Emergence of global immunisation partnerships in supporting global goals and interventions.

Evolution of global immunisation mandates and growing donor fatigue. Five articles examined the evolution of global immunisation policies [21–25], starting with the global Expanded Programme on Immunisation (EPI), launched by WHO in 1974 to accelerate immunisation against six diseases at a time when less than 5% of the world’s children were immunised. EPI built on the success of smallpox eradication and, by 1990, had administered Bacille-Calmette-Guerin (BCG), polio, and measles vaccines to 80% of children under 13 months old globally [21, 22]. Hardon and Blume [21] examined five subsequent vaccine initiatives: (1) Universal Childhood Immunisation (UCI), launched in 1984 by WHO and UNICEF to accelerate EPI; (2) the Global Polio Eradication Initiative launched in 1988; (3) the Vaccine Independence Initiative (VII), launched in 1991 by UNICEF to overcome temporary budget shortfalls and maintain supplies; (4) the Children’s Vaccine Initiative (CVI), also launched in 1991, to promote new vaccine technologies and determine the feasibility of a single-dose multivalent vaccine; and (5) Gavi (formerly the Global Alliance for Vaccines and Immunisations) launched in 2000. Fig 2 provides a timeline of global immunisation mandates and launches of these initiatives, ending with the launch of COVAX in 2020.

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Fig 2. Timeline of global immunisation mandates.

https://doi.org/10.1371/journal.pgph.0002834.g002

Several authors identified donor fatigue in the 1990s as a factor in UNICEF’s creation of VII [21, 23]. Its importance was that, unlike its predecessors, it encouraged LMIC governments to take on greater responsibility for meeting vaccine needs, supporting them through subsidies for purchases. These governments were required to establish domestic vaccine budgets as a condition of participating in the pooled procurement mechanism, although UNICEF absorbed the risk of payment defaults. VII succeeded in increasing MICs’ self-reliance but less so for LICs.

The rise of GHPs as brokers between public and private actors. Four articles linked the origins of GHPs to events in the late 1980s and early 1990s [10, 21, 25, 26], when a series of developments coincided, including détente following the collapse of the USSR and the resulting reduction of decades of rivalry between superpowers competing for influence in poorer countries, the emergence of HIV, and the growth of public-private partnerships in sectors such as health and education in high-income countries (HICs).

GHPs were seen as a means of concentrating efforts at scale and raising large sums of money that could be spent on increasingly innovative vaccine technologies [10, 21, 25, 26]. CVI was co-sponsored by WHO, UNICEF, the United Nations Development Programme (UNDP), the World Bank, and the Rockefeller Foundation, and had substantially greater private sector involvement than its predecessors. This approach was initially very appealing to donors. However, tensions soon arose, particularly as European donors felt it was overly focused on technical solutions reflecting commercial interests [21]. CVI did develop improved vaccine technologies using PDPs but failed to mobilise needed resources to deliver and sustain immunisation programmes [21, 26]. These developments occurred alongside growing emphasis on health as a driver of economic growth, exemplified by the 1993 World Development Report [27], and the importance of ensuring interventions were cost-effective. The Millennium Development Goals provided further stimulus, leading governments to find new ways of funding development that gave private actors increasing influence in global health policy decision-making [10, 22]. Increasingly, public-private partnership structures came to be seen as essential in any global response.

Four articles described how this new worldview led to GHPs acting as either integrators or brokers of knowledge, working toward a common goal to achieve vaccine mandates, often focusing on technical progress [28–31]. This brokering role was particularly prominent in intellectual property issues, with GHPs acting in “mediating asymmetric economic relationships between HICs and LMICs” while ensuring that “these initiatives do not seek to explicitly challenge the rules of international trade, global finance or the [IP] rights regime that underpin the neoliberal system of economic governance, viewed by many as the basis of continuing North-South intra-country inequities” [31]. Thus, proposed solutions worked within the “rules of the game” and did not challenge established power relationships.

