Introduction

In the past, developing new antibiotics appeared to be the easiest solution to overcome resistant pathogens. As certain antibiotics became less effective against evolving bacteria, treatment for infections could be supplemented or replaced by newer generations of the same antibiotic or by a new, more effective class of antibiotic. The world saw a boom in new antibiotics and classes between 1940 and 1990 as pharmaceutical companies leveraged scientific breakthroughs and were rewarded with high-value patents (Pew Charitable Trusts, Reference Trusts2016; Silver, Reference Silver2011). However, due to a combination of financial, regulatory, and scientific barriers to continued development of new antibiotics, the focus of research and development (R&D) shifted away to other therapeutic areas (Renwick & Mossialos, Reference Renwick and Mossialos2018). In 1990, there were 18 major pharmaceutical companies active in antibiotic R&D, but today there are only eight (Access to Medicine Foundation, 2018; Butler, Blaskovich & Cooper, 2013). Since then, the number of new antibiotics marketed each decade has significantly decreased and no novel classes of antibiotics with distinct chemical structures have been developed (Pew Charitable Trusts, Reference Trusts2016) (Figure 6.1). This void in discovery and development has meant that the antibiotic pipeline is frighteningly thin relative to the unrelenting advance of antibiotic resistance.

Figure 6.1 Number of new classes of antibiotic discovered or patented each decade.

Source: Pew Charitable Trusts, Reference Trusts2016. Originally adapted from Silver, Reference Silver2011

The global community is beginning to accept the severity of antibiotic resistance and is scrambling to make up for lost time in antibiotic R&D. Promisingly, numerous major international and national initiatives have been started in recent years to help fund, coordinate, and incentivize antibiotic R&D programmes (Simpkin et al., Reference Simpkin, Renwick and Kelly2017). With the recent flurry of action it is important, however, to take stock and assess the current state of the global market for antibiotics and antibiotic innovation, in order to identify any necessary policy adjustments. To this end, this chapter aims to identify progress and assess the challenges in fostering antibiotic R&D, as well as highlighting some key policy gaps that must be addressed.

The antibiotic pipeline

Although the antibiotic pipeline is improving, it is not nearly robust enough to match clinical need and respond to the rising rates of resistance in deadly pathogens. In early 2017, the World Health Organization (WHO) (2017a) published a priority pathogens list (PPL), which outlines the antibiotic-resistant bacteria that pose the greatest threat to global public health (Table 6.1). This list aims to guide antibiotic R&D based on medical need as opposed to the economic factors that have traditionally directed antibiotic investment. At the top of this list, categorized as “critical”, are the Gram-negative, carbapenem-resistant strains of Acinetobacter baumannii, Pseudomonas aeruginosa, and the Enterobacteriaceae family. In 2013, the US Centers for Disease Control and Prevention (CDC) published a US-focused urgent threats list for antibiotic resistance, which highlighted many of the same pathogens (US CDC, 2013).

In September 2017, the WHO published an in-depth analysis of the global development pipeline for antibacterial agents (World Health Organization, Reference Organization2017b). The report shows how 32 antibiotic therapies that are active or possibly active against a PPL pathogen are the subject of clinical trials: 14 in phase I clinical trials, 8 in phase II, and 10 in phase III (Figure 6.2). Based on optimistic clinical trial attrition rates, the report estimates that the entire pipeline could be expected to yield 10 new approvals. As with most drug developments, the R&D and market approval process is lengthy. The phase III antibiotics are three to five years from potentially reaching the market. However, the phase I and II antibiotics have development timelines of at least five to 10 years and successful progression to marketing approval is far from certain. Antibiotics in phase I clinical trials have only a 14% likelihood of reaching the market. This means that of the 10 phase I antibiotics targeting resistant Gram-negative bacteria only one or two will succeed.

Figure 6.2 The number of antibiotics in clinical development possibly active against WHO PPL pathogens (2017) and the number of alternative therapies to antibiotics in clinical development (2017).

Note: PPL: Priority Pathogens List.

