COMBINE Programme: Streamlining EU Combined Studies for Medicines, Devices, and Diagnostics

December 17, 2024

Introduction to the COMBINE Programme

The European Union has taken a significant step towards streamlining combined studies involving medicinal products, medical devices, and in vitro diagnostics (IVDs) through the COMBINE Programme. Endorsed by national authorities across Member States, the programme aims to address long-standing challenges that hinder the efficiency of clinical trials and regulatory approvals under the Clinical Trials Regulation (CTR), Medical Device Regulation (MDR), and In Vitro Diagnostic Regulation (IVDR).

The Need for Streamlined Combined Studies

Combined studies, which investigate the use of multiple healthcare products—such as a medicinal product with a medical device or companion diagnostic—are essential for advancing patient care and supporting innovative treatments. However, the fragmented regulatory processes across the CTR, MDR, and IVDR create significant hurdles:

Administrative Complexity: Sponsors face parallel and often redundant assessment processes across Member States, leading to delays.
Ambiguities in Regulation: Overlapping requirements on reporting and classification of studies often result in confusion.
Harmonisation Gaps: Diverging approaches among national competent authorities slow down multi-country studies.

These challenges risk delaying the development and availability of critical healthcare solutions, impacting patients and stifling innovation.

The COMBINE Programme: A Collaborative EU Initiative

To overcome these challenges, the European Commission launched the COMBINE Programme, a cross-sector initiative designed to foster collaboration between regulatory authorities, ethics committees, and stakeholders. By unifying processes and addressing gaps at the interface of CTR, MDR, and IVDR, the COMBINE Programme sets out to:

Simplify and harmonise the approval of combined studies across the EU.
Improve collaboration between national competent authorities, the European Medicines Agency (EMA), ethics committees, and sponsors.
Enhance Europe’s competitiveness in clinical research, aligning with the recommendations of the Draghi Report.

A Phased Approach to Change

The COMBINE Programme will be implemented over the coming years through seven cross-sector projects that focus on key areas such as piloting single assessment processes, harmonising serious adverse event (SAE) reporting, and enhancing advisory services for sponsors. The programme reflects a shared commitment to supporting innovation while ensuring patient safety and regulatory efficiency across the EU.

The Seven Cross-Sector Projects of the COMBINE Programme

The COMBINE Programme will be implemented through seven cross-sector projects, each addressing specific challenges in the regulatory landscape of combined studies. These projects represent a collaborative effort between national competent authorities, ethics committees, the European Medicines Agency (EMA), and other stakeholders to streamline processes, harmonise reporting, and improve advisory services for sponsors.

1. Piloting a Single Assessment Process for Multi-Country Combined Studies

Objective: Introduce a coordinated, unified assessment process for combined studies involving medicinal products, medical devices, and in vitro diagnostics across multiple EU Member States.
Why It Matters: Current processes require separate national submissions under different frameworks (CTR, MDR, and IVDR). This pilot project aims to reduce duplication, align timelines, and ensure a single, streamlined review process.
Outcome: A harmonised approach that accelerates study approvals, reduces administrative burden, and improves efficiency for sponsors conducting multinational combined studies.

2. Harmonisation of Serious Adverse Event (SAE) Reporting Processes

Objective: Align the reporting requirements for Serious Adverse Events (SAEs) across the CTR, MDR, and IVDR frameworks.
Challenges Addressed: SAEs are reported differently under each regulation, creating confusion and inefficiencies for sponsors and regulators. Lack of harmonised processes delays decision-making and impacts patient safety monitoring.
Outcome: A unified, consistent SAE reporting process that improves clarity, facilitates timely reporting, and ensures compliance across sectors.

3. Clarifying the Interface Between Clinical Trials and Medical Device Regulations

Objective: Resolve regulatory ambiguities where the Clinical Trials Regulation (CTR) intersects with the Medical Device Regulation (MDR) and IVD Regulation (IVDR).
Key Questions Addressed: When does a study require a Clinical Trial (CT), a Clinical Investigation (CI), or a Performance Study (PS)? How should combined studies be classified and approved under multiple regulatory frameworks?
Outcome: Clear, harmonised guidelines for sponsors and regulators to navigate the interface between these regulations, ensuring smoother approvals and regulatory compliance.

4. Enhancing Advisory Services for Sponsors

Objective: Explore new opportunities for providing coordinated, cross-sector advice to sponsors conducting combined studies.
Why It Matters: Sponsors often face uncertainty when designing combined studies due to fragmented regulatory advice. A lack of centralized guidance increases the risk of regulatory non-compliance and delays.
Outcome: Improved advisory mechanisms, such as coordinated pre-submission meetings, that help sponsors navigate regulatory complexities, streamline submissions, and accelerate study timelines.

5. Facilitating Knowledge Exchange Between National Authorities

Objective: Promote collaboration and knowledge sharing among national competent authorities, ethics committees, and regulatory bodies.
Key Actions: Establish platforms for cross-sector dialogue and exchange of best practices. Encourage joint discussions on shared challenges, such as study assessments, adverse event reporting, and ethical considerations.
Outcome: A stronger, more unified regulatory network capable of addressing challenges efficiently and supporting the successful implementation of combined studies across the EU.

6. Aligning Regulatory Timelines and Approval Processes

Objective: Harmonise the timelines and approval procedures for combined studies under the CTR, MDR, and IVDR frameworks.
Challenges Addressed: Variations in national processes and timelines result in delays, particularly for multi-country studies. Sponsors face inconsistent requirements, creating additional administrative burden.
Outcome: A coordinated approach that aligns national approval processes, ensures predictable timelines, and fosters greater consistency across Member States.

7. Strengthening Stakeholder Engagement for the COMBINE Programme

Objective: Foster open dialogue and collaboration with key stakeholders, including sponsors, clinicians, patient representatives, and ethics committees.
Why It’s Important: Involving stakeholders ensures that the solutions developed under the COMBINE Programme are practical, efficient, and patient-centric. Enhanced engagement helps address real-world challenges faced by industry and clinicians in conducting combined studies.
Outcome: Improved stakeholder collaboration that ensures the programme’s goals align with industry needs, supports innovation, and prioritises patient outcomes.

Driving Regulatory Innovation Through the COMBINE Programme

The seven cross-sector projects under the COMBINE Programme address the core challenges of combined studies by streamlining processes, clarifying regulatory requirements, and fostering collaboration across the EU. These efforts are essential for improving efficiency, reducing delays, and enabling the development of innovative treatments that combine medicines, medical devices, and diagnostics.

Why the COMBINE Programme Matters

The COMBINE Programme represents a pivotal step toward addressing the regulatory inefficiencies that have long challenged combined studies involving medicinal products, medical devices, and diagnostics. By introducing streamlined processes, harmonising reporting requirements, and fostering collaboration, the programme delivers tangible benefits for all stakeholders.

