MAPGuideⓇ
Equitable Access Toolkit
How Are Access Plans Included in
Funding Agreements?
As shown in GHIAA’s Equitable Access Pyramid, there are many ‘access provisions’ that need to be considered to achieve the objective of making a funded product sustainably affordable and available to all those who need it. An access plan can be a key tool in establishing and coordinating the concrete actions that a product developer will take as part of its development and commercialization activities to achieve equitable access to a safe and efficacious final product.
Access plans often include considerations related to a number of the building blocks of equitable access, including achieving a cost of goods that meets affordability requirements, developing a product with an appropriate profile for target countries, sustainably manufacturing a sufficient volume of the product to meet demand, and obtaining the required regulatory approvals.The activities detailed in the access plan can be used to identify key project milestones and performance metrics against which the impact of a funded project can be monitored and measured.
Some funding agreements specifically require the creation of an access plan or strategy, whereas others integrate this concept into broader product development, manufacturing and supply, or marketing plans. Initial plans are incorporated into some funding agreements as an annex, but other agreements take the approach of requiring the developer to establish a plan at a later stage (for example, reaching a certain clinical trial phase). In either case, both the funder and developer should consider an access plan as a ‘living’ document which evolves along with the product development process. Reviewing and updating this ‘living’ document is often the responsibility of the joint project steering committee or a similar governance body.
To further define Your Global Access commitments, You are required to complete a Global Access Strategy and any other Global Access activities and documentation listed in the Reporting & Payment Schedule. The Global Access Strategy should address the following concepts with respect to all Funded Developments: (a) identification of Background Technology at the outset of the Project and any Funded Developments created during the Project and specific strategies to ensure access to such Funded Developments and Background Technology; (b) agreements and/or procedures for transfers of materials and data among Project Collaborators or third parties relevant to the Project; (c) reporting processes for the creation of Funded Developments to both the Project management team and to the Foundation as well as the publishing and dissemination of the knowledge and information gained from the Project; (d) strategies to secure, manage and allocate intellectual property rights associated with the Funded Developments or Background Technology in a way that ensures Global Access while providing incentives for future potential private sector participation; and (e) anticipated development, commercialization and sustainability strategies during and after the Project to ensure that Global Access can be met.
Source: taken from a grant agreement between the Bill & Melinda Gates Foundation (Funder) and Arsanis (Developer) for the preclinical development of a monoclonal antibody treatment for respiratory syncytial virus infections. Read in context.
The [Developer] will work with the [Funder] to develop (by the time of completion of Phase II clinical trials) and execute a manufacturing and supply plan that will enable to be met the reasonably expected demand in Developing Countries for any Products. […] The manufacturing and supply plan could involve the use of manufacturing partners and support from donors, and the specific level and allocation of funding responsibilities in such plan will be decided as mutually agreed in good faith in writing by the parties based on a fair allocation of the expected benefits between Developing Countries and developed countries.
Source: taken from a strategic relationship agreement between the Bill & Melinda Gates Foundation (Funder) and Arsanis (Developer) in connection with an $8 million investment by the Foundation to support a Staphylococcus aureus antibody development program. Read in context.
When its Product enters Phase III trials (or Phase IIb trials, if they are intended as the pivotal trials to support registration, or otherwise, when the [Developer] is preparing a Product that is not a therapeutic or preventative for First Approval as defined in Section [x] below), the [Developer] shall create and provide to the [Funder] within ninety (90) days, a plan reasonably describing how it intends to meet the above stewardship and access obligations for the Product, (the “Stewardship and Access Plan”). The Stewardship and Access Plan shall not include confidential business information and shall include:
(i) Strategy to support access and stewardship (e.g. proposed reliable production with sufficient capacity, supply systems, the broad approach to product labelling, and the broad approach to ensure economic barriers to access are as low as reasonably possible);
(ii) Identifying obstacles and constraints to access and stewardship;
(iii) Exploitation strategy for Project IP Rights, including whether it is planned for the Project IP Rights to be transferred to a third party;
(iv) Strategy to ensure marketing approvals are received for key territories in a timely manner; and
(v) Strategy for monitoring effectiveness of access and stewardship, including proposed metrics to measure success.
