Companion Diagnostics: Playing 5D Chess in Regulatory Development

The Complex Landscape of Companion Diagnostic Development
Multiple Boards, Multiple Rules: Global Regulatory Landscapes
The Co-Development Gambit: Strategic Coordination
Clinical Performance: The Endgame Strategy
Strategic Considerations for Success
The Precision Medicine Imperative
Mastering the Regulatory Chessboard

In traditional chess, players must think several moves ahead, considering how each piece movement affects the entire board. But imagine if the board had multiple dimensions, the rules changed mid-game, and success depended on coordinating not just your own pieces, but an entirely separate set operated by a pharmaceutical partner. Welcome to the world of companion diagnostics (CDx) development – where regulatory strategy requires the strategic thinking of 5D chess.

The Complex Landscape of CDx Development

Companion diagnostics (CDx), which is essential in precision medicine, is evolving toward a personalised treatment approach. One example of such application is a CDx test that identifies patients who can benefit from a specific drug and those who experience side effects of drugs for safe and effective treatment. Just as a chess grandmaster must simultaneously track multiple threats and opportunities across the board, CDx developers must navigate the intricate interplay between diagnostic performance, therapeutic efficacy, and regulatory compliance across multiple jurisdictions.

The complexity arises from the importance of CDx for the clinical use of biomarkers. Strict regulation is essential… Unlike traditional in vitro diagnostics (IVDs) that operate independently, CDx requires co-development with therapeutic products, creating a regulatory game of tactics where moves in the diagnostic pathway directly impact the pharmaceutical pathway – and vice versa.

Multiple Boards, Multiple Rules: Global Regulatory Landscapes

The chess analogy becomes even more apt when considering that regulatory agencies (FDA, EMA, MFDS, and MHRA) each operate with distinct requirements, much like playing simultaneous matches with different rule sets. Recent analysis reveals significant variations in how these regulatory bodies approach CDx validation.

The FDA emphasizes “devices that monitor response to treatment” within their CDx definition, while the EMA focuses more narrowly on patient selection and adverse reaction prediction. As another example, the Korean MFDS takes a risk-based approach, requiring demonstration that “the safety, efficacy, and efficiency of the drug are directly affected by the performance of the device.”

The UK’s post-Brexit regulatory landscape adds another dimension to this complexity. The UK MHRA is developing new regulations where companion diagnostics, software and AI diagnostic IVDs will be brought in scope of future UK regulations, representing a significant departure from the previous 30-year regulatory framework. The UK regulations will show significant alignment with the new UK MDR regulations and EU regulations while maintaining UK-specific adoptions.

These differences create what regulatory specialists often describe as a multi-dimensional regulatory matrix. Each agency requires different evidence packages, for example:

• FDA: Class II or III devices following 510(k) or PMA pathways;
• EMA: Class C devices under IVDR requiring conformity assessment carried out by a Notified Body; and
• UK MHRA: Transitioning to new MDR framework with International Recognition Procedures and alignment with EU standards while maintaining post-Brexit sovereignty.

The Co-Development Gambit: Strategic Coordination

Perhaps the most challenging aspect of the CDx chess game is the co-development requirement. Although co-development as a process does not require simultaneous development of the IVD companion diagnostic and the therapeutic product from beginning to end, the availability of an IVD with ‘market-ready’ analytical performance characteristics” is crucial for successful regulatory approval.

This creates a strategic puzzle where IVD companies must coordinate their development timelines, clinical trial designs, and regulatory submissions with pharmaceutical partners. The chess analogy holds: one poorly timed move can cascade into significant delays or regulatory setbacks for both products.

From an R&D perspective, lateral flow and other point-of-care technologies face additional challenges. While these platforms offer advantages in terms of accessibility and rapid turnaround times, they must demonstrate analytical performance equivalent to more complex laboratory-based assays used in pivotal clinical trials. This often requires sophisticated bridging studies to establish concordance between the clinical trial assay (CTA) and the commercial CDx platform.

Clinical Performance: The Endgame Strategy

Clinical validation of CDx through well-designed clinical studies demonstrating the ability of the test to identify patients likely to respond to the treatment represents the endgame.

