Master Alliance Provisions Guide (MAPGuide)

Key Agreement Provisions for Supporting
Product Availability

Ensuring that a product is ‘available’ to the populations that need it requires the consideration of multiple factors. This commentary examines how agreement provisions can support the achievement of product availability by addressing three key issues:

1. Developing Appropriate and Adoptable Products for use by all relevant populations

2. Timely Regulatory Approval for use in all relevant markets

3. Sufficient and Timely Supplies of the product when and where it is needed

1. Appropriate and Adoptable Products

The WHO develops Target Product Profiles (TPPs) and Preferred Product Characteristics (PPCs) for vaccines, therapeutics, diagnostics, and medical devices for health products for which it has identified a need. These profiles act as guidance for developers to ensure that a product is appropriate and adoptable for the populations that need it.

The ability of a product to meet the relevant TPP is often a consideration for funders when making a decision to enter into a development partnership. Those TPPs can then be included in funding agreements as an attachment or appendix in order to ensure continued alignment and work to develop a product that meets the intended characteristics. However, inclusion of a TPP may not be appropriate for very early stage discovery and research work when not enough is known about the likely potential characteristics of a final product.

In addition to a TPP, agreement provisions can support the adoption of a funded product in target communities by requiring developers to take steps to promote product awareness and provide training for appropriate usage by local medical practitioners.

Examples from the MAPGuide

“Development Plan” shall mean a development plan outlining the non-clinical and clinical development plans and CMC plans for the Drug Product to meet the criteria of the TPP, which Development Plan is attached as Schedule 1 hereto, as amended from time to time in accordance with the terms of this Agreement.

Related definitions: “Target Product Profile” or “TPP” shall mean the set of potential characteristics and attributes for the Drug Product, described in Schedule 5 hereto, and revised from time to time by mutual consent through the JSC;

Source: Taken from a collaboration agreement between DNDi/GARDP and Entasis for the development of Gonorrhea medication. Read in context.

[Developer] will use reasonable and diligent steps to:

(i) conduct all clinical trials specified in the [Integrated Product Development Plan] to meet the Minimum TPP and keep the [Funder] promptly informed of any information impacting the Product’s ability to meet the Minimum TPP thereunder or that is otherwise deemed to impact the Project or timelines by three (3) months or more

Related Definitions: The Minimum TPP for this agreement can be seen here.

Source: Taken from a global access commitments agreement between the Bill & Melinda Gates Foundation (Funder) and Novavax (Developer) for the development of an affordably-priced RSV vaccine for use in maternal immunization to provide RSV protection in low income countries. Read in context.

Beginning in the year immediately following year in which any Program Product receives European or FDA approval/clearance, the Company shall allocate $50,000 per year to the Global Access Committee to work on training programs to be conducted by the Company or by partners approved by the Global Access Committee, such as the WHO, Gates Foundation and others, in Target Countries on the use of the Program Products with a target of training leading practitioners each year in the Target Countries, as defined by the Global Access Committee, as well as to work on access and promoting demand in the Target Countries. The Company shall work with global health authorities and partner organizations, including but not limited to the World Health Organization, the Clinton Health Access Initiative (CHAI), and the Bill & Melinda Gates Foundation (BMGF) and use commercially reasonable efforts to have the Program Products added to protocols and treatment guidelines.

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.

 

2. Timely Regulatory Approval

Regulatory, or marketing, authorization for a product grants to the Marketing Authorization Holder (MAH) to distribute or market a medical product, and for health care providers to administer or prescribe that product, for a given indication within a certain jurisdiction. Obtaining this authorization from the relevant authorities in a timely manner is an essential step in ensuring that a funded product is available in target markets. To achieve this, funding agreements need to include provisions that address how and when authorization for the product will be sought from different regulatory authorities. The product may not be at a sufficiently advanced stage of development for the parties to set out a full regulatory strategy at the time an agreement is signed, but the agreement can still contain commitments to do so at a certain point in the project.

