Team-NB clarifies CDx changes under IVDR Annex IX 5.2

November 11, 2025

What the new Team-NB paper covers

Team-NB has adopted an updated position paper (Version 2, 22 Oct 2025) clarifying which changes to companion diagnostics (CDx) under IVDR Annex IX, section 5.2 must be reported to the Notified Body (NB) and when consultation with the medicinal products authority (EMA or relevant national authority) is required. Under Annex IX 5.2(f), manufacturers must inform their NB before making changes that affect performance, intended use, or suitability of the device in relation to the medicinal product. The NB then decides whether a new conformity assessment is needed or a supplement to the EU technical documentation certificate is sufficient, and whether consultation with the medicinal products authority is required.

The paper also notes that manufacturers are responsible for determining if a change requires consultation and must document and justify a decision not to consult; justifications must be available to competent authorities on request. In general, a change that requires consultation should be considered reportable to the NB.

Legacy CDx under Article 110(3)

For legacy CDx (per MDCG 2022-8), significant changes to design or intended purpose cause loss of legacy status (per MDCG 2022-6) and trigger a new IVDR conformity assessment involving a NB and a consultation with the medicinal products authority.

How Team-NB categorizes changes (with examples)

The annex introduces a practical flow that first asks: Does the anticipated change affect the CDx’s suitability for the medicinal product? Depending on the answer, changes fall into three groups.

1) No EMA/National authority consultation required

(“NO” path in the flow; changes out of scope of medicinal product authority consultation)
Examples:

Change in critical raw material or its supplier
Platform transfer (e.g., validation on a new NGS platform)
Extension of CDx shelf-life
New supplier for a reagent
New place of market in distant sales

2) Follow-up consultation (supplement) — change within the scope of the original consultation

Examples:

New limitation in use of the CDx (e.g., cross-reactivity)
Medicinal product restriction impacting the CDx claim
Large-panel NGS tumour profiling device: addition of tissue type for an existing INN
Changes to analytical parameters of the CDx
Change in reagent presentation (e.g., liquid vs lyophilized) that impacts the CDx claim

3) Initial consultation (new conformity assessment) — change outside the scope of the original consultation

Examples:

Medicinal product extension impacting the CDx claim
Addition of a new sample type that changes intended purpose
Addition of a new/expanded target patient population
Large-panel NGS tumour profiling device: additional INNs after initial certification
Addition of additional mutations with outcome data

Important: Team-NB stresses that the annex examples are illustrative, and final determinations are case-specific based on detailed evaluation.

Practical takeaways for CDx teams

Treat changes that likely affect design or intended purpose as reportable and assess them with supporting evidence.
Document your consultation decision (including rationale for no consultation) and keep it ready for competent authorities.
For legacy CDx, avoid significant changes to design/intended purpose unless you’re prepared for loss of legacy status and a new IVDR assessment with consultation.
Refer to the EMA homepage (or relevant EU/EEA medicinal product authority) for process details on consultations.

Why this matters

This Team-NB paper gives CDx manufacturers and their partners a shared interpretation baseline with Notified Bodies and medicinal product authorities, reducing ambiguity around when to notify the NB and when to seek EMA/national consultation after a change. The included flow and examples help teams pre-classify changes and plan evidence/consultation pathways efficiently.

Need a CDx-focused partner?

If you’re planning or assessing CDx changes under IVDR and want a clear pathway through NB reporting and EMA/national consultations, talk to MDx CRO—a consultancy dedicated to companion diagnostics strategy, clinical evidence, and regulatory execution.

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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IVDR Performance Studies and the ISO 20916:2024 Revision

Performance studies in gene therapy trials: from assay cut-offs to clinical impact

October 31, 2025

In gene therapy, your in-vitro diagnostic (IVD) doesn’t sit on the sidelines—it drives clinical decisions. If a result screens a participant in/out, times dosing, or informs safety management, you’re in IVDR performance study territory with ISO 20916 as the operational backbone. Treat the IVD like a product under evaluation, not a lab tool, and design a study that proves it’s fit for the exact decision your trial needs.

What actually triggers a performance study in gene therapy?

Use the simplest rule of thumb: does the assay influence patient management? If yes, plan for an IVDR Article 58 performance study in parallel with your clinical trial authorization. Typical triggers:

Eligibility/stratification: AAV neutralizing antibody (NAb) or total-antibody (ELISA) results that gate inclusion/exclusion or set a dosing window.
Patient monitoring: Assays that guide timing or continuation (e.g., changes in humoral markers relevant to vector readiness).
CDx trajectory: When the test is essential for safe and effective use, your evidence should be built to scale toward CDx—even if you’re not filing as CDx yet.

