Providing for Health Emergency Response in Funding Agreements

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Equitable Access Toolkit

Providing for Health Emergency Response in Funding Agreements

Funding agreements for health products or technologies with known or potential applications as medical countermeasures against disease outbreaks, epidemics, or pandemics may include provisions intended to support rapid and equitable response to such health emergencies. Some key considerations for these provisions are:

Response triggers

A common approach to triggering health emergency response obligations in funding agreements is by linking them to the declaration of a PHEIC by WHO or a similar declaration by a national or regional public health authority. An additional mechanism used in some agreements is to allow the funder to identify a state of “increased preparation need” to enable the start of response-related activities prior to an official declaration by a public health authority.

Access to investigational product

Provisions related to the manufacturing and stockpiling of investigational product can facilitate the rapid start of clinical trials during a public health emergency. These provisions may address questions including who can direct use of the investigational stockpile, the circumstances under which it can be used, the expected stockpile volume and location(s), and how it will be paid for.

Access to approved product

Funding agreements often include supply commitments that require funded partners to reserve a specified volume or proportion of total production capacity of a funded product for supply to public health purchasers. An additional approach that may be used to support emergency response is a requirement for the funded partner to manufacture a product stockpile to be distributed as directed by the funder or another party selected by the funder.

Agreements may also include enforcement and continuity mechanisms, such as a requirement to identify, and conduct a technology transfer to, one or more third party manufacturers that could provide additional manufacturing capacity if a funded partner is unwilling or unable to meet demand during a public health emergency.

Project scope changes

Some funding agreements include mechanisms for alterations to the scope of activities if required to support health emergency response, along with corresponding adjustments to the amount of funding. Some examples include:

- A right for the funder to request additional product development and/or commercialization activities;
- Agreement from the funded partner that it will not proceed with a clinical trial in an outbreak if there is a limited pool of potential trial participants and an alternative product is deemed to have greater potential for success;
- A requirement for the funded partner to cooperate with, and making information available to, global or regional, or national coordination mechanisms; and/or
- A requirement for the funded partner to make data and materials rapidly available to the research community, including in accordance with outbreak response protocols such as the WHO 2016 Guidance for Managing Ethical Issues in Infectious Disease Outbreaks and WHO 2016 Guidance Good Participatory Practices in Trials of Interventions Against Emerging Pathogens.

In some cases, the funder may also commit to undertaking activities in parallel with the funding agreement to support the funded partner’s emergency response activities. For example, facilitating access to raw materials and consumables or supporting accelerated regulatory approval pathways.

Examples from the MAPGuide

Response triggers

Outbreak based on public health agency declaration; increased preparation need determined by funder

“Increased Outbreak Preparation Need” means when, having considered all reasonably accessible and relevant information including epidemiological data, travel and migration patterns and the likely availability of other products or product candidates, [Funder] determines, in its sole discretion in consultation with experts (for example a sub-group or subcommittee of [Funder]’s Scientific Advisory Committee that [Funder] determines has appropriate expertise), that there is a heightened need for the Product to address potential Outbreaks.
“Outbreak” means a Public Health Emergency of International Concern declared by WHO, or a public health emergency on a national or regional scale declared by one or more public health agencies, in each case as a result of a material increase in the number of cases of people infected with [Disease] including any regional out-break, an epidemic or a pandemic.

Source: taken from a USD $23.4 million funding agreement between CEPI (Funder) and Valneva (Developer). Partner types: philanthropic funder, industry; Product type: Chikungunya vaccine; Development stage at signature: phase 3 clinical trials. Read in context.

Access to investigational product

Ready Reserve for further development and emergency use; option for delegation to WHO

[Funder] may instruct and fund [Developer] to undertake the manufacturing and maintenance of a Ready Reserve of Clinical Trial Material through an additional Work Package, which may include doses from consistency batches if so directed by [Funder]. For purposes of this Agreement, a “Ready Reserve of Clinical Trial Material” means a quantity of doses for potential use in a clinical trial, which [Product] has not yet received a marketing approval. Such Ready Reserve of Clinical Trial Material may be used for further clinical trials, to advance product development and for emergency use subject to obtaining all necessary regulatory approvals and consents, in each case in emergency situations based on national or international guidance (such as from WHO) or in such other manner, in each case as [Funder] may reasonably determine. If required by [Funder], an additional Work Package covering such activities shall be negotiated expeditiously and in good faith by the Parties.
Management of Ready Reserve. The Parties agree that [Funder] may delegate the management of the Ready Reserve of Clinical Trial Material to WHO or another [Funder] designee, at its discretion.