Some important considerations for agreement provisions addressing regulatory obligations include:

a. Party responsible for regulatory authorizations: Product development funding agreements usually assign responsibility for making regulatory submissions and obtaining and maintaining approvals to the product developer or manufacturer. The developer or manufacturer is then the party with legal responsibility for the accuracy and quality of the data supporting the regulatory submission, as well as the ongoing risk and obligations related to pharmacovigilance and other post-authorization activities.

b. Relevant regulatory authorities: There are a number of potential national and regional authorities from which marketing authorizations can be sought. While it is common for product developers to first seek approval from a Stringent Regulatory Authority (now also referred to as WHO Listed Authorities), this is unlikely to be sufficient to enable sale and administration of a product in LMIC markets. Product development funding agreements therefore need to contain obligations to follow regulatory pathways relevant to the target markets for the finished product. This could include an application to the WHO Prequalification (PQ) programme, which is recognized by multilateral procurement agencies such as Gavi, The Global Fund, and UNICEF, as well as to national regulatory agencies (NRAs), or regional authorities such as the ZaZiBoNa Initiative, the East African Community, the Caribbean Regulatory System and the new African Medicines Agency.

c. Type of authorization needed: The appropriate type of authorization that should be sought by a developer for a funded product depends on the intended circumstances of use. The exact terminology used to describe the authorization type needs to be determined based on both the applicable regulatory authority(ies) and the product type – drugs and vaccines may have different regulatory pathways to diagnostics and medical devices. However, some general categories to be considered are: 

Full marketing authorizations – these authorizations are based on a thorough review of a complete application for marketing authorization, such as an MAA in the EU and an NDA or BLA in the US, which demonstrates the quality, safety and efficacy of a medical product.

Accelerated approval processes – these authorizations can be granted by NRAs for situations including:

      • A public health emergency which cannot be sufficiently addressed by existing products. These authorizations include Emergency Use Authorizations and Emergency Use Listings which were issued by the FDA and WHO respectively for COVID-19 vaccines, diagnostics and therapeutics; or
      • A product that can address unmet medical needs to the extent that the benefit of immediate availability of the product outweighs the risk of its use for the relevant patient population. These authorizations may also be used in the event of public health emergencies, such as the EMA’s use of conditional marketing authorizations for COVID-19 vaccines and therapeutics.

While there are differences between how emergency use and conditional authorizations are used in different jurisdictions, the authorizations are usually granted on the basis of less comprehensive data than would be required for a full marketing authorization due to the time constraints associated with addressing urgent needs. However, these authorizations are also time-limited and for longer-term marketing authorization, the MAH will need to obtain and submit further clinical data. 

Compassionate use authorizations– these apply to the legal use of an unauthorized medicine under strict conditions.  They are limited to use by patients with life-threatening, long-lasting and/or seriously debilitating illnesses, and the product must be in active development for the relevant indication.

Orphan product designations – these are for products used to treat rare diseases (e.g., incidence of <5/10000 in the EU or <200,000 in the US). These products may be authorized on the basis of clinical studies that would be insufficiently statistically powered for a full marketing approval due to the scarcity of relevant patients.  Orphan Product Authorizations exist, in part, to create incentives to developers as the markets for the products are necessarily small.

d. Development and monitoring of a regulatory strategy: Product development funding agreements often require the developer to create a regulatory strategy which can include items such as the indication(s) for which a product is being developed, target SRAs or NRAs for regulatory submissions, expected submission and authorization timelines, and go/no-go decision points. Regulatory strategy is a critical area requiring early agreement between a funder and developer in order to ensure aligned expectations as to how and when a product will be made available in target markets. For this reason, agreement provisions related to regulatory strategies may require the developer to consult with the funder about the initial development of, and continued progress on, the strategy. Progress monitoring related to the regulatory strategy is sometimes included in the responsibilities of a project steering committee and/or as part of the funder’s periodic reporting obligations

In addition to progress updates, agreement provisions related to regulatory obligations often also require the developer to share data and documentation with the funder such as draft and final copies of submissions, clinical trial applications, adverse event reporting and other safety-related data.