Treat these as combined trials (IMP + IVD). Align the performance study application with the drug CTA so approvals move together.

Build the right “assay stack” for AAV programs

Design your assay plan around the decisions your trial must make. In combined trials (IMP + IVD), that usually means separating screening, decision-making, and context/supporting activities—and documenting exactly which assay output drives which action in the CPSP and APR.

1) Screening assays

Purpose: Identify participants who may be eligible for dosing or further evaluation.
Typical methods: Total antibody (ELISA) and/or neutralizing antibody (NAb) assays.
Predefine: intended purpose, the output used for screening, cut-off, QC/controls, and invalid/repeat handling.
Regulatory note: If screening impacts enrollment/timing, it’s within IVDR performance study scope—reflect this in the protocol and dossier.

2) Decision-making assays

Purpose: Provide the result that directly guides patient management (e.g., eligibility for AAV dosing or readiness after a waiting/intervention period).
Typical method: Cell-based NAb assay when the decision depends on functional inhibition of transduction.
Predefine: a validated cut-off and how it’s applied at the decision point; acceptance criteria (controls/repeats), handling of invalid/borderline results, and any repeat-testing logic.

3) Context/supporting assays

Purpose: Provide supporting information (e.g., PCR/NGS for inclusion criteria or other exploratory markers) without driving patient management unless explicitly pre-specified.
Governance: These may be exploratory assays; do not let them influence decisions unless pre-declared.

Designing the CPSP: endpoints that matter (and survive small-N)

Tie endpoints to the decision you must defend. In rare diseases, power is constrained—precision and transparency carry weight.

Primary, decision-linked endpoints (illustrative):

Proportion below cut-off at the dosing/decision point.
Time-to-negativity (post-intervention or natural decline).
Duration of sustained negativity.
Change from baseline in NAb titers.

Key secondaries (analytical + feasibility + safety):

Analytical performance in operations: run-level QC pass rate, invalid/repeat rate, assay deficiencies/deviations.
Feasibility: turnaround time from collection to result, pre-analytical robustness (freeze–thaw, transport windows, matrix effects), stability.
Safety: AEs from sample collection/device use as per IVDR performance study reporting.

Correlative (pre-specified, descriptive):
Relate NAb kinetics to other humoral markers (e.g., total IgG, capsid-specific antibodies) where it clarifies the biology without over-claiming.

When your IVD sample size is constrained by the gene therapy protocol, say so. Set precision targets for agreement or proportions and specify how you’ll treat indeterminates/missing—regulators prefer realistic clarity over decorative p-values.

From LDT to IVDR: documentation that actually wins

Many gene therapy assays start as lab-developed tests or adapted RUO methods. Under IVDR you need an Analytical Performance Report (APR), not just a conventional validation report. The APR:

Maps analytics to intended purpose and clinical decision.
Uses a structured narrative per characteristic: Purpose → Study design → Statistics → Acceptance criteria → Results → Conclusion.
References applicable frameworks (IVDR, ISO, MDCG) and integrates ICH Q2(R2)/Q14 principles within the IVDR lens.
Justifies non-applicable GSPR requirements explicitly instead of hiding them.

What reviewers expect to “see on the page”

Analytical sensitivity: LoD/LoQ with methods, not just point estimates.
Analytical specificity: cross-reactivity, interference, matrix effects—demonstrated, not assumed.
Accuracy (trueness/bias): vs. reference materials/known concentrations across the measuring range.
Precision: repeatability, reproducibility and intermediate precision (operators, days, instruments).
Measuring interval/reportable range: tied to clinical decisions.
Robustness & stability: small-parameter changes; specimen/reagent stability across the actual logistics.
Traceability: metrological traceability to reference materials or SI units wherever feasible.

Bridging without back-tracking

If you migrate platforms or laboratories, pre-declare equivalence boundaries, commutable panels, and the statistical approach before you switch. Link the APR to the Design History File and ultimately to the Performance Evaluation Report to keep evidence audit-ready.

Operational blueprint: lab-centric, ISO 20916–aligned execution

Programs that run smoothly accept a basic truth: lab operations are clinical operations when an assay drives decisions.

Risk-based monitoring (ISO 20916): Prioritize calibration records, control runs, instrument logs, sample accountability, LIMS audit trails, and lab-critical SDV.
Clear RACI across stakeholders: pharma sponsor, diagnostic partner, central lab, CRO(s). Assign a single “owner of truth” for eligibility calls and a documented adjudication path for gray-zone results.
Sample governance: pre-analytical controls (shipping, temperature, freeze–thaw limits), redraw/retest SLAs, and chain-of-custody that survives inspection.
Safety integration: define device-side AE/device-deficiency flows and their handshakes with the IMP SAE process—who reports what, where, when—and hold joint drills before FPI.

