A companion diagnostic under IVDR is an in vitro diagnostic device whose purpose is essential for the safe and effective use of a specific medicinal product. IVDR places companion diagnostics in Class C and requires consultation with the European Medicines Agency or a competent authority on the suitability of the companion diagnostic for the medicinal product. The regulatory path is longer and more expensive than a typical IVD path, and the coordination with the pharmaceutical sponsor is the single biggest project-management variable for a CDx startup.

By Tibor Zechmeister and Felix Lenhard.

TL;DR

  • IVDR Regulation (EU) 2017/746 defines and regulates companion diagnostics, referred to as CDx, as a distinct category of in vitro diagnostic device.
  • A companion diagnostic is a device intended to identify patients suitable, or unsuitable, for treatment with a specific medicinal product, or to identify patients at risk of adverse reactions .
  • Companion diagnostics are generally classified as Class C under IVDR Annex VIII .
  • EMA consultation is typically required. The notified body consults EMA or a competent authority on the suitability of the CDx relative to the medicinal product .
  • Performance evaluation for a CDx is tightly coupled to the clinical development programme of the medicinal product. The coordination with the pharmaceutical sponsor is a first-class planning item, not an afterthought.
  • The CDx path is longer than a standard Class C IVD path. Startups should plan 24 to 36 months from first notified body contact to CE mark depending on complexity.

Why CDx is a category of its own (Hook)

Tibor has seen companion diagnostics trip up both IVD-native startups and pharma-adjacent startups. The IVD team assumes the project is a standard Class C IVD and budgets accordingly, then discovers the EMA consultation and the coordination obligation with the pharmaceutical sponsor. The pharma-adjacent team assumes the IVD is a minor add-on to the medicinal product programme and discovers the full weight of IVDR technical documentation, QMS, notified body scrutiny, and post-market obligations.

Felix coaches both kinds of founders through the same reality check. The companion diagnostic path is not a sub-category of IVD work and it is not a sub-category of pharma work. It is a joint project with two regulatory regimes touching it at the same time. The project manager who runs it has to understand both sides.

The good news is that the path is well-trodden. The first wave of CDx devices under IVDR are already CE marked. The lessons are learnable. The path is long, not mysterious.

What IVDR actually says (Surface)

IVDR defines a companion diagnostic in Article 2 . The working definition is an IVD that is essential for the safe and effective use of a specific medicinal product to:

  1. Identify patients who are most likely to benefit from the medicinal product before or during treatment, or
  2. Identify patients likely to be at increased risk of serious adverse reactions as a result of treatment with the medicinal product.

The exact wording in the regulation should be quoted from the consolidated text rather than paraphrased in submissions .

Three regulatory consequences follow from a device being a companion diagnostic.

Classification. Companion diagnostics are classified as Class C under IVDR Annex VIII. There is a specific rule that assigns CDx to Class C . Class C means notified body involvement is required, technical documentation is reviewed at the Class C depth, and the scrutiny on performance evaluation is at the Class C level.

EMA consultation. When a notified body assesses a companion diagnostic, it is required to consult the European Medicines Agency, or a national competent authority for medicinal products, on the suitability of the companion diagnostic for the medicinal product concerned . The consultation asks EMA or the competent authority whether the CDx is suitable in its intended use for the specific medicinal product. The notified body cannot issue the certificate until this consultation is concluded.

Performance evaluation tied to the medicinal product. The performance evaluation of a CDx has to demonstrate that the device reliably identifies the patient population for which the medicinal product is indicated. This typically means the CDx is used in the clinical trials of the medicinal product, generating the clinical performance data for the CDx at the same time the pivotal trial generates efficacy data for the drug.

Intended purpose and labelling. The intended purpose of a CDx must make the connection to the specific medicinal product explicit. The label and instructions for use have to be consistent with the medicinal product's Summary of Product Characteristics.

A worked example (Test)

Consider a startup developing a next-generation sequencing assay that identifies patients with a specific genetic variant. A pharmaceutical company is developing a targeted therapy for patients with that variant. The startup and the pharmaceutical sponsor enter a collaboration in which the assay is used in the pivotal trial of the drug.

The regulatory path:

  1. Classification. The assay is a companion diagnostic. IVDR places it in Class C. The startup plans for Class C notified body scrutiny.
  2. Notified body selection. The startup selects an IVD notified body with experience in companion diagnostics and molecular diagnostics. The IVD notified body pool is small, and the CDx-experienced subset is smaller. Starting this search early is essential.
  3. Performance evaluation strategy. The scientific validity of the variant as a predictor of response to the drug is built during the drug's development. The analytical performance of the assay is demonstrated through standard validation. The clinical performance is demonstrated using samples from the drug's pivotal trial.
  4. EMA consultation. The notified body submits the technical documentation for the CDx and triggers consultation with EMA on the CDx suitability for the specific medicinal product. The consultation is not a rubber stamp. EMA scrutinises the analytical and clinical performance of the assay in the context of the drug's indication.
  5. Coordination with the pharmaceutical sponsor. The CDx label and the drug's Summary of Product Characteristics have to be consistent. The launch timing of the CDx CE mark and the drug's marketing authorisation have to be coordinated. If the CDx is available but the drug is not, the CDx has limited clinical utility. If the drug is available but the CDx is not, physicians cannot identify eligible patients.
  6. Post-market obligations. Post-market performance follow-up, vigilance, and periodic safety update reports apply at the Class C level. The CDx and the drug have parallel post-market obligations that have to be coordinated.

This is a 24 to 36 month project from serious regulatory work starting to CE mark, depending on the complexity of the assay, the readiness of the drug's pivotal trial, and the notified body queue.

The Subtract to Ship playbook (Ship)

Step 1. Confirm CDx status. Not every biomarker assay used alongside a drug is a companion diagnostic in the IVDR sense. If the assay is essential for the safe and effective use of a specific medicinal product, it is a CDx. If it is a general biomarker assay with multiple downstream uses, the classification question is different. Write a one-page position on whether the device is a CDx under IVDR Article 2 and cite the reasoning.

Step 2. Agree the joint regulatory plan with the pharmaceutical sponsor. The collaboration agreement has to address the IVDR technical documentation ownership, the data access for performance evaluation, the EMA consultation triggers, the launch coordination, and the post-market commitments. Do this before the clinical trial enrols the first patient, not during regulatory submission.

Step 3. Start notified body conversations 18 to 24 months before target CE mark. The IVD notified body pool is small, the CDx-experienced subset is smaller, and the consultation step with EMA adds time to the review.

Step 4. Build the QMS around EN ISO 13485:2016+A11:2021 with CDx-specific procedures. The QMS has to include procedures for the joint CDx-drug regulatory coordination, the EMA consultation interface, and the labelling consistency check.

Step 5. Write the classification justification as a standalone document. Even though CDx classification is relatively straightforward, the justification document is what a notified body asks for first. Cite the IVDR article defining CDx, cite the Annex VIII rule assigning CDx to Class C, and sign the document.

Step 6. Plan EMA consultation as a specific work package. It is not an afterthought. The notified body initiates it, but the manufacturer has to produce the evidence EMA will review. Budget time for EMA questions and responses.

Step 7. Do not over-promise the CE mark date to investors. CDx timelines are subject to variables the startup does not fully control: drug trial readout, EMA consultation turnaround, notified body queue. A conservative 24 to 36 month plan is honest. A 12 month plan is not.

Reality Check

  1. Have you confirmed, in writing with cited IVDR articles, that your device is a companion diagnostic under IVDR Article 2?
  2. Is your collaboration agreement with the pharmaceutical sponsor explicit on IVDR roles, data access, and launch coordination