Examples from the MAPGuide

[Developer] will, or will obligate its Sub-Awardee(s) to, use reasonable endeavours to obtain regulatory approvals and licensure for the Product in Non-Traveler’s Market Countries where there is a demand for the Product. The Parties, through the [Joint Monitoring and Advisory Group], may discuss and agree on a list of such Non-Traveler’s Market Countries in which to seek such approvals and licensure and on a schedule for seeking such approvals and licensure, and [Developer] will, or will obligate its Sub-[Developer](s) to, use reasonable endeavours to meet such schedule in such countries.

Source: taken from a development funding agreement between CEPI (funder) and Novavax (developer) for a COVID-19 vaccine. Read in context.

[Developer] shall:

(i) use best endeavours to obtain Emergency Use Authorisation and Emergency Use Listing for the [product] by no later than [***] after the expected date set out in the Regulatory Submission Plan, and in any event by no later than [***] after submission for WHO assessment through the Emergency Use Listing or WHO Prequalification procedure; and shall ensure WHO submission is no later than the time of submission to the Stringent Regulatory Authority which is appointed to be the National Regulatory Authority of Record; and

(ii) use Commercially Reasonable Endeavours to obtain Regulatory Approval for the [product], by no later than [***] after the expected date set out in the Regulatory Submission Plan.

[Developer] shall use Commercially Reasonable Endeavours to obtain such regulatory approvals as are required to enable the [product] to be used in each [country] where allocated COVAX Doses are intended to be sold pursuant to this Agreement, taking into account cost, complexity of obtaining approval in such [country] and the benefit of such regulatory approval.

Related Definitions: 

  • “Regulatory Approval” means: (a) Marketing Authorisation Approval from a Stringent Regulatory Authority; or (b) WHO Prequalification;
  • “Regulatory Submission Plan” means the plan prepared and submitted by [Developer] that will include timelines of required clinical and regulatory submission activities to facilitate approval of the [product] by the WHO for Emergency Use Listing and for Emergency Use Authorisation and Regulatory Approval.

Source: taken from an advance purchase agreement between Gavi (purchaser/funder) and Novavax (developer) for a COVID-19 vaccine. Read in context.

 [Developer] will use reasonable and diligent steps to:

  • consider utilizing WHO’s joint regulatory review mechanism for clinical trial approvals in Developing Countries provided always that all regulatory activity decisions will be Company’s sole responsibility; 
  • submit an applicable dossier to WHO for WHOPQ of the Product for Maternal Immunization in Developing Countries by [**]; […]
  • Promptly upon WHOPQ, seek local Developing Country registration, to the extent such Developing Country participates, for Released Product for Maternal Immunization through the WHO Collaborative Registration Procedure (CRP); and 
  • Pursue applicable regulatory approval of Released Product for Maternal Immunization in those countries listed on Appendix A as “Additional Countries” after WHOPQ, and, upon such approval, commit to make such Released Product available to Public Sector Purchasers in such countries at a price per dose to be negotiated in good faith by the parties.

Source: taken from a global access commitments agreement between the Bill & Melinda Gates Foundation (funder) and Novavax (developer) for the development of an affordably-priced RSV vaccine for use in maternal immunization to provide RSV protection in low income countries.

Subject to specific Work Packages, [Developer] shall provide the following reports, notifications and samples to [Funder]: […]
Safety Issues. The [Developer] shall notify [Funder] and relevant JMAG members immediately by email (with receipt acknowledgement) as well as in writing in accordance with Clause 21.9:
(i) on receipt of any information that raises any material concerns regarding safety or efficacy of Product or the Platform;
(ii) where any data relating to a Product discloses a serious adverse event;
(iii) where a serious adverse event is suspected;
(iv) on the occurrence of a serious adverse event, serious adverse reaction, or any other material safety signal;
(v) of any Product recalls; and
(vi) of any recommendations from the data safety monitoring board for a clinical trial of a Product to end a clinical trial;
(together, the “Safety Issues”).
Pharmacovigilance. The [Developer] shall notify [Funder] promptly in writing of any relevant event under any pharmacovigilance activities.