Source: World Health Organization, Reference Organization2017b; Pew Charitable Trusts Reference Trusts2017

A compounding problem is that most of the pipeline drugs are redevelopments of classic antibiotic compounds or are combination therapies of existing antibiotic molecules. These types of less original antibiotics are at higher risk of quickly losing effectiveness in clinical practice because of cross-resistance. According to the WHO pipeline analysis, there are eight products in development that offer innovation in terms of having at least one of the following criteria: (1) absence of cross-resistance to existing antibiotics, (2) new chemical class, (3) new target, or (4) new mechanism of action. There are only two drugs that are truly innovative across all four WHO criteria: one targets P. aeruginosa and the other Staphylococcus aureus. The WHO analysis concluded that the current antibacterial pipeline is inadequate for the soaring resistance rates (World Health Organization, Reference Organization2017b). This sentiment was echoed in the Access to Medicine Foundation’s 2018 AMR Benchmark Report, which is an independent assessment of key industry players across a spectrum of AMR priorities related to R&D, production and manufacturing, and appropriate access and stewardship (Access to Medicine Foundation, 2018). Of note, Pew Charitable Trusts conducts a concise and useful biannual antibiotic pipeline analysis and the most recent update, as of September 2018, reiterates these general findings (Pew Charitable Trusts, Reference Trusts2018).

A fledgling portfolio of alternative therapies to antibiotics is now emerging and includes vaccines, immune stimulation, bacteriophages, lysins, probiotics, antibodies and various peptides. Initially, these products would likely supplement typical antibiotic regimens as adjunctive or preventive therapies. In March 2017, a Pew Charitable Trusts analysis found that there are 30 nontraditional antibacterial therapies in the development pipeline: six in phase I clinical trials, 19 in phase II, and five in phase III trials (Figure 6.2) (Pew Charitable Trusts, Reference Trusts2017). Of these, nine products are vaccines, nine are antibodies, and the remainder are probiotics, lysins and peptide immunomodulators. However, an earlier review of these alternative treatments estimated that this pipeline will require more than £1.5 billion in sustained investment over 10 years to translate most of these projects into investable ventures and eventually marketable products (Czaplewski et al., Reference Czaplewski, Bax and Clokie2016). Another ongoing challenge with some alternative therapies, such as bacteriophages, is that there is minimal regulatory precedent for FDA and EMA licensure, making it challenging for developers and regulators to know how to proceed (Cooper, Khan Mirzaei & Nilsson, 2016).

Barriers to antibiotic R&D

The success rate of moving an antibiotic from basic research to market approval is estimated to be between 1.5% and 3.5%. This process can typically take 15 years (O’Neill, Reference O’Neill2015a). The economic, regulatory, and scientific barriers to antibiotic R&D can best be categorized based on the steps of the antibiotic value chain: initial research, preclinical trials, clinical trials, market approval, and, finally, commercialization (Chorzelski et al., Reference Chorzelski, Grosch and Rentmeister2015). These barriers are important to consider when designing and targeting future incentives to support antibiotic R&D.

The basic and discovery research behind understanding and identifying new molecules for candidate drugs has been scientifically challenging. Bacteria, particularly Gram-negative varieties, have proven highly resilient to recent experimental mechanisms of destruction (Pew Charitable Trusts, Reference Trusts2016). In addition, scientific expertise in this area is currently lacking and is still recovering from the discovery void that began in 1990 (Silver, Reference Silver2011). The preclinical stage is ominously referred to as the “valley of death” (So et al., Reference So and Ruiz-Esparza2012). Discovery research has predominantly been tackled by academics funded by the public sector, while clinical trials have been the domain of private pharmaceutical companies, thus leaving a gap in funding and appropriate actors to move from one to the other.

Antibiotic clinical trials are costly, estimated at roughly $130 million to take a drug candidate through Phases I to III. Many drug candidates will be discarded on the way, at a financial loss. The average cost of post-approval follow-on trials can amount to an additional $146 million (O’Neill, Reference O’Neill2015a). These costs and uncertainties are often prohibitively high for small and medium enterprises (SMEs) (Renwick, Brogan & Mossialos, Reference Renwick, Simpkin and Mossialos2016). Despite the challenge of economies of scale, SMEs represent approximately 85% of the share of antibiotics in clinical development (Chorzelski et al., Reference Chorzelski, Grosch and Rentmeister2015). An added practical challenge is that recruiting patients with acute bacterial infections for clinical trials is logistically difficult due to the short treatment windows and lack of rapid point-of-care diagnostic tools to identify potential participants.

Market approval of new antibiotics is necessary for ensuring the drug’s quality, safety and efficacy. However, there are procedural differences between drug regulatory agencies in approving antibiotics that make global licensing unduly time-consuming and expensive (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016). These differences relate to patient selection criteria, definitions of clinical end-points, specification of statistical parameters, and rules regarding expedited approvals (Chorzelski et al., Reference Chorzelski, Grosch and Rentmeister2015).

