Biotechnology and the transformation of vaccine innovation: The case of the hepatitis B vaccines 1968-2000.

The approval, from 1986, of a series of recombinant hepatitis B vaccines was a landmark both in the growth of biotechnology and in the development of the vaccine innovation system. In this paper, we show how the early development of the hepatitis B vaccines was shaped by a political and economic context that newly favoured commercialisation of academic research, including the appropriation and management of intellectual property; we elucidate the contingent interests and motivations that led new biotechnology companies and established pharmaceutical businesses to invest in developing recombinant vaccines specifically against hepatitis B; and we show how these and other factors combined to make those vaccines an unexpected commercial success. Broadening the scope of our analysis to include not just North America and Europe but also low- and middle-income countries, we show how the development of the hepatitis B vaccines facilitated the emergence of a two-tier innovation system structured by tensions between the demands for commercial profitability on the one hand, and the expectation of public health benefit for low- and middle-income countries on the other.

Biosimilars and the long game.

Despite greater certainty for biosimilar markets and regulation, the change that was seen in the small-molecule pharmaceuticals market with the rapid entrance of emerging-country generics suppliers will not be replicated exactly. The long game has yet to be played out, and recent changes in regulation, science, and production technology are likely to impact on future patterns of partnership and production.

A Global Health Diagnostic for Personalized Medicine in Resource-Constrained World Settings: A Simple PCR-RFLP Method for Genotyping CYP2B6 g.15582C>T and Science and Policy Relevance for Optimal Use of Antiretroviral Drug Efavirenz.

The use of pharmacogenomics (PGx) knowledge in treatment of individual patients is becoming a common phenomenon in the developed world. However, poorly resourced countries have thus far been constrained for three main reasons. First, the cost of whole genome sequencing is still considerably high in comparison to other (non-genomics) diagnostics in the developing world where both science and social dynamics create a dynamic and fragile healthcare ecosystem. Second, studies correlating genomic differences with drug pharmacokinetics and pharmacodynamics have not been consistent, and more importantly, often not indexed to impact on societal end-points, beyond clinical practice. Third, ethics regulatory frames over PGx testing require improvements based on nested accountability systems and in ways that address the user community needs. Thus, CYP2B6 is a crucial enzyme in the metabolism of antiretroviral drugs, efavirenz and nevirapine. More than 40 genetic variants have been reported, but only a few contribute to differences in plasma EFV and NVP concentrations. The most widely reported CYP2B6 variants affecting plasma drug levels include c.516G>T, c.983T>C, and to a lesser extent, g.15582C>T, which should be considered in future PGx tests. While the first two variants are easily characterized, the g.15582C>T detection has been performed primarily by sequencing, which is costly, labor intensive, and requires access to barely available expertise in the developing world. We report here on a simple, practical PCR-RFLP method with vast potentials for use in resource-constrained world regions to detect the g.15582C>T variation among South African and Cameroonian persons. The effects of CYP2B6 g.15582C>T on plasma EFV concentration were further evaluated among HIV/AIDS patients. We report no differences in the frequency of the g.15582T variant between the South African (0.08) and Cameroonian (0.06) groups, which are significantly lower than reported in Asians (0.39) and Caucasians (0.31). The g.15582C/T and T/T genotypes were associated with significantly reduced EFV levels (p=0.006). This article additionally presents the policy relevance of the PGX global health diagnostics and therefore, collectively makes an original interdisciplinary contribution to the field of integrative biology and personalized medicine in developing world. Such studies are, in fact, broadly important because resource-constrained regions exist not only in developing world but also in major geographical parts of the G20 nations and the developed countries.

An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics".

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.

H3Africa and the African life sciences ecosystem: building sustainable innovation.