Source: taken from a development funding agreement between CEPI (funder) and CureVac (developer) for the development of CureVac’s mRNA platform for the rapid manufacturing of vaccines against infectious diseases. Read in context. 

3. Sufficient and Timely Supplies

There are a number of supply-related aspects that can be addressed by provisions aiming to ensure sufficient and timely supply of medical products to populations that need them:

a. Responsibility for fulfillment: some funding agreements anticipate that the development partner will fulfill the required supply volume for the agreement territory through its own manufacturing capacity or manufacturing network. Another approach is to require the developer to identify and transfer technology to an alternative manufacturer in a low- or middle-income country (LMIC) who will be responsible for fulfilling supply requirements for certain territories. The alternative manufacturer approach can also be used as a ‘back-up’ option in the event that the developer cannot meet the requirements themselves.

Examples from the MAPGuide

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 expected demand will be determined by the [Funder] and the Company based upon review of the [Funder’s] target markets for the applicable product and other relevant considerations, including cost-effectiveness. […] 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 Gates Foundation (funder) and Arsanis (developer) in connection with an $8 million investment by Gates to support a Staphylococcus aureus antibody development program. Read in context.

 

To facilitate achievement of the [equitable access] conditions set out in Clauses [x], [Developer] has agreed to transfer its technology to an LMIC manufacturer […] [Developer] will, within [***] of the signature date of this Agreement, […], sign a Sub-Awardee agreement with an LMIC manufacturer, which […] shall obligate such LMIC manufacturer to manufacture the Product for regular supply in all Non-Traveler’s Market Countries that have a demand for Product and to supply the Product to Non-Traveler’s Market Countries under the conditions of [affordable price clause]. Prior to signing such Sub-Awardee agreement with an LMIC manufacturer and prior to completion of technology transfer to enable such LMIC manufacturer to manufacture and supply the Product to Non-Traveler’s Market Countries, [Developer] shall fulfill manufacturing and supply obligations for Non-Traveler’s Market Countries as set out in the IPDP [integrated product development plan].

Source: CEPI – Valneva Chikungunya Vaccine Funding development agreement. Read in context. The required agreement for an LMIC manufacturer was subsequently signed between Valneva and Instituto Butantan.

If the [Funder] reasonably determines that a third-party manufacturer is needed to achieve [Developer’s] price and volume commitments, [Developer] must license and transfer the IP needed for production to the third party at the [Funder’s] expense. The obligation is limited to transfers that allow production for Developing Countries. 

Source: taken from a strategic relationship agreement between the Gates Foundation (funder) and Arsanis (developer) related to an investment by the Gates Foundation for the purpose of supporting a Staphylococcus aureus antibody development program. Read in context.

[Licensor] will be responsible for the exclusive […] manufacture and supply of CAMB to [Licensee] for Distribution in the Territory and for all costs associated therewith. Prices at which [Licensor] will sell CAMB to [Licensee] are set out in section [x] below.

(a) Should [Licensor] be unable to meet [Licensee]’s Distribution needs as evidenced by failure to meet *** of [Licensee]’s forecast needs for *** consecutive quarters, [Licensee] shall be able to engage a secondary supplier to meet any [Licensor] shortfall in [Licensee]’s supply needs with the assistance of [Licensor]. However, in every instance, [Licensee] shall purchase the full quantity of CAMB available from [Licensor] prior to engaging a secondary manufacturer. Should [Licensee] engage a secondary supplier due to [Licensor] shortfall of [Licensee]’s Distribution needs, [Licensee] will revert back to [Licensor] as the exclusive supplier of [Licensee]s needs once [Licensor] is able to show manufacturing capacity equivalent to *** of [Licensee]’s forecast needs for any upcoming quarter.