For Sponsors and Manufacturers: Streamlined Approval Processes

Simplified Submissions: The COMBINE Programme eliminates duplication by piloting a single assessment process for multi-country combined studies.
Reduced Administrative Burden: Sponsors will no longer have to navigate fragmented processes under the CTR, MDR, and IVDR, reducing time spent on regulatory paperwork.
Faster Approvals: Harmonised timelines and improved coordination across Member States will accelerate approvals for combined studies, enabling quicker market entry for innovative products.

For a sponsor conducting a clinical trial of a medicinal product alongside a performance study of an IVD, the single assessment process reduces redundant national submissions, ensuring a smoother and faster pathway to approval.

For National Competent Authorities and Ethics Committees: Improved Collaboration and Efficiency

Unified Approach: The programme fosters collaboration between national authorities, ethics committees, and the EMA, ensuring consistency in study evaluations.
Knowledge Sharing: By facilitating the exchange of best practices, authorities can address common challenges, such as adverse event reporting and interface ambiguities, more effectively.
Efficient Use of Resources: Coordinated assessment processes streamline workflows, reducing the strain on regulatory bodies and ensuring a more efficient allocation of resources.

For Patients: Faster Access to Innovative Treatments

Accelerated Innovation: By simplifying regulatory pathways, the COMBINE Programme ensures that groundbreaking treatments—such as combined therapies and diagnostics—reach patients more quickly.
Improved Safety: Harmonised serious adverse event (SAE) reporting enhances patient safety by ensuring timely and consistent monitoring across all regulatory sectors.
Personalised Medicine: Combined studies enable the development of advanced solutions, such as companion diagnostics paired with targeted therapies, leading to more tailored and effective treatment options.

In diseases like cancer, where combined studies often involve companion diagnostics and therapies, delays in approval can mean a delay in access to life-saving treatments. The COMBINE Programme aims to eliminate these delays, prioritising patient needs.

For the EU: Enhancing Global Competitiveness

Addressing Recommendations from the Draghi Report: The Draghi Report underscored the importance of regulatory efficiency in maintaining the EU’s leadership in clinical research and innovation. The COMBINE Programme aligns directly with these goals, strengthening Europe’s position as a global hub for clinical trials.
Attracting Global Studies: A streamlined, harmonised approach makes the EU more attractive for multinational combined studies, encouraging sponsors to invest in research within Europe.
Supporting Innovation Ecosystems: By addressing regulatory hurdles, the programme fosters an environment conducive to innovation, benefiting SMEs, manufacturers, and healthcare systems.

The COMBINE Programme positions Europe as a leader in integrated clinical research, ensuring the EU remains competitive in the rapidly evolving MedTech and pharmaceutical industries.

Driving Real-World Impact Across Sectors

By addressing the challenges of combined studies, the COMBINE Programme delivers a balanced solution that benefits all stakeholders. For sponsors, it reduces complexity and accelerates approvals. For regulators, it ensures efficiency and collaboration. Most importantly, for patients, it enables faster access to innovative treatments that improve healthcare outcomes.

The COMBINE Programme and EU Competitiveness

The COMBINE Programme is not only a solution to regulatory complexity but also a cornerstone of the EU’s broader strategy to maintain global competitiveness in clinical research and medical innovation. By streamlining processes and fostering collaboration, the programme positions Europe as a leading region for conducting combined studies that integrate medicinal products, medical devices, and diagnostics.

Addressing the Recommendations of the Draghi Report

The Draghi Report, which outlines key priorities for strengthening Europe’s economic and technological competitiveness, highlights the importance of a streamlined regulatory environment for innovation in clinical research. The COMBINE Programme directly supports these recommendations by:

Reducing Regulatory Complexity: Simplifying combined studies ensures a faster path from research to patient access, allowing Europe to stay ahead of global competition.
Promoting Innovation: A harmonised and efficient system encourages sponsors and manufacturers to invest in research and development within the EU.
Improving Market Access: By removing administrative barriers, new treatments can reach the market sooner, boosting Europe’s role as a leader in health innovation.

Strengthening the EU as a Global Hub for Clinical Research

1. Attracting Multinational Studies

Global sponsors often face challenges when navigating fragmented regulatory systems in the EU. The COMBINE Programme resolves these issues by:

Offering single, coordinated assessments for multi-country studies.
Harmonising timelines and reporting requirements under the CTR, MDR, and IVDR frameworks.

This streamlined approach makes the EU a more attractive destination for conducting global clinical studies, ensuring sponsors can leverage Europe’s vast expertise, resources, and patient access.

2. Fostering Cross-Sector Innovation

The growing trend of personalised medicine relies on combining medicinal products with diagnostic devices. The COMBINE Programme removes regulatory hurdles that delay the integration of:

Companion diagnostics: Ensuring that innovative treatments are paired with advanced diagnostics for targeted patient care.
Advanced therapies: Supporting innovative combined treatments for diseases such as cancer, cardiovascular conditions, and rare diseases.

By addressing these challenges, the EU fosters a dynamic environment where innovation can thrive across sectors, benefiting both industry and patients.

3. Supporting Small and Medium Enterprises (SMEs)

The COMBINE Programme simplifies regulatory pathways, which is particularly critical for SMEs in the MedTech and pharmaceutical sectors. These companies often face resource constraints when navigating complex regulations. By providing:

Clear guidance on the interface between CTR, MDR, and IVDR.
Access to advisory services for combined studies.
Predictable timelines through harmonised processes.

The programme ensures SMEs can bring innovative products to market faster, strengthening Europe’s innovation ecosystem.

Delivering Economic and Healthcare Benefits

The successful implementation of the COMBINE Programme will not only drive regulatory efficiency but also deliver far-reaching benefits across Europe:

Economic Growth:

Attracting more clinical trials and combined studies generates investments in research and development, boosting the EU economy.
Improved innovation pathways strengthen the global competitiveness of EU-based manufacturers and sponsors

Healthcare Advancements:

Patients benefit from accelerated access to cutting-edge treatments that combine medicinal products, medical devices, and diagnostics.
A harmonised system ensures safer, more effective healthcare solutions reach the market efficiently.

For a European SME developing an innovative therapy paired with a diagnostic IVD, the streamlined approval process reduces delays, allowing faster market entry and broader patient access.

The EU’s Vision for Clinical Research Leadership

Through the COMBINE Programme, the European Union reaffirms its commitment to fostering innovation, supporting collaboration, and maintaining its position as a global leader in clinical research. By addressing regulatory inefficiencies and harmonising processes, the programme ensures that Europe remains an attractive hub for sponsors, manufacturers, and researchers driving the next generation of medical advancements.

Key Takeaway

The COMBINE Programme is a critical initiative that strengthens Europe’s competitive edge in clinical research. By simplifying pathways for combined studies, fostering innovation, and aligning with strategic goals outlined in the Draghi Report, the programme sets the stage for economic growth, global leadership, and improved patient outcomes across the EU.

Implementation and Next Steps for the COMBINE Programme

The successful roll-out of the COMBINE Programme requires a structured, phased approach to ensure that its ambitious goals are achieved efficiently and effectively. By leveraging cross-sector collaboration, pilot projects, and continuous evaluation, the programme sets the stage for lasting regulatory improvements across the EU.

