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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.

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.

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.

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.


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

A: 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.

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

A: 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.

Q: What documentation is required for a follow-on CDx?

A: 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.

Q: How are devices transitioning from IVDD to IVDR handled?

A: 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.

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

A: 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.

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?

  1. Expertise: Our in-depth knowledge of CDx, IVDR, and EU regulations offers unparalleled support.
  2. Collaboration: Working closely with clients, we tailor our approach to meet specific needs.
  3. Efficiency: Our insights and guidance save valuable time and resources, simplifying complex regulatory pathways.
  4. 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.

Carlos Galamba IVDR consultant expert

Author: Carlos Galamba, Founder and Head of IVD

Carlos has spent the past 18 years in the IVD sector, primarily at the renowned Notified Body, BSI. There, he not only built an extensive global network with leading EU Notified Bodies but also pioneered as the first in-house clinician for IVDs. Carlos spearheaded the BSI clinical oversight process, paving the way for hundreds of CE markings for IVDs. Prior to his regulatory roles, Carlos honed his expertise as a senior scientist in prestigious UK diagnostic institutions, working with various IVD technologies giving him a thorough understanding of the field’s unique demands. Beyond BSI, Carlos served as Vice President for Diagnostics at RQM+, the world’s largest medtech consultancy and was also an inspector with the MHRA. Currently, he serves as an independent advisor to the EU Commission, sharing his vast knowledge and experience with a variety of stakeholders.

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