Source: taken from a research collaboration and license agreement between BioDelivery Sciences International (licensor) and DNDi (licensee) for the parties to to assess the efficacy of CAMB (a formulation of Amphotericin B) in the treatment of visceral leishmaniasis and for DNDi to subsequently register and distribute CAMB primarily in low- and middle-income countries. Read in context.

(a) The Commercialization Plan for Targeted Territories:

(i) No later than six (6) months after the First Approval, unless otherwise agreed by the Parties, the [Developer] will describe in a confidential commercialization plan (the “Commercialization Plan”) the key countries where it intends to market the Product (the “Targeted Territories”). The list of Targeted Territories shall not be inconsistent with the [Developer]’s most recent Stewardship and Access Plan and will be updated by the [Developer] from time to time based on actual developments. The Commercialization Plan should be reasonably detailed as appropriate for a marketed Product. […]

(b) Negotiation of Voluntary Mechanisms for Other Territories:

(i) For countries that are not Targeted Territories (the “Other Territories”), the [Developer] and the Wellcome Trust will explore mechanisms to achieve stewardship and access objectives. This process will begin with a joint business plan addressing the Other Territories. This business plan will lay out reasonable goals and mechanisms for making the Product available in such Other Territories consistent with access and stewardship objectives. While informed by the Wellcome Trust’s overall stewardship and access objectives, this negotiation process will set the metrics and goals in the Other Territories that are acceptable to both Wellcome Trust and the [Developer].

(ii) This business plan should include a mechanism for the Wellcome Trust (or the Wellcome Trust’s nominee) to access all intellectual property required to commercialize the Product in the Other Territories, including Project IP Rights and background intellectual property (including intellectual property which may block the exploitation of Project IP rights).

(iii) The Subrecipient and the Wellcome Trust may consider the following potential mechanisms for accessing intellectual property rights referenced in [this] Section [x]:

 

1. A voluntary sublicensing agreement process between the Subrecipient and the Wellcome Trust (or the Wellcome Trust’s nominee);
2. A Subrecipient supply arrangement between the Subrecipient and the Wellcome Trust (or the Wellcome Trust’s nominee) to ensure the Product is made available to ensure access is provided to the Wellcome Trust, or another party specified by the Wellcome Trust, with a specified number of doses at an agreed upon cost for distribution solely in the Other Territories;
3. Creation of a joint venture between the Subrecipient and the Wellcome Trust (or the Wellcome Trust’s nominee) to promote access to the Product within an appropriate stewardship framework;
4. The voluntary transfer by the Subrecipient to the Wellcome Trust (or its nominee) of intellectual property rights necessary for the Wellcome Trust to develop and exploit the Product in the Other Territories, consistent with its access and stewardship objectives; and
5. Payment of a reasonable royalty by the Wellcome Trust for background intellectual property.

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. The Wellcome Trust, a funder of CARB-X, also has certain rights under the agreement related to achieving stewardship and access objectives. Read in context.

b. Required volume: Funding agreements may take a number of approaches to determining the required supply volume to be fulfilled by a developer or alternative manufacturer. The approach used may in part depend on the type of product being developed and the ease with which timing and volume of demand can be anticipated. Agreements related to products for pandemic or epidemic response might include the creation of a product stockpile ready to be deployed when needed. Another option, which can also be used alongside a stockpile obligation, is to leave the determination of required volume to the procurement agencies purchasing the product for the agreement territory. A third option is to require a certain proportion of a developer’s total manufacturing capacity to be used to supply the agreement territory.

Examples from the MAPGuide

[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 an outbreak response agreement between CEPI (funder) and Variation Biotechnologies Inc (developer) for the development of COVID-19 vaccine candidates.

Within [***] of receipt of marketing approval for the Product from the FDA, [Developer] will produce, at [Developer] 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 Awardee’s Traveler’s Market and will replenish such stock on a rolling basis at [Developer’s] cost. The stock in [these paragraphs] 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 […] and the storage costs of such Safety Stock, incurred prior to dispatch to the Affected Territory, shall be borne by [Developer].