The Subrecipient shall update the Stewardship and Access Plan and provide it to the PTE when the Product is first approved by any of the FDA, EMA (or national authorities), or Japan’s PMDA (the “First Approval”). After First Approval, the Stewardship and Access Plan shall be updated if there are significant market or product changes, or if events so require. The Subrecipient shall use best reasonable efforts to comply with its Plan at all times.
The Stewardship and Access Plan will be a non-confidential document and will be publicly posted on the [Funder] website.
Source: taken from the template CARB-X (Funder) cost-reimbursement agreement with subrecipients (Developer) for the early stage development of antibiotics, vaccines, and rapid diagnostics against bacterial threats. Read in context.
Within six (6) months of the Effective Date or such longer period as may otherwise be agreed in writing (including by email), the Parties shall agree a detailed Manufacturing and Supply Plan for the supply of the Drug Product through the JSC. The Manufacturing and Supply Plan shall be based on the following principles:
the Parties shall develop a detailed forecasting, supply, access and implementation plan for the supply of the Drug Product and define related operational supply chain management processes to ensure availability and access of the Drug Product in the Field with the consultation, as appropriate, of one or more funding agencies or partners, e.g., the World Health Organisation; […]
Source: Taken from a collaboration agreement between DNDi/GARDP and Entasis for the development of Gonorrhea medication. Read in context.
Within [timing] the [Developer] shall deliver to [Funder] a Marketing Plan which will describe the [Developer]’s planned activities to make the Product available for stockpile in accordance with the definition of “Market” or otherwise in preparation for an Outbreak or Increased Outbreak Preparation Need. […]. The [Developer] shall review and, where appropriate, update the marketing plan at least once every calendar year and will deliver to [Funder], not less than one (1) month prior to the commencement date of the revised marketing plan, the revised marketing plan together with an update on the implementation of the marketing plan.
Source: taken from an anonymized product development funding agreement. Read in context.
The Global Access Coordinator, who shall initially be [Name] (or another person mutually agreeable to the [Developer] and [Funder]), will lead the Company’s efforts to market the Products to Global Health Purchasers in Target Countries and to ensure overall customer success in Target Countries, in accordance with a plan to be prepared by the Global Access Committee on or prior to [date – 3 months after effective date] (the “Global Access Plan”). The activities of the Global Access Coordinator, which activities shall be consistent with the Global Access Plan, shall be overseen jointly by the [Developer]’s senior management and the Global Access Committee.
Source: taken from a global health agreement between the AXA Prime Impact Master Fund (Funder/Investor) and Revelation Biosciences (Developer) for the development of a therapeutic for allergic rhinitis and a diagnostic for respiratory virus infections. Read in context.
Commitment to Equitable Access. [Funder] is committed to achieving equitable access to the results of all [Funder]-supported programmes pursuant to the “Equitable Access Policy” referenced in [Funder]’s Third Party Code. Equitable Access means that a Project Vaccine is available first to populations at risk when and where they are needed at affordable prices. For clarity, it is [Funder]’s intention that the price of a Project Vaccine shall be commercially sustainable to the manufacturer.
Project Vaccine Registration. [Developer] shall cooperate with [Funder], and at [Funder]’s cost, take such actions as are mutually agreed to register Project Vaccines in countries identified as priorities. If [Developer] is not the license holder for purposes of registration in a given country, then [Developer] shall be responsible for ensuring that its Subawardee facilitate such registrations as requested by [Funder]. [Developer] shall utilize WHO pre-qualification or similar registrations systems to the extent available.