Gavi was launched in 2000. As a successor to CVI, it embodied and reinforced the priority to expand and sustain uptake of cost-effective vaccines and develop new vaccine technologies. Countries became eligible for Gavi support if their Gross National Income (GNI) per capita was ≤US$ 1,000 over the previous three years [21]. Unlike its predecessors, Gavi was not led by a UN agency but governed by a board of 16 institutional members. Five are permanent (i.e., BMGF, the Vaccine Fund, WHO, UNICEF, World Bank), and 11 rotate to reflect different constituencies (i.e., LMICs [2 seats], HICs [3], NGOs [1], LMIC industry [1], HIC industry [1], foundations [1], technical health institutes [1], research and academia [1]). Jean Stéphenne, former president of SmithKline Biologicals, which produced the combined DTP-hepatitis B vaccine, outlined the conditions for industry participation at the first Gavi Partners’ meeting in Noordwijk, the Netherlands, in 2000. These included a guarantee of “‘reasonable prices’, support for a credible and sustainable market, respect for international property rights, a tiered pricing system including safeguards against re-exporting products from lower-income countries to high-priced markets, and a prohibition on compulsory licensing” [21]. Gavi made aid contingent on increased immunisation coverage performance, which overlooked weaknesses in health information systems in most applicant countries. This was already recognised in the UCI initiative, with Hardon and Blume [21] reporting problems in Ghana, Mozambique, and Tanzania, none of which could provide the required data on DTP3.

GHPs for product development.

Six articles described PDP successes in encouraging innovation [26, 32–36]. PDPs used public money to reduce risks for private companies undertaking high-cost research while subsidising development and commercialisation processes [26, 37]. Examples include the Drugs for Neglected Diseases Initiative (DNDi), the International AIDS Vaccine Initiative (IAVI), and the Malaria Vaccine Initiative (MVI). However, Sunyoto argued that their successes cannot remove the need to transform the current research and development system to address unmet health needs [36].

The most significant criticism of the PDP model is that it seeks to reconcile two conflicting principles, that the public sector should be responsible for addressing population needs within a finite budget and that the private sector should maximise profits [32, 34, 35]. It also avoids challenging an intellectual property regime that reinforces the private sector’s considerable power over pricing [32, 36]. This means other financial mechanisms are needed to procure products for LMIC markets [24, 38]. Some authors also noted how PDPs confer additional benefits to manufacturers, allowing them to enhance public reputation as they portray themselves as acting in the public interest to solve complex problems [26, 36]. A further concern about PDPs is their overall lack of local stakeholder engagement. Some have attempted to engage local stakeholders in decision-making processes related to regulatory processes and clinical trial management [22, 39]. However, there is still some way to go to incorporate the co-production approaches increasingly used in other settings [40].

PDPs support the growth of globally competitive vaccine manufacturers in LMICs [31, 37, 39, 41]. The expansion of manufacturing capacity in LMICs facilitates regional development of vaccine technologies, prompting LMICs to partner in the vaccine innovation process [39]. This occurs through public and private-sector investments, with PATH and BMGF playing essential roles as supporters and facilitators [37]. For example, the Serum Institute of India (SII) is now the largest producer of vaccines globally by volume. BMGF subsidised much of SII’s portfolio, including rotavirus, human papillomavirus (HPV) and pneumococcal vaccines [31]. Moran and Stevenson found that “the Foundation’s leadership believes the world needs several companies like the SII with global distribution capacity to meet demand projections and diversify risks” [31].

Five articles contended that PDPs fulfil their intended purpose by developing new drugs, vaccines, and other technologies despite longstanding state and market failures [28–30, 39, 42]. For example, by the end of 2004, global health partnerships, including PDPs, were responsible for nearly 75% of neglected disease drug development and negotiated conditions for IP rights [28, 31, 32]. DNDi developed eight new treatments for malaria, leishmaniasis, Chagas Disease, sleeping sickness, paediatric HIV, and hepatitis C. Hayter and Nisar [39] noted that PDPs developed strategies to motivate company and university participation in instances where IP protection was a barrier to collaborative governance. Licensing plans included co-assigning patents with commercial partners or not patenting at all. Chataway et al. [28] and Moran and Stevenson [31] highlighted IAVI’s attempt to monitor how the financial consequences of intellectual property rights should be shared between public and private actors by brokering a negotiated agreement in which private actors retain IP rights and IAVI retains the right to obtain licences to contract other vaccine manufacturers if the original company should decline to produce the vaccine for LMICs at reasonable quantities and prices.