Interest in genomics research in African populations is experiencing exponential growth. This enthusiasm stems in part from the recognition that the genomic diversity of African populations is a window of opportunity for innovations in postgenomics medicine, ecology, and evolutionary biology. The recently launched H3Africa initiative, for example, captures the energy and momentum of this interest. This interdisciplinary socio-technical analysis highlights the challenges that have beset previous genomics research activities in Africa, and looking ahead, suggests constructive ways H3Africa and similar large scale science efforts could usefully chart a new era of genomics and life sciences research in Africa that is locally productive and globally competitive. As independent African scholars and social scientists, we propose that any serious global omics science effort, including H3Africa, aiming to build genomics research capacity and capability in Africa, needs to fund the establishment of biobanks and the genomic analyses platforms within Africa. Equally they need to prioritize community engagement and bioinformatics capability and the training of African scientists on these platforms. Historically, the financial, technological, and skills imbalance between Africa and developed countries has created exploitative frameworks of collaboration where African researchers have become merely facilitators of Western funded and conceived research agendas involving offshore expatriation of samples. Not surprisingly, very little funding was allocated to infrastructure and human capital development in the past. Moving forward, capacity building should materialize throughout the entire knowledge co-production trajectory: idea generation (e.g., brainstorming workshops for innovative hypotheses development by African scientists), data generation (e.g., genome sequencing), and high-throughput data analysis and contextualization. Additionally, building skills for political science scholarship that questions the unchecked assumptions of the innovation performers be they funders, scientists, and social scientists, would enable collective innovation that is truly sustainable, ethical, and robust.

The Structural Genomics Consortium: A Knowledge Platform for Drug Discovery: A Summary.

The Structural Genomics Consortium (SGC) supports drug discovery efforts through a unique, open access model of public-private collaboration. This study presents the results of an independent evaluation of the Structural Genomics Consortium, conducted by RAND Europe with the Institute on Governance. The evaluation aimed to establish the role of the SGC within the wider drug discovery and PPP landscape, assessing the merits of the SGC open access model relative to alternative models of funding R&D in this space, as well as the key trends and opportunities in the external environment that may impact on the future of the SGC. It also established the incentives and disincentives for investment, strengths and weaknesses of the SGC's model, and the opportunities and threats the SGC will face in the future. This enabled us to assess the most convincing arguments for funding the SGC at present; important trade-offs or limitations that should be addressed in moving towards the next funding phase; and whether funders are anticipating changes either to the SGC or the wider PPP landscape. Finally, we undertook a quantitative analysis to ascertain what judgements can be made about the SGC's past and current performance track record, before unpacking the role of the external environment and particular actors within the SGC in developing scenarios for the future.

Ready to put metadata on the post-2015 development agenda? Linking data publications to responsible innovation and science diplomacy.

Metadata refer to descriptions about data or as some put it, "data about data." Metadata capture what happens on the backstage of science, on the trajectory from study conception, design, funding, implementation, and analysis to reporting. Definitions of metadata vary, but they can include the context information surrounding the practice of science, or data generated as one uses a technology, including transactional information about the user. As the pursuit of knowledge broadens in the 21(st) century from traditional "science of whats" (data) to include "science of hows" (metadata), we analyze the ways in which metadata serve as a catalyst for responsible and open innovation, and by extension, science diplomacy. In 2015, the United Nations Millennium Development Goals (MDGs) will formally come to an end. Therefore, we propose that metadata, as an ingredient of responsible innovation, can help achieve the Sustainable Development Goals (SDGs) on the post-2015 agenda. Such responsible innovation, as a collective learning process, has become a key component, for example, of the European Union's 80 billion Euro Horizon 2020 R&D Program from 2014-2020. Looking ahead, OMICS: A Journal of Integrative Biology, is launching an initiative for a multi-omics metadata checklist that is flexible yet comprehensive, and will enable more complete utilization of single and multi-omics data sets through data harmonization and greater visibility and accessibility. The generation of metadata that shed light on how omics research is carried out, by whom and under what circumstances, will create an "intervention space" for integration of science with its socio-technical context. This will go a long way to addressing responsible innovation for a fairer and more transparent society. If we believe in science, then such reflexive qualities and commitments attained by availability of omics metadata are preconditions for a robust and socially attuned science, which can then remain broadly respected, independent, and responsibly innovative. "In Sierra Leone, we have not too much electricity. The lights will come on once in a week, and the rest of the month, dark[ness]. So I made my own battery to power light in people's houses." Kelvin Doe (Global Minimum, 2012) MIT Visiting Young Innovator Cambridge, USA, and Sierra Leone "An important function of the (Global) R&D Observatory will be to provide support and training to build capacity in the collection and analysis of R&D flows, and how to link them to the product pipeline." World Health Organization (2013) Draft Working Paper on a Global Health R&D Observatory.