Finally, the economic reward for commercializing a new antibiotic is minimal or negative relative to other therapeutic areas, such as neurologic or cardiovascular drugs (So et al., Reference So, Gupta and Brahmachari2011). At present, novel antibiotics are not destined to generate significant revenue even with their immense public health value. Potential sales volumes are restricted by short treatment durations and hospital stewardship programmes that limit access. In addition, the large overlap in clinical application of newly patented antibiotics with existing generic alternatives places downward pressure on prices (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016).

Incentivizing antibiotic innovation

A significant amount of research has explored the policy proposals for minimizing these barriers and incentivizing companies to pursue R&D in the antibiotic field. Push and pull incentives are broadly used to classify the two main types of mechanisms for supporting antibiotic R&D (Mossialos et al., Reference Mossialos, Morel and Edwards2010). Push incentives reduce the cost of researching and developing new antibiotics. Examples of push incentives include research grants, access to shared resources, and product development partnerships to split R&D costs (Table 6.2). Pull mechanisms increase the potential revenue of a successfully marketed antibiotic. This may be through outcome-based rewards that directly increase revenue such as monetary prizes, reimbursement premiums, advanced market commitments to purchase the drug, and patent buyouts by governments. If large enough, outcome-based pull rewards could replace the traditional revenue stream generated by the sales volumes of a licensed antibiotic. This concept is referred to as “delinkage” since the antibiotic’s revenue would be delinked or decoupled from its sales, thus removing the incentive to promote the drug’s use (Rex & Outterson, Reference Rex and Outterson2016). Alternatively, pull mechanisms may be legal or regulatory, providing incentives such as accelerated procedures for marketing approval or extensions to the patent period. Different push and pull mechanisms have unique advantages and disadvantages and experts generally agree that a combination of both types is necessary to provide effective incentives for R&D. As of 2015, there were 47 different incentives available or proposed for antibiotic developers that ranged from simple push or pull mechanisms to complex hybrid models (Renwick, Brogan & Mossialos, Reference Renwick, Simpkin and Mossialos2016).

Table 6.2 Push and pull incentives for antibiotic development

Push incentive strategies
Supporting open access to research	Funding translational research
Grants for scientific personnel	Tax incentives
Direct funding	Refundable tax credits
Conditional grants	Product development partnership

Outcome-based pull incentive strategies
End prize	Research tournament
Milestone prize	Advanced market commitment
Pay-for-performance payments	Strategic Antibiotic Reserve
Patent buyout	Service-availability premium
Payer license

Lego-regulatory pull incentive strategies
Accelerated assessment and approval	Anti-trust waivers
Market exclusivity extensions	Sui generis rights
Transferable intellectual property rights	Value-based reimbursement
Conservation-based market exclusivity	Targeted approval specifications
Liability protection	Priority review vouchers

Source: Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016.

Designing a global incentive package for stimulating antibiotic innovation is a complex task with numerous variables. Policy-makers need a methodology for selecting a complete and realistic set of incentives from the surfeit of candidates. In 2015, the authors of this chapter published a possible framework to help policy-makers with this challenge (Renwick, Brogan & Mossialos, Reference Renwick, Simpkin and Mossialos2016) (Figure 6.3). The framework has three consecutive phases. The first phase involves fashioning a core incentive package targeting the economic criteria necessary for rebalancing the market. This core incentive package must:

Figure 6.3 Framework for developing a holistic incentive package for antibiotic development.

Note: NPV: net present value; SME: Small–medium sized enterprise.

Source: Simpkin et al., Reference Simpkin, Renwick and Kelly2017

1. 1) improve the profitability of developing and commercializing a novel antibiotic;

2. 2) make market participation feasible for SMEs;

3. 3) encourage investment by large pharmaceutical companies;

4. 4) facilitate cooperation across all stakeholders including patients, academics, policy-makers, regulators, and industry.

The second step requires adjusting the core incentive package to address public health goals pertaining to sustainability and patient access to new antibiotics. The final step considers the implementation and operational practicalities that are specific to national context.

Key initiatives incentivizing antibiotic R&D

A 2016 review found that there are 58 active initiatives directly incentivizing the development of antibiotics at global, EU, and national levels, including in the UK, France, Germany, Netherlands, Sweden, the USA, and Canada (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016). These initiatives are programmes that employ one or more push or pull incentive mechanism. An added nine initiatives were identified as offering indirect incentives through economic and policy research or the coordination of strategic actions on AMR. The number of active initiatives in this field continues to rise and several programmes have been initiated since this review was conducted. The following section describes the main antibiotic R&D initiatives at multilateral and EU levels, as well as key initiatives from the USA and the UK, who are leaders at the national level in this field.