Source: taken from a development funding agreement between [Funder] (funder) and Valneva (developer) for manufacturing and late-stage clinical development of a Chikungunya vaccine. Read in context.

Upon an election to make and sell a [product] to Public Sector purchasers in Developing Countries, [Developer] shall manufacture, supply and sell, or cause to be manufactured, supplied and sold, the [product] for use in designated Developing Countries for a period of time to be agreed upon by the Parties following licensure of a [product] in a Developing Country.  [Developer] shall fill, or cause to be filled, Developing Country requirements for [product] by using commercially reasonable efforts to supply [product] to Public Sector purchasers in such quantities and timeframes sufficient to fulfill the purchase orders for use in Developing Countries.

Source: taken from a development funding & collaboration agreement between PATH (funder) and Aridis (developer) for the formulation development of a rotavirus vaccine. Read in context.

[Developer] shall:[…]

  • during the Pandemic Period, subject only to the [Developer]’s supply obligations under the Pre-existing Agreements including Section 6.3.1 of the Canada Agreement) which have been communicated to [Funder] as required under the [product development plan], offer the Volume Commitment Percentage of the [Product] produced pursuant to Clause [x] for purchase by Gavi, [Funder] or their respective designees pursuant to Clause 15.3 during the Pandemic Period. For clarity, [Developer] may not allocate or agree to supply such [Product] doses to other third parties, other than as required pursuant to the Pre-existing Agreements, during the Pandemic Period without the express written permission of Gavi, [Funder] or their respective designee; […]
  • subject only to the [Developer]’s supply obligations under the Pre-existing Agreements (including Section 6.3.1 of the Canada Agreement) which have been communicated to [Funder] as required under the iPDP, use its Commercially Reasonable Efforts to provide an amount of doses to be reasonably determined by [Funder] based on the [Developer]’s worldwide supply capacity and the level and timing of [Funder]’s funding contribution to the global initiative “Access to COVID-19 Tools (act) Accelerator” so as to ensure availability for all, subject to the inclusion of satisfactory liability protection (which may include participation in the Gavi no fault compensation programme) and regulatory conditions. This Agreement does not cover specific details with regard to the provision of doses to the COVID-19 Tools (act) Accelerator to be concluded and agreed separately with the relevant parties involved.

Related definitions: 

Canada Agreement” means the agreements between the Strategic Innovation Fund of Canada and [Developer] executed Sept 16th 2020 including any extensions or amendments thereto, provided that any such amendment is consistent with [Funder]’s rights hereunder.

Pandemic Period” means the period of time beginning on 30 January 2020, when the World Health Organization (or “WHO”) declared COVID-19 to be a Public Health Emergency of International Concern (or “PHEIC”), and ending on the earlier of (1) the date on which WHO declares that the COVID-19 PHEIC is over or (2) the date determined by [Funder], in its reasonable discretion in consultation with the [Developer] and based on epidemiological data published by WHO.

Pre-existing Agreements” means the agreements entered into by the [Developer] prior to the Effective Date details of which are set out in Exhibit H.

Volume Commitment Percentage” means the relevant percentage of the [Developer]’s capacity to produce [Product] together with Trusted Manufacturer, where the relevant percentage shall be calculated as follows: **% for any [Product] for which [Funder] provides preclinical funding, **% for any [Product] for which [Funder] funds through Phase 1 clinical study, **% for any [Product] for which [Funder] funds through Phase 2 clinical study, **% for any [Product] for which [Funder] funds through Phase 3 clinical study, and **% for any [Product] for which [Funder] funds through to (i) approval and registration as set out in the iPDP; (ii) WHO pre-qualification or emergency use listing; and (ii) reasonably sufficient commercial manufacturing capabilities as required to meet [Developer]’s obligations hereunder. In the event that [Funder] co-funds with a third party organization, [Developer], [Funder] and the third party organization will negotiate an appropriate Volume Commitment Percentage commensurate with the respective interests of the party, funding contributions and stage of investment (provided always that such Volume Commitment Percentage shall be no lower than the Volume Commitment Percentage applicable to the funding stage immediately prior to the latest stage to which [Funder] has provided funding).