Global Allocation. It is the Parties’ expectation that a global allocation and purchasing entity (the “Global Allocation Body”) shall be constituted within six (6) months after the Effective Date of this Agreement to purchase, allocate, and direct the distribution of COVID-19 vaccines including Project Vaccine. [Developer], will negotiate, in good faith a separate agreement or purchase order to supply Project Vaccine as may be required by the Global Allocation Body in such agreement or purchase order to the Global Allocation Body during the Pandemic Period and after the Pandemic Period for LMICs. For the purposes of this paragraph “Pandemic Period” means the period of time between the date that WHO declared COVID-19 to be a PHEIC [Public Health Emergency of International Concern] (that is, 30 January 2020) and the date that WHO declares the PHEIC to have ended including any period of a COVID-19 pandemic re-emergence as declared by the WHO.
Pandemic Period Production and Supply. During the Pandemic Period, Awardee shall:
(a) produce Project Vaccine as described in the Work Package(s), if not greater;
(b) provide the JMAG with a regularly updated [***] statement of its actual capacity and a forecast of its planned capacity for manufacturing of Project Vaccine;
(c) provide the JMAG with [***] advance written notice of each manufacturing run for the Project Vaccine;
(d) supply up to [***] of the quantity of the Project Vaccine produced for purchase by the Global Allocation Body pursuant to Clause [x – Global Allocation Body] during the Pandemic Period. For clarity, Awardee may not allocate or obligate Project Vaccine doses to other third parties during the Pandemic Period that conflicts with its obligations under this Clause [x]; and
(e) discuss in good faith with JMAG how to achieve its requirements for doses of Project Vaccine, including any potential increase in Awardee’s manufacturing capacity.
Post-Pandemic Period Production and Supply. After the Pandemic Period, Awardee shall continue to produce and supply Project Vaccine for purchase as required by the Global Allocation Body pursuant to Clause [x – Global Allocation Body].
Pricing Objectives. The Parties acknowledge that the price of the Project Vaccine is critical to achieving Equitable Access during the Pandemic Period. Accordingly, Awardee agrees that its pricing shall be reasonable to achieve Equitable Access for populations in need of a Project Vaccine as well as an appropriate return on investment for vaccine manufacturers that make on-going supply commercially sustainable. The Parties acknowledge that the availability of pandemic insurance as described in Clause [x] shall be a relevant cost factor in Equitable Access. For clarity, the purchase of Project Vaccine by the Global Allocation Body or by any other purchasing agent(s) designated by CEPI shall be considered to have satisfied the pricing requirements for Equitable Access.
Costs and Sales. Consistent with the commitments in Clauses [x to x – above], Awardee shall:
(a) provide written [***] updates to the JMAG regarding its COGs for Project Vaccines and discuss relevant product development decisions that could affect COGs; and
(b) sell the Project Vaccine doses to the Global Allocation Body during and after the Pandemic Period pursuant to Clause [x – Global Allocation Body].
Information about Production, Supply, Pricing and Sales. Upon written request by [Funder], Awardee shall provide reasonable information about its COGs, production, supply, pricing and sales of Project Vaccine sufficient to evaluate whether such activities meet the Equitable Access Policy.
Audit of Cost of Goods. No more than [***] and at [Funder]s reasonable cost, [Funder] shall have the right to review or to designate an external auditor (which shall be an internationally recognized certified public accounting firm, not engaged on a contingent basis) to review Awardee’s financial records relevant to the information provided in Clause [x – information about production, supply, pricing and sales]. Such audits will be conducted during normal operating hours in a manner to minimize disruption to Awardee’s business. In event that the audit concludes that the COGs and production, allocation, supply or pricing of Project Vaccine doses are not substantially in accordance with the achievement of Equitable Access as described in Clause [x – commitment to equitable access], then Awardee shall: [***]. The provisions of this Clause [x] shall apply to any Sub-Grant Awardees and Trusted Collaborators.
Manufacturing in Multiple Countries. Awardee shall use [***] to establish operational manufacturing facilities in one or more geographically dispersed manufacturing sites as described in the Work Packages.
Equitable Access Plan. The foregoing commitments regarding Equitable Access shall constitute the “Equitable Access Plan.” This Equitable Access Plan shall be reviewed by JMAG no less than annually and shall take into account changes in COGs over time, production yield and volume and production economics. The Equitable Access Plan shall be regularly updated during the term of this Agreement.