Source: taken from a development funding agreement for up to USD $33 million between CEPI (Funder) and Variation Biotechnologies (Developer). Partner types: non-profit funder, industry; Product type: COVID-19 vaccine; Development stage at signature: early stage development. Read in context.

Funder right to direct use of investigational product

Once an Outbreak Notice has been provided, [Funder] shall have the right to direct how any Product manufactured pursuant to Clause [x – investigational product stockpiles] may be used and to whom it may be provided.
Investigational Product Stockpiles. Following the successful completion of a Phase 2 clinical study supported under the Project, [Funder] may request that Awardee undertake, at [Funder]’s expense, the manufacturing of a stockpile of Investigational Product. Such Product may be used for further clinical trials in Outbreak conditions to advance vaccine development, or pursuant to an emergency use authorization, in each case in emergency situations based on national or international guidance (such as WHO). An additional Work Package covering this activity will be negotiated expeditiously and in good faith by the Parties.

Source: taken from CEPI’s (Funder) template funding agreement for its CfP3(i) funding call, supported by the European Commission’s Horizon 2020 programme. Partner types: non-profit funder; Product type: Rift Valley Fever and Chikungunya vaccines; Development stage at signature: early- through to late-stage clinical development. Read in context.

Access to approved product

Safety stock

Within [***] of receipt of marketing approval for the Product from the FDA, [Developer] will produce, at [Developer]’s own cost, a [***] safety stock comprised of not less than two hundred thousand (200,000) doses of final Drug Product. For clarity, [Developer] will use commercially reasonable best efforts to keep such deadline of [***], however, it will be subject to the lead times of [Developer]’s contract manufacturers and the time required for the release testing of the Product. [Developer] may use such safety stock to supply the [Developer]’s Traveler’s Market and will replenish such stock on a rolling basis at [Developer]’s cost. The stock in paragraph [x] and this paragraph [x] is referred to as (“Safety Stock”).
In case of an Outbreak or Increased Outbreak Preparation Need, [Funder] may utilize such Safety Stock in the Affected Territory by giving notice in writing to [Developer] and [Developer] will dispatch all or some only of the Safety Stock, as instructed by [Funder] and [Funder] shall pay any reasonable costs incurred in connection with the utilization of the Safety Stock, including but not limited to transportation, distribution and storage in the Affected Territory. For clarity, [Developer] shall make no charge for the supply of the Safety Stock allocated to and used by [Funder] in accordance with this paragraph 15.2 (iii) and the storage costs of such Safety Stock, incurred prior to dispatch to the Affected Territory, shall be borne by [Developer].
If the Safety Stock is used by [Funder] in the case of an Outbreak or Increased Outbreak Preparation Need, [Funder] or such third parties as [Funder] may nominate shall be responsible for the costs of transportation of such Safety Stock from [Developer]’s facility. If, following the use of the Safety Stock as directed by [Funder], [Funder] wishes to replenish the Safety Stock, [Developer] shall produce such quantities of Product as are required to replenish the Safety Stock and [Funder] shall pay [Developer] for the costs of the production of such Product.
[Funder] will notify [Developer] in writing in the event of an Outbreak or if there is an Increased Outbreak Preparation Need, in each case identifying the Affected Territory (“Outbreak Notice”). Once an Outbreak Notice has been provided by [Funder], [Funder] shall have the right to direct how the Safety Stock referred to in Clause [x] or any Product manufactured pursuant to Clause [x – preparation for outbreaks] may be used and to whom it may be provided in the Affected Territory. […]

Identification of "trusted collaborator" by end of phase 2:

At the time that Awardee submits a Phase 2 study report to [Funder] (or at any earlier time), Awardee will propose a third party, for example, a Sub-Awardee, as a preferred alternative to itself (“Trusted Collaborator”), that is capable of performing the work and would be prepared to undertake activities pursuant to Clauses [x] in the event that Awardee declines [Funder]’s request to do so, or if Awardee and [Funder] do not reach agreement on a new Work Package. Alternatively, [Funder] may propose a Trusted Collaborator to Awardee. Neither Party may unreasonably decline to accept the designation of a proposed Trusted Collaborator.
As described in the IPDP, or otherwise upon designation of a Trusted Collaborator pursuant to Clause [x], Awardee will promptly and diligently provide all necessary guidance, information, materials and assistance reasonably required by the Trusted Collaborator to accomplish the activities that may be requested by [Funder] under Clauses [x] (“Technology Transfer”) at [Funder]’s reasonable cost.

