PRODUCT DEVELOPMENT PARTNERSHIPS
v1.0 researched and written by Danielle Navarro, edited by Suerie Moon, last updated January 2019
The literature around product development partnerships is considerable*, with a focus on the structure adopted by Product Development Partnerships (PDPs) and analysis of specific initiatives.
Product Development Partnership
SYNTHESIS OF THE LITERATURE
The goal of PDPs is to develop new, public health-related medical products tapping into the research and development assets and skills of multiple actors. PDPs started to form in the mid-1990s, beginning with the International AIDS Vaccine Initiative and Medicines for Malaria Venture (Abuduxike and Aljunid 2012).
The World Health Organization’s Special Programme for Research and Training in Tropical Diseases (TDR) played a central role in the emergence of PDPs by providing an international framework for coordinating infectious disease research activities in the decades prior. In addition, philanthropic foundations, in particular the Bill and Melinda Gates Foundation and Rockefeller Foundation, helped establish and maintain the existence of PDPs (Munoz et al. 2015).
PDPs are usually non-profit entities that have separate and distinct legal personalities. They are characterized as collaboration partnerships between public and private sector parties (Kulkarni et al. 2015) and usually use a “multi-candidate/portfolio approach” in addressing poverty-related diseases (Technopolis Group 2014). PDPs often involve entities in countries where the targeted diseases are endemic (Burrows et al. 2014). PDPs focus on neglected diseases affecting developing countries -- categorized by WHO as Types II and III,” or those that mostly affect poor populations (Billington 2016). The non-profit character of PDPs allows them to operate without shareholder or profit requirements. However, it is noted that they rely on funding from external parties to achieve their purpose (Bishai et al. 2011). It has also been noted that PDPs often share the monetary burden and uncertainties with their partners with respect to drug development (Burrows et al. 2014). Munoz et al. (2015) provide a detailed analysis of the governance structure and limitations of PDPs, the latter including, e.g. adequate financing for new chemical entities, level of skill of PDP project managers and organization size, unclear agenda setting processes, and lack of transparency (Munoz et al. 2015). Another paper focused on the PDP “development and management” processes (De Pinho Campos, Norman, and Jadad 2011). Two papers described the collaborations with partners of PDPs (Bio Ventures for Global Health 2012; Grace 2010). Ziemba (2005) focused on critical areas that impact the success of PDPs, such as financing and governance structure. It is noted in the study that there is minimal representation of developing countries in the PDP Boards and committees, and that PDPs should seek funding from developing countries, who are the target recipients of the products, among other possible sources of funds (Ziemba 2005).
PDPs have been referred to as “virtual organizations” (Technopolis Group 2014; Munoz et al. 2015), “virtual R&D” (Billington 2016), “system integrators” (Munoz et al. 2015), and “integrator or knowledge broker” (Huzair 2012) since they do not usually engage in hands-on R&D activities but instead coordinate and collaborate with partners who perform said activities (Munoz et al. 2015). PDPs usually develop multiple drugs or medical technologies simultaneously, which allow them to hedge against potential failures of some of their product development projects (Billington 2016).
PDPs adopt individual policies to ensure access to the resulting medical products by those who need them (Munoz et al. 2015). A common PDP objective is guaranteeing the affordability of the resulting medical product to the target patient populations, who are usually in low and middle income countries (Billington 2016). PDPs’ focus on affordable and accessible drugs advances the concept of R&D for health “as a global public good” (Keusch et al. 2010). However, it has been observed that PDPs widely differ with respect to their approaches to managing intellectual property (Munoz et al. 2015).
Some of the literature focuses on specific PDP organizations. A sampling of PDP initiatives are available: http://www.technopolisgroup.com/wpcontent/uploads/2014/11/141118_PDP_Review_Technopolis_Group4.pdf and https://www.wto.org/english/res_e/booksp_e/pamtiwhowipowtoweb13_e.pdf.
Drugs for Neglected Diseases initiative (DNDi) is one of the larger PDPs and has developed 6 new products in a relatively short period of time (Médecin Sans Frontières 2013). DNDi is noted for its non-exclusive license agreements and cost-plus product pricing contractual stipulations that facilitate long-term access to the resulting medical technologies (World Health Organization, World Intellectual Property Organization and World Trade Organization 2012). Sabin Vaccine Institute and the Infectious Disease Research Institute, among other PDPs, have been credited for spearheading vaccine development for neglected tropical diseases (Beaumier et al. 2013). Huzair (2012) identified the World Health Organization-led “influenza vaccine innovation system” as a PDP, which however is unique from other PDPs because it has WHO as its main controlling and guiding entity (Huzair 2012). Hanlin noted the character of the South African AIDS Vaccine Initiative as a national, rather than the more usual international, PDP (Hanlin 2006).