Common pitfalls (and the fix)

Copy-pasting a validation report into IVDR—without showing how analytics support the clinical decision.

Fix: Rewrite into an APR aligned to the intended purpose; connect every analytic claim to the use case.

Pretending power exists in tiny cohorts.

Fix: Pre-specify precision not power; make QC-forward primary endpoints; keep clinical associations descriptive.

Letting exploratory assays creep into decision-making ad hoc.

Fix: Lock the assay stack and decision logic in the CPSP; label everything else exploratory.

Underplaying pre-analytical risk.

Fix: Measure it (transport windows, freeze–thaw), set acceptance criteria, and track at run-level.

Ambiguity in roles and safety.

Fix: Publish a RACI and an integrated safety matrix early; rehearse escalations.

Sponsor checklist

Decide early if the assay changes patient management → if yes, plan an IVDR performance study.
Lock claims, cut-offs, and gray zones; write the CPSP to those decisions.
Choose your study model (prospective/retrospective/bridging) to match real sample access and clinical trial needs.
Produce an APR with complete traceability and justified non-applicable requirements.
Stand up lab-centric monitoring (ISO 20916), eTMF rigor, and LIMS auditability.
Align device and drug safety reporting—on paper and in practice.
Embrace small-N: set precision goals, prioritize QC endpoints, and keep associations descriptive.
Think CDx-ready: structure today’s evidence so tomorrow’s filing doesn’t start from zero.

How MDx CRO accelerates combined gene therapy studies

We run the device side of your combined trial end-to-end: strategy, CPSP/APR/PER authorship, submissions, ISO 20916-aligned operations, lab-centric monitoring and SDV, data/biostats, and inspection-ready traceability. We design performance studies that mirror real clinical decisions, so approvals and operations move in lockstep.

Let’s co-design your performance study

Speak with our IVD & gene therapy team

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Spanish IVD Regulation 2025 – New Royal Decree Updates for IVD Manufacturers, Sponsors, and Labs

October 21, 2025

On 21 October 2025, the Council of Ministers approved Spain’s new Royal Decree for in vitro diagnostic devices. AEMPS confirmed the approval and explained that the decree complements IVDR (EU) 2017/746, strengthens patient protection, and adds national rules on language, in-house manufacturing, performance studies, and vigilance. This development anchors the Spanish IVD Regulation 2025 and sets clear obligations for manufacturers, sponsors, and laboratories. (Official announcement: AEMPS)

Spanish IVD Regulation 2025: What Changed and Why It Matters

The Spanish IVD Regulation 2025 replaces Royal Decree 1662/2000. It clarifies how IVDR applies in Spain and fills Member-State choices, including competent authority, language regime, Article 5(5) in-house devices, genetic testing and counseling, a national marketing register, performance study authorization, and vigilance and market control.

The regulation aims to raise quality, ensure traceability, and speed up corrective actions. It also improves access to certain self-tests through pharmacy channels.

Quick Guide for Busy Teams (Manufacturers, Sponsors, Labs)

Confirm what the Spanish IVD Regulation 2025 changes for your role.
Map licensing, registration, language, Article 5(5), ISO 15189, performance studies, and vigilance to owners and deadlines.
Prepare Spanish-language materials and set up traceability and incident reporting workflows.
Labs should plan ISO 15189 and Article 5(5) notifications to AEMPS.

Competent Authority and Language Rules under the Spanish IVD Regulation 2025

AEMPS is the competent authority for IVDs in Spain. Under the Spanish IVD Regulation 2025, user-facing materials for devices marketed in Spain must appear in Spanish. That includes labels, IFU, and safety notices. Regulatory submissions to AEMPS should include Spanish content. Co-official languages may be added, but Spanish is mandatory.

Action: Audit labeling, IFU, FSNs, PMS templates, and performance study files. Plan translations and version control.

Facility Licensing: Manufacturers, Sterilizers, and Importers

The Spanish IVD Regulation 2025 requires operating licenses for manufacturers, sterilizers, and importers before they place devices on the market. AEMPS evaluates facilities, personnel, and quality systems.

Each site must appoint a Technical Responsible Person (national role) and meet IVDR oversight led by a PRRC. One qualified person can cover both if they meet the criteria.

Transitional rule: Existing third-party manufacturers get up to one year from entry into force to secure the new license. Existing licenses remain valid until renewal or change, which then follow the new procedure.

