The pathway to IVDR certification for companion diagnostics (CDx) can be overwhelming due to the complexity of the certification process. Certification from a notified body was not previously required, as they were self-certified under IVDD. In addition, certification to IVDR requires an external consultation process (note that the information provided in this blog post is specific to consultation with the European Medicines Agency, EMA ). The 5 tips below will help you prepare for your notified body review and external consultation for your CDx. Also, if you would like to learn how RQM+ can support your specific IVD-related projects, please let us know.

1. Know the differences between companion diagnostics in the US versus EU

Since companion diagnostics were previously self-certified under IVDD, the only experience with regulatory approval that many CDx manufacturers have is with FDA. When working towards IVDR certification, it is important to understand the differences between the definition of CDx between FDA and IVDR.

In the EU under IVDR, CDx is defined as a device which is essential for the safe and effective use of a corresponding medicinal product to identify, before and/or during treatment:

  • Patients who are most likely to benefit from the corresponding medicinal product
  • Patients likely to be at increased risk of serious adverse reaction as a result of treatment with a corresponding medicinal product

A similar definition exists for FDA; however, the FDA definition also includes devices used to monitor response to treatment with a particular therapeutic product, for the purpose of adjusting treatment to achieve improved safety or effectiveness. This last indication is not present in the EU definition, and devices used for monitoring a treatment response are not considered companion diagnostics. In addition, the FDA recognizes a related class of devices known as complementary diagnostics. These are defined as tests that identify a biomarker-defined subset of patients that responds well to a drug and aid risk/benefits assessments for individual patients, but that are not a prerequisite for receiving the drug. Complementary diagnostics are not defined in the IVDR and do not require any special considerations for CE marking.

When preparing for the conformity assessment process for IVDR, be sure to consider the differences between the US and EU regulations and create your technical file accordingly.

For devices that have already gone through FDA approvals, this may include editing reports or creating new documentation to meet the EU legislation. 


2. Understand the options and the EMA consultation process

The EMA has published guidance on its website regarding the consultation process (Medical devices | European Medicines Agency ( Read the guidance documents and be sure that you understand the requirements and timelines.

The EMA has also made public the companion diagnostic assessment report template.

This template includes guidance text for the reviewer on the type of information and data that should be included; this document is a great resource to reference when drafting your SSPs and IFUs.

The consultation process includes the following steps:

  • Notification of intent to apply (from notified body)
  • Appointment of Rapporteurs from EMA
  • Pre-submission meeting (optional)
  • Application Submission
  • Question/response period
  • Opinion Rendered


3. Prepare the SSP and IFU with the consultation in mind

The purpose of the consultation process for CDx is to confirm the suitability of the device for use with the concerned medicinal product(s), with a focus on the performance and use claims of the device. The only documents submitted to the EMA or competent authority for a CDx consultation are the draft summary of safety and performance (SSP) and draft instructions for use (IFU). These documents must include enough information for the EMA to assess the suitability of the device for use with the medicinal product. A brief summary of performance characteristics that would typically be accepted by the notified body will not be enough information for the EMA to perform the consultation.

Be sure to include information regarding scientific validity, analytical performance and clinical performance.

  • Scientific validity should demonstrate the biomarker selection including association of the analyte with clinical condition or physiological state.
  • Summary of the performance evaluation should include both analytical and clinical performance and descriptions of the study design in addition to results.
  • Clinical performance should include a description of the clinical data, description of changes to the device during or after clinical data generation that may impact results, and cut-off point selection rationale.

The documents should also include robust discussion of the risk/benefit determination and limitations of the device. Avoid using a single statement that the benefits outweigh the risk and instead include a description and justification for acceptability of the major residual risks that remain for the device.


4. Build extra time into your planning

The process for certification of CDx devices is more extensive compared with other devices. This is because of the added steps of the external consultation process in addition to the conformity assessment performed by the notified body. The EMA requires notification of intent to submit a device at least three months in advance of the expected date of submission. The notified body is likely going to perform the bulk of the conformity assessment ahead of submitting a letter of intent. This ensures that the device being put forward for consultation is likely to have a positive outcome for the conformity assessment prior to sending the letter of intent. After the 3-month notification period, the documents are submitted to EMA, and there is a 60-day review period... which may be extended up to 120 days before final recommendation is made. This is in addition to the notified body review and can take anywhere from 8-18 months to complete.

Considering these extended timelines, you should waste no time in preparing your files and engaging with a notified body to ensure timely certification of your devices before the transition deadlines.

Also consider timelines when making changes  to the device after the initial certification, especially for changes to the claims or the addition of other medicinal products to the intended purpose. These changes will require both notified body review and another consultation with EMA.


5. Collaborate with your notified body

Use the resources that are available to you.

While the notified body is not allowed to offer consultation regarding your device, they can provide valuable information regarding the CDx process and specific details on the information EMA will be reviewing.

Arrange a meeting prior to submitting your technical documentation to understand any additional details that may be needed for your SSP and IFU, but that are not included in the best practice guidance documents or other general IVDR guidance available. This is also a great time to engage the notified body to understand their previous experiences with EMA and receive details on the process that may not be publicly available on the EMA website.

If you are looking for more general information on IVDR certification, please review our IVD services page and/or contact us for support on your IVD-related projects. RQM+’s global team of clinical, technical, and top industry experts push the boundaries of excellence and we would be delighted to partner with you.

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