Several studies analyzed specific projects carried out by PDPs. Gordon, Røttingen, and Hoffman (2014) provided a case study on the creation of the Meningitis Vaccine Project (MVP), and the development of the MenAfriVac vaccine, which involved multiple public and private partners including the WHO and PATH (Gordon, Røttingen, and Hoffman 2014). The strategy for the MenAfriVac vaccine project was mainly influenced by the demand from African governments for a sustainable price of US$0.50 per dose (Gordon, Røttingen, and Hoffman 2014; Kulkarni et al. 2015; Bishai et al. 2011). Kulkarni et al. (2015) noted that the project succeeded due to the important factors of “transparency and an intense and close collaboration” of the parties, which allowed for proper know-how and technology transfer, i.e. crucial non-exclusive patent licenses for needed technology (Kulkarni et al. 2015). Bishai et al. (2011) emphasized the MVP’s organizational structure, which is described as having a lattice form, and the willingness of businesses based in developing countries to undertake projects of PDPs for reasons other than profit. MVP showcased the ability of PDPs to facilitate transfer of technology and ensure affordability of medical technology (Bishai et al. 2011). Ubben and Poll (2013) focused on the development process for the drug Eurartesim undertaken by Medicines for Malaria Venture and its partner, emphasizing the collaborative strength in the PDP model (Ubben and Poll 2013). Luiza et al. (2017) and Wells, Diap, and Kiechel (2013) analyzed the drug development process of ASMQ-FDC, an anti-malaria drug developed by DNDi and its partners (Luiza et al. 2017; Wells, Diap, and Kiechel 2013).
The annual G-FINDER studies provide detailed, regularly-updated information on funding for PDPs (and for neglected disease R&D more broadly). Based on the 2017 G-Finder Report, USD 420 million was invested in PDPs in 2016, which was the least amount noted for PDP funding since 2007. 75% of this amount was directed to tackling HIV/AIDS, malaria and tuberculosis. Gates Foundation funding to PDPs dropped in 2016, yet it still accounted for the largest proportion of overall PDP funding at 54%. The sources of PDP funding in 2016 were philanthropic organizations, governments of high income countries and multilateral organizations, providing 57%, 39% and 3.4% of the funds respectively. PDP funding in the past 10 years followed a similar pattern with the Gates Foundation and bilateral aid agencies providing the bulk of finances at close to 90%. However, funding levels in 2016 may be influenced by the fact that PDPs follow funding cycles. At least 40-50% of the yearly PDP funding went to the 3 PDPs receiving the most funds for that year, which in 2016 were the International AIDS Vaccine Initiative (IAVI), Medicines for Malaria Venture (MMV) and Programme for Appropriate Technology in Health (PATH). In the past 10 years, PATH was the PDP that received the most funding (Chapman et al. 2017). Tables indicating the amounts and sources of PDP funding for the period 2007 to 2016 are available at http://policycuresresearch.org/downloads/Y10_G-FINDER_full_report.pdf.
Meredith and Ziemba (2008) noted that PDPs have led 85% of the R&D for 106 neglected disease products since 2000 (Meredith and Ziemba 2008). PDP drug development projects initially focused mainly on drug repurposing. It has been noted that while PDPs had several new chemical entities (NCE) in clinical trials (Munoz et al. 2015), there were relatively few that had been brought to market. We found three PDP-developed NCEs: Pretomanid developed by the TB Alliance, Dihydroartemisinin-piperaquine (Eurartesim) developed by MMV, and Fexinidazole for sleeping sickness developed by DNDi.
Munoz et al. (2015) provide a table of PDPs and the diseases they tackle as well as a list of PDPs and the drugs they developed. Malaria has been noted to be the top disease tackled by PDPs (Munoz et al. 2015). Abuduxike and Aljunid (2012) included a brief numerical summary of the products being developed by PDPs in 2009, categorized according to their development stage (Abuduxike and Aljunid 2012). Young et al. (2018) used a modified Portfolio to Impact model to approximate the costs and launches of 538 out of the 685 product candidates identified from the neglected disease pipeline (Young et al. 2018).
Munoz et al. (2015) argued that donors determine the priority areas for drug R&D and the terms governing the use of funds. Because PDPs rely on donors for funding, there may be a dissonance between the priorities of donors and disease-endemic countries. Further, since PDPs rely on short-term funds, their long-term financial viability is uncertain and affected by financial pressures on their donors. Furthermore, the extent to which PDPs collaborate with each other is generally not publicly-visible, and may result in unnecessary inefficiencies (Munoz et al. 2015).