Action: Confirm license status, designate the responsible person, and prepare for renewal under the new framework.

Marketing Register and Traceability

The decree creates a Spanish marketing register for devices placed on the market. Manufacturers, authorized representatives, and importers must notify product information to support traceability and market surveillance. The register complements EUDAMED and UDI.

Transitional rule: Spain will activate notifications when the register is operational. Until then, use existing national channels.

Action: Build a clean data set for device identifiers, certificates, and supply chains. Prepare to submit once AEMPS opens the register.

In-House Devices (Article 5(5) IVDR): What Labs Must Do Now

Scope and intent

The Spanish IVD Regulation 2025 regulates in-house IVDs made and used within the same health institution. Labs must justify need: a commercial CE-marked device cannot meet the specific clinical need. No industrial-scale production. No commercial supply to third parties.

Quality and documentation

In-house devices must meet IVDR GSPRs. Labs should keep a technical file (intended purpose, risk management, analytical and clinical performance, V&V, SOPs, and labeling for internal use).

ISO 15189 accreditation

Labs that manufacture in-house devices must obtain ISO 15189 accreditation for the manufacturing scope. Spain ties this to the transitional schedule.

Notification to AEMPS

Before starting in-house manufacture, labs must notify AEMPS and submit the Article 5(5) declaration. They must designate a responsible person for the in-house manufacturing process.

Action for labs: Launch ISO 15189 projects, finalize Article 5(5) templates, and prepare the AEMPS notification package.

Genetic Testing: Information and Counseling

The Spanish IVD Regulation 2025 requires clear information and appropriate counseling for genetic testing. Health professionals must explain limits, implications, and result interpretation. This duty applies before and after testing.

Health professionals and centers must obtain explicit informed consent from individuals before performing a genetic test. The patient must be made aware of the nature and purpose of the test and consent in writing (except where law may exempt certain public health screening). This goes beyond standard consent, recognizing the personal and familial implications of genetic data.

Before the test, patients should be informed about what the test can and cannot tell them, and after the test, a qualified professional should explain the results and any recommended follow-up. This requirement ensures genetic tests (such as those for hereditary disease risk) are not delivered without context or support, helping patients make informed decisions.

These obligations apply to genetic IVDs regardless of whether they are done in-house or as commercial tests. For example, a direct-to-consumer genetic test kit (if allowed on the market) would need to be accompanied by processes that ensure the purchaser gets necessary information and counseling. However, most genetic tests are administered in clinical settings; the decree effectively standardizes the practice of genetic counseling as part of testing.

Action: Update consent forms, patient information sheets, and SOPs for genetic counseling, including training for staff.

Performance Studies in Spain

All performance studies in Spain must first obtain a favorable opinion from an accredited Research Ethics Committee (REC) and authorization from the health center’s management where the study will be conducted. This applies to any study using human specimens or data for evaluating an IVD’s performance, ensuring ethical considerations (informed consent, data protection, etc.) are addressed early.

When you need authorization

Interventional clinical performance studies and other studies involving risks require AEMPS authorization before first participant. Ethics approval remains mandatory.

What sponsors must prepare

Spanish protocol (CPSP), Investigator’s Brochure, and informed consent.
Insurance/indemnity for participants and a clear liability framework. The decree explicitly requires compensation for damages and defines the liability regime for sponsors. Sponsors should budget for a clinical trial insurance policy and follow the decree’s rules on coverage minimums and conditions (similar to drug trial insurance requirements in Spain).
Monitoring, data management, and safety reporting plans aligned with IVDR. Upon study completion, results (whether positive, negative, or inconclusive) should be documented and may need to be reported in the public database or to AEMPS.

Studies with CE-marked devices

If the study adds invasive or burdensome procedures or goes outside intended use, sponsors should request authorization and notify AEMPS.

Action for sponsors: Build a Spain-ready dossier, confirm insurance, and align timelines with AEMPS and ethics reviews.

Vigilance and Market Control

The Spanish IVD Regulation 2025 reinforces vigilance. Manufacturers must report serious incidents and FSCAs to AEMPS. Healthcare professionals and institutions should also report incidents. Authorities will coordinate inspections and market control actions.

For instance, if an IVD test yields false results that lead to patient harm, the manufacturer has to notify AEMPS and submit a Spanish-language safety notice so that users in Spain can be adequately informed. This ensures critical safety information is effectively communicated and mitigated in the local context.

The decree emphasizes that healthcare professionals, health institutions, and even patients/users have a responsibility to report any suspected serious incidents to AEMPS. Spain is thus bolstering a culture of vigilance: a lab that encounters a device malfunction or a clinician who notices a pattern of erroneous results should alert the authorities. The more comprehensive the reporting, the better AEMPS can intervene to prevent harm.