Two articles proposed alternatives to the PDP model, redirecting PDP funds to build existing public sector pharmaceutical manufacturing capacities in LMICs. Stevenson and Youde [43] and Stevenson [26] noted how this would eliminate the profit motive inherent in PDPs and ensure that demand is met. This approach was leveraged by DNDi, which combined existing HIC public-sector research institution resources and only used pharmaceutical firms as contractors if necessary [26]. In this way, PDPs have duplicated pre-existing public-sector research organisations that share similar mandates yet lack funds. Stevenson [26] noted that by declaring access to preventative and therapeutic health technologies a fundamental tenet of global health policy, governments and enablers of global health partnerships made manufacturers vital to global public health. Efforts could be re-directed to support scaling up existing public-sector health technology production capabilities, for example, in Brazil and Cuba. Meanwhile, PDPs operating outside the direct control of governments and the UN system will continue being relied upon to produce needed health technologies for LMIC populations.

GHPs for improved access.

Access partnerships include GHPs, such as Gavi, which focus on procuring and delivering vaccine technologies. Four articles discussed Gavi’s accomplishments in increasing access to vaccines in LMICs through AMCs [37, 39, 44, 45]. Jaupart et al. found that Gavi made an important contribution to increasing vaccine uptake in LICs, noting a 12.0% increase in DPT coverage (95% CI 6.6–17.5) and an 8.8% increase in measles-containing vaccine (MCV) coverage (95% CI 3.6–14.0) from its inception until 2016 [45]. This was consistent with findings by Gandhi, who also concluded that Gavi had mixed results in addressing between-country inequities in immunisation uptake [44].

Six articles argued that market-oriented incentives like AMCs were necessary to ensure LMICs obtained adequate quantity, quality, affordability, and sustainability of vaccines [32, 35, 36, 46–48]. Thus, HIC donors channelled development financing into specialised programmes that included AMCs, which they considered could address between-country access inequities [44]. This funding model was initially embraced in 2007 by BMGF, Canada, Italy, Norway, Russia, and the UK, pledging US$ 1.5 billion to accelerate the development of a new pneumococcal vaccine [46].

The premise behind AMCs is that they tackle static and dynamic distortions in the vaccine market through a legally binding commitment to purchase vaccines on predetermined terms. This reduces risks to the pharmaceutical industry and aims to stimulate development and manufacturing of such health technologies [32]. The AMC model sought to address market failure but continues to experience shortcomings in supporting innovative vaccine technologies and price regulation. Though the AMC model successfully incentivises pharmaceutical companies to engage with issues relating to the supply of and demand for vaccines, it has yet to be successful in convincing companies to develop new technologies [38, 49]. This failure is explained by the AMC’s shift from the original intention of developing new vaccine technologies to focusing on increasing production capacity and purchasing and distributing existing vaccines. This shift effectively locked in a price to be paid to vaccine manufacturers, thus providing two multinational producers—GSK and Pfizer, as opposed to vaccine manufacturers located in LMICs such as SII—with a fixed profit level and no incentive to reduce unit prices, with consequences for vaccine accessibility in LMICs [39].

Cernuschi et al. [46] and Siagian and Osorio [49] discussed challenges with the AMC model, such as long-term competition between first- and second-generation vaccine manufacturers. Second-generation suppliers have little incentive to participate as they face technical barriers to market entry [46]. Though supporters of AMCs intended that the model would promote competition to ensure lower prices and avoid supply interruptions, donors did not want to establish differential terms for different suppliers, opting for a “one size fits all” contract [49].

Several articles questioned the sustainability of partnerships, highlighting their heavy donor dependence, especially on Gavi, despite attempting to reassure industry partners about the long-term viability of sustaining vaccine markets in LMICs [38, 48, 49]. Authors suggested exploring less pro-cyclical funding and finding ways for the AMC design to match long-term predictable donor commitments with final buyers’ budgetary capacity [46].