COMBINE Programme Phased Rollout

The COMBINE Programme will be implemented in three key stages over the coming years:

1. Stage 1: Pilot and Early Initiatives (2024–2025)

Key Focus:

Launch the pilot for a single assessment process for combined studies involving medicinal products and medical devices across multiple Member States.
Initiate harmonisation efforts for Serious Adverse Event (SAE) reporting, streamlining processes under the CTR, MDR, and IVDR

Actions:

Identify candidate combined studies for the single assessment pilot.
Establish cross-functional task forces to develop and test harmonised SAE reporting frameworks.

Outcome: Early learnings from pilot initiatives will inform best practices and provide actionable insights for scaling solutions across the EU.

2. Stage 2: Scaling and Integration (2025–2026)

Key Focus:

Expand successful pilot initiatives, integrating the single assessment process into broader multi-country studies.
Strengthen cross-sector collaboration by enhancing knowledge exchange between national authorities and ethics committees.

Actions:

Roll out the harmonised assessment framework to additional Member States.
Launch training programmes to support national authorities, ethics committees, and sponsors in implementing new processes.
Develop and publish clear interface guidance to resolve ambiguities between CTR, MDR, and IVDR.

Outcome: A more unified and harmonised approach to combined studies across Member States, improving regulatory efficiency and reducing delays.

3. Stage 3: Full Implementation and Evaluation (2026–2027)

Key Focus:

Achieve full implementation of the programme’s objectives, ensuring long-term sustainability and continuous improvement.
Monitor progress and evaluate the impact of the COMBINE Programme on EU clinical research and innovation.

Actions:

Conduct comprehensive evaluations of the programme’s milestones, assessing its success in streamlining combined studies and supporting stakeholders.
Strengthen engagement with sponsors, clinicians, and patient representatives to identify opportunities for further refinement.
Publish progress reports to share achievements, challenges, and next steps.

Outcome: A fully harmonised regulatory framework that makes the EU a global leader in supporting combined studies of medicinal products, medical devices, and diagnostics.

Key Stakeholders Driving Implementation

The successful implementation of the COMBINE Programme depends on collaboration among a wide range of stakeholders, including:

National Competent Authorities (NCAs): Leading the development and execution of pilot initiatives and harmonised frameworks at the Member State level.
European Medicines Agency (EMA): Providing regulatory expertise, scientific consultation, and coordination for multi-country studies.
Ethics Committees: Aligning ethical review processes with the programme’s streamlined assessment objectives.
Sponsors and Manufacturers: Engaging in pilot studies, providing feedback, and adopting new processes to improve study timelines and regulatory compliance.
Clinicians and Patient Representatives: Contributing real-world perspectives to ensure that the programme prioritises patient safety and healthcare innovation.

Monitoring Progress and Ensuring Accountability

To ensure the COMBINE Programme delivers its objectives, robust monitoring and evaluation mechanisms will be implemented:

Regular Progress Reports: Published at key milestones to assess the programme’s impact, identify challenges, and showcase achievements.
Feedback Loops: Stakeholder input, including sponsors, NCAs, and ethics committees, will be collected to refine processes and address emerging issues.
Performance Metrics: Defined to measure success, including:
- Reduction in approval timelines for multi-country combined studies.
- Increased consistency in serious adverse event reporting.
- Improved clarity on the interface between clinical trials and medical device regulations.

Building a Sustainable Future for Combined Studies

The COMBINE Programme is not just a short-term solution but a long-term framework for driving innovation and efficiency in EU clinical research. By fostering collaboration, aligning processes, and prioritising continuous improvement, the programme ensures that Europe remains at the forefront of healthcare innovation.

What’s Next for Stakeholders?

As the COMBINE Programme progresses, stakeholders can expect:

Opportunities to Participate in Pilots: Sponsors and manufacturers are encouraged to engage with pilot projects for the single assessment process.
Clearer Guidance: Publication of harmonised frameworks and interface clarifications to reduce regulatory ambiguity.
Improved Communication: Enhanced dialogue between regulators, sponsors, ethics committees, and patient representatives.

By working together, all stakeholders can contribute to the success of the COMBINE Programme, ensuring it delivers its vision of a harmonised, streamlined regulatory environment for combined studies.

Key Takeaway: The phased implementation of the COMBINE Programme marks a transformative shift in the EU’s approach to combined studies. Through pilots, collaboration, and continuous evaluation, the programme sets the foundation for faster, more efficient approvals that benefit sponsors, regulators, and—most importantly—patients.

Conclusion: A Unified Vision for Combined Studies

The COMBINE Programme marks a pivotal step in the European Union’s commitment to creating a harmonised, efficient, and collaborative regulatory framework for combined studies. By addressing long-standing challenges at the intersection of the Clinical Trials Regulation (CTR), Medical Device Regulation (MDR), and In Vitro Diagnostic Regulation (IVDR), the programme sets a clear path toward innovation, competitiveness, and improved patient care.

Transforming Regulatory Efficiency

Through its seven cross-sector projects, the COMBINE Programme delivers concrete solutions to streamline combined studies:

Simplifying approvals with a single assessment process for multi-country studies.
Aligning serious adverse event (SAE) reporting across sectors to ensure safety and consistency.
Clarifying regulatory interfaces to resolve ambiguities between clinical trials and device regulations.
Fostering collaboration among national competent authorities, ethics committees, and stakeholders to promote knowledge exchange and efficiency.

These efforts reduce administrative burdens, harmonise timelines, and improve access to clear, actionable regulatory guidance.

COMBINE Programme Supporting Innovation and Competitiveness

By eliminating regulatory fragmentation and ensuring consistent, coordinated processes, the COMBINE Programme positions the EU as a global leader in clinical research and medical innovation.

Sponsors and manufacturers benefit from faster approvals and streamlined pathways, enabling them to bring innovative treatments to market more efficiently.
Patients gain quicker access to integrated healthcare solutions, including advanced therapies, medical devices, and companion diagnostics.
National authorities and ethics committees operate within a more efficient, harmonised framework, reducing duplication and ensuring safety.

In alignment with the Draghi Report recommendations, the COMBINE Programme strengthens Europe’s competitive edge, attracting global investment and driving economic growth in the MedTech and pharmaceutical sectors.

Looking Ahead: A Future of Innovation and Collaboration

The COMBINE Programme is more than a regulatory initiative; it is a transformative vision for the future of clinical research in the EU. By fostering collaboration, harmonising processes, and streamlining combined studies, the programme paves the way for a new era of healthcare innovation.

As Europe continues to lead the charge in medical and clinical advancements, the COMBINE Programme will play a critical role in ensuring that innovative treatments reach patients faster, safer, and more effectively.

Key Takeaway: The COMBINE Programme unifies the efforts of regulators, stakeholders, and innovators to streamline combined studies, strengthen Europe’s leadership in clinical research, and deliver groundbreaking healthcare solutions to patients across the EU.

Call to Action for the COMBINE Programme

Are you planning or conducting a combined study involving medicines, medical devices, or diagnostics? The MDx team is here to help you navigate the complexities of the COMBINE framework. Contact us today to streamline your regulatory strategy and ensure the success of your combined study.