Technology transfer if certain triggers are met

To the extent such technology transfer has not already occurred, at such time as is mutually agreed between the Parties, and on such terms as agreed between the Partner and the relevant third party, acting in good faith, each Partner shall use all reasonable endeavours to transfer or grant licenses or sublicenses to its Background IP, Project Data and Project IP (including, for the avoidance of doubt, all product data, product dossiers, and regulatory submissions submitted to a Regulatory Authority in relation to the Project Vaccine) necessary for the manufacture of the Project Vaccine to a Selected Manufacturer to manufacture such vaccines to address an Outbreak or Increased Outbreak Preparation Need, provided that the foregoing obligations shall apply only if:
(i)[Funder] reasonably anticipates that the Partners cannot meet[Funder]’s good faith and reasonable estimate of the anticipated demand of public-sector customers in, or purchasing on behalf of, LMICs, in the timeframe required to address an Outbreak or Increased Outbreak Preparation Need and at a price consistent with the pricing provisions contained in Clause [x]; and
(ii) the Partners have the right to grant necessary licenses or sublicenses to a third party under agreements with Third Party Collaborators, after using reasonable endeavours to secure such rights.

Source: taken from a USD $34.8 million funding agreement between CEPI (Funder) and the University of Oxford and Barinthus Biotherapeutics (Developers). Partner types: non-profit funder, industry/academic institution; Product type: MERS vaccine; Development stage at signature: early stage development. Read in context.

Funder right to seek "trusted manufacturers" to meet demand, provide warm base capacity and/or manufacture stockpiles

Subject to specific Additional Work Packages, [Funder] has the right during the Project Term to pursue the appointment of additional Trusted Manufacturers where such additional capacity is necessary or useful to:
develop and/or increase Manufacturing capacity for Products for use in the Field in the Affected Territory to satisfy demand or likely demand;
develop and provide warm base Manufacturing capacity for emergency planning and contingency planning;
Manufacture emergency stockpiles of Products for use in the Field in the Affected Territory.
Partner shall consider [Funder]’s requests for additional Trusted Manufacturers in good faith and shall within [*****] of receipt of such request notify [Funder] in writing whether the Partner agrees or declines to support the appointment of additional Trusted Manufacturers by [Funder] together with the grounds for its decision.

Source: taken from a USD $34 million funding agreement between CEPI (Funder) and CureVac (Developer). Partner types: philanthropic funder, industry; Product type: mRNA platform technology; Development stage at signature: preclinical. Read in context.

Project scope changes

Right for funder to request additional pandemic response project

If during the conduct of the [Statement of Work] there is a need for an emergency response to a pandemic of an infectious disease that has not already been partnered with a third party [***], the [Funder] can request the [Developer] to accept a grant-funded project in response to such pandemic, and the [Developer] may elect to accept such funding at its sole discretion, which may include the development of a drug, vaccine or diagnostic, and the [Developer] will negotiate in good faith with the [Funder] to reach agreement on such pandemic response project.

Source: taken from a strategic relationship letter agreement between the Gates Foundation (Funder) and BioNTech (Developer) signed in relation to a USD $55 million investment in BioNtech by the Foundation. Partner types: philanthropic funder, industry; Product type: products for the prevention or treatment of TB and HIV; Development stage at signature: preclinical. Read in context.