BMGF dominance.

Several articles identified the creation of BMGF in 2000 as a critical event in the growing role of non-state actors in global health [10, 26, 31, 43]. The enormous resources it commands, dwarfing those from many donor countries and the budgets of some international agencies, give it vast influence. For example, its endowment had already reached US$46.8 billion in 2018, and it had awarded a cumulative US$50 billion in grants and US$3.2 billion in development assistance for health (DAH) in that year. This accounted for over 8% of that year’s global total, making it the third-largest single source of DAH funds after the US and the UK [43]. Unsurprisingly, BMGF is not a passive donor, and its support has focused on specific, often technological, innovations rather than strengthening health systems holistically.

Six articles examined the work of BMGF, highlighting its material, ideational and agenda-setting influences on global health policymaking [10, 26, 32, 42, 43, 50]. Several argued that it weakens international bodies such as WHO and the UN, thus “rendering less relevant multilateral fora where [LMICs] have a voice.” For example, WHO was marginalised in the design and governance of the Access to COVID-19 Tools Accelerator (ACT-A) with traditional multilateral governance—based on national governments—giving way to multi-stakeholder oversight [50]. Yet, while some criticised this development on the grounds of transparency, others argued that it is an understandable response to the “glacial speed” with which many multilateral initiatives progress. In contrast, some GHPs, such as the International AIDS Vaccine Initiative (IAVI), are praised for their more agile response, drawing on techniques more usually associated with the private sector [21, 22, 24].

Stevenson and Youde [43] argued that the influence that BMGF can exert in global health governance is less a reflection of its ability to usurp state power than the abdication of states’ responsibilities. From this perspective, partnerships involving major philanthropic organisations have brought urgently needed resources to bear on complex problems that have long stymied individual governments and the constellation of international actors. This has led governments to look to these arrangements to achieve goals that have proven elusive for the international system. This is exemplified by the support given to GHPs such as Gavi.

Five articles noted how the resources available to GHPs led to their presence at high-level decision-making fora becoming institutionalised [30, 42, 47, 51, 52], despite concerns about their democratic legitimacy and accountability [43]. Commentators contrasted their authority, derived from their resources, with their weak claims to legitimacy. Authority implies a degree of power. Legitimacy refers to the normative right to exercise that authority, requiring the assent of those directly impacted [43]. Some questioned the assumption that private participation in global health is necessary for solving complex problems, given the absence of any mechanism for democratic oversight of internal decision-making in BMGF [43].

WHO’s diminishing authority.

Several authors considered the impact of GHPs on WHO’s role and influence [10, 25, 26, 43, 50]. As a normative organisation accountable to its member states, WHO’s action is politically constrained [25]. Wenham et al. [25] saw this as an example of a “principal agent relationship”, where WHO’s agency is limited and determined by the compliance and consensus of states, resulting in political interference, whilst also attempting to be an apolitical technical actor. Periodic strengthening initiatives, including the 2005 International Health Regulations revision, have had limited success [10, 50]. In contrast, private philanthropic organisations have much greater freedom, especially those whose authority is concentrated in one or several individuals, such as BMGF. This freedom could make BMGF well-suited to resolve global health challenges. However, the idea that a few private individuals should drive global health policy is problematic, particularly given that WHO’s legitimacy is derived from its 194 member states [43].

GHP funding and interventions have taken a vertical corporatist approach to addressing global health challenges that is incompatible with the more horizontal health systems-oriented approaches endorsed by WHO and countries for achieving vaccine equity. Consequently, evidence suggests that continued usage of GHPs in global health decision-making resulted in the gradual relegation of WHO to peripheral decision-making, acting as a coordinator rather than a leader in governance [26, 43]. Equally, many see approaches based on business models as further excluding LMICs from decision-making processes, exacerbating health technologies access issues [10, 26, 50].

