Integrating equitable access conditions into antimicrobial R&D incentive mechanisms

Aanika Dalal
Jun 2
11 min read

Updated: Jul 15

During the 2024 UN High-Level Meeting on Antimicrobial Resistance (AMR), stakeholders set an ambitious goal to achieve a 10% reduction in global AMR-related mortality by 2030. To achieve this, the political declaration set a sub-commitment to: “explore, encourage and promote a range of innovative incentives and financing mechanisms… including push and pull incentives, in the development of new health products and technologies, while committed to ensuring that mechanisms are in place for equitable access, particularly in developing countries” (United Nations).

This target identifies the need for policies that reinvigorate the antimicrobial research and development (R&D) pipeline—an issue that has been well-established in the recent decade (Boluarte and Schulze). However, much of the policy discourse has centred on the needs of high-income countries (HICs), largely neglecting the second component of this target: ensuring that there are policies and pathways in place to promote equitable global access.

Even when new antimicrobials are successfully developed, they rarely become widely accessible (Cecchini et al.). The vast majority of newly approved antimicrobials are registered only in HICs, meaning that even with a sufficiently robust antimicrobial pipeline low and middle income countries (LMICs) would still struggle to get access to the products that they need. Beyond the ethical imperative of ensuring equitable access, limited availability of essential antimicrobials in LMICs may actively contribute to AMR. Restricted access often leads to suboptimal prescribing practices, increased reliance on substandard or falsified medicines, and prolonged use of broad-spectrum antimicrobials—all of which accelerate resistance rates (Access to Medicine Foundation). Given that LMICs bear the majority of the AMR burden, ensuring sustainable antimicrobial availability will be essential to achieving the 10% mortality reduction target.

Although a range of interventions and policies will be necessary to comprehensively address global access challenges, one key component is the implementation of global access conditionalities—policy mechanisms that tie explicit access requirements to government and philanthropic funding and incentives for antimicrobial R&D and market shaping mechanisms. By integrating such conditions into both push funding and pull incentives mechanisms, policymakers can help ensure products are developed and reach populations with the greatest unmet need (Simpkin et al).

However, it is important to recognise that there are costs associated with providing access to antimicrobials and other medical products. These conditionalities must therefore be carefully designed to support equitable access without undermining the effectiveness of incentive mechanisms as drivers of innovation. To achieve this, it will be essential to make sure that incentive structures are sufficiently sized to accommodate these global access requirements and that additional funding streams are provided to support other critical activities such as paediatric drug development. Post-market entry incentives should be structured to include additional rewards for meeting access and stewardship requirements (or reducing incentive size when they are not met) (GHIAA).

Governments and funders must also complement these efforts through strategies such as pooled procurement, regulatory harmonisation, support for nonprofit drug developers, and public-private partnerships (Cohn et al.).

In this post, we analyse current precedents of access conditionalities and review existing literature emphasising the role of access conditions in antimicrobial R&D incentives. Based on this, we compile a set of recommendations detailing the types of conditions that could be included, their key components, and examples from which they can be modelled after.

Access and stewardship plans

Ensuring access to vulnerable patient populations and that products can be stewarded properly requires robust planning, long before these products come to market. During the development process, companies should consider, in detail, how they plan to provide access to and ensure stewardship of their products (G7 Health Ministers). These plans should be publicly accessible and include detailed descriptions of the methods used to meet predefined requirements around availability, pricing, registration and stewardship, as well as the frequency and approach by which compliance will be monitored and evaluated (Access to Medicine Foundation). Developers should work to identify the populations most likely to benefit from the product, where these populations are located, and any relevant demographic or clinical characteristics. This information should then be used to inform the list of territories that the developer intends to commercialise in (“target territories”) and territories that they have no plans to commercialise in (GHIAA).

Early planning to provide access to the most vulnerable populations can inform clinical trial design and relevant product formulations, reducing the need to carry out additional trials or make product alterations later in the development lifecycle. This approach ensures that access and stewardship are not afterthoughts, but fundamental components of antimicrobial development aligned with global health equity. This planning can also inform early interactions with national regulatory agencies, who should work collaboratively with developers to ensure their products can be quickly approved upon successful completion of clinical trials.