Action: Maintain robust PMS plans, trend analysis, Spanish FSNs, and clear internal reporting lines. Hospitals should assign a vigilance lead and train teams.

Self-Test Access and Pharmacy Channels

Notably, the new rules remove the prescription requirement for at-home self-testing kits (e.g. self-tests for glucose, pregnancy, COVID-19, etc.), making them more accessible. However, even without needing a prescription, these self-diagnostic products can only be sold through pharmacies (in-store or via an official pharmacy website) to ensure proper guidance on use. High-risk tests or those used for critical decisions may still require a prescription or professional administration.

Action: Manufacturers should confirm packaging, leaflets, and e-commerce pharmacy guidance in Spanish.

Transitional Timelines You Should Track

Entry into force: The decree takes effect after BOE publication.
Licensing: Existing third-party manufacturers have up to one year to obtain the new operating license.
Marketing register: Notification duties start when the register goes live.
In-house devices: Spain applies the IVDR timelines. Labs must meet Article 5(5) conditions and ISO 15189 by the dates set in the transitional provisions and related guidance.
Legacy devices: Spain honors the IVDR transition for legacy IVDs and preserves specific old-rule processes until systems fully switch over.

Action: Put a dated compliance tracker in place for licensing, Article 5(5), ISO 15189, registry readiness, and vigilance.

Implications by Stakeholder

IVD manufacturers

Secure or update operating licenses.
Localize labels/IFU into Spanish.
Prepare marketing register data.
Strengthen PMS and vigilance interfaces with AEMPS.

Hospital and private labs

Confirm Article 5(5) eligibility and prepare technical documentation for the in-house test.
Achieve ISO 15189 for manufacturing scope.
Notify AEMPS and assign the in-house responsible person.
Update genetic testing consent and counseling SOPs.

How MDx CRO Helps You Execute

Regulatory strategy and submissions

We align IVDR with the Spanish IVD Regulation 2025 and prepare AEMPS submissions (licenses, notifications, marketing register onboarding when live).

ISO 15189 and Article 5(5)

We run gap assessments, build SOPs, and guide labs to ISO 15189 accreditation for in-house manufacture. We prepare the Article 5(5) declaration and AEMPS notification package.

Performance studies

We plan and manage interventional and risk-involving performance studies in Spain. We handle AEMPS authorization, ethics submissions, monitoring, and safety reporting. MDx can also act your IVD performance study legal representative in the EU.

Vigilance and PMS

We design Spanish-compliant PMS frameworks, incident workflows, and FSNs. We help you interface with AEMPS and prepare for inspections.

Contact MDx CRO

Written by:

David Tomé

President

Clinical research leader and MedTech entrepreneur with deep expertise in medical devices, IVDs & precision medicine, with global study experience.

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MDx CRO at MPP 2025: Aligning Companion Diagnostics and Drug Development under IVDR

October 20, 2025

Precision medicine needs alignment, not lighter rules

Europe’s precision medicine ecosystem advances when diagnostics and medicines move in lockstep. The real bottleneck is not regulation itself; it is the structural divergence between the Clinical Trials Regulation and the IVDR. In our work across oncology and rare disease programmes, we repeatedly see how separate clocks, committees, documentation and reporting streams create avoidable friction. Our message at MPP 2025 was simple: bring both tracks together from the start and design one plan that satisfies clinical utility and regulatory rigor at the same time.

CDx and drug trials: bridging IVDR and CTR

When a biomarker guides enrolment or treatment and the assay is not CE-marked for that purpose, Article 58 triggers a performance study alongside the medicinal trial. That study’s endpoints, analytical validation and risk–benefit narrative must be coherent with the drug protocol, because outcomes like PFS, OS and ORR depend on the test defining the right population. Misalignment costs time; EFPIA’s 2023 evidence shows many sponsors facing six to twelve-month delays linked to IVDR requirements, which ultimately pushes patient access further out.

What MDx CRO presented at MPP 2025

At the Medtech & Pharma Platform Annual Conference on 16 September 2025 at the Novartis Campus in Basel, Carlos Galamba, CEO at MDx CRO, joined the session “IVDs, CDx & Personalized Medicine: Moving from Compliance to Innovation,” chaired by Fatima Bennai-Sanfourche of Bayer and Andreas Emmendoerffer of Roche. The panel brought together Antonella Baron from the European Medicines Agency, Heike Möhlig-Zuttermeister of TÜV SÜD, and patient advocate David Haerry of Positive Council Switzerland, alongside MDx.

