F O C U S O N U.S. D R U G D E V E LO P M E N T CFC OO NCM SU OMSRT A O EO NI N T
The role of public–private partnerships in addressing the biomedical innovation challenge Maya Said and Elias Zerhouni
Without a step change in the productivity of pharmaceutical research and development, it will be difficult to tackle the public health challenges facing societies worldwide. Public–private partnerships could play a key role in achieving this step change, but they need to be well designed and led.
Maya Said is Vice President of Strategy, External Innovation and Science Policy, and Elias Zerhouni is President, Global Research & Development, Sanofi, 54 rue La Boétie, 75008 Paris, France. Correspondence to E.Z. e‑mail: Elias.Zerhouni@ sanofi.com doi:10.1038/nrd4438
Starting with the remarkable success of the public– private partnerships (PPPs) formed across governments, academia, industry and patients’ organizations to fight the HIV/AIDS epidemic and the success of the international Human Genome Project in the 1990s, we have progressively learned the value of breaking artificial institutional barriers and creating greater trust — the essential component of all successful partnerships. Examples now abound, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) led by the US National Institutes of Health (NIH) to discover the earliest manifestations of Alzheimer’s disease, the Critical Path Initiative launched by the US Food and Drug Administration (FDA) in 2004 to improve regulatory science, and the more recent Innovative Medicines Initiative (IMI) and NIH programmes to accelerate target discovery or validation and tool development such as biomarkers. Novel emerging precompetitive collaborations, such as the TransCelerate BioPharma consortium to improve clinical development and Project Data Sphere (launched by the CEO Roundtable on Cancer) to share patient-level data from previous cancer trials, are just a few illustrations of the rising importance of PPPs globally (see Further information). Among the various partnership models for biomedical innovation, PPPs and precompetitive collaborations provide a particular benefit in that they bring together stakeholders across the health-care ecosystem and, if well designed, align incentives, investments and efforts to address bottlenecks in the research and development (R&D) process. As a result, they can greatly accelerate drug discovery and development, and are an essential component of the emerging R&D ecosystem given that no single stakeholder possesses all the elements needed to address many of the innovation challenges.
Rationale for public–private partnerships Typically, biomedical PPPs are formed to address certain classes of problems such as: • the need to assemble sufficiently large biological or population samples to achieve statistical significance or new insights through cooperative approaches; • the need for multidisciplinary expertise as well as the sharing of exponentially increasing knowledge and access to complex or novel technologies to discover new mechanisms or validate new targets, thus creating common precompetitive resources; • the need to address regulatory complexity through harmonization and validation; and, when necessary engage in scientific efforts to establish standards; • the need to execute large projects over a sustained period of time to reach a sufficient scale and enable discovery or translation through shared resources or the creation of large data sets with complex analytics; • the need to anticipate and rapidly address significant public health threats. In our experience, successful partnerships require clarity of purpose, strong but consensus-driven leadership, adaptive governance and, above all, efficient resource and operational planning. At Sanofi R&D, we have developed a simple set of rules to judge the many opportunities now available for consortium participation. These are based on: whether the purpose of the PPP is clearly stated with specific and measurable goals; whether the subject area is aligned with our strategic priorities and addresses an issue of high relevance to all participants not addressable in any other way within a reasonable time frame; whether the necessary resources and associated milestones are predefined and precommitted; and whether accountability, governance and decision rules are clearly specified and appropriately align incentives.