Source: taken from an outbreak response agreement between CEPI (Funder) and Variation Biotechnologies Inc (Developer) for the development of COVID-19 vaccine candidates.

The [Developer] agrees to manufacture Access Country Doses in an amount based on a rolling forecast provided by the Foundation to the [Developer] of expected demand for Access Country Doses up to a maximum of [*****] of its New Facility Total Manufacturing Capacity (or the reasonable equivalent thereof in the event the New Facility is combined with or replaced by other manufacturing facilities, including, without limitation, as a result of a Change in Control). For such purpose, the Foundation will provide the [Developer] with at least [*****] prior notice before it is required to begin manufacturing Access Country Doses. Unless and until such notice has been given by the Foundation, the [Developer] will have the right to allocate 100% of its New Facility Total Manufacturing Capacity at the [Developer’s] discretion.

Related Definitions:

Access Country Doses” means vaccines and drugs the Company has developed using funds from the Foundation or Foundation-supported Entities in connection with Projects and that are intended for use in the Access Countries (including, without limitation, vaccines and drugs for use in clinical trials).

Source: taken from a development funding agreement between the Gates Foundation (funder) and CureVac (developer) in relation to the Gates Foundation’s investment in Series B shares in CureVac. The investment is to be used solely to fund a new manufacturing facility which can be used to manufacture vaccines and drugs in support of the Gates Foundation’s equitable access objectives, or to continue development and use of CureVac’s mRNA platform technology to advance drug and vaccine candidates in support of the equitable access objectives. Read in context.

The volume of Program Products made available for the Global Health Purchasers […] shall meet the demands of the Global Health Purchasers, as confirmed by the Global Access Committee, up to 20% of the Company’s annual unit sales volume (unless adjusted jointly by a majority of the Board of Directors and Global Access Committee); it being understood, however, that the Company shall have the right to supply more at its sole discretion.
Related definitions:
Global Access Committee” refers to a joint steering committee to oversee the Company’s efforts in Target Countries. The Global Access Committee shall be comprised of up to four (4) members: (i) one individual appointed by the Company; (ii) one individual appointed by the Investor (the “AXA IM Prime Impact Fund Appointee”); and (iii) up to two additional individuals unaffiliated with the Company or the Investor, and appointed upon mutual agreement of the Company and the Investor.

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.

[T]he 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 GARDP and Entasis for the development and commercialization of Gonorrhoea Medication. Read in context.

c. Timely supplies: Funding agreements for products that are likely to have a high demand in high income countries (for example, pandemic vaccines) may also need to consider the prioritization of supplies to the agreement territory in order to ensure that LMICs are not pushed to the bottom of the order queue in favor of countries with more leverage and purchasing power.

Examples from the MAPGuide

[Developer] shall ensure that the first [w%] of doses of Product Manufactured in the first [v] years after scale-up shall be provided as directed in writing by Funder in accordance with the Funder Equitable Access Policy.

Source: taken from an anonymized product development funding agreement. Read in context.

During the Early Supply Period, [Developer] shall deliver at least [***] ([***) (measured [***]) of all [product] to the COVAX Buyers, and in accordance with the Interim Delivery Schedule, at the relevant COVAX Participant Price; and in so doing, give first priority to supplying such COVAX Doses (in relation to prioritising delivery timescales, provision of information and other supply terms). […]

Absent action pursuant to the USA Defense Protection Act or equivalent regional laws or regulations applicable to the [product], [Developer] shall not attempt to circumvent or take any steps to prejudice the priority of the COVAX Facility.

Source: taken from an advance purchase agreement between Gavi (purchaser/funder) and Novavax (developer) for a COVID-19 vaccine. Read in context.