Get in touch with the MDx team now to accelerate innovation and bring your study to life!

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MDCG 2020-16 Rev.3 classification rules

July 9, 2024

MDCG 2020-16 Rev.3 classification rules provide essential guidance on how to classify in vitro diagnostic medical devices (IVDs) under the EU IVDR. The latest revision enhances clarity, addresses known ambiguities, and strengthens consistency in how Annex VIII classification rules are applied. For manufacturers, understanding these updates is critical to ensuring correct classification, smoother conformity assessment, and regulatory compliance.

This article covers two areas:

the key updates introduced in Rev.3, and
how the guidance applies to major IVD categories, including Companion Diagnostics (CDx), Next‑Generation Sequencing (NGS), self‑testing, and Near‑Patient Testing (NPT).

Key Updates in MDCG 2020-16 Rev.3 classification rules

New Definition of “Kit”

Rev.3 introduces a formal definition of a kit:
A set of components packaged together and intended for a specific IVD examination or part of it.
This definition improves consistency in how kit-based products are classified.

Rule 3(a) – Updated Examples

Monkeypox Virus has been added to the list of organisms under this rule, reflecting current public‑health priorities.

Rule 4(a) – Clarifications for Self‑Testing IVDs

Rev.3 provides detailed guidance for the classification of self‑testing devices:

Devices for detecting pregnancy, fertility, cholesterol, glucose, erythrocytes, leukocytes, and bacteria in urine remain Class B.
Devices detecting both a Class C marker and an exception marker are Class C, following implementing rules 1.8–1.9.
Devices meeting the criteria under rules 1.8–1.9 can be Class D, including self‑tests for HIV from fingerprick blood.

Information Society Services

Devices used within online services are considered self‑testing devices only when the lay user performs part of the testing procedure.
Specimen-only actions (e.g., stabilizing or collecting the sample) do not make a device self‑testing.

Standalone Specimen Receptacles

Specimen-only collection kits offered online are not classified as self‑testing.

Examples in Rev.3

Glucose meters/strips for capillary blood → Class C
Calprotectin tests with lay interpretation via image upload → Class C
HIV antibody self‑tests (fingerprick) → Class D

Rule 5(c) – Expanded Rationale and Examples

Definition and Classification

Specimen receptacles are defined as containers (evacuated or non‑evacuated, empty or prefilled) for the primary containment and transport of biological specimens.
They are classified as Class A, as they do not perform any analytical function.

Use in Kits

Specimen receptacles included in kits for specimen collection remain Class A, even when accompanied by non‑IVD components.

User Actions

Actions such as gargling, pipetting, or adding buffer—when required solely to maintain specimen integrity—are not considered part of the testing procedure.

Combination Use

Specimen receptacles and the subsequent IVD are classified separately under implementing rule 1.2.

Examples

Standalone urine cups, stool containers, saliva tubes, blood spot cards → Class A
Lay‑use kits for saliva or stool collection for SARS-CoV‑2 or occult blood testing → Class A

Rule 6 – Updated Example

The example for Influenza A/B now refers to a highly virulent strain rather than a non‑pandemic one.

Classification of Key Diagnostic Technologies in MDCG 2020-16 Rev.3

Next‑Generation Sequencing (NGS)

Rev.3 highlights the role of NGS across several rules:

Rule 3(f) (Companion Diagnostics) – NGS identifies variants linked to therapeutic response.
Rule 3(h) (Cancer Diagnostics) – Supports cancer staging and genomic profiling.
Rule 5(a)–(b) (General Laboratory Use) – Includes library prep reagents, PCR thermocyclers, NGS sequencers, and other instruments essential for genetic analysis.

Companion Diagnostics (CDx)

Under Rule 3(f):

CDx devices are essential for the safe and effective use of specific medicinal products. They are used to:

Identify suitable patients for targeted therapies
Detect risks of adverse reactions
Support treatment decisions before or during therapy

Examples provided in Rev.3 include:

KRAS/NRAS variant detection for colorectal cancer
PD‑L1 IHC tests for immunotherapy selection
NGS‑based CDx for multi‑gene therapy selection

A decision flowchart in Annex II helps manufacturers determine whether an IVD qualifies as a CDx.

Self‑Testing Devices (Rule 4(a))

Self‑testing IVDs must be usable by laypersons without compromising analytical performance. Rev.3 emphasizes:

Ease of use
Safety
Minimised risk of misuse

Near‑Patient Testing (NPT) Devices (Rule 4(b))

NPT devices are designed for rapid clinical decision-making in point‑of‑care settings.
Rev.3 ensures clear differentiation between self‑testing and near‑patient testing based on user type, setting, and intended use.

MDCG 2020-16 Rev.3 classification rules provide crucial clarifications that support more consistent application of the IVDR. By refining definitions, expanding examples, and clarifying rules for CDx, NGS, self‑testing, and near‑patient testing, the guidance helps manufacturers classify devices accurately and reduce regulatory uncertainty.

Written by:

Alice Toomey-Smith

Regulatory Director, IVD

Quality & Regulatory Affairs leader with global IVD expertise, guiding products to compliance across EU IVDR, FDA & beyond.

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MDx: Your Dedicated CRO for IVD Clinical Studies in the EU

August 24, 2023

Introduction

In the rapidly evolving world of in vitro diagnostics (IVD), manufacturers are increasingly understanding the need for rigorous clinical performance studies. Such studies form the backbone for ensuring the safety, efficiency, and overall market readiness of IVD devices. With the European Union’s (EU) stringent regulatory environment, conducting these studies requires expertise and precision. That’s where MDx CRO, a trusted name in IVD Contract Research and regulatory consulting, stands out.

Why are IVD Clinical Studies Imperative?

Evidence-based Decision Making: Clinical performance studies furnish the data that can prove the diagnostic accuracy, precision, and utility of IVD devices. They help manufacturers refine their offerings and justify their product claims.
Regulatory Adherence: Ensuring compliance with the EU’s In Vitro Diagnostic Regulation (IVDR) and standards like ISO 20916 is non-negotiable. Clinical studies often form the bedrock in gaining these credentials and opening up the European market.

Navigating the Challenges with MDx CRO

Whether you’re a fledgling startup or an established IVD giant, challenges like site selection, study design, effective monitoring, and regulatory adherence can be daunting. This is where MDx CRO can be your guiding light:

Proven Expertise: With its legacy in the IVD realm and former Notified Body experts on board, MDx CRO offers unparalleled insights into effective study design, ensuring manufacturers derive actionable insights every time.
Network of Clinical Sites: Owing to its years in the industry, MDx CRO has built strong affiliations with leading clinical sites, guaranteeing timely and efficient study conduct.
Regulatory Insight: Navigating the IVDR and ISO 20916 maze becomes simpler with MDx CRO’s regulatory consulting wing, which ensures manufacturers always stay on the right side of the law.
End-to-End Monitoring: With a keen focus on detail, MDx CRO ensures every study stays on track, protocols are maintained, and data integrity remains uncompromised.