Success requires demonstrating three critical elements:

1. Scientific validity of biomarker associations
2. Analytical performance of the diagnostic platform
3. Clinical performance in patient stratification

Recent regulatory developments have heightened scrutiny of clinical evidence requirements. Companion diagnostics are increasing clinical demand globally and regulatory frameworks for clinical validation are strengthening. This trend reflects the growing recognition that inadequate CDx performance can lead to inappropriate treatment decisions, as evidenced by recalls by regulatory bodies such as the FDA due to false-positives and other concerns.

Strategic Considerations for Success

Just as successful chess requires thinking multiple moves ahead, CDx development demands long-term strategic planning. Key considerations include:

• Analytical Validation Strategy: Platform selection must balance performance requirements with manufacturability and scalability. Lateral flow technologies, while attractive for point-of-care applications, require careful optimisation to achieve the precision and accuracy needed for patient stratification.
• Multi-Jurisdictional Planning: The regulatory chess game now involves coordinating across multiple jurisdictions with evolving frameworks. While the UK maintains transitional arrangements allowing “CE marked medical devices compliant with EU MDR can be placed on the Great Britain market up until the sooner of expiry of certificate or June 30, 2030,” manufacturers must prepare for diverging requirements. The MHRA aims to streamline market access for medical devices by recognising regulatory approvals from certain countries, but specific companion diagnostics (CDx) and co-packaged devices face restrictions.
• Clinical Trial Design: Clinical studies are conducted depending on whether pharmaceuticals and the CDx are co-developed, and bridging studies to evaluate device compatibility can also be conducted. The choice between prospective and retrospective study designs significantly impacts development timelines and regulatory acceptance across all jurisdictions.

European Harmonization Challenges: While EU member states operate under IVDR, the UK’s departure creates complexity and uncertainty for a period. Brexit introduced divergence, although the UK is now moving towards closer alignment with modern European standards.

• Global Regulatory Harmonization: While regulatory differences persist, “if an effective internationally harmonized clinical process framework is established for enhanced clinical regulation, it can contribute to providing a more personalized and effective treatment.“

The Precision Medicine Imperative

The pressure in this evolving regulatory landscape is mounting. Demand for companion diagnostics (CDx) is on the rise as the healthcare industry shifts towards precision medicine, and, around the world, healthcare systems understand that the effective use of precision medicine relies on dependable and validated companion diagnostics. These tools are crucial for accurately identifying which patients will benefit from specific therapies.

Although there’s a significant chance to improve patient outcomes in this growing market, and lower healthcare costs, the extensive data required to build a solid framework can be very time-consuming. This could potentially slow down the co-development and approval processes for new drugs and companion diagnostics.

Conclusion: Mastering the Regulatory Chessboard

 Success in companion diagnostics development demands the strategic foresight of a chess grandmaster; balancing analytical performance, clinical validation, regulatory compliance, manufacturing scalability, and commercial readiness, all at once.

Thriving in this environment requires more than technical know-how; it calls for a clear regulatory strategy from day one, seamless collaboration between diagnostic and pharmaceutical partners, and the agility to adapt as global requirements shift. Above all, the goal remains constant: bringing validated, high-quality diagnostic tools to market that empower clinicians to deliver targeted, effective treatments to the right patients.

Abingdon Health stands out in this demanding arena. With fully integrated CDMO operations in both the UK and US, Abingdon offers end-to-end companion diagnostics support – from assay development through analytical and clinical validation, technical file compilation, and successful regulatory submissions across FDA, CE, UKCA, and other global frameworks. Our regulatory team has an exceptional track record, including a 100% success rate on FDA Breakthrough submissions and over 100 FDA registrations to date. We combine deep lateral flow expertise, ISO-certified and FDA-compliant processes, and advanced manufacturing capabilities to ensure that our partners move confidently from concept to commercialization.

Biotech and pharma innovators are finding that partnering with Abingdon Health means having a trusted expert at every move—anticipating challenges, streamlining regulatory pathways, and accelerating time to market. In the high-stakes game of companion diagnostics, preparation, strategy, and flawless execution are non-negotiable. With Abingdon Health, you have a proven partner committed to your success at every step. Get in touch today to discuss your needs.