Priority for certain clinical studies

[Developer] acknowledges that the pool of subjects available in areas of Outbreak to participate in a clinical study to test products such as the Product may be limited. Accordingly, if [Funder] reasonably determines in consultation with experts (for example a sub-group or subcommittee of [Funder]’s Scientific Advisory Committee that [Funder] determines has appropriate expertise) that a product other than the [Developer]’s Product has substantially greater potential, as determined in accordance with WHO guidance or relevant local regulatory guidance and should be used for a particular clinical study of subjects in areas of Outbreak, the [Developer] agrees that it shall abide by such decision and will not proceed with any clinical study of the Product with subjects from areas of Outbreak unless agreed with [Funder]. In the event that [Developer] must discontinue a clinical study of the Product in areas of Outbreak according to [Funder]´s determination pursuant to this Clause [x], then [Funder] shall (i) cooperate with [Developer] in an appropriate wind down of the study and (ii) to the extent not funded in advance by [Funder], reimburse [Developer] for [Developer]’s reasonably incurred non-cancellable expenses relating to such discontinued clinical study. For clarity, [Developer] shall not pay back any sums already received from [Funder] that have been actually spent by [Developer] in connection with such discontinued clinical study. For the purposes of this Clause, [Funder] agrees that nothing in this Clause [x] will prevent (i) [Developer] from undertaking a Pivotal Study in any country; or (ii) [Developer] fulfilling its obligations under its risk management plan prepared by [Developer] in connection with its biologics license application in any country, including but not limited to post registration efficacy trials or any other commitment with any relevant regulatory authority to conduct a clinical study that would support the development of the Product . For the purposes of this Agreement, “Pivotal Study” shall mean a clinical study designed to fulfil the requirement for the filing of an application for a marketing authorization for a Product and that is acceptable to the relevant regulatory authority as a basis for the grant of a marketing authorization.

Actions in response to an outbreak

[…] In consultation with relevant public health authorities in the Affected Territory, [Funder] may request that [Developer] discuss in good faith whether and how the Project Results could be utilized in response to the Outbreak Notice. [Developer] is committed to use commercially reasonable best efforts to address Outbreaks and Increased Outbreak Preparation Need wherever they occur in the world. Following receipt of an Outbreak Notice, [Developer] will use its commercially reasonable best efforts to increase the supply of Product available for use by [Funder] or its nominees to an amount which equals at least [***] of the production forecast for the Products prepared by [Developer] immediately prior to service of the Outbreak Notice and [Developer] will use its commercially reasonable best efforts to ensure that such increased capacity is available for delivery to [Funder] within [***] of the date of service of the Outbreak Notice. For clarity, [Developer] will use commercially reasonable best efforts to keep such deadline of [***] (including discussing with [Developer]’s contract manufacturers how they can meet the proposed deadlines), however, [Developer]’s ability to meet deadlines will be subject to the lead times of [Developer]’s contract manufacturers and the time required for the release testing of the Product. In the event that [Funder]’s request for Product to meet the increased demand during an Outbreak or Increased Outbreak Preparation Need is in excess of the quantities that [Developer] is able to supply to [Funder] based on [Developer]’s commercially reasonable best efforts, [Developer] shall not be obliged to supply Product to [Funder] under this Clause [x] to the extent that the supply of such quantities of Product to [Funder] would result in [Developer] being in breach of any binding contracts in existence on the date of service of the Outbreak Notice (which for the avoidance of doubt may include the supply of Products to customers for [Developer]’s Traveler’s Market or in connection with any clinical trials). […]
Additional Product Development. Pursuant to an Outbreak Notice, [Funder] may request that [Developer] undertake additional Product development at [Funder]’s expense or undertake other activities, including the pursuit of regulatory approvals and licensure to the extent not already obtained, with the aim of addressing the needs of the Affected Territory. An additional Work Package covering these activities will be negotiated expeditiously and in good faith by the Parties.
Trusted Collaborator: Promptly after receipt of a written request from [Funder] (or at any earlier time), [Developer] will propose a third party, for example, a Sub-Awardee, as a preferred alternative to itself (“Trusted Collaborator”), that is capable of performing the work and would be prepared to undertake activities pursuant to Clause [x – preparation for outbreaks] in the event that [Developer] declines [Funder]’s request to do so, or if [Developer] and [Funder] do not reach agreement on a new Work Package. [Funder] may also propose a Trusted Collaborator to [Developer]. Neither Party may unreasonably decline to accept the designation of a proposed Trusted Collaborator.