Next steps in global antibiotic development incentivization

The extensive array of antibiotic R&D incentives is commendable, and strides have been made towards reviving the antibiotics pipeline. However, the current incentive package has major gaps and deficiencies that inhibit the transition from basic science research all the way to bedside access. The end goal should be a continuum of incentivization that reflects the economic need, cost distribution, and barriers of the entire antibiotic value chain. Different types of incentives are better suited for tackling different stages of this value chain (Figure 6.4). To achieve this continuum, there is a need to adjust push incentivization to increase funding of preclinical and clinical development, support global regulatory harmonization and provide added legal or regulatory incentives to facilitate market approval. There is also a need to introduce a variety of outcome-based pull incentives to ensure the commercialization and distribution of licensed antibiotics. These incentive changes must involve inter-initiative coordination and be made within the context of broader public health goals related to sustainability, patient access, and medical need.

Figure 6.4 Continuum of incentivization across the antibiotic value chain

Source: Adapted from Simpkin et al., Reference Simpkin, Renwick and Kelly2017

Push incentives, such as grants for researchers and direct project funding, are best used to facilitate the earlier stages of R&D from basic science up to clinical development. Most push funding for antibiotic R&D is directed towards basic antimicrobial science and less so towards clinical development. An estimated 86% of European national-level public funding of antibiotics was in this category (Kelly et al., Reference Kelly, Zoubiane and Walsh2015). The JPIAMR, DG-RTD, CARB-X, NIAID, UK Research and Innovation, and NIHR, preferentially fund antimicrobial basic science. While early-stage push funding of antimicrobial science is integral to the R&D process, there is a need for more late-stage push funding of preclinical and clinical trials to help translate scientific innovation into marketable products. The overemphasis on early-stage push funding reflects the fact that basic science lends itself more easily to being partitioned into projects requiring smaller individual monetary commitments than clinical trials do. In addition, public funders can more easily justify supporting nonprofit academic work. Basic science is largely the domain of academia and, as a result, private companies often do not benefit from early-stage push funding. Yet clinical trials, which are usually operated by private companies, are by far the most expensive aspect of R&D (O’Neill, Reference O’Neill2015a). SMEs are the most impacted by the lack of late-stage push funding as they often struggle to raise the capital necessary for clinical trials (Renwick, Brogan & Mossialos, Reference Renwick, Simpkin and Mossialos2016).

As more drug candidates transition to clinical development, early-stage push funding could be pooled and reallocated to late-stage push funding to ensure viable antibiotics make it to the market approval stage. In addition, programmes such as BARDA and the IMI’s COMBACTE, which specifically fund clinical trials, could be further expanded. As demonstrated in the WHO pipeline analysis, most antibiotics and alternative therapies are in phase I clinical trials and could immediately benefit from late-stage push funding (World Health Organization, Reference Organization2017b). It will be important to balance this shorter-term strategy with the need to maintain a steady inflow of novel drug candidates identified through early discovery programmes.

Lego-regulatory (legal or regulatory) pull incentives, like those offered by the EMA and FDA, are most effective at facilitating progress through the market approval stage. Both the EMA and FDA offer several incentives that decrease the approval timeline for antibiotics: regulatory guidance, expedited pathways, and conditional market authorization. The primary value of these incentives comes from indirectly increasing the effective patent period of the antibiotic since it reaches the market earlier (Mossialos et al., Reference Mossialos, Morel and Edwards2010). But, there is a balance to be struck between speeding up the approval process and ensuring that licensed drugs meet standards for quality, safety, and efficacy (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016). It is unlikely that these regulatory processes can be shortened any further without sacrificing regulatory standards. In addition, many of the pipeline antibiotics are not expected to be high-volume products and therefore adding to their effective patent period does not translate into meaningful revenue. Market exclusivity extensions suffer from this same problem. Therefore, it may be worthwhile to explore alternative incentives that allow priority review (e.g. priority review vouchers (PRVs)) or market exclusivity extensions (e.g. transferable intellectual property rights (TIPRs)) to be transferred from an approved antibiotic to another product in the developer’s portfolio that would benefit more from the longer effective patent period (Ferraro, Towse & Mestre-Ferrandiz, Reference Ferraro, Towse and Mestre-Ferrandiz2017). Incentives such as PRVs and TIPRs could provide a market incentive to license new antibiotics without requiring upfront government funding. However, it is important to be aware that PRVs and TIPRs do not incentivize antibiotic commercialization and they could have broader pharmaceutical market consequences (Mossialos et al., Reference Mossialos, Morel and Edwards2010; Ferraro, Towse & Mestre-Ferrandiz, Reference Ferraro, Towse and Mestre-Ferrandiz2017).