Why MDx CRO?

Simply put, MDx CRO isn’t just a service provider – it’s a partner in your IVD journey. Our seasoned team understands the unique challenges IVD manufacturers face, making them an indispensable asset in your product’s journey from concept to the European market.

Conclusion

IVD clinical studies, while challenging, present a golden opportunity to IVD manufacturers to rigorously validate their product’s claims. In the intricate web of EU regulations, manufacturers need more than just expertise; they need a partner. And who better than MDx CRO, which has consistently demonstrated excellence in study design, monitoring, and ensuring complete regulatory compliance? Choose MDx CRO, and let’s work together to bring transformative and reliable IVD devices to the EU market.

FAQs about IVD Clinical Studies and MDx CRO:

What are IVD Clinical Studies?
- IVD clinical studies refer to rigorous research and evaluations conducted to determine the safety, efficiency, and overall performance of in vitro diagnostic (IVD) devices.
Why are IVD Clinical Studies important in the EU?
- The EU has stringent regulatory requirements. IVD clinical studies provide the necessary evidence to support product claims, ensuring compliance with the EU’s In Vitro Diagnostic Regulation (IVDR) and international standards like ISO 20916.
What challenges can manufacturers expect while conducting IVD studies in the EU?
- Manufacturers may face challenges like site selection, creating an effective study design, regular study monitoring, and ensuring compliance with EU regulations and standards.
How does MDx CRO help with these challenges?
- MDx CRO offers expertise in study design, has affiliations with top clinical sites, provides regulatory consulting for EU standards, and ensures end-to-end study monitoring to maintain the quality and integrity of data.
Is MDx CRO suitable for both startups and established manufacturers?
- Absolutely! Whether you’re a startup entering the IVD market or a seasoned manufacturer, MDx CRO’s tailored solutions cater to the unique needs of every client.
How does MDx CRO ensure compliance with the IVDR and ISO 20916?
- MDx CRO boasts a regulatory consulting wing with deep knowledge of IVDR and ISO 20916, ensuring manufacturers receive accurate guidance and assistance throughout their IVD device’s journey to the market. Our team of former Notified Body experts on board help design studies that meet CE mark expectations
What advantages does MDx CRO offer in terms of site selection for IVD studies?
- With its extensive experience and industry connections, MDx CRO has built relationships with leading clinical sites for a variety of technologies and clinical applications, ensuring timely and efficient study initiation and execution.
How does partnering with MDx CRO impact the success rate of IVD devices in the EU market?
- With MDx CRO’s comprehensive services, from design to monitoring and regulatory guidance, manufacturers enhance their chances of a successful and compliant IVD product launch in the EU.
Where can I learn more about MDx CRO’s success stories or case studies?
- It’s best to reach out to MDx CRO directly or visit our website for detailed testimonials, case studies, and more insights into our work.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and former BSI IVDR reviewer with deep experience in CE marking high-risk IVDs, companion diagnostics, and IVDR implementation.

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IVD Regulatory Services by MDx CRO

August 9, 2023

At MDx CRO, our specialized IVD regulatory services cater not only to in vitro diagnostic medical device manufacturers, but also companion diagnostics (CDx). Moreover we work with companies and their pharma partners, laboratories, suppliers, IVD subcontractors and more. Our in-depth knowledge and expertise make us stand out in the constantly evolving landscape of IVD regulations.

Why Choose MDx CRO for IVD Regulatory Services?

IVD Compliance Mastery: MDx CRO assists IVD manufacturers throughout the entire product life cycle. We ensure you achieve and maintain compliance with IVD regulations across various countries.
Regulatory Expertise: We not only understand the EU IVDR regulation but are also proficient in the transition from IVDD to IVDR, the FDA IVD requirements in the US, and pre-submission reviews. This comprehensive know-how ensures your product’s smooth and swift entry into the US and EU medical device markets.
Tailored Services: Be it a start-up, SME, or multinational company, MDx CRO’s bespoke IVD consultancy services are designed to meet your unique needs.

Our IVD Regulatory Service Spectrum

New Device Development: We guide you through design, development, and market access strategy formulation based on your intended purpose.
Regulatory Transitions: Navigate the shifts from IVDD to IVDR effortlessly with our expert insights into necessary requirements and adjustments.
Market Expansion: From the US FDA to EU-IVDR, our regulatory submission support ensures you comprehend and meet the distinct requirements of global markets.
Commercialization Support: MDx CRO ensures that your device meets all prerequisites for commercial distribution, including device labeling, training materials, and regulatory submissions.

Engage with Seasoned Experts in Regulatory services

Our specialists, equipped with industry-centric design and development skills fused with regulatory acumen, are here to provide unparalleled guidance. IVD analytical and clinical performance support can significantly benefit from our specialized expertise.

IVD Manufacturers’ Guide

IVD Regulatory Strategy: We assist in devising the most fitting regulatory approach for your IVD products with our unique IVD roadmap solutions.
IVD Technical File Support: Let us help in completing or reviewing your IVD Technical Files to ensure full compliance with the IVDR (EU) 2017/746, paving the way for a hassle-free CE-IVD approval.
Gap Analysis: Gauge the difference between your Quality Management System and IVDR (EU) 2017/746 requirements to stay ahead.
Mock & Supplier Audits: Be audit-ready always with our comprehensive audit services, including our IVDR pre-submission service.

Embracing Quality and Excellence by MDx CRO

At MDx CRO, quality is our benchmark. Our global team, adept at vendor auditing for diagnostic and laboratory partners, ensures QMS audits in compliance with globally recognized standards.

MDx CRO’s integrated approach, assures sponsors of audit compliance, helping them prepare for any potential international regulatory inspections.

Join forces with MDx CRO and navigate the intricate world of IVD regulations with confidence. Let’s embark on this transformative journey together!

Contact us today to discuss your project needs!

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Companion Diagnostics IVD Consultancy within the EMA Framework: Comprehensive Guidance

August 8, 2023

The field of companion diagnostics IVD (CDx) represents a confluence of technological innovation, regulatory compliance, and patient care. As personalized medicine becomes an integral part of healthcare, the regulatory framework governing CDx, including the In Vitro Diagnostic Medical Devices Regulation (IVDR), has become more complex. This scenario calls for a specialized companion diagnostics consultancy. MDx CRO is at the forefront of this arena, offering expertise and guidance in the process for CDx consultation with the European Medicines Agency (EMA), Notified Body preparation and IVDR compliance within the European Union (EU).

Companion Diagnostics IVD and their Role

CDx are in vitro diagnostic (IVD) tests designed to provide information that is essential for the safe and effective use of a corresponding medicinal product. Their applications could include:

Identifying patients who are most likely to benefit from a particular therapeutic product.
Determining patients’ suitability for specific treatments.
Monitoring responses to ongoing treatments.