Source: taken from a development funding agreement between CEPI (Funder) and Novavax (Developer) for a COVID-19 vaccine. Read in context.
Example considerations for access plans
Access plans related to funding agreements have most often been treated as confidential documents that are not publicly shared and are redacted from agreements disclosed in accordance with SEC filing or freedom of information requirements. However, there are sources of information that provide examples of specific actions that can be, and have been, included in access plans.
Stewardship and Access Plan Development Guide
The Stewardship and Access Plan Development Guide (“the Guide”) was produced to support CARB-X funding recipients with the development of a Stewardship and Access Plan (SAP) in accordance with the terms of CARB-X’s funding. The terms state that developers must provide a SAP to CARB-X within 90 days of a funded product entering pivotal clinical trials (Phase 2b or 3). These SAPs will be made publicly available on CARB-X’s website.
The Guide, which was developed by a cross-sector working group, is endorsed by the Wellcome Trust and other CARB-X funders. Some of the considerations set out in the Guide are most readily applicable to antimicrobial resistance (AMR) products and funding agreements with a structure similar to that of CARB-X, but many elements are useful to funders and product developers more generally seeking guidance on the development of access plans.
The Guide identifies the following key areas to be addressed in a SAP:
- Product description – The product description includes details of the product indication(s), target population and conditions for use.
- Identification of obstacles and constraints to stewardship and access – Obstacles and constraints may include factors such as the availability and cost of raw materials, or manufacturing and scale-up challenges. The identification of potential challenges should include factors within and outside of a developer’s control, as well as consideration of issues that may arise later in the development process.
- Strategies for timely marketing approvals – The establishment of an effective strategy could include identification of the expected sequence of marketing applications, plans for additional clinical trials for specific indications or vulnerable populations, and plans to use accelerated registration mechanisms such as the WHO’s collaborative procedures.
- Strategies for supporting global stewardship and access across territories – Recipients of CARB-X funding can identify the territories in which they do and do not intend to market the funded product. The funding recipients are required to consider strategies to support stewardship and access even in the territories where they will not market the product. This could include consideration of factors such as pricing and marketing strategies, out-licensing and tech transfer, partnerships with purchasing organizations, supply chain and manufacturing strategies, surveillance systems, educational programmes, and diagnostic test development.
- Strategies for project intellectual property rights – CARB-X funding recipients are required to consider how they intend to prevent intellectual property rights from creating barriers to access, particularly in territories where they will not market the funded product. Strategies may include partnerships or licensing agreements with third parties such as GARDP or the Medicines Patent Pool (MPP).
- Strategies for monitoring the effectiveness of stewardship & access activities – The Guide notes that the Access to Medicine Foundation (ATMF) publishes an AMR Benchmark report which will identify whether the product developer has implemented the activities detailed in the SAP following first registration of the product. CARB-X funding recipients are encouraged to work closely with ATMF.
The Access to Medicine Index
The Access to Medicine Foundation, which also supported the development of the SAP Guide discussed above, identifies best practice approaches used by the pharmaceutical companies within the scope of the Access to Medicine Index (“the Index”). ATMF indicates that access plans developed for products supported by funding from global health funders are generally of higher overall quality, although it does not specify which examples are directly related to funding agreements.
While they may not be a direct product of obligations under funding agreements, the best practices identified in the Index can be useful for funders and product developers seeking examples of concrete actions that can be included in an access plan. These examples include:
- Product profiles that meet patient needs – as discussed in more detail here, consideration of a product profile that is appropriate for patients in lower-income settings is an important factor in supporting equitable access. Strategies for addressing the specific needs of target populations should be built into an access plan.
ATMF highlights the approach of Novo Nordisk, which acted on research from Médecins Sans Frontières and the University of Geneva to re-evaluate the thermal stability of its human insulin products. Novo Nordisk is now making submissions to regulatory authorities in more than 50 countries to revise storage guidance so that the insulin can be stored at up to 30°C without refrigeration for four weeks before opening, instead of needing to be stored in a refrigerator.