NATURE REVIEWS | DRUG DISCOVERY
VOLUME 13 | NOVEMBER 2014 | 789 © 2014 Macmillan Publishers Limited. All rights reserved
COMMENT Challenges and lessons learned Although PPPs can bring great benefits to pharmaceutical companies, they often represent complex structures and can pose a real managerial challenge. Over the years, there have been a number of issues raised by PPPs that are not managed well or that have poor leadership, which have led companies to become more selective and stringent in evaluating which PPPs to participate in. Some of the issues we have observed include: • misalignment with the company’s internal strategy; • missing alignment and buy-in on strategy and objectives within the project; • complexity in decision-making and loss of autonomy; • different expectations by partners (for example, patent versus publication); • different research cultures leading to poor outcomes; • outcomes not justifying the time and resources invested; • negligence of intellectual property issues leading to issues with exploitation of results; • diverting energy and resources away from core aims and ‘mission drift’; • substantial administration costs to fulfil the requirements for funding from governmental agencies; • duplication of efforts and resources at a regional and global level. As various stakeholders gain more experience establishing and managing these partnerships, lessons learned are being integrated at the outset into the structure and governance of newly created PPPs or used to evolve existing ones. The IMI in Europe provides a good example of such integration. Unlike some PPPs where the contribution from the pharmaceutical partner is mostly in cash provided to co-finance the public partners, in IMI the dedicated resources provided by the pharmaceutical partner (mostly in-house scientists as well as compounds and samples) are financially matched by the government bodies for funding for the public partners and the biotechnology companies. Projects within the partnership are defined primarily based on issues identified by pharmaceutical companies themselves. This model has required pharmaceutical companies to form ulate relevant projects at the outset and integrate their own dedicated people into the partnership and hence more tightly collaborate with the academic partners and biotechnology companies, not just sponsor the work. For the companies that commit a significant number of people and prioritize the collaboration within their own R&D strategy, it provides them with a vested interest to participate in the leadership of the partnership. In our experience, PPPs are most successful if the partners from pharmaceutical companies, academic institutions, small and medium-sized enterprises, regulators and stakeholders are supported through an independent and neutral facilitator to act as a platform for the ‘call for proposals’ launching process as well as the conduit for funding from governmental sources. The neutral platform initiates and drives the process to gain input from public stakeholders and supports dialogue with regulatory authorities, which is crucial to ensure that the results lead to the introduction of new
pharmaceuticals addressing real unmet medical needs. It is also important to set up an appropriate consortium management structure not only to ensure efficient and quick operational decision-making on a day-to-day basis but also integrate all partners and stakeholders in strategic decisions driving towards successful execution of the project. The recently announced IMI 2, the renewed IMI partnership under the €80 billion Horizon 2020 programme, provides a good example. For each of the priority areas identified, a ‘Strategic Governance Group’ (SGG) is currently being established, bringing together the key decision makers in the specific area from the industry side and tightening the alignment of internal strategy with a portfolio of projects both within the IMI 2 as well as external initiatives. This concept has been proactively supported by Sanofi in the metabolic disorder area (SGG Diabetes), where this SGG is up and running and the first projects of interest have been identified. As a PPP is a complex structure by itself, it is also important that the rules for participation as well as the rules for contractual, financial and intellectual property regulations be as simple as possible while also reflecting the necessary means and boards for efficient steering and maximizing the value of the project. The IMI European Lead Factory is an example where the set-up of a large infrastructure as a joint high-throughput screening facility to screen selected targets with an innovative pooledcompound library required a sophisticated legal and intellectual property framework.
Conclusion In conclusion, the complexity of the challenges facing us as a community dedicated to improving public health requires that we develop more open, collaborative and networked innovation to advance knowledge, promote more efficient R&D models, and recognize that solutions will increasingly require well-designed and led PPPs. Furthermore, as an increasing number of PPPs rise to the challenge, it will be equally important to explore opportunities for better harmonization and coordination on a worldwide basis, as cross-cultural efforts are likely to further stimulate and enhance innovation while greatly increasing the impact and efficiency of these partnerships. Acknowledgements M.S. and E.Z. would like to thank J. Bouthier, B. Stowasser and the Sanofi IMI team for their contributions to this article.
Competing interests statement
The authors declare competing interests: see Web version for details.
FURTHER INFORMATION Accelerating Medicines Partnership: http://www.nih.gov/science/amp/ index.htm Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products: http://www.fda.gov/downloads/scienceresearch/ specialtopics/criticalpathinitiative/criticalpathopportunitiesreports/ ucm113411.pdf Innovative Medicines Initiative: http://www.imi.europa.eu/ Project Data Sphere: https://www.projectdatasphere.org/projectdatasphere/ html/home.html TransCelerate BioPharma: http://www.transceleratebiopharmainc.com ALL LINKS ARE ACTIVE IN THE ONLINE PDF
790 | NOVEMBER 2014 | VOLUME 13
www.nature.com/reviews/drugdisc © 2014 Macmillan Publishers Limited. All rights reserved
The role of public–private partnerships in addressing the biomedical innovation challenge Maya Said and Elias Zerhouni
Without a step change in the productivity of pharmaceutical research and development, it will be difficult to tackle the public health challenges facing societies worldwide. Public–private partnerships could play a key role in achieving this step change, but they need to be well designed and led.