The Impact of IVDR on Companion Diagnostics

The IVDR sets out robust legal requirements for in vitro diagnostic medical devices, including CDx. Key aspects include:

Enhanced Patient Safety: Ensuring the quality and reliability of CDx IVDs.
Stricter Oversight: Increased scrutiny of the CDx development and approval process. Unlike the previous directive, CDx now require conformity assessment by a Notified Body, an independent organization designated to assess the compliance of medical devices and in-vitro diagnostics. In addition, CDx are also assessed by a medicines authority, most likely the EMA (European Medicines Agency), but a competent authority could also be involved .
Comprehensive Technical Documentation: Increased clinical evidence requirements are particularly notable in the IVDR. MDx CRO can help CDx manufacturers and their drug partners gather the necessary data to support their CDx application. This data may include clinical trial data (clinical performance data), analytical data, and safety data. Manufacturers must provide robust clinical evidence to demonstrate the performance, safety, and clinical utility of the CDx.

There are a number of other factors that can affect the approval process for CDx in the EU. These factors include:

The availability of data: Both the Notified Body and the EMA will need to have access to data from clinical trials that demonstrate the safety and effectiveness of the CDx.
The complexity of the CDx: The more complex the CDx, the more difficult it will be to assess its safety and effectiveness.
The novelty of the CDx: If the CDx involves new technologies or indications, the EMA and the Notified Body will need to take a more cautious approach to its approval. Different scenarios will play a role on the extent of scrutiny involved, including co-developed CDx scenarios, follow-on CDx, and CDx already on the market under the old IVD directive.

Understanding the EMA Companion Diagnostics Consultation Procedure

The consultation procedure is initiated by the notified body when it receives an application from a CDx manufacturer. The medicinal product involved could be a medicine already authorised for marketing in the EU or a medicine undergoing approval. Aligning drug and diagnostic development processes can help to ensure that the results of the clinical trials are accurate and reliable, and that the medicine is safe and effective when used with the CDx.

Aligning timelines in the drug and diagnostic (CDx) development process can help to ensure that the clinical trials for the medicine are conducted in a way that is consistent with the intended use of the CDx.

Upon application for a CDx IVD approval, the notified body will submit a letter of intent to the EMA, along with a technical dossier that describes the CDx and the medicinal product.

The EMA will then appoint a rapporteur, who will be responsible for reviewing the technical dossier and issuing a scientific opinion on the suitability of the CDx for use with the medicinal product. The rapporteur will also consider the views of any other interested parties, such as the applicant for the medicinal product, the manufacturer of the CDx, and patient groups.

The EMA will provide its scientific opinion on the CDx aspects that relate to the medicine to the notified body. The notified body will then use the EMA’s opinion to make a decision on whether to grant the CE mark to the CDx, in accordance with the regulatory requirements of the in vitro diagnostics regulation (EU IVDR).

EMA procedure timetables play a major role in the success of the consultation and turn around times for responses can be extremely short. Manufacturers should factor this in as they plan for their CDx submissions. There is the possibility to request a pre-submission meeting which will include representatives from Notified Bodies, EMA and could also include the drug manufacturer – this is used strictly to align on procedural and timing considerations (it is not used to provide feedback on study design or the content of the technical documentation).

One of the key documents used in the consultation and submitted by the notified body to the EMA is the SSP (Summary of Safety and Performance). The EMA expects manufacturers to use the SSP template provided in MDCG 2022-9. A lot more detail is expected in the SSP when compared to the information provided in the IFU. For example, detail on concordance studies is needed, particularly for co-developed CDx when different versions of a diagnostic have been used throughout the clinical development program.

MDx CRO: Your Partner in Companion Diagnostics Consultancy

Our companion diagnostics consultancy services encompass every stage of development, approval, and post-market surveillance:

Guidance on IVDR Requirements: In-depth support in understanding and meeting the specific demands of IVDR as they relate to CDx. MDx CRO can help a diagnostics company identify the specific requirements that apply to its CDx. For example, the requirements for a CDx that is intended to assess a patient’s suitability for treatment may be different from the requirements for a CDx that is intended to be used to monitor a patient’s response to treatment.
Preparation for Notified Body Assessment: Tailored strategies for successful assessment of a CDx under the IVDR: Assistance with compiling and submitting the necessary technical documentation and quality related documents.
Providing training to the manufacturer’s staff: MDx CRO can provide training to the manufacturer’s staff on the EMA’s requirements for CDx, as well as the notified body’s assessment process and expectations. This training will help to ensure that the manufacturer’s staff are prepared to answer any notified body questions and increase chances of success.
Stakeholder Communication: Facilitating communication with all relevant parties.
Global Perspective: Navigating international considerations for CDx in multi-country studies.
Post-Market Support: Focused on maintaining the highest standards through ongoing compliance monitoring with IVDR and other regulatory requirements. This includes implementing strong post-market surveillance processes and Post-Market Performance Follow-up (PMPF) evaluations, monitoring the CDx’s performance in real-world clinical settings, tracking and analyzing adverse events related to CDx usage, and conducting ongoing studies to evaluate the long-term impact and effectiveness of the CDx.

Why MDx CRO for Companion Diagnostics IVD Consultancy?

Expertise: Our in-depth knowledge of CDx, IVDR, and EU regulations offers unparalleled support.
Collaboration: Working closely with clients, we tailor our approach to meet specific needs.
Efficiency: Our insights and guidance save valuable time and resources, simplifying complex regulatory pathways.
Commitment: Our dedication to excellence, patient safety, and innovation sets us apart.

Navigating the multifaceted world of companion diagnostics in the EU, with the added complexity of IVDR, requires a dedicated and skilled partner. MDx CRO stands ready to be your guide in this critical journey, ensuring alignment with all regulatory standards. Reach out to explore how our companion diagnostics consultancy can be the key to unlocking your CDx potential in the EU’s dynamic regulatory environment.

Frequently Asked Questions on COmpanion Diagnostics Consultancy

What is a co-developed Companion Diagnostics in the context of EMA consultation?

A co-developed CDx is a device developed alongside a medicinal product for either initial authorization or a change of indication. This can include development during a pivotal clinical trial or a bridging study, with sufficient documentation to ensure performance alignment.

How does a follow-on CDx differ from a co-developed CDx?

A follow-on CDx seeks the same indication as the original CDx but is not developed in parallel with the medicinal product. The follow-on CDx targets the same biomarker but may not be based on the same technology. It should be highly comparable to the original in performance, safety, and effectiveness.

What documentation is required for a follow-on CDx?

Sufficient documentation must be provided for a follow-on CDx to prove that its analytical performance is comparable to the original CDx and that there’s no impact on clinical performance incompatible with the safe and effective use of the medicinal product.

How are devices transitioning from IVDD to IVDR handled?

Devices initially marketed under Directive 98/79/EC (IVDD) that transition to IVDR fall under the co-developed or follow-on scenarios, depending on how they were initially developed.

Is it possible to proceed with a single CDx consultation procedure for multiple authorized medicinal products and indications?

Yes, if a device’s intended purpose includes several authorized medicinal products and indications, it’s recommended to proceed with one single CDx consultation procedure. All concerned medicinal products should be listed in the intention to submit a letter by the Notified Body and in the application form.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and former BSI IVDR reviewer with deep experience in CE marking high-risk IVDs, companion diagnostics, and IVDR implementation.