CARB-X, one of the largest funders of antimicrobial development, requires each of the companies it funds to develop a Stewardship and Access Plan and make it publicly available within 90 days of the product entering Phase 3 clinical trials. In collaboration with GARDP, Wellcome, the UK and US governments, and the Access to Medicines Foundation, they have developed a planning guide to support developers with this process (Access to Medicine Foundation).

Intellectual property management and licensing

Although intellectual property (IP) rights can play a key role in ensuring innovators can receive an adequate return on investment, it is well recognised that IP rights can create significant barriers to equitable global access of pharmaceutical products. In particular, IP rights often restrict the ability of alternative manufacturers to produce, register, and distribute affordable versions of the product in LMICs, even when originators have limited market penetration within these contexts (Oxfam America; Drugs for Neglected Diseases initiative).

To address this issue, public funding and incentives should come with requirements around management of IP and the use of early licensing to reach underserved patient populations. Entities with a global health focused mission, such as GARDP and Medicines Patent Pool (MPP), can play a crucial role in the licensing process and potentially distribute the product in any territories where the developer doesn’t intend to commercialise. These licenses should be non-exclusive, containing the right to sub-license, and the developer should support any out-licensing partner with technology transfers to enable the partner to manufacture, register and supply the drug within the territories it is responsible for. Based on countries’ income-level, moderate and tiered royalties might be appropriate (Cohn et al.).

An example of this type of IP management is the antimicrobial license agreement between GARDP, the Clinton Health Access Initiative (CHAI), and Shionogi for cefiderocol in 135 countries. Under this agreement, GARDP will manufacture and commercialise cefiderocol through sub-licensees in a large range of countries that would usually have delayed access (if any) to newer antimicrobials (GARDP). Bugworks, a CARB-X portfolio company, also recently granted GARDP a license to manufacture and commercialise its antimicrobial BWC0977-IV in 146 countries.

Price and supply framework

Affordable pricing is very often a barrier to access to new antimicrobials (and other medicines) within LMICs. Given this, developers should ensure fair pricing structures for antimicrobials while also working to achieve a robust and sustainable supply chain, particularly in LMICs (G7 Health Ministers).

If the developer wishes to commercialise the product within LMICs, the drug should be provided at cost plus pricing. To make this approach more efficient and enforceable, funders should pre-define what types of costs should be included in the calculation of cost of goods (COGs) or manufacturing. Funders should also require audit rights which would enable them to verify that the final price of the product has been calculated in accordance with the agreement. Over time, developers should make reasonable efforts to reduce the COGs and these pricing benefits should be passed onto LMICs as part of the cost-plus pricing scheme. To make such pricing models viable, other funding mechanisms (e.g., pull incentives within HICs) must provide sufficient financial returns to developers (GHIAA).

A precedent for this comes from a 2020 agreement between the AXA Prime Impact Master Fund and Revelation Biosciences, which required the company to make its therapeutic for allergic rhinitis and diagnostic products for respiratory virus infections available to non-profit and public-sector purchasers in LMICs at no more than 30% above COGs (GHIAA).

Registration framework

Developers should ensure that their products are registered in all intended commercial territories within an agreed timeframe (G7 Health Ministers). Within LMICs, prioritisation should be given to those with the highest burden of disease the drug is indicated for. Specifically, developers should:

Provide a clear list of target territories for commercialisation.
Ensure product registration in all listed markets within an agreed timeframe.
Independently, or in collaboration with non-profit partners or funders, conduct:
- Studies in paediatric and neonatal populations
- Studies generating real-world evidence, especially in LMIC-relevant settings and for resistant infections.
Where appropriate, pursue registration through the WHO Prequalification Programme and/or the WHO Collaborative Registration Procedure to expedite national regulatory approvals.
Develop compassionate use and named patient programs to support access to critically ill patients before full registration can be achieved

Given the high costs that can be associated with some of these activities, these requirements would be addressed with support from public-private partnerships who can help strengthen regulatory capacity through the establishment of clinical trial networks and streamlined registration processes (Cohn et al; Laxminarayan).