[Developer will] supply up to [***] of the quantity of the [product] produced for purchase by the Global Allocation Body […] during the Pandemic Period. For clarity, [Developer] may not allocate or obligate [product] doses to other third parties during the Pandemic Period that conflicts with its obligations under this Clause [x].

Related definitions:

  • Global Allocation Body” refers to a global allocation and purchasing entity […] to purchase, allocate, and direct the distribution of COVID-19 vaccines.
  • 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.

Source: taken from a development funding agreement between CEPI (funder) and Novavax (developer) for a COVID-19 vaccine. Read more.

[Developer] shall:[…] supply [Product] doses to COVAX in a timely manner that enables COVAX represented economies to receive [Product] in a similar timeframe to other third party customers.

Source: taken from an outbreak response agreement between CEPI (funder) and Variation Biotechnologies Inc (developer) for the development of COVID-19 vaccine candidates.

d. Continuity of Supply: Some funding agreements anticipate potential risks to maintaining sufficient and timely supply of a product due to disruptions to supply chains or to other business as usual processes. Some of the ways in which agreements can address these risks are through the inclusion of contingency or business continuity plans, and/or the identification of alternative manufacturers who could continue manufacture and supply operations in the event that the developer is unable to do so.

Government funding entities may also be able to apply priority ratings (for example, the U.S. Defense Priorities and Allocations System) if an agreement relates to development of a product to address a health emergency. These ratings enable a developer to require prioritized supply timelines from the subcontractors in their supply chain, therefore securing access to resources which may be in scarce supply.

Examples from the MAPGuide

Developer Contingency plan: [Developer] shall create and maintain a contingency plan, reasonably approved by [Funder], to address the possible impacts of the [pandemic] on its own organization as relates to the Project, as described in the [product development plan]. 

Product Continuity Plan: Because of the exigent nature of the Outbreak, the [product development plan] shall include a Project Continuity Plan that, at a minimum, shall address the following items: […]

  • responsibilities and level of access on the part of other collaborators, Subawardees and consortium members, if any, to Project Results and Enabling Rights;
  • management of key Project Materials through participants in the Project and other entities such as the BioEscrow® deposit service of the American Type Culture Collection;
  • identification of a proposed third party, for example, a Subawardee, under contract to [Developer] that is capable of performing the activities in agreed Work Packages, Additional Work Packages or a Project Expansion (“Trusted Collaborator”), in the event that [Developer] is unable to continue its activities under this Agreement or declines [Funder’s] request to undertake additional Work Packages or a Project Expansion; and
  • at least a preliminary identification of one or more geographically dispersed manufacturing sites, under contract with [Developer], to produce [product] for use in the Field (“Trusted Manufacturer”). [Developer] shall make a final designation of one or more Trusted Manufacturers, in consultation with [Funder], and prior to the start of a Phase II clinical trial.

Manufacturing in Multiple Countries: [Developer] shall use [***] to establish operational manufacturing facilities in one or more geographically dispersed manufacturing sites as described in the Work Packages.

[Developer] Representation: During the Term of this Agreement, [Developer] shall: […] notify [Funder] promptly if it becomes aware that any actions are likely or have already been taken by the government of any country in which [Developer] shall conduct Project activities that may adversely affect [Developer]’s commitments in this Agreement, including Equitable Access. For clarity, such government actions may relate, for example, to the exercise of eminent domain or sovereign rights over Project Vaccine doses.

Source: taken from a development funding agreement between CEPI (funder) and Novavax (developer) for a COVID-19 vaccine. Read in context.

Related Commentaries

Product availability needs to be supported by sustainability obligations that ensure that supplies are available for as long as they are needed.

For national or multilateral procurement agencies to be able to acquire a product, it must be affordable as well as available.

All of the elements contributing to product availability should be included in an effective access plan.

Concrete steps taken to ensure product availability for target populations, such as regulatory submissions and signature of procurement contracts, can be incorporated into the development milestones set out in the agreement

Authors: Bridie Telford, Liz Fuller, Britnae Purdy

First publication date: November 21, 2022