Industry Insights & Regulatory Updates

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Companion diagnostic studies: BSI & TÜV SÜD Lead the Way in CDx Certification

June 6, 2023

The field of personalized medicine is experiencing notable progress as BSI and TÜV SÜD, two of the largest Notified Bodies in the European Union, have issued their first Companion Diagnostic (CDx) Certificates under the In Vitro Diagnostics Regulation (IVDR). This achievement carries substantial implications for manufacturers of in vitro diagnostics (IVD) and Contract Research Organizations (CRO) such as MDx CRO. MDx is a specialized IVD CRO with expertise in conducting clinical performance studies, including companion diagnostic studies, as stakeholders adapt to the changing landscape of CDx.

Key Milestone Reached: 1st IVDR CDx Certificates Officially Issued

BSI The Netherlands (2797) issued its first CDx certificate in May, 2023, to Invivoscribe, Inc. for their LeukoStrat® CDx FLT3 Mutation Assay, a vital tool in tailoring treatment for acute myelogenous leukaemia (AML) patients with FLT3 ITD and TKD gene mutations.

Earlier, TÜV SÜD Product Service GmbH had made its mark as the issuer of the world’s first CDx certificate in accordance with the IVDR, awarded to Roche Diagnostics GmbH for a qualitative immunohistochemical cancer biomarker assay. This assay detects the programmed death-ligand 1 (PDL1) expression pattern, enabling identification of patients who will benefit most from a specific therapeutic treatment.

The milestones reached by Invivoscribe, Inc. and Roche Diagnostics GmbH signal to other manufacturers the effectiveness of the IVDR regulatory framework in certifying these devices. Furthermore, it testifies to the successful collaboration between manufacturers, EMA, and Notified Bodies, paving the way for similar certifications in the future.

Understanding the Impact of IVDR on Companion Diagnostics

Companion diagnostic devices like these are key in advancing personalized medicine, as they are clinically validated to determine patients’ likelihood of responding to a specific treatment. However, the enforcement of the IVDR has increased the regulatory oversight for these devices, pushing most into risk Class C, necessitating Notified Body review prior to being placed on the market.

The IVDR’s new risk classification concept has expanded the role of Notified Bodies like BSI and TÜV SÜD, requiring them to oversee more than 80% of IVD devices, a significant rise from the previous 10-15% under the IVD Directive. These regulatory changes underscore the value of experienced CROs like MDx CRO in supporting manufacturers through this intricate process.

Under the IVDR, CDx products, once free from Notified Body involvement, are now classified as Class C and must undergo a Notified Body conformity assessment. This process requires consultation with the European Medicines Agency (EMA) or the Competent Authority (CA) for medicinal products, as per the 2001/83/EC directive, which lengthens the overall conformity assessment process. Manufacturers must factor in this increased timeline, especially with the IVDR requiring Class C CDx products to be CE-marked by May 2026.

Choose MDx CRO for Reliable Companion Diagnostic Studies

As a trusted IVD CRO partner, MDx, with its extensive experience in managing IVD clinical performance studies including companion diagnostic studies, is equipped to assist clients through the evolving CDx and regulatory landscape. By optimizing innovative diagnostic solutions and ensuring full regulatory compliance in our CDx clinical trials, we strive to contribute to the delivery of top-tier personalized medicine, enhancing patient care worldwide.

Contact us today to learn how MDx CRO can partner with you to help bring your companion diagnostic to market.

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MedTech Europe IVDR Clinical Evidence Requirements: Key Updates in the 3rd Edition

March 4, 2023

MedTech Europe IVDR Clinical Evidence Requirements have evolved again with the release of the third edition of the MedTech Europe eBook. This updated 129‑page resource provides deeper clarity on how manufacturers and regulatory teams can navigate clinical evidence expectations under the EU In Vitro Diagnostic Regulation (IVDR).

The new edition includes expanded examples, refined explanations, updated diagrams, and improved flow—making it an essential tool for all IVD stakeholders.

Below is a clear summary of the most important updates and what they mean for IVD and CDx manufacturers.

What’s New in the MedTech Europe IVDR Clinical Evidence Requirements eBook (Version 3)

Stronger Guidance for Companion Diagnostics (CDx)

CDx receives significant attention in the new edition, appearing in 20 out of 129 pages. The guidance helps CDx developers:

Define analytical and clinical performance endpoints
Establish cut‑off values and clinical benefit claims
Understand clinical data sources and scientific validity
Plan and conduct clinical performance studies for CE marking

The eBook also includes flowcharts showing how CDx developers should engage with EU Competent Authorities, and clarifies comparator selection and follow‑on CDx requirements.

Use of Non‑EU Clinical Data

A major clarification covers how to use clinical data generated outside the EU to support performance evaluation claims. This guidance helps manufacturers:

Determine when non‑EU data is acceptable
Ensure alignment with IVDR expectations
Strengthen global clinical evidence strategies

Updated Intended Purpose/Intended Use Guidance

The eBook expands its section on intended purpose by:

Adding updated examples aligned with IVDR definitions
Introducing a new COVID‑19 example
Emphasizing the need for a specific medical purpose

These updates help manufacturers ensure their intended purpose statements are precise, defensible, and MDR‑compliant.

Refined Guidance on Scientific Validity and Clinical Evidence

Improved Layout and Clarity

Chapters on scientific validity and clinical evidence have been reorganized to improve flow. Manufacturers now benefit from:

Clearer definitions
Step‑by‑step expectations
Better alignment with IVDR Annex XIII

This helps teams understand the level of evidence required for high‑risk IVDs.

Updated Use of Published Testing Data

The chapter on published experience now includes:

More rigorous scientific expectations
Additional requirements for evaluating routine testing data

This supports more robust scientific validity assessments for high‑risk IVD claims.

Equivalence and Similarity: New Clarifications

The updated chapter on equivalence focuses on performance evaluation concepts, not clinical equivalence as used in the MDR for medical devices. The new edition:

Refines the tool used to demonstrate equivalence
Clarifies similarities versus equivalence thresholds
Includes clearer examples and decision tools

This is especially relevant for Class C and D devices.

New Chapter on Benefit‑Risk Determination

A major addition is a new chapter dedicated to benefit‑risk determination, including:

How to assess benefit‑risk for IVDs that guide clinical decisions
When benefit‑risk claims align devices closer to CDx requirements
How to structure benefit‑risk information within Technical Documentation

This chapter strengthens alignment with IVDR Annex I, GSPRs, and clinical evaluation requirements.

Additional Technical Documentation Updates

The eBook also updates its chapter on documentation to reinforce:

Consistency across the product lifecycle
Alignment with the cyclical nature of clinical evidence generation
Traceability between clinical performance, scientific validity, and intended purpose

These updates support stronger conformity assessment submissions.