Harmonization between the EMA and the FDA’s market approval requirements has been a step towards lowering market approval costs and time. However, the EMA and FDA regulatory processes are relatively similar unlike the Japanese PMDA or Chinese Food and Drug Administration. Harmonization efforts among these agencies will prove more challenging but could further relieve companies of duplicative regulatory approval costs. Including the PMDA in TATFAR was a laudable starting-point.

Push funding and legal or regulatory incentives can drive viable antibiotics to licensing; however, they are weak incentives for the commercialization and distribution of the product. Net profits from sales of an innovative new antibiotic are perceived to be limited for several reasons, especially when compared to therapeutic areas with the highest sales revenues; for example, oncologic, anti-diabetic, and anti-rheumatic drugs (EvaluatePharma, 2017). A novel antibiotic would be reserved as a last resort or may only target a rare resistant pathogen, which restricts potential sales revenue. High product prices are unlikely to compensate for low sales volume because of the considerable overlap in effectiveness between existing antibiotics. Also, future rapid-point-of-care diagnostic tools could cut into the revenue potential for newly marketed antibiotics (Outterson et al., Reference Outterson, Powers and Daniel2015). Therefore, large outcome-based pull incentives are necessary in the absence of a viable market. Pull incentives have the added benefit of potentially allowing SMEs to secure venture capital for clinical trials. However, pull incentives for antibiotics have been mostly absent from current funding initiatives. The only outcome-based pull incentives currently available are relatively limited advanced market commitments (AMCs) offered by BARDA and GARDP for certain low-volume antibiotics (Simpkin et al., Reference Simpkin, Renwick and Kelly2017).

Market entry rewards (MERs) have repeatedly been recommended by major reports and journal articles as an effective pull incentive for antibiotic commercialization (Ferraro, Towse & Mestre-Ferrandiz, Reference Ferraro, Towse and Mestre-Ferrandiz2017; Rex & Outterson, 2017; Simpkin et al., Reference Simpkin, Renwick and Kelly2017; O’Neill, Reference O’Neill2016; Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016; Chorzelski et al., Reference Chorzelski, Grosch and Rentmeister2015). A MER is a financial prize for the successful development and licensure of an innovative antibiotic. To receive the prize, a developer must ensure that the antibiotic meets predefined product criteria and adheres to postmarket authorization conditions related to sustainability and patient access as specified by the payer. It is expected that a MER would need to be approximately $1–2 billion per first-entrant novel antibiotic to entice developers to invest in R&D and gamble on inventive antibiotic projects (DRIVE-AB, 2018). Practically, a prize of this size might be paid out as instalments over five to seven years. This would create a guaranteed revenue stream for the developer, spread out payer expenditures, and provide the payer with leverage if the developer chose to deviate from the agreed MER conditions. MERs can also be designed to have varying degrees of delinkage. Delinkage, in the context of a MER, refers to how much of a MER winner’s revenue can be generated from sales volume (Rex & Outterson, Reference Rex and Outterson2016). A fully-delinked MER would pay for the antibiotic patent or licence in return for access to the drug at the cost of production. A partially delinked MER would still allow developers to generate some revenue from antibiotic sales. A fully delinked MER would thus need to be much larger than a partially delinked MER. Numerous other design variations, stipulations, and augmentations can be applied to the basic MER model to achieve various market goals. However, this is beyond the scope of this chapter. Both the 2018 DRIVE-AB final report and the 2017 Office of Health Economics report offer in-depth discussion of and recommendations for MER design and costing (DRIVE-AB, 2018; Ferraro, Towse & Mestre-Ferrandiz, Reference Ferraro, Towse and Mestre-Ferrandiz2017).