Maya Said is Vice President of Strategy, External Innovation and Science Policy, and Elias Zerhouni is President, Global Research & Development, Sanofi, 54 rue La Boétie, 75008 Paris, France. Correspondence to E.Z. e‑mail: Elias.Zerhouni@ sanofi.com doi:10.1038/nrd4438
Starting with the remarkable success of the public– private partnerships (PPPs) formed across governments, academia, industry and patients’ organizations to fight the HIV/AIDS epidemic and the success of the international Human Genome Project in the 1990s, we have progressively learned the value of breaking artificial institutional barriers and creating greater trust — the essential component of all successful partnerships. Examples now abound, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) led by the US National Institutes of Health (NIH) to discover the earliest manifestations of Alzheimer’s disease, the Critical Path Initiative launched by the US Food and Drug Administration (FDA) in 2004 to improve regulatory science, and the more recent Innovative Medicines Initiative (IMI) and NIH programmes to accelerate target discovery or validation and tool development such as biomarkers. Novel emerging precompetitive collaborations, such as the TransCelerate BioPharma consortium to improve clinical development and Project Data Sphere (launched by the CEO Roundtable on Cancer) to share patient-level data from previous cancer trials, are just a few illustrations of the rising importance of PPPs globally (see Further information). Among the various partnership models for biomedical innovation, PPPs and precompetitive collaborations provide a particular benefit in that they bring together stakeholders across the health-care ecosystem and, if well designed, align incentives, investments and efforts to address bottlenecks in the research and development (R&D) process. As a result, they can greatly accelerate drug discovery and development, and are an essential component of the emerging R&D ecosystem given that no single stakeholder possesses all the elements needed to address many of the innovation challenges.
Rationale for public–private partnerships Typically, biomedical PPPs are formed to address certain classes of problems such as: • the need to assemble sufficiently large biological or population samples to achieve statistical significance or new insights through cooperative approaches; • the need for multidisciplinary expertise as well as the sharing of exponentially increasing knowledge and access to complex or novel technologies to discover new mechanisms or validate new targets, thus creating common precompetitive resources; • the need to address regulatory complexity through harmonization and validation; and, when necessary engage in scientific efforts to establish standards; • the need to execute large projects over a sustained period of time to reach a sufficient scale and enable discovery or translation through shared resources or the creation of large data sets with complex analytics; • the need to anticipate and rapidly address significant public health threats. In our experience, successful partnerships require clarity of purpose, strong but consensus-driven leadership, adaptive governance and, above all, efficient resource and operational planning. At Sanofi R&D, we have developed a simple set of rules to judge the many opportunities now available for consortium participation. These are based on: whether the purpose of the PPP is clearly stated with specific and measurable goals; whether the subject area is aligned with our strategic priorities and addresses an issue of high relevance to all participants not addressable in any other way within a reasonable time frame; whether the necessary resources and associated milestones are predefined and precommitted; and whether accountability, governance and decision rules are clearly specified and appropriately align incentives.