Carlos Galamba of MDx CRO presenting at MPP 2025 in Basel on aligning companion diagnostics with drug development under IVDR. — **Carlos Galamba, CEO at MDx CRO presenting at the MPP conference**

Evidence on delays and the impact on patients

The data are unambiguous: EFPIA’s survey indicates 43 percent of companies estimated six to twelve-month delays due to IVDR, with downstream consequences for trial starts and patient inclusion across major disease areas. Every month lost to mis-sequenced processes or unclear governance is a month patients wait for targeted therapies.

Signals from regulators, notified bodies, and patient advocates

The discussion reflected a clear appetite for convergence. EMA perspectives on embedding companion diagnostics under IVDR, TÜV SÜD’s insights on conformity assessment for CDx, and the patient community’s call for earlier access all point in the same direction: coordinated planning and earlier dialogue across agencies, notified bodies and sponsors.

Key insights from the MPP panel and fellow presenters

Compliance versus innovation is the wrong debate. The practical path forward is compliance and innovation together: a single evidence plan, shared endpoints, and a unified risk–benefit narrative that treats the diagnostic and the drug as interdependent elements of one therapy journey. That is how companion diagnostics under IVDR accelerate, rather than delay, precision medicine.

How MDx CRO accelerates CDx from design to approval

MDx builds one cross-functional plan from day one, aligning clinical and device protocols, mapping Article 58 triggers, and sequencing submissions so site start-up and “first sample tested” are not held back by documentation gaps. Our teams scrutinise analytical validation, prepare CPSPs and Annex XIV packages aligned to ISO 20916, and train investigators on device-specific safety reporting and sample flows across multilingual EU sites. This integrated approach has delivered a consistent approval track record for CDx submissions.

Operational playbook for combined studies in Europe

Effective combined studies require clear governance between drug and device sponsors, modular and wave submissions across Member States, separate informed consents for the CDx component where appropriate, and proactive scientific advice with EMA or NCAs for borderline cases. With local regulatory intelligence and language capability across Europe, we coordinate roles and documentation so CTR and IVDR remain synchronised throughout the study lifecycle.

Acknowledgment to MPP and our co-presenters

Our thanks to the Medtech & Pharma Platform Association for convening this timely discussion and to the session chairs and speakers who brought regulatory, conformity assessment and patient perspectives to the same table: Fatima Bennai-Sanfourche, Andreas Emmendoerffer, Antonella Baron, Heike Möhlig-Zuttermeister and David Haerry.

Partner with MDx CRO to make CDx work under IVDR

If your programme depends on biomarker-driven enrolment or treatment decisions, partner with a team that speaks CTR and IVDR fluently. MDx CRO compresses timelines, de-risks submissions and delivers companion diagnostics that make precision medicine real for the patients who need it most

Contact MDx Today

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MDx CRO at ESMO 2025 (Berlin): Advancing IVDR Transitions & Combined Clinical Trials

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MDx CRO at ESMO 2025 (Berlin): Advancing IVDR Transitions & Combined Clinical Trials

October 20, 2025

MDx CRO presented new evidence and hands‑on learnings at ESMO 2025 that reinforce our position as the partner of choice for IVDR transitions and combined clinical trials involving investigational IVDs. We were first author on a poster with Fulgent Genetics and contributors to a Servier poster—both centered on the operational and regulatory realities of bringing high‑impact oncology diagnostics into clinical practice under the EU IVDR.

Highlights from our ESMO 2025 posters

Fulgent Genetics & MDx CRO — MDx CRO first author

Title: IVDR Compliance Challenges in Certifying a Large‑Scale NGS Panel for Hereditary Cancer

What it covers:

Practical blueprint for transitioning a comprehensive, service‑based NGS hereditary cancer panel under IVDR.
Defining intended use and scientific validity across a large gene set; end‑to‑end technical documentation; bioinformatics validation aligned to IEC 62304/82304; and notified‑body engagement strategy.
Lessons on right‑sizing verification/validation and building a living evidence package to support CE‑marking.

Why it matters: Sponsors and lab developers gain an actionable path for moving complex NGS services to IVDR compliance—without slowing clinical programs.

MDx CRO at ESMO 2025 in Berlin presenting a poster on IVDR compliance for NGS large panels for germline disease testing with Fulgent Genetics — **Dr. Marketa Svobodova, Precision Medicine Director & Carlos Galamba, CEO at MDx – Poster presentation at ESMO 2025 in Berlin**

Servier & MDx CRO (CHONQUER study) — MDx CRO contributor

Title: Navigating Regulatory Complexity in Combined Studies under CTR and IVDR (CHONQUER)

What it covers:

How combined trials (drug + investigational IVD) trigger dual oversight under CTR and IVDR and the knock‑on effects for timelines, submissions, and site activation across EU member states.
Operational patterns that accelerate approvals: early CPS planning, consolidated documentation, and aligned ethics/competent authority strategies.