Huzair (2012) suggested that PDPs may benefit from having a main knowledge and coordinating entity (Huzair 2012). Bishai et al. (2011) have argued that PDPs must have a flexible, more disaggregated project structure, engage public laboratories as possible resources for technologies similar to the US Food and Drug Administration’s Center for Biologics Evaluation and Research, as well as engage more the WHO in their projects in order to benefit from its technical expertise and relationships with international and national actors (Bishai et al. 2011). Årdal, Alstadsæter, and Røttingen (2011) suggested that PDPs should finance more open source drug discovery projects, and noted that some PDPs, to a certain extent, already use open-source mechanisms in their R&D processes (Årdal, Alstadsæter, and Røttingen 2011).
Bhatia and Narain (2010) and Billington (2016) suggested a PDP model to tackle the need for new antibiotics R&D (Bhatia and Narain 2010, Billington 2016); in 2016 the Global Antibiotic R&D Partnership (GARDP) was created for this purpose.
Updated analysis of the successes and failures of PDPs, especially on new chemical entities developed by PDPs
Operational costs of PDPs, in general, and costs specific to PDP R&D activities
Analysis of intellectual property and access policies and practices of PDPs
More information on the governance structure and processes of PDPs and the impact it can have on their decisions
 “Our Pipeline – Pretomanid,” TB Alliance, accessed on 30 October 2018, https://www.tballiance.org/portfolio/compound/pretomanid.
 “Frequently asked questions about Eurartesim,” Medicines for Malaria Venture, accessed on 30 October 2018, https://www.mmv.org/access/products-projects/eurartesim-dihydroartemisinin-piperaquine/frequently-asked-questions-about.
 “Fexinidazole (HAT),” Drug for Neglected Diseases Initiative, accessed on 30 October 2018, https://www.dndi.org/diseases-projects/portfolio/fexinidazole/.
CITED PAPERS WITH ABSTRACTS
Abbott, Frederick. 2016. “Excessive Pharmaceutical Prices and Competition Law: Doctrinal Development to Protect Public Health.” UC Irvine Law Review 6 (3): 281."Abstract: Public health budgets and individual patients around the world struggle with high prices for pharmaceutical products. Difficulties are not limited to low income countries. Prices for newly introduced therapies to treat hepatitis C, cancer, joint disease and other medical conditions have entered the stratosphere. In the United States, state pharmaceutical acquisition budgets are at the breaking point -- or have passed it -- and treatment is effectively rationed. Competition/antitrust law has rarely been used to address “excessive pricing” of pharmaceutical products. This is a worldwide phenomenon. In the United States, the federal courts have refused to apply excessive pricing as an antitrust doctrine, either with respect to pharmaceutical products or more generally. Courts in some other countries have been more receptive to considering the doctrine, but application in specific cases has been sporadic, including with respect to pharmaceuticals. This remains a paradox of sorts. Competition law experts acknowledge that one of the principal objectives of competition policy is to protect consumers against the charging of excessive prices. The currently preferred alternative is to address the “structural problems” that allow the charging of excessive prices. That is, “fixing the market” so that the underlying defect by which excessive prices are enabled is remedied. There is a fundamental problem with the “fixing the market” approach when addressing products protected by legislatively authorized market exclusivity mechanisms such as patents and regulatory marketing exclusivity. That is, mechanical aspects of the market are not broken in the conventional antitrust sense. Rather, the market has been designed without adequate control mechanisms or “limiters” that act to constrain exploitive behavior. Political institutions, such as legislatures, that might step in are constrained by political economy (e.g., lobbying), and do not respond as they should. Competition law and policy should develop robust doctrine to address excessive pricing in markets lacking adequate control mechanisms. This article will focus specifically on the pharmaceutical sector because of its unique structure and social importance. This focus is not intended to exclude the possibility that development of excessive pricing doctrine would be useful in other contexts. This article is divided into two parts. The first addresses competition policy and why it is appropriate to develop the doctrine of excessive pricing to address distortions in the pharmaceutical sector. The second addresses the technical aspect of how courts or administrative authorities may determine when prices are excessive, and potential remedies. The policy prescription of this article is twofold: first, the United States should incorporate excessive pricing doctrine in its antitrust arsenal, and; second, other countries should maintain the status quo with respect to multilateral competition rules that allow them flexibility to develop and refine doctrine, including excessive pricing doctrine, that is best suited to their circumstances and interests. Link: https://scholarship.law.uci.edu/ucilr/vol6/iss3/3/