The key barrier to implementing a MER programme is the cost. With the 10-year goal of bringing 10 to 15 novel antibiotics to market, a MER programme is estimated to cost between $10 and $30 billion (DRIVE-AB, 2018; Ferraro et al., Reference Ferraro, Towse and Mestre-Ferrandiz2017; O’Neill, Reference O’Neill2015a). Such a MER programme would provide large payouts of $1–2 billion for first entrants and increasingly smaller prizes for follow-up therapeutic products. A MER fund of this scale can only be practically achieved by pooling financial commitments from numerous countries and institutions into a ring-fenced endowment. For a MER programme to effectively pull antibiotics to the market, it is important that developers perceive this fund to be guaranteed by participating governments and protected from other public expenditures. This type of international fund for MERs has been recommended by various journal articles and international reports, such as the UK’s AMR review, the Boston Consulting Group’s report for the GUARD initiative, and DRIVE-AB (DRIVE-AB, 2018; Hoffman et al., Reference Hoffman, Caleo and Daulaire2015; Renwick, Brogan & Mossialos, Reference Renwick, Simpkin and Mossialos2016; Rex & Outterson, Reference Rex and Outterson2016; Stern et al., Reference Stern, Chorzelski and Franken2017; O’Neill, Reference O’Neill2016). Despite the abundance of expert literature calling for an international MER programme, no nation has been willing to take the lead in establishing such a global fund or make a firm financial commitment. This inaction stems from the large sums involved, insufficient political support, the complexity of coordinated action, and a lack of capacity and expertise to implement such a scheme. In lieu of a global MER programme, alternative outcomebased pull incentives could be applied such as corporate tax incentives, value-based pricing and reimbursement strategies, and national AMCs for bulk purchasing (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016). These strategies are generally weaker incentives but do not require the same upfront financial commitment as a MER programme and thus may be more politically palatable.

Global cooperation and communication will be essential to creating the described continuum of antibiotic incentivization. Presently, national governments, global institutions, nongovernmental organizations, and industry are independently investing their resources in antibiotic R&D projects and funding programmes (Renwick, Simpkin & Mossialos, Reference Renwick, Simpkin and Mossialos2016). This is partially responsible for the current mismatched and incomplete global incentives. In addition, many of the antibiotic R&D initiatives operate in isolation from other initiatives despite their commonalities. There is a clear risk of duplicating efforts with initiatives that have similar mandates and receive interweaving funding from different payers. Therefore, there is a need for a global governing body that can coordinate antibiotic R&D incentive programmes at an international level and guide their operation at national levels. This global governing body could establish a unified direction for international antibiotic R&D incentives and guide incentive programmes towards achieving a more balanced global R&D incentive profile. Having such an entity would also help ensure that broader AMR goals related to global sustainability, patient access, and medical need are reinforced by the individual incentives.

Other recent reports such as the UK Review on Antimicrobial Resistance (O’Neill, Reference O’Neill2016) have also referred to the need for a global body to coordinate, prioritize and mobilize resources for fighting AMR without defining how this might be established and what form it might take. The most concrete proposal emerged from the G20 summit in Hamburg in 2017 where G20 leaders called for “a new international R&D Collaboration Hub to maximize the impact of existing and new antimicrobial basic and clinical research initiatives as well as product development” (G20 Leaders’ Declaration, 2017). The Global Antimicrobial Resistance Collaboration Hub is now being established in Germany with support from the Bill and Melinda Gates Foundation and the Wellcome Trust but requires political and financial support from many countries if it is to become an effective international instrument against AMR. It is intended that the Hub will coordinate efforts to promote antimicrobial research and encourage global involvement and investment and that its scope will include all stages of the antimicrobial development pipeline, as well as vaccines, alternative therapies and new diagnostic tools. It will be open to all countries and to nongovernment donors. Members will be expected to release additional investment in national and/or international research, but there will not be a set tariff for involvement.

Conclusion

Adding innovative antibiotics to the treatment arsenal is a critical aspect to addressing the AMR crisis. Incentives are necessary for overcoming the multitude of scientific, regulatory, and economic barriers that impede progress through the entire antibiotic value chain. Over recent years, many international, European, and national-level incentive programmes have been implemented to foster the antibiotic value chain. These have helped to lift the clinical pipeline for antibiotics out of dormancy. However, the recent progress in R&D is not nearly sufficient to counteract the rapid advancement of resistance rates. The current global incentive package could be improved by ensuring that a continuum of incentives is offered to developers, reflecting the economic need, cost distribution, and barriers of the antibiotic value chain. A global governing body that provides overarching guidance to international and national-level incentive programmes will be necessary to achieving such a continuum and the establishment of the Global Antimicrobial Resistance Collaboration Hub is a promising initiative to make such a governing body a reality.