Scope expansion or limitation

The Parties acknowledge the possibility that, as the Outbreak develops in ways not foreseen in the initial Work Package(s), a Project Expansion may become essential. For example, the extent or severity of the Outbreak may increase, the Project Vaccine may be prioritized by public health authorities for clinical studies and/or manufacture or advances in vaccine technology may permit acceleration of the Project. Alternatively, it may become necessary for [Funder] to limit Project scope or defer certain activities. For example, the WHO may determine that the Outbreak is no longer a Public Health Emergency of International Concern (“PHEIC”), third party products may be prioritized for development or deployment by an international decision-making process, [Funder] may need to focus its resources on other product in its portfolio, or the Project Vaccine may not appear to meet Outbreak response needs.
Implementing Changes in Project Scope or Timing. At the request of either Party, and as a matter of urgency, the Parties shall discuss in good faith: (i) whether a Project Expansion may be undertaken at [Funder]’s cost through modification of an existing Work Package, approval of an additional Work Package or utilization of the Project Continuity Plan in Clause [x – continuity]; or (ii) how best to limit Project scope or defer certain activities in a Work Package. For clarity, during the Outbreak, [Funder] reserves the right to terminate a Work Package if this is necessary in its sole discretion, provided [Funder] pays [Developer] all costs incurred or obligated to date and including any non-cancellable costs under such Work Package, and also provided that, if requested by [Funder], [Developer] shall reasonably demonstrate the incurred, obligated or non-cancellable nature of such costs.

Source: taken from a development funding agreement for up to USD $384 million between CEPI (Funder) and Novavax (Developer). Partner types: non-profit funder, industry; Product type: COVID-19 vaccine; Development stage at signature: phase I clinical trials. Read in context.

Dissemination of data and results for the outbreak community

Dissemination of Project Results to the Broader Outbreak Community. As described in the [product development plan] and elsewhere in this Agreement, or as otherwise agreed by the [Joint Monitoring and Advisory Group], and subject to the payment by [Funder] of actual costs and reasonable protection for [Developer]’s rights under this Agreement, [Developer] shall disseminate Project Results (excluding any chemistry, manufacturing and controls (“CMC”) data, or any information that would violate relevant privacy laws, or any information that [Developer] can reasonably demonstrate to [Funder] is sensitive and should not be so disseminated) with the broader Outbreak research community, such as disease-specific assays and standards, animal models, correlates of protection or risk, or diagnostics and epidemic preparedness mechanisms.
Publication of Project Data for the Outbreak Research Community. Project Data shall be shared rapidly with the broader community, consistent with Awardee’s requirements as a public company, in accordance with (i) WHO’s 2016 Guidance for Managing Ethical Issues in Infectious Disease Outbreaks; (ii) WHO’s 2016 Guidance on Good Participatory Practices in Trials of Interventions Against Emerging Pathogens; (iii) and Wellcome Trust’s Statement on Sharing Research Data and Findings Relevant to the Coronavirus (COVID–19) Outbreak to which CEPI is a signatory.

Cooperation with global coordination mechanism

At the [Funder]’s request, the Parties agree to negotiate in good faith to modify and amend this Agreement, including the Global Access Commitments, to align with any applicable allocation, procurement and/or coordination mechanism established under the Access to Covid–19 Tools Accelerator, a WHO–led Global Collaboration to accelerate the development, production and equitable access to new Covid–19 diagnostics, therapeutics and vaccines.

Source: taken from a global access and price commitments agreement between the Gates Foundation (Funder) and Icosavax (Developer), signed in connection with a USD $10 million grant agreement between the parties. Partner types: philanthropic funder, industry; Product type: COVID-19 vaccine; Development stage at signature: preclinical. Read in context.

What actions should funders or other stakeholders take to facilitate the funded partner’s emergency response activities?

What are the requirements to make the product available at an affordable price?

How will the agreement parties ensure that the product is appropriate for use in the settings where disease outbreaks are most likely to occur?

What are the requirements to ensure that products manufactured for emergency response meet appropriate quality standards?

Are there any special considerations for the conduct of clinical trials and sharing of trial results during disease outbreaks?

How should data and results arising from the funded project be shared to further the field, both during and outside of health emergencies?

Should there be additional or more frequent reporting requirements during a health emergency to ensure up-to-date information on product development progress or manufacturing capacity?

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.

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