Transparency

To support accountability and fair access, developers should ensure transparency across all key aspects of product development and commercialisation. This includes:

Disclosing all sources of public funding received during the development of the drug (DRIVE-AB). This aligns with requirements currently proposed in the European Commission’s framework for an EU pull incentive.
Providing auditable COGs reports for LMIC supply, enabling fair pricing assessments. Funders and designated third parties should retain rights to verify these cost calculations. (GHIAA)
Making publicly available the licensing agreements and any related global access and stewardship plans, to promote consistency with global health objectives and facilitate external scrutiny.(Access to Medicine Foundation)

Together, these measures would help ensure that publicly supported innovations are made accessible under fair and transparent terms, especially in LMICs.

Paediatric development

Because paediatric market approval can lag behind adult approval by up to a decade, developers should prioritise the early development of paediatric formulations. Wherever feasible, paediatric development should occur concurrently with adult development, particularly for diseases that disproportionately affect children. (Access to Medicine Foundation; DRIVE-AB).

Environmental standards

To minimise the environmental drivers of antimicrobial resistance, developers should adhere to the AMR Industry Alliance’s Antibiotic Manufacturing Standard. This includes implementing appropriate waste management, discharge limits, and environmental controls during the manufacturing process to ensure that production does not contribute to the emergence or spread of resistance. (AMR Industry Alliance; Cama et al.)

Stewardship framework

Developers should implement appropriate stewardship strategies to preserve the effectiveness of their product and reduce the risk of resistance (Access to Medicine Foundation). These strategies must be tailored to the specific challenges of LMICs, including limited surveillance capacity, financial and health system constraints, and workforce shortages and work alongside existing national and global programs (Shamas et al.). This could include:

Prohibiting financial incentives for employees or organisations based on sales volume
Requiring monitoring and sharing global post-marketing resistance data, particularly through platforms like Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the AMR Register
Prohibit promotion or expansion of use for inappropriate or unnecessary indications
Support or establish surveillance systems to track resistance trends and inform mitigation strategies

Furthermore, if an appropriate diagnostic is already available, developers should submit a plan for its responsible use alongside the antimicrobial. If no such diagnostic exists, where relevant, they should collaborate with partners such as the Foundation for Innovative New Diagnostics (FIND) to develop suitable diagnostics to support stewardship of their product.

In partnership with global stakeholders, developers should help facilitate appropriate information sharing to ensure existing surveillance and stewardship infrastructure has adequate knowledge about the product to track resistance over time. Costs associated with stewardship and surveillance should be earmarked within pull funding to prevent access requirements from undermining innovation.

Next Steps

The lack of timely and affordable access to effective antimicrobials is a key driver of resistance worldwide (Access to Medicine Foundation).To address this challenge, global policies must support a mutually reinforcing mix of research and development, equitable global access, and responsible stewardship. Ensuring that effective antimicrobials reach not just HICs but also vulnerable populations and regions with high unmet needs is critical to managing the AMR crisis on a global scale.

In this post, we explored the role of access conditionalities in facilitating equitable global access to novel antimicrobials and the types of conditions which should be included. However, significant further analysis is needed to address the practical aspects of their implementation. Future work could focus on conducting economic modelling to estimate the cost of meeting different types of access requirements (e.g., paediatric formulation development, registration in LMICs, technology transfer for licensing). These cost estimates would help inform how funding levels and incentive structures should be adjusted to ensure that access requirements do not compromise the effectiveness of R&D funding and incentives. In parallel to this, it will be important to engage directly with developers, especially SMEs, to understand operational constraints and identify supportive structures that encourage participation without disincentivising innovation.

With the goal in mind of ensuring access to effective antimicrobials for everyone who needs them, regardless of location or demographics, properly considered conditionalities could lay out the framework which developers and partners work to. Ultimately, the integration of access conditionalities into antimicrobial R&D funding and incentive mechanisms is not a silver bullet. However, it is a necessary step towards ensuring that investments in antimicrobial innovation translate into tangible global health impact.

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