The Multidimensional Chessboard of ATMP Development
Why No Single Opening Wins the Same Game Twice
Executive Summary
Developers of advanced therapy medicinal products (ATMPs) face a regulatory landscape best understood not as a linear development checklist but as a multidimensional game of chess. Four regional players - the UK, the European Union, the United States and China - each maintain distinct expectations, regulations and product development pathways, whilst also continually evolving their legislation to attract developers and accelerate the development of innovative therapies. In this environment, there is no universally correct sequence to navigate the regions. The optimal move depends on which country, at which time, for which product, and for which modality - and a move that is optimal today may be different tomorrow as the rules of the contest and data change over time.
The Four-Player Board
The contest is overseen by four regional regulators, each offering developers different opportunities to accelerate programmes:
• United Kingdom (MHRA) - the proposed Rare Disease Therapies Regulatory Framework, alongside a strong reputation for the quality of its scientific assessment.
• United States (FDA) - an already comparatively quick and risk-proportionate approach to Phase I studies with accelerated IND pilot programmes under consideration to further speed early clinical entry.
• European Union (EMA) and its constituent Member States - the upcoming reform of the General Pharmaceutical Legislation, which will reshape incentives and procedures whilst aiming to bring convergence amongst EU member states.
• China - the investigator-initiated trial (IIT) pathway, which offers speed to clinical data but currently carries heightened caution.
Each region presents its own regulations with its own pathways (or “framework”), and each is making continual advances to remain globally competitive. A Queen’s Gambit in one region, a Sicilian Defence in another - the result is a board on which the same product can be advanced through very different opening moves depending on where and how the developer chooses to play first. There is no universally applicable opening, only the one best suited to the developer’s long game.
Why the Right Move Changes
Because all four regulators are simultaneously amending their frameworks, the strategic value of any given pathway is unstable. A framework that offers the fastest route to patients today, may be superseded, tightened or overtaken by a particular region's reform or even a competitor decision later. The developer must therefore weigh the current state of play and potential future opportunities rather than a fixed rulebook.
China's IIT pathway illustrates this vividly. It offers a route to rapid clinical experience, but three recently announced deaths - spanning a base-editing trial for a rare neurodevelopmental disorder, a CRISPR gene-editing trial for Duchenne muscular dystrophy, and an in vivo CAR-T trial for an autoimmune disease - have been disclosed across separate IITs over the past year opening questions on China as a starting point for development. This has meant some developers are not fully utilising pathways in the region, while others are proceeding with greater caution. Speed and risk are not fixed attributes of a pathway - they move with events.
Convergence, Divergence and Competition
Regulators operate under a shared principle: converge where they can, diverge only where there is genuine need. Alignment reduces duplication and helps patients globally. Yet the same regulators are also competing with one another to be the jurisdiction of choice that attracts and retains developers and increases the opportunity to grant first approvals. This tension - cooperative in principle, competitive in practice - is precisely what multiplies the opportunities a developer must evaluate, and what makes a single global strategy difficult to prescribe in advance.
Leveraging International Precedents and Recognition
A key component to winning the game is of the ability to know when and how to leverage regulatory precedent (both directly and indirectly), combined with deep local understanding of individual regional pathways alongside international interplay opportunities and recognition procedures. These international recognition procedures are not symmetrical, and three factors govern the direction in which recognition can flow:
1. Development Stage
Typically international recognition procedures are only applicable at the marketing authorisation stage, however within Europe the ability to leverage a clinical trial approval from a Reporting Member State to add additional countries to a trial can facilitate time to initial clinical trial startup and enable trial expansion within Europe later.
2. Market Size
Market size frequently dictates which direction commercial recognition will travel. Approvals from larger markets tend to carry greater downstream leverage, and developers must sequence their filings with this asymmetry in mind.
3. Quality of the Regulator's Assessment
The reputation and rigour of the assessing regulator can offset a disadvantage in market size. The UK is a strong example and since the MHRA has a good reputation for the quality of its assessment and hence a UK approval may bilaterally be recognised in support of an approval in a larger market despite the difference in market size, and can unilaterally serve as a reference regulator for other, smaller markets.
Strategic Implications for Developers
• There is no default opening. The appropriate moves depends on product, modality, timing and target region simultaneously.
• Play the position, not a fixed script. Ongoing legislative change means the plan should be revisited continuously, not set once.
• Mind your move order. The sequence matters when data generation to derisk other regional opportunities is advantageous and recognition procedures depend on market size and assessment quality.
• Don’t mistake speed for a winning attack. A fast pathway can become a cautionary one, as recent events show.
• Let a strong opening earn you momentum. A rigorous first approval - such as from the MHRA - can unlock disproportionately large downstream value.
Conclusion
ATMP development is a contest played across four boards at once, against opponents who are simultaneously collaborating and competing, on a set of rules that is constantly being rewritten. Winning - getting a product to patients fastest in a chosen region - requires treating regulatory strategy as a live, multidimensional game where the game is played in all regions concurrently rather than a fixed route. The developers who succeed will be those who read the current state of play, anticipate the next move, and sequence their approvals to turn each regulator's strengths, and each region's asymmetries, to their advantage.
About PrimeRA Pharma Partners
PrimeRA Pharma Partners provides senior regulatory and development leadership for cell and gene therapy companies pursuing international development. Our partners bring extensive regulatory, CMC and clinical-development experience across the EU, UK and US, working alongside client teams to provide clear direction, support critical decisions and maintain continuity through each stage of programme development.
PrimeRA brings together four core pillars — Leadership, Delivery, Representation, and Insight — spanning embedded senior regulatory direction, regulatory authoring and submission delivery, agency engagement, and independent strategic evaluation of programmes, portfolios and regulatory pathways. For eligible overseas sponsors, PrimeRA can also act as a named FDA US Agent, EU Representative and MHRA UK Representative. CMC leadership is integrated throughout, connecting development and manufacturing strategy with the regulatory requirements that shape clinical development and market access.
This article is provided for general informational and educational purposes only. It reflects the views and experience of PrimeRA Pharma Partners, LLP and does not constitute regulatory, legal, or investment advice, nor should it be relied upon as such. Regulatory requirements and outcomes vary by product, programme, jurisdiction, and the specific circumstances of each applicant. Nothing in this article guarantees or implies any particular regulatory outcome, decision, timeline, or designation. References to regulatory authorities (including the MHRA, EMA, and FDA) do not imply any endorsement, affiliation, or approval by those authorities. For advice specific to your programme, please contact PrimeRA Pharma Partners directly.