The Index also provides details of GSK’s activities to adapt product packaging and brochures for an antibiotic product. The adaptations included bespoke blister packaging for use in high humidity environments, an AI-enabled chatbot to educate patients in low-literacy regions, and oral suspensions and flavored dosing syringes for children.
- Product registrations – ATMF has emphasized the importance of broad and timely registration of products in low- and middle-income countries (LMICs). As discussed in more detail here, product development funding agreements often require funded developers to obtain regulatory approvals for certain markets, although the detailed strategies for timely product registration in each relevant market need to be established in an access plan. As a further action to be considered for access plans, ATMF notes that there is limited tracking of product registrations in low-income countries and that increased transparency is needed in this area. Johnson & Johnson is given credit as the only company in the scope of the Index to have publicly disclosed the list of countries in which it has registered its multidrug-resistant tuberculosis (TB) medicine.
- Partnering to reach patients – Establishing partnerships with local and international organizations seeking to increase access to medical products in a certain field or in certain communities is an important part of planning to ensure that products can reach the patients who need them. Identification of opportunities for such collaborations should be identified as part of the development of an access plan.
ATMF highlights the example of Bayer, which collaborated with the Population Council to create the public-private ICA Foundation. Through the ICA Foundation, Bayer supports the donation and distribution of a Bayer-manufactured contraceptive product in resource-poor settings. The product was originally developed through a collaboration between Bayer and the Population Council.
- Voluntary licensing and technology transfer agreements – As discussed in more detail here, some product development funding agreements require the funded product developer to partner with another manufacturer to support the achievement of pricing and supply requirements for lower-income markets. These provisions also include obligations around technology transfer to ensure that the third party manufacturer is able to successfully produce the funded product. But opportunities for voluntary licensing and technology transfer arrangements should be considered as part of an access plan even if the product developer is not specifically required to do so.
The Index highlights Novartis’ recent agreement with the MPP as setting a ‘precedent’ in licensing an innovative, on-patent cancer medicine. While not the only option for partnering, ATMF notes that working with the MPP can help developers to establish transparent license agreements with appropriate conditions for facilitating equitable access. Other best practice examples related to voluntary licensing in the Index include Viiv Healthcare’s agreements with Mylan and Aurobindo in India to expedite development of more affordable pediatric formulations of its HIV combination product, as well as several companies engaging in technology transfers for the local manufacturing of antibiotics.
- Healthcare capacity strengthening – As well as planning for partnerships that can support patient access to products, product developers need to consider the capacity of local healthcare systems for distribution and administration of the product, particularly in lower-income countries. Access plans should assess specific needs and identify concrete actions to support governments and local organizations in strengthening their capacity.
ATMF highlights the work undertaken by Novo Nordisk to establish the Changing Diabetes in Children (CDiC) program, with the aim of improving access to care for children with type 1 diabetes in LMICs. CDiC collaborates with governments, local partners and other organizations to raise public awareness of diabetes, strengthen healthcare capacity and increase access to human insulin.
- Measurement and disclosure of outcomes – as discussed in more detail here, it is important for global health funders and product developers to be able to measure the impact of their activities and investments. Access plans should address the intended approach to monitoring, evaluating, and disclosing the fulfillment and outcomes of activities intended to support equitable access.
Through a case study on Novo Nordisk’s CDiC initiative, ATMF raises the opportunity for product developers to use third parties to conduct independent assessments. Further, a commitment to transparency by publicly disclosing the findings of such an assessment provides a foundation for future learnings and improvements to access strategies.
Related Commentaries
Access plans are a key tool for ensuring the achievement of the equitable access objectives of a product development funding agreement, in particular:
This toolkit has been built based on the data in the MAPGuide and the GHIAA team’s experience of negotiating and implementing agreements. We intend that the toolkit will evolve and expand over time based on input from MAPGuide users and availability of new agreements showing examples of alternative approaches. We welcome ongoing constructive dialogue around these materials and encourage you to contact us or fill in our feedback survey to share your thoughts, questions and suggestions.
Author: Bridie Telford
First publication date: December 7, 2022
Last updated: January 27, 2023