The perceived weakness of UN organisations, such as WHO, has created a gap that non-state actors are attempting to fill. Such moves are often welcomed, given the opportunities for additional resources. As a leading donor and frequent partner, BMGF has demonstrated it will work through WHO and not wait for or defer to WHO to create new initiatives. BMGF justifies this approach by evidencing the success of Gavi and GFATM, showing that alternative organisational structures can provide financial support, promote drug and vaccine development, and build necessary health infrastructure [43]. At the same time, BMGF’s adoption of a public-private partnership model means its goals depend on whether its public sector partners can fulfil their commitments. Stevenson and Youde [43] argued that one of the biggest threats to this model is the unwillingness of BMGF’s government partners to adequately complement its activities, e.g., by scaling up technologies that have been developed or by delivering and implementing these technologies due to insufficient infrastructure in countries. Given its limited capacity and imbalanced resources, some argued that WHO was ill-equipped to enter sustained collaborations with non-state actors, especially the pharmaceutical industry.

Six articles described GHPs’ lack of transparency and accountability [10, 22, 26, 32, 43, 50], noting concerns about the transparency of decision-making processes and the need for global mechanisms to hold GHPs accountable. Lack of transparency and accountability make it difficult to examine the successes and failures of specific interventions [53]. Some also saw this lack as a means to increase private interest representation in decision-making processes. Ruckert and Labonté, in an analysis of 23 GHPs, found that most decision-makers were from the corporate sector and argued that this could create conflicts of interest. For example, BMGF maintains substantial equity in the Coca-Cola Corporation [10], and its grants encourage LMIC communities to become business affiliates of Coca-Cola despite Coca-Cola products contributing to the growing global burdens of obesity and diabetes. Articles have argued that this could partially explain BMGF’s focus on infectious diseases despite NCDs constituting more than half of all deaths in LMICs [10, 43].

GHPs create disease-funding silos.

GHPs’ focus on product development and delivery for specific diseases undermined horizontal and systems-oriented efforts to reduce disease spread [43]. Three articles described the GHP model as a barrier to addressing the social determinants of health (SDH), such as poverty or social exclusion, resulting in “agenda skewing” [10, 25, 32]. Few GHPs focus on the contribution of SDH to global disease burden. For example, TB shows a strong socioeconomic gradient, with poor and marginalised populations more likely to contract TB due to malnutrition or inadequate access to health services [10]. One article noted how few GHPs have explicit objectives for poverty alleviation or robust means to demonstrate that their interventions benefit poorer populations despite having equity objectives [43]. This is important as certain GHPs working on TB have reduced mortality but been less successful in reducing incidence, reflecting a focus on treatment rather than prevention [43]. Consequently, disease funding silos and segmentation were created, with most international funding directed towards infectious instead of non-infectious diseases. For example, BMGF directs approximately 97% of its financial disbursements towards infectious diseases—with less than 3% to NCDs—and 45% of total PDP funding is from BMGF, resulting in the model’s financial reliance on BMGF [10]. PDPs remain the primary means for incentivising technical innovation and transferring proprietary technologies to actors’ intent on strengthening public health in LMICs [32, 48].

Four articles referred to the increased “financialisation” of the vaccine ecosystem and GHP initiatives’ heightened focus on financial risks to the pharmaceutical industry rather than global public health risks [50, 53–55]. Financialisation is “the rise of financial concepts, motives, practices and institutions” [53]. This approach informed how COVAX approached vaccine production and distribution. Both Stein [53] and Storeng et al. [55] argued that COVAX’s focus on “financialisation” and corporate risk management undermined its goals of achieving global vaccine equity. Both also considered this focus could be the reason behind COVAX’s refusal to support global health policies challenging the global IP regime or corporate privileges, despite providing pharmaceutical companies with both push and pull subsidies. However, this has not benefitted COVAX, as vaccine manufacturers consistently prioritised bilateral deals with wealthier countries instead of supplying COVAX. This was illustrated by vaccine manufacturer Moderna, which reserved most of its doses for bilateral deals with HICs despite receiving funding from CEPI that included conditions on equitable access [55]. However, Moderna only entered an agreement with COVAX in May 2020 for approximately 500 million doses to be delivered in the second half of 2021, and “only after committing to delivering billions of doses first in bilateral deals” [55].