The influenza vaccine innovation system and lessons for PDPs.

As Product Development Partnerships (PDPs) emerge and evolve in response to the need for vaccines, this paper re-examines the oldest and most successful PDP in the vaccine field; that which year after year, produces and reinvents influenza vaccines. This paper describes the influenza vaccine production and innovation system and reviews some of its most recent major innovations. Innovation in this system is a result of collaborative partnerships between various actors from both the public and private sector. It is argued that the influenza vaccine innovation system is a Product Development Partnership (PDP), be it an unconventional one, with a central coordination role allocated to the WHO rather than a private company or charitable/not for profit entity. The unusual structure of this PDP overcomes some of the organizational issues surrounding vaccine research and production faced by other documented PDPs. These are first, the need to coordinate knowledge flow via an effective knowledge broker. Second, the need to build in-house capacity and fund essential research and elements of production where private partners find involvement too risky or costly.

Capacity for a global vaccine safety system: the perspective of national regulatory authorities.

Confidence in vaccine safety is critical to national immunization strategies and to global public health. To meet the Millenium Development Goals, and buoyed by the success of new vaccines produced in developing countries, the World Health Organization has been developing a strategy to establish a global system for effective vaccine pharmacovigilance in all countries. This paper reports the findings of a qualitative survey, conducted for the WHO Global Vaccine Safety Blueprint project, on the perspectives of national regulatory authorities responsible for vaccine safety in manufacturing and procuring countries. Capacity and capabilities of detecting, reporting and responding to adverse events following immunization (AEFI), and expectations of minimum capacity necessary for vaccine pharmacovigilance were explored. Key barriers to establishing a functional national vaccine safety system in developing countries were identified. The lack of infrastructure, information technology for stable communications and data exchange, and human resources affect vaccine safety monitoring in developing countries. A persistent "fear of reporting" in several low and middle income countries due to insufficient training and insecure employment underlies a perceived lack of political will in many governments for vaccine pharmacovigilance. Regulators recommended standardized and internationally harmonized safety reporting forms, improved surveillance mechanisms, and a global network for access and exchange of safety data independent of industry.

Twenty-first century vaccinomics innovation systems: capacity building in the global South and the role of Product Development Partnerships (PDPs).

The availability of sequence information from publicly available complete genomes and data intensive sciences, together with next-generation sequencing technologies offer substantial promise for innovation in vaccinology and global public health in the beginning of the 21st century. This article presents an innovation analysis for the nascent field of vaccinomics by describing one of the major challenges in this endeavor: the need for capacities in "vaccinomics innovation systems" to support the developing countries involved in the creation and testing of new vaccines. In particular, we discuss the need for understanding how institutional frameworks can enhance capacities as intrinsic to a systems approach to health technology development. We focus our attention on the global South, meaning the technically less advanced and developing nations in Africa, Asia, and Latin America. This focus is timely and appropriate because the challenge for innovation in postgenomics medicine is markedly much greater in these regions where basic infrastructures are often underresourced and new or the anticipated institutional relationships can be fragile. Importantly, we examine the role of Product Development Partnerships (PDPs) as a 21st century organizational innovation that contributes to strengthening fragile institutions and capacity building. For vaccinomics innovation systems to stand the test of time in a context of global public health, local communities, knowledge, and cultures need to be collectively taken into account at all stages in programs for vaccinomics-guided vaccine development and delivery in the global South where the public health needs for rational vaccine development are urgent.