Why it matters: Oncology sponsors can de‑risk global programs by anticipating IVDR‑specific requirements—and partnering with an IVD CRO that has worked both sides of the fence.

MDx CRO presented a poster at ESMO 2025 (Berlin) on combined CTR + IVDR clinical studies with Servier. — **Dr. Marketa Svobodova, Precision Medicine Director at MDx – poster presentation at ESMO 2025 – CHONQUER study, a combined study under IVDR/CTR**

Key takeaways for sponsors

IVDR transitions—end to end. MDx CRO supports dossier strategy, clinical performance studies (ISO 20916), scientific validity, and notified‑body engagement for CE‑marking.
Combined trials, simplified. We design and run CPS and combined CTR + IVDR studies, harmonizing submissions across multi‑country portfolios.
Oncology‑ready operations. Deep experience with molecular prescreening, NGS workflows, and drug–device coordination for precision oncology.

Need a quick debrief? Contact our IVD CRO team for a walkthrough of how these findings translate to your IVDR transition or combined study plan.

FAQs

What does MDx CRO do for IVDR transitions?

We provide end‑to‑end support—from intended‑use definition and scientific validity to clinical performance studies, technical documentation, and notified‑body engagement.

How does MDx CRO support combined CTR + IVDR studies?

We plan and execute CPS and combined trials, consolidating submissions and aligning ethics/competent authority requirements to reduce delays.

Can MDx CRO help with NGS panel validation under IVDR?

Yes. We design right‑sized verification/validation programs and bioinformatics validation aligned with IEC 62304/82304.

Where can I get the ESMO 2025 posters?

Both PDFs are available at the ESMO platform; contact us for a guided readout.

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TGA guidance (Oct 2025): IVD Companion Diagnostics (CDx) Requirements in Australia

October 16, 2025

What’s new

TGA IVD companion diagnostics requirements are now clearly explained in the Therapeutic Goods Administration’s guidance on IVD companion diagnostics (CDx) in Australia (updated 16 October 2025). Their revised companion diagnostics framework, adds process diagrams, a companion testing plan concept for medicine/biological sponsors, clearer clinical performance expectations, and case studies showing how the pathway works in practice.

This blog post summarises the definition of a CDx, Class 3 IVD classification, ARTG inclusion, companion testing plans, and the TGA CDx List.

What is a CDx under Australian law?

A companion diagnostic is an IVD (commercial or in‑house) that provides information essential for the safe and effective use of a corresponding medicine or biological—for patient selection, risk of serious adverse reactions, or treatment monitoring. To qualify, the test must be referenced in the Product Information (PI) for the medicine or in the Instructions for Use (IFU) of the biological. Tests used only for cell/tissue compatibility are excluded from the CDx definition.

This definition underpins the TGA IVD companion diagnostics requirements for medicines and biologicals that rely on patient selection testing.

Note: The term “a particular medicine or biological” can also cover a class of products with a similar mechanism of action, not only a single named product.

When does an indication require CDx testing?

An indication requires CDx testing when both:

the medicine’s PI (or biological IFU) states that CDx testing is essential, and
the CDx claims it is intended for that testing to enable use of the medicine/biological.
This may apply to some (not all) indications of a medicine.

To aid transparency, the TGA recommends a PI “flag phrase” indicating that testing is essential and that clinical practice testing should be adequately comparable to the pivotal trial testing; the TGA also publishes a CDx List of approved tests.

How the TGA applies CDx requirements: Class 3 IVDs and ARTG inclusion

Classification: Under TGA IVD companion diagnostics requirements, all CDx—commercial and in-house—are Class 3 IVDs (including in‑house CDx).
Separate ARTG entries: Each CDx requires its own ARTG inclusion with a Unique Product Identifier (UPI) defined by the manufacturer.
Application audit: CDx applications are subject to a mandatory application audit unless supported by specified comparable overseas regulator documentation (e.g., EU IVDR, FDA PMA, PMDA, HSA, Health Canada).
Concurrent submissions: While encouraged, concurrent medicine/CDx submissions are not mandatory; however, a CDx application should only be submitted if the corresponding indication is approved or under concurrent review.

From companion testing plans to ARTG submissions, MDx CRO streamlines the end-to-end CDx pathway in Australia, aligning clinical, regulatory, and quality workstreams to the TGA’s expectations.