NATURE REVIEWS | DRUG DISCOVERY
VOLUME 13 | NOVEMBER 2014 | 789 © 2014 Macmillan Publishers Limited. All rights reserved
COMMENT Challenges and lessons learned Although PPPs can bring great benefits to pharmaceutical companies, they often represent complex structures and can pose a real managerial challenge. Over the years, there have been a number of issues raised by PPPs that are not managed well or that have poor leadership, which have led companies to become more selective and stringent in evaluating which PPPs to participate in. Some of the issues we have observed include: • misalignment with the company’s internal strategy; • missing alignment and buy-in on strategy and objectives within the project; • complexity in decision-making and loss of autonomy; • different expectations by partners (for example, patent versus publication); • different research cultures leading to poor outcomes; • outcomes not justifying the time and resources invested; • negligence of intellectual property issues leading to issues with exploitation of results; • diverting energy and resources away from core aims and ‘mission drift’; • substantial administration costs to fulfil the requirements for funding from governmental agencies; • duplication of efforts and resources at a regional and global level. As various stakeholders gain more experience establishing and managing these partnerships, lessons learned are being integrated at the outset into the structure and governance of newly created PPPs or used to evolve existing ones. The IMI in Europe provides a good example of such integration. Unlike some PPPs where the contribution from the pharmaceutical partner is mostly in cash provided to co-finance the public partners, in IMI the dedicated resources provided by the pharmaceutical partner (mostly in-house scientists as well as compounds and samples) are financially matched by the government bodies for funding for the public partners and the biotechnology companies. Projects within the partnership are defined primarily based on issues identified by pharmaceutical companies themselves. This model has required pharmaceutical companies to form ulate relevant projects at the outset and integrate their own dedicated people into the partnership and hence more tightly collaborate with the academic partners and biotechnology companies, not just sponsor the work. For the companies that commit a significant number of people and prioritize the collaboration within their own R&D strategy, it provides them with a vested interest to participate in the leadership of the partnership. In our experience, PPPs are most successful if the partners from pharmaceutical companies, academic institutions, small and medium-sized enterprises, regulators and stakeholders are supported through an independent and neutral facilitator to act as a platform for the ‘call for proposals’ launching process as well as the conduit for funding from governmental sources. The neutral platform initiates and drives the process to gain input from public stakeholders and supports dialogue with regulatory authorities, which is crucial to ensure that the results lead to the introduction of new
pharmaceuticals addressing real unmet medical needs. It is also important to set up an appropriate consortium management structure not only to ensure efficient and quick operational decision-making on a day-to-day basis but also integrate all partners and stakeholders in strategic decisions driving towards successful execution of the project. The recently announced IMI 2, the renewed IMI partnership under the €80 billion Horizon 2020 programme, provides a good example. For each of the priority areas identified, a ‘Strategic Governance Group’ (SGG) is currently being established, bringing together the key decision makers in the specific area from the industry side and tightening the alignment of internal strategy with a portfolio of projects both within the IMI 2 as well as external initiatives. This concept has been proactively supported by Sanofi in the metabolic disorder area (SGG Diabetes), where this SGG is up and running and the first projects of interest have been identified. As a PPP is a complex structure by itself, it is also important that the rules for participation as well as the rules for contractual, financial and intellectual property regulations be as simple as possible while also reflecting the necessary means and boards for efficient steering and maximizing the value of the project. The IMI European Lead Factory is an example where the set-up of a large infrastructure as a joint high-throughput screening facility to screen selected targets with an innovative pooledcompound library required a sophisticated legal and intellectual property framework.
Conclusion In conclusion, the complexity of the challenges facing us as a community dedicated to improving public health requires that we develop more open, collaborative and networked innovation to advance knowledge, promote more efficient R&D models, and recognize that solutions will increasingly require well-designed and led PPPs. Furthermore, as an increasing number of PPPs rise to the challenge, it will be equally important to explore opportunities for better harmonization and coordination on a worldwide basis, as cross-cultural efforts are likely to further stimulate and enhance innovation while greatly increasing the impact and efficiency of these partnerships. Acknowledgements M.S. and E.Z. would like to thank J. Bouthier, B. Stowasser and the Sanofi IMI team for their contributions to this article.
Competing interests statement
The authors declare competing interests: see Web version for details.
FURTHER INFORMATION Accelerating Medicines Partnership: http://www.nih.gov/science/amp/ index.htm Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products: http://www.fda.gov/downloads/scienceresearch/ specialtopics/criticalpathinitiative/criticalpathopportunitiesreports/ ucm113411.pdf Innovative Medicines Initiative: http://www.imi.europa.eu/ Project Data Sphere: https://www.projectdatasphere.org/projectdatasphere/ html/home.html TransCelerate BioPharma: http://www.transceleratebiopharmainc.com ALL LINKS ARE ACTIVE IN THE ONLINE PDF
790 | NOVEMBER 2014 | VOLUME 13
www.nature.com/reviews/drugdisc © 2014 Macmillan Publishers Limited. All rights reserved