Heller, Peter S. “The Prospects of Creating ‘Fiscal Space’ for the Health Sector.” Health Policy and Planning 21, no. 2 (March 1, 2006): 75–79. https://doi.org/10.1093/heapol/czj013."Abstract: Not Available Link: https://academic.oup.com/heapol/article/21/2/75/554947
Lexchin, Joel. 2015. “Drug Pricing in Canada.” In Pharmaceutical Prices in the 21st Century, 25–41. Adis, Cham. https://doi.org/10.1007/978-3-319-12169-7_2."Abstract: Not available Link: https://link.springer.com/chapter/10.1007/978-3-319-12169-7_2
Love, James. 2012. “Affidavit: Natco Pharma Limited versus Bayer Corporation.” https://www.keionline.org/sites/default/files/aff-jameslove_13Feb2012_as_Filed.pdf."Abstract: Not available Link: https://www.keionline.org/sites/default/files/aff-jameslove_13Feb2012_as_Filed.pdf
Ottersen, Trygve, Riku Elovainio, David B. Evans, David McCoy, Di Mcintyre, Filip Meheus, Suerie Moon, Gorik Ooms, and John-Arne Røttingen. 2017. “Towards a Coherent Global Framework for Health Financing: Recommendations and Recent Developments.” Health Economics, Policy, and Law 12 (2): 285–96. https://doi.org/10.1017/S1744133116000505."Abstract: The articles in this special issue have demonstrated how unprecedented transitions have come with both challenges and opportunities for health financing. Against the background of these challenges and opportunities, the Working Group on Health Financing at the Chatham House Centre on Global Health Security laid out, in 2014, a set of policy responses encapsulated in 20 recommendations for how to make progress towards a coherent global framework for health financing. These recommendations pertain to domestic financing of national health systems, global public goods for health, external financing for national health systems and the cross-cutting issues of accountability and agreement on a new global framework. Since the Working Group concluded its work, multiple events have reinforced the group’s recommendations. Among these are the agreement on the Addis Ababa Action Agenda, the adoption of the Sustainable Development Goals, the outbreak of Ebola in West Africa and the release of the Panama Papers. These events also represent new stepping stones towards a new global framework. Link: https://www.cambridge.org/core/journals/health-economics-policy-and-law/article/towards-a-coherent-global-framework-for-health-financing-recommendations-and-recent-developments/32B84686FD13D7CB340643D798832095
Wirtz, Veronika J., Hans V. Hogerzeil, Andrew L. Gray, Maryam Bigdeli, Cornelis P. de Joncheere, Margaret A. Ewen, Martha Gyansa-Lutterodt, et al. 2017. “Essential Medicines for Universal Health Coverage.” The Lancet 389 (10067): 403–76. https://doi.org/10.1016/S0140-6736(16)31599-9."Abstract: Not available Link: https://www.thelancet.com/action/showPdf?pii=S0140-6736%2816%2931599-9
World Health Organization. n.d. “Essential Medicines.” WHO. http://www.who.int/medicines/services/essmedicines_def/en/.Abstract: Not available Link: http://www.who.int/medicines/services/essmedicines_def/en/
Xu, Ke, David B Evans, Kei Kawabata, Riadh Zeramdini, Jan Klavus, and Christopher J L Murray. 2003. “Household Catastrophic Health Expenditure: A Multicountry Analysis.” The Lancet 362. http://www.who.int/health_financing/documents/lancet-catastrophic_expenditure.pdf."Abstract: Not available Link: http://www.who.int/health_financing/documents/lancet-catastrophic_expenditure.pdf
* For the purposes of this review, we have established three categories to describe the state of the literature: thin, considerable, and rich.
- Thin: There are relatively few papers and/or there are not many recent papers and/or there are clear gaps
- Considerable: There are several papers and/or there are a handful of recent papers and/or there are some clear gaps
- Rich: There is a wealth of papers on the topic and/or papers continue to be published that address this issue area and/or there are less obvious gaps
Scope: While many of these issues can touch a variety of sectors, this review focuses on medicines. The term medicines is used to cover the category of health technologies, including drugs, biologics (including vaccines), and diagnostic devices.
Disclaimer: The research syntheses aim to provide a concise, comprehensive overview of the current state of research on a specific topic. They seek to cover the main studies in the academic and grey literature, but are not systematic reviews capturing all published studies on a topic. As with any research synthesis, they also reflect the judgments of the researchers. The length and detail vary by topic. Each synthesis will undergo open peer review, and be updated periodically based on feedback received on important missing studies and/or new research. Selected topics focus on national and international-level policies, while recognizing that other determinants of access operate at sub-national level. Work is ongoing on additional topics. We welcome suggestions on the current syntheses and/or on new topics to cover.