Request a CDx consultation

The companion testing plan (for medicine/biological sponsors)

Every new indication that requires CDx testing must include a companion testing plan (dated and version‑controlled) describing how Australian patients will access at least one adequate test. This is central to meeting TGA IVD companion diagnostics requirements. Four options are available:

Option 1: A commercial CDx ARTG application is planned/underway (provide device submission details and sponsor contact).
Option 2: An in‑house IVD CDx will be accredited under the National Pathology Accreditation Scheme (provide lab details, accreditation timeline, and quality/access reassurances).
Option 3: Standard Australian testing is expected to deliver comparable clinical outcomes to the pivotal trials (provide detailed justification).
Option 4: None of the above—TGA reviews full device data within the medicine dossier (appropriate when no onshore testing is expected).

If Option 4 is used, TGA may add a condition of registration requiring the sponsor to maintain and update the plan (e.g., in case of supply interruption, regulatory action, or material changes to test methodology). Approval of an indication can proceed even when no ARTG‑listed or accredited CDx is available, provided an adequate plan exists; however, a commercial CDx must be in the ARTG (or an in‑house CDx accredited) before supply in Australia.

Clinical trial assay evaluation & comparability

When an indication requires CDx testing, TGA evaluates the clinical trial assay used in the pivotal studies—reviewing scientific validity, analytical performance, clinical performance, and clinical utility. Subsequent CDx must show clinical comparability to the trial assay, typically via concordance and/or bridging studies (or other appropriate evidence) aligned to the trial assay’s core characteristics.

Responsibilities at a glance

Medicine/Biological sponsors must:

Use the TGA CDx identification guide to determine if CDx testing is essential.
Consider consequences of false positives/negatives, test failures or no result.
Include: (a) evidence to support evaluation of the clinical trial assay, and (b) a companion testing plan nominating at least one adequate test.
Note: The framework does not require a one‑to‑one link between an indication and a single proprietary CDx; it focuses on the core characteristics of testing.

Device sponsors must:

Submit an IVD medical device application for ARTG inclusion of the CDx (indicating the application is for a CDx and providing the UPI).
Demonstrate comparability to pivotal trial testing and meet Essential Principles; applications may undergo audit as above.
Ensure the corresponding indication is approved or under concurrent review.

In-house IVD CDx, NATA accreditation and NPAAC obligations

Pathology laboratories may develop/modify in‑house tests for use as CDx. Class 1–3 in‑house IVDs are not included in the ARTG, but require NATA accreditation, identification of CDx in the TGA notification test list, and compliance with the NPAAC standard. Under a NATA–TGA MoU, NATA can request TGA technical assistance during evaluation of in‑house CDx performance; TGA is not otherwise involved in the accreditation decision.

TGA CDx List

The TGA publishes a CDx List showing approved commercial CDx linked to corresponding indications (with in‑house CDx to be added). The list is informational (not a regulatory instrument) and may lag recent approvals by up to one month.

Transitional arrangements and change control

Transition: CDx previously included in the ARTG as Class 2 or 3 before 1 Feb 2020 (and certain in‑house IVDs) may continue supply until 31 Dec 2028; a new compliant application is required to continue supply thereafter.
Changes: Sponsors manage post‑market device changes via the TGA Device Change Request process.

Key takeaways (quick reference)

All CDx are Class 3 IVDs and require separate ARTG inclusion (commercial) or NATA accreditation (in‑house).
Every relevant medicine/biological indication must include a companion testing plan (Options 1–4).
TGA assesses the clinical trial assay and expects comparability evidence for subsequent CDx.
Approval can proceed without on‑shore CDx if a robust plan exists, but supply requires ARTG inclusion or in‑house accreditation.

FAQs

Are all CDx Class 3 IVDs in Australia?

Yes. The regulations specify all CDx (commercial and in‑house) are Class 3 IVDs.

Can an indication be approved if no Australian CDx is available yet?

Yes—if a suitable companion testing plan is in place; however, a commercial CDx must be in the ARTG (or an in‑house CDx accredited) before legal supply.

What goes into a companion testing plan?

Identify at least one adequate test and choose Option 1–4 with supporting details (e.g., ARTG application in progress, in‑house accreditation, justification that standard testing is adequate, or full device data reviewed within the medicine dossier).

Will the PI show that CDx testing is essential?

The TGA recommends a PI “flag phrase” indicating testing is essential and should be comparable to trial testing; approved tests appear on the TGA CDx List.

Written by:

Carlos Galamba

CEO

Senior regulatory leader and advisor to top 10 global precision medicine companies with deep experience in high-risk IVDs including companion diagnostics.

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