MAPGuideⓇ
Equitable Access Toolkit
Product Registration Commitments for Funded Products
Product registration refers to the process of obtaining marketing approval (also referred to as marketing authorization or product licensure) from a competent regulatory authority to permit the distribution of a product in a particular country. Timely product registration in the access territories within the scope of a funding agreement is a key step in achieving equitable access to a funded product.
Funding agreements can include product registration provisions ranging from general “best efforts” commitments to achieving timely registration, to detailed obligations to apply for marketing approvals from specified regulatory authorities within certain timeframes. Detailed obligations are likely to be more effective when the agreement parties have a clear understanding of the available regulatory pathways for the product.
Where there is uncertainty over regulatory pathways at the time of agreement signature, “best efforts” commitments can be linked to a requirement for the parties to establish a detailed regulatory strategy as part of an access plan. Agreements may also include mechanisms for a funder to review and provide input to regulatory strategies and submissions through requirements to share draft copies of submissions and/or as part of the responsibilities of a joint steering committee or access committee.
In some cases funders may also engage in parallel activities to support regulatory alignment or the development of pathways for novel products such as digital health technologies and innovative diagnostics.
Key considerations for establishing product registration commitments in agreement provisions or access plans include:
Identification of the marketing authorization holder;
The relevant regulatory authorities from which to seek approval;
The type of approval required; and
The expected timeline for regulatory submissions.
Marketing authorization holder
A marketing authorization holder (MAH) is the party with the 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.
In some cases, funding agreements require the funded partner to assume this responsibility, however in earlier stage funding agreements (for example, where the funded partner is a university or small biotech company), the parties may anticipate that product registration will be undertaken by a future development partner. Funded partners may also pass through product registration responsibilities to third party manufacturers in connection with licensing and technology transfer commitments to facilitate affordable access in certain markets.
Relevant regulatory authorities
It is common for product developers or manufacturers to first seek marketing approval from a Stringent Regulatory Authority (SRA), or WHO Listed Authority (WLA), such as the US FDA, the EMA, or the UK MHRA. However, for a funded product to be available in all countries within the scope of a funding agreement, marketing approval must be obtained from a regulatory authority with jurisdiction in each country (sometimes referred to as the “competent regulatory authority”). In some cases, this may be a national regulatory authority (NRA), but there may be opportunities to leverage regional bodies and collaborative registration procedures such as ZaZiBoNa, the East African Community, the Caribbean Regulatory System, the African Medicines Agency, the WHO Collaborative Registration Procedure (CRP) or the EMA Medicines4All procedure.
Additionally, funded products may need to achieve WHO Prequalification (WHO PQ) to be eligible for purchase by some procurement agencies such as Gavi, The Global Fund, and UNICEF.
Type of authorization
The appropriate type of marketing authorization for a funded product depends on the intended circumstances of use, and the terminology used to describe the authorization type needs to be determined based on both the applicable regulatory authority(ies) and the product type (for example, drugs and vaccines may have different regulatory pathways to diagnostics and medical devices). Some general categories to be considered are outlined below.
Full marketing authorizations
Full marketing 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
Accelerated approvals such as emergency use or conditional authorizations may be used in circumstances including: (i) a public health emergency which cannot be sufficiently addressed by existing products (e.g., Emergency Use Authorizations and Emergency Use Listings issued by the FDA and WHO respectively for COVID-19 countermeasures); or (ii) a product addressing 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.
Compassionate use authorizations
Compassionate use authorizations 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
Orphan product designations 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 designations exist, in part, to create incentives to developers as the markets for the products are small.
Priority Review Vouchers
The US FDA can award PRVs for innovative products for the prevention or treatment of certain diseases. Where relevant, funding agreements may anticipate application for a PRV as part of the regulatory strategy for the product, along with provisions establishing how the parties will share any related commercial benefits.
Submission timeframe
Funding agreements may seek to reduce the time lag between first marketing approval from an SRA and marketing approval in countries in the agreement access territory by including obligations for the funded party (or their sub-awardee) to apply for WHO PQ and/or NRA approval within a certain period after first approval. Agreements may also provide for the parties to agree on a schedule for seeking approval in different countries at a later point in the development process.
Examples from the MAPGuide
Awardee will ensure the LMIC manufacturer will use commercially 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 JMAG, 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 Awardee will, or will obligate its Sub-Awardee(s) to, use commercially reasonable endeavours to meet such schedule in such countries.
Awardee will ensure that the LMIC manufacturer will use commercially reasonable endeavours to obtain WHO prequalification for the Product.
Source: taken from a USD $41.3 million funding agreement between CEPI (Funder) and Valneva (Developer). Partner types: philanthropic funder, industry; Product type: Chikungunya vaccine; Development stage at signature: licensed product. Read in context.
[Developer] will use reasonable and diligent steps to:
- […]
- 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 Gates Foundation (Funder) and Novavax (Developer) signed in relation to a USD $83 million grant from the Foundation to Novavax. Partner types: philanthropic funder, industry; Product type: RSV vaccine; Development stage at signature: late stage clinical trials. Read in context.
[Developer] shall consult regularly with [Funder] regarding regulatory strategy for a Project Vaccine and shall provide advance copies of all regulatory submissions for review and comment by [Funder] no later than [***] prior to their contemplated submission to a regulatory authority. If a final version is not available by [***] prior to submission, then a mature draft version can be submitted to [Funder] for review at that time. Additionally, [Developer] shall put copies of the following on a confidential electronic archiving service designated by [Funder]:
(a) all submissions to regulatory authorities and regulatory filings in respect of a Project Vaccine together with all data included or referenced therein (other than ministerial submissions that do not involve safety or efficacy issues); and
(b) material documents and information exchanged between any regulatory authority and the [Developer] relating to a Project Vaccine.
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 1 clinical trials. Read in context.
Are there complementary activities that could be undertaken by the funder or other stakeholders to facilitate product registration?
Will the funded partner be required to grant rights of reference and/or exclusivity waivers as part of licensing and technology transfer commitments for the purposes of facilitating equitable access?
When and how will the funded partner provide updates on its product registration activities? Will information marketing approval information be reported more broadly for the awareness of relevant stakeholders?
Will periodic review of the regulatory strategy be part of the responsibilities of a joint steering committee?
Will the funder have rights of reference to the funded partner’s regulatory filings if an access license is exercised?
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.