Why These Updates Matter for IVD Manufacturers

The third edition of MedTech Europe IVDR Clinical Evidence Requirements helps manufacturers:

Strengthen clinical evidence packages
Build more defensible performance evaluations
Understand how to design compliant CDx strategies
Prepare for Notified Body scrutiny
Navigate global clinical data integration

The eBook remains free to download on the MedTech Europe website and is considered one of the most practical, industry‑aligned resources available today.

How MDx CRO Supports IVDR Clinical Evidence Requirements

MDx CRO specializes in regulatory, clinical, and quality support for IVD and CDx manufacturers. With IVDR requirements expanding sharply, manufacturers increasingly rely on expert partners to navigate:

Intended purpose analysis
CDx development strategy
Clinical performance study design
Scientific validity assessments
GSPR checklists and technical documentation
QMS alignment (ISO 13485, ISO 14971, ISO 15189)
Notified Body interactions
AEMPS and Competent Authority submissions

Whether you need end‑to‑end support or targeted expertise, our MedTech regulatory team helps ensure your IVD meets all MedTech Europe IVDR Clinical Evidence Requirements.

MedTech Europe is making the Third Version available to be downloaded free of charge from its website, making it an essential resource for anyone involved in the IVD industry.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and former BSI IVDR reviewer with deep experience in CE marking high-risk IVDs, companion diagnostics, and IVDR implementation.

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Roche Ventana PD-L1 Assay Gets CE Mark as NSCLC CDx

October 5, 2022

In a landmark announcement, Roche has revealed that its Ventana PD-L1 (SP263) Assay has received CE IVD approval, setting a new standard in the personalized treatment of non-small cell lung cancer (NSCLC). This cutting-edge diagnostic test now stands as a beacon of hope for patients with locally advanced and metastatic NSCLC, identifying those who are eligible for treatment with the groundbreaking immunotherapy, Libtayo (cemiplimab).

Bridging the Gap in Lung Cancer Treatment

Lung cancer remains the most prevalent and lethal cancer worldwide, with NSCLC accounting for up to 85% of all cases. The challenge of treating this disease lies in its late diagnosis, often at a stage where traditional therapies have limited efficacy. However, the advent of immunotherapy has introduced a new horizon of treatment options, necessitating precise diagnostic tools to identify suitable candidates.

The Role of Ventana PD-L1 (SP263) Assay

The Ventana PD-L1 (SP263) Assay is at the forefront of this medical evolution, designed to detect the expression of the PD-L1 protein on tumor and immune cells. The expression level of PD-L1 has been closely linked to the efficacy of PD-1/PD-L1 immunotherapy drugs, making it a critical factor in tailoring treatment plans for individual patients. The assay’s approval is based on the results of the Phase III EMPOWER-Lung 1 study, which underscored the potential of Libtayo monotherapy in improving patient outcomes.

Expanding Treatment Options with “Roche PD-L1”

With this CE mark approval, the Ventana PD-L1 SP263 Assay (Roche PD-L1) is the only CE IVD product in the market with NSCLC indications for four different immunotherapy drugs, thereby broadening the spectrum of treatment options available to oncologists and their patients. This development is a testament to Roche’s commitment to advancing personalized medicine and improving access to life-saving treatments.

Jill German, Head of Pathology Lab at Roche Diagnostics, highlighted the significance of this breakthrough: “With our companion diagnostics, we can ensure each patient receives the most appropriate targeted treatment. This approval not only broadens the treatment landscape for advanced lung cancer patients but also marks a pivotal step in our journey towards personalizing healthcare.”

A Step Towards Personalized Healthcare

The CE mark for the Ventana PD-L1 (SP263) Assay represents more than just a regulatory milestone; it signifies a shift towards a future where cancer treatment is tailored to the individual, maximizing efficacy while minimizing unnecessary exposure to potentially ineffective therapies. As the global medical community continues to make strides in the fight against lung cancer, the role of precise, reliable diagnostics will only become more crucial.

In embracing these advancements, we inch closer to a world where lung cancer, once a formidable foe, becomes a manageable condition, with patients receiving treatments designed for their specific biological makeup. The journey towards personalized healthcare is long and fraught with challenges, but with innovations like the Ventana PD-L1 (SP263) Assay, the path becomes clearer, offering new hope to those battling lung cancer.

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Companion Diagnostics in Precision Medicine: Driving Targeted Therapies

November 27, 2021

Precision medicine is transforming healthcare by tailoring treatments to the unique characteristics of each patient. At the core of this transformation are companion diagnostics (CDx), innovative tools that identify biomarkers to determine which patients will benefit from specific therapies and who may be at risk of adverse effects. Far from being a niche, CDx has become a driving force behind the approval and success of targeted treatments.

Between 2015 and 2019, approximately 65% of EMA and FDA drug approvals involved a biomarker, highlighting just how central biomarker-driven strategies have become to modern drug development (EMA | FDA Drug Approvals). Biomarkers are not just supportive; they are often decisive in shaping regulatory pathways and patient outcomes. For oncology in particular, the integration of CDx has redefined standards of care.

Today, the FDA has approved 44 companion diagnostics, many of them linked to therapies in oncology (FDA Companion Diagnostics). Among these, non-small cell lung cancer (NSCLC) and colorectal cancer represent the largest categories, reflecting both the high global disease burden and the rapid progress in targeted oncology drugs. These CDx tests help clinicians select therapies based on mutations such as EGFR, ALK, KRAS, or BRAF, directly connecting molecular profiles to treatment decisions.

Implications for pharma

The implications of these numbers are significant. For pharmaceutical companies, co-developing a therapy and its companion diagnostic has become the new normal, especially in oncology, immunology, and rare diseases. Regulatory bodies such as the FDA and EMA increasingly expect biomarker strategies to be integrated from the earliest stages of clinical development, not treated as afterthoughts. For patients, CDx represents a more hopeful and personalized pathway — ensuring that the right drug reaches the right individual at the right time.

Developing and validating a companion diagnostic, however, is complex. It requires robust clinical evidence, alignment with both drug and diagnostic regulatory frameworks, and careful planning of multi-country trials. Under the EU In Vitro Diagnostic Regulation (IVDR), CDx is classified as Class C with mandatory notified body involvement, underscoring the high standards for evidence and compliance required in Europe.At MDx CRO, we work with pharmaceutical and diagnostic partners to integrate CDx into precision medicine programs. From regulatory strategy and clinical trial design to biomarker validation and post-market surveillance, we provide the expertise needed to bring these critical tools from concept to approval. Our experience spans oncology, infectious disease, and immunology, giving us a strong foundation to support the next generation of biomarker-driven therapies.

Future outlook

Companion diagnostics have moved from a specialized innovation to a central pillar of precision medicine. With over 40 FDA-approved CDx today and biomarker involvement in the majority of new drug approvals, the trend is clear: the future of medicine will increasingly depend on diagnostics and therapeutics working hand in hand. The challenge for innovators is not whether to pursue CDx, but how to design the right strategy to meet scientific, regulatory, and clinical demands.

If you are developing a targeted therapy or considering a companion diagnostic program, contact MDx CRO to learn how we can help accelerate your path to approval and ensure your innovations reach the patients who need them most.

Industry Insights & Regulatory Updates

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