimal training. During the panel discussions it became clear that the RNTCP is open to new technologies that are emerging but requires support in evaluating those for the program. The government needs to embrace new technologies with increased budgets for innovative tools, and clarify mechanisms to deal with questions such as how and when to phase out older tests and incorporate new technologies. Sputum smear microscopy, the diagnostic test currently used by the RNTCP has many limitations [11] . In contrast to the public sector, sputum smears are underused in the vast, unregulated private sector in India which provides care for over half of all TB patients in the country [12,13] . Instead, TB is often diagnosed with inaccurate serological (antibody) tests that have been discouraged by the WHO [14] . Furthermore, a vast majority of Indian laboratories have virtually no form of accreditation or quality standards. The business case & public health rationale for innovation in diagnostics Mark Perkins, Foundation for Innovative New Diagnostics, provided an overview of the current approaches available for TB diagnosis. Although many tools are now WHO endorsed and available, many have not been scaled-up in India. The current in-vitro diagnostics market, particularly molecular tests, in India is dominated by imported, expensive products. But as Peter Small, of the Bill and Melinda Gates Foundation, argued, India has the potential to solve its TB problem with ‘home-grown’ solutions. Just as Indian pharmaceuticals and biotech companies revolutionized access to high-quality, affordable AIDS drugs and hepatitis vaccines through generic production, Indian diagnostic companies could become the world’s hub for high-quality generic diagnostics. Small emphasized that India now also has the potential to lead the world in developing entirely new TB products. 22 The Indian industry has done well with generic products but the transition to innovation is not an easy one. Rishikesha Krishnan, from the Indian Institute of Management, Bangalore, emphasized that capacities to innovate in Indian companies are improving, but still weak, and often challenged by a nonconducive culture for innovation that has a low tolerance for failures and does not instil creative confidence. The development of new technologies will require changes in corporate culture but also progressive policies by the government to increase funding and partnership opportunities between government, donors, researchers and the private industry. Krishnan concluded that the National Innovation Council in India [103] had a great opportunity to play a catalytic role in supporting innovations in TB [104] . Virander S Chauhan, International Centre for Genetic Engineering and Biotechnology, New Delhi, provided an overview of the challenges involved in establishing links between academia and industry in India, and offered suggestions for tackling this problem. Currently, industry–academia relations are mostly based on informal arrangements, primarily driven by individuals and their personal relationships. There are few formal mechanisms to support and sustain industry–academia collaborations. What is the nature and size of TB diagnostics market in India? A preliminary analysis by Ajay Bakshi from McKinsey and Company suggests that the market in India might be in the ballpark of US$100 million, although there is uncertainty surrounding the estimates from the private sector. During the discussions, it became apparent that the market size is probably higher than this estimate. The RNTCP screens over 7.5 million people with suspected active TB every year, and a similar number seek care in the private sector. Thus, at least 15 million individuals with suspected TB need to be tested every year, and should translate into a fairly sizeable market. In addition, diagnostics will be needed to diagnose extrapulmonary TB, multidrug-resistant TB, childhood TB and latent TB infection. Repeated testing will also be required for monitoring success of TB therapy. Chris Dye, Office of Health Information, WHO, presented data showing the expected increase in patient numbers owing to recent infections among young adults and association with other chronic diseases such as diabetes. He emphasized that the public health impact of new diagnostics will depend on sensitivity and specificity of the test, ability to ensure high cure rates and whether diagnostic delays can be reduced. Some participants pointed out that if a good point-of-care test were to be developed, it might open the option of intensive and active case finding at the community level, increasing the overall number of patients identified. Furthermore, if a new test were to be developed on a platform that can be used for other diseases, then this opens new markets beyond TB. Lastly, since India accounts for a fifth of the global TB burden, there is a large potential market outside of India. Clearly, a more refined TB market analysis will be enormously helpful to engage both industry and funders. What do industries care about & what do they need? Industry representatives described their experiences with innovation and constraints that they faced. As summarized by Chandrasekhar Expert Rev. Mol. Diagn. 12(1), (2012) TB diagnostics in India: creating an ecosystem for innovation Nair, BigTec Labs, Bangalore, the challenges include: lack of clear definition of minimum and optimum target product profiles (TPP) from the RNTCP, users or donors; unclear size of the TB diagnostics market; limited access to sample repositories (for test development and validation) and limited funding for TB research and development; poor regulatory mechanisms to evaluate new tests and assure quality; unclear WHO prequalification process for TB tests; general difficulties in accessing knowledge and qualified human resources required for innovation; lack of awareness about funding opportunities; weak or nonexistent collaboration between RNTCP and industry, between industry and academia; and general disconnect with the end user. Companies, especially those not working in TB, seem to want ‘mentorship’ or technical advice on TB, and it is not clear who they can approach for such issues. When and how should companies engage with the RNTCP for advice, possible endorsement or evaluation? Jasjig Mangat, Omidyar Network, India, provided the venture capitalist (VC) perspective on TB. The perceived small or unclear market size, or low level of spending on TB are seen as risks for VC investments. On the other hand, there are new opportunities for VCs because of renewed governmental commitment, increase in health insurance coverage, rise in the burden of chronic diseases, and improving infrastructure and economic growth in India. However, very few VCs in India are aware of the TB problem, and this conference highlighted the need to engage them proactively. Since industry interest in TB research and development is low, Jaykumar Menon, X Prize Foundation, CA, USA, spoke about the exciting possibility of an innovation prize for a novel TB diagnostic in India. He emphasized the potential that prizes have for spurring technology, business and social innovation, and provided insights on how this potential could be harnessed for good public health in the case of TB. In general, participants were excited about this possibility and wanted to learn more about prize models and how they might work in TB [105] . Meeting Report Several participants urged the RNTCP to clearly articulate its diagnostic needs and publish clearly defined TPP that test developers and industry partners and funders can aim for. In particular, industry representatives were keen to learn more about what type of TB tests need to be developed for various indications (e.g., active TB, latent TB, multidrug-resistant TB and point-of-care testing). What is the exact procedure for companies to access the government market for TB tests? How will the RNTCP decide on which tests to scale-up, and how much is the RNTCP willing to spend? What is the target price that companies should aim for? How to innovate new diagnostics that fit local contexts? Innovative delivery models will need to be used to drive access to innovative diagnostics, according to Puneet Dewan, WHO, New Delhi. A key challenge is how new tools fit into the existing diagnostic ecosystem [15] as the panels on ‘improving quality, regulation and market dynamics’ and ‘engaging private sector for delivery innovations’ made clear. Such questions should be considered early on in the design process as they have crucial implications for how the new tool will look like, costs involved, time required, and what effort and practices end users will need to put in. The reason that serological tests are so widely used despite their poor performance is because they neatly fit into the existing ecosystem [16] , which incentivizes tests that are neither too expensive nor too cheap and allow all stakeholders involved (e.g., manufacturers, distributors, laboratories and doctors) to receive a share of the profits. Decisions concerning design of new diagnostics and guidelines have consequences for patients, laboratory workers, physicians, programme officers, community workers and policy makers. These stakeholders need to be engaged early. What was accomplished & what needs to be done? Challenges in crossing boundaries & engaging stakeholders Throughout the conference it became clear that there is a general lack of collaboration and coordination, and lack of clarity on what various stakeholders engaged in TB diagnostics want: who is the consumer and what does she/he need? What does industry want and need to innovate in TB? What are the diagnostic needs of the RNTCP (TPP)? How can governmental agencies (e.g., Department of Biotechnology, Indian Council of Medical Research, Translational Health Science and Technology Institute and Council of Scientific and Industrial Research) work together in supporting TB innovations? As more TB products are developed, it is not clear which agency or organization can conduct head-to-head validation studies to identify the best products for scale-up. More importantly, which agency or organization should take on a convening role to bring together key stakeholders that make up the complete value chain for TB innovations in India? This calls for a clear mission statement by a governmental or funding agency on how to move forward and what is required. www.expert-reviews.com As Dinesh Puri, Medived Innovations, Bangalore, emphasized, India has already made a big contribution in generic drugs, and is making a contribution in affordable medical devices. There is no reason why India cannot innovate in TB. The Bangalore conference was a successful first step to begin a dialog among the stakeholders and to support networking among potential partners. A lot more needs to be done. A major challenge will likely be in continuing the engagement of various stakeholders. Soumya Swaminathan, National Institute for Research in Tuberculosis, Chennai, proposed that an Indian National Alliance for TB Diagnostics be formed to support, fund and guide diagnostics test developers, academics and industry, liaise with governmental agencies such as RNTCP and Drug Controller General of India, and to test and validate any new promising technologies, through the network of already existing research institutions. The conference showed that there is an urgent need to improve and strengthen all sorts of structures supporting innovation in diagnostics. It also showed that while technology offers solutions, we cannot focus too narrowly on the development of new tools while neglecting the need to innovate delivery systems, 23 Meeting Report Engel, Kenneth & Pai partnerships, funding, regulatory and communication mechanisms among all stakeholders. As Javid Syed, Treatment Action Group, NY, USA pointed out, innovations in TB will also require the support of civil society, media and patient groups, which can bring attention to the need for new TB tools, advocating for scaleup of new products that are already available, and advocacy for increased investment in TB research and development. Acknowledgements The Bangalore conference benefited immensely from various partners. St. John’s Research Institute hosted the conference and provided logistical support. Funding was provided by Global Health Strategies, New Delhi, India, and McGill University, Montreal, Canada. Technical partners included the Bill & Melinda Gates Foundation; International Centre for References 1 2 3 World Health Oganization. Global Tuberculosis Control. World Health Organisation, Geneva, Switzerland (2010). Wallis RS, Pai M, Menzies D et al. Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice. Lancet 375(9729), 1920–1937 (2010). Batz HG, Cooke GS, Reid SD. Towards Lab-Free Tuberculosis Diagnosis. Treatment Action Group; Stop TB Partnership; Imperial College London; Medecins Sans Frontiers (2011). 4 Zorlu G. India takes the lead on tuberculosis innovation. Nat. News doi:10.1038/news.2011.489 (2011) (Epub ahead of print). 5 Economist Intelligence Unit. Healthcare in Asia. The Innovation Imperative. A white paper by the Economist Intelligence Unit (2011). 6 Small PM, Pai M. Tuberculosis diagnosis – time for a game change. N. Engl. J. Med. 363(11), 1070–1071 (2011). 7 24 8 Chaturvedi K, Chataway J, Wield D. 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