MAPGuideⓇ
Equitable Access Toolkit
Product Registration Commitments for Licensed 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. License and collaboration agreements may include product registration provisions as part of a party’s commitments to facilitating timely access to, and availability of a licensed product. However, the use of such provisions is likely to depend on the scope and purpose of the agreement. In particular:
Upstream agreements for products in early-stage development, might include high level statements related to marketing approvals as part of the access principles under the agreement [link], but they may be less likely to include concrete commitments and timelines due to limitations in the information available about potential regulatory pathways for the product and/or because the licensee unlikely to be the eventual marketing authorization holder for the product.
Downstream agreements entered into specifically for the purpose of facilitating access to a licensed product may include detailed obligations for a licensee to apply for marketing approvals from specified regulatory authorities within certain timeframes.
Some considerations for establishing product registration commitments in license and collaboration agreements, where appropriate, include: (i) who will be responsible for product registration; (ii) whether licensed rights include rights of reference to regulatory filings; (ii) the regulatory authorities from which to seek authorization; (iv) the type of authorization required; and (v) the expected timeline for making the required regulatory submissions.
Responsibility for product registration
Some agreements may anticipate the division of product registration responsibilities for different markets between the agreement parties. For example, a PDP or non-profit developer may take responsibility for the access territory, while a commercial partner takes responsibility for high income markets.
The establishment of the respective roles and responsibilities of the parties may be set out in agreement provisions or through the development of a regulatory strategy, potentially connected to an access plan.
Rights of reference
Some agreements include commitments from one or more of the parties to grant a right of reference to its regulatory submissions and/or to grant regulatory exclusivity waivers to another party if necessary for product registration purposes. This allows a licensee to use data previously submitted by a licensor in support of regulatory applications, potentially removing the need to conduct additional clinical trials, and reducing the amount of time needed to obtain marketing approval.
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 licensed 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.
Licensed products may additionally 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 licensed 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, license and collaboration 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
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
As between the Parties, the [Licensee] will be solely responsible for conducting all activities relating to obtaining Regulatory Approvals with respect to the Licensed Product in the Licensed Field in the Territory, including preparing and submitting Regulatory Submissions and attending meetings with Regulatory Authorities.
[…]
[Licensor] hereby grants to the [Licensee] (which the [Licensee] may extend to its sublicensees and contractors) a Right of Reference to Regulatory Submissions (and underlying Information) submitted by or on behalf of Atreca (including those of its Affiliates and [Licensor] Sublicensees) to the extent necessary or useful for the exercise of the [Licensee]’s rights granted pursuant to this Agreement.
[…]
[Licensor] and the [Licensor] Sublicensees and contractors may use and reference the [Licensee]’s Shared Data (including data generated prior to and including clinical trial applications (e.g., IND submissions or comparable applications to a Regulatory Authority if filed outside of the United States), clinical trial data, documents pertaining to the design or implementation of clinical studies, including the Trial Master File (TMF) or equivalent, and any Regulatory Submissions) and the [Licensee] Biological Materials generated, made, or produced by [***] or other third parties, as sublicensees of the [Licensee] hereunder, […] for commercial purposes (i.e., any purposes other than internal research purposes, including Development, Manufacture, and Commercialization of the [Licensor] Antibodies) outside the Territory (“Commercial License“).
Source: taken from a license agreement between Atreca, Inc (Licensor) and Gates Medical Research Institute (Licensee). Partner types: non-profit research institute, industry; Product type: prophylactic malaria mAb; Development stage at signature: pre-clinical. Read in context.
The Regulatory Strategy (including timelines and milestones) for the registration of the Product shall be defined by the Parties, following the high–level Access and Implementation Plan. Upon agreement on the Regulatory Strategy for a country, the Parties shall jointly establish a detailed Access and Implementation Plan for such country to ensure availability of the Product through public and private distribution channels in the Territory on an Affordable Basis. The Regulatory Strategy will for the time being be based on the process under Article 58 of Regulation (EC) No. 776/2004 and on the local registration requirements in the Territory. Any other regulatory mechanism that could facilitate registration of a Product in the Field in the Territory shall be considered by the Parties and could possibly lead to a change in the Regulatory Strategy upon written agreement between the Parties.
The Party responsible for a relevant clinical trial shall lead and be responsible for the Regulatory Strategy of such clinical trial in consultation with the other Party.
Partner shall be responsible for obtaining and maintaining Marketing Authorizations for the Product covering the Territory.
The roles and responsibilities of the Parties are defined by the Parties in the Regulatory Responsibilities Plan. In case of contradictions between the Regulatory Responsibilities Plan and the terms of the main body of this Agreement, the terms of the main body of this Agreement shall prevail. The Parties shall also undertake their roles and activities at all times with the goal of making a Product available on an Affordable Basis in the Field in the Territory as early as possible.
[…]
Support for Registration. [PDP] shall use its Reasonable Efforts to assist Partner in obtaining the Marketing Authorisation of the Product for use in the Field in the Territory, and in answering questions from any Regulatory Authority with respect to the Product.
Source: taken from DNDi’s template Development Collaboration and License Agreement. Partner types: PDP, industry/academic institutions; Product type: treatments for neglected diseases; Development stage at signature: template intended for use from Phase 1 clinical trials through to proof of concept in humans. Read in context.
Licensee shall submit a complete file for WHO Pre-qualification or any SRA approval within 36 months from the Effective Date for any existing formulation of the Products, or within a period to be agreed among [Head Licensor], [Licensor] and Licensee for any new formulation of the Product. Licensee will diligently pursue such applications following submission. The Licensee agrees, where applicable and to the extent that it is able: (a) to not seek; and (b) to waive, regulatory exclusivity in the Territory in relation to any data relating to the Products.
Source: taken from a form of sublicense attached to a license agreement between Merck (Head Licensor) and MPP (Licensor). Partner types: multilateral, industry; Product type: COVID-19 therapeutic (molnupiravir); Development stage at signature: late clinical/pending EUA. Read in context.
The Licensed Products will be registered in certain priority countries as designated by [Licensor], upon agreement with [Funder] to determine the registration plan and timeline.
Source: taken from commercialization agreement term sheet attached to a patent and know-how license between the University of Washington (Head Licensor) and the Medicines Patent Pool (Licensor). The license grant to MPP was required under a related grant agreement between Unitaid (Funder) and University of Washington. Partner types: multilateral, academic institution; Product type: HIV therapeutic (long-acting injectable); Development stage at signature: pre-clinical. Read in context.
Licensee shall file for WHO Pre-qualification or any Stringent Regulatory Authority approval as soon as possible and in any event not later than within 36 months from the Sublicence Effective Date in each case using the fastest approval route possible and will diligently pursue such applications following submission.
The Licensee shall file for Regulatory Approval for the Product before the Relevant Regulatory Authority in each country of the Territory as soon as possible and in any event not later than 36 months from the Sublicense Effective Date and will diligently pursue such applications following submission.
Related definitions:
- “Regulatory Approval” shall mean, in relation to each country of the Territory and each Product, the receipt of a marketing authorisation associated with that Product for that country.
- “Relevant Regulatory Authority” shall mean (i) in relation to a particular country in the Territory, any applicable federal, national, regional, state, provincial, or local regulatory agencies, departments, bureaus, commissions, councils or other government entities regulating or otherwise exercising authority with respect to the Products in that country, or (ii) WHO pre-qualification programme where such approval has been deemed adequate by the authority referred to in (i).
Source: Taken from the form of sublicense annex of a license agreement between Novartis (Head Licensor) and MPP (Licensor). Partner types: industry, multilateral; Product type: cancer therapeutic (nilotinib); Development stage at signature: licensed product on WHO EML. Read in context.
As required by [Licensor], in the event that any [Product is] included in WHO Guidelines or in the expression of interest for WHO pre-qualification of medicines, Licensee shall apply for WHO pre-qualification or FDA conditional approval for each such Product so included no later than by the third anniversary of any such inclusion.
Source: Taken from a license agreement between Gilead (Head Licensor), MPP (Licensor), and Arene Lifesciences (Licensee). Partner types: industry, multilateral; Product type: HIV treatment and PreP; Development stage at signature: licensed product. Read in context.
If Licensee obtains, and verifies to [Licensor] that it has obtained, all applicable Marketing Authorizations for each of the eighteen (18) Target Countries within three (3) years of the earlier of the date upon which [Licensor] receives (a) FDA approval; or (b) WHO PQ for the Product, then [Licensor] will consider appointing Licensee as a preferred partner (subject to Licensee fulfilling other relevant selection criteria) with respect to any future product formulation of [product] which [Licensor] is intending to license.
Source: taken from a Gilead template license agreement for generic manufacturing. Partner types: industry; Product type: multi-drug-resistant HIV treatment and PrEP (lenacapavir); Development stage at signature: licensed product (treatment), phase 3 clinical trials completed (PrEP). Read in context.
Are there complementary activities that could be undertaken by the agreement parties or other stakeholders to facilitate product registration?
Will the development of a strategy for product registration be incorporated into an access plan attached to the agreement?
Will the licensee be required to grant rights of reference and/or exclusivity waivers as part of sublicensing and technology transfer commitments for the purposes of facilitating equitable access?
What information will the licensee report to the licensor in relation to 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?
Is there a mechanism to require the grant of sublicenses or the reversion of rights to the licensor if the licensee is unable, or chooses not to, apply for marketing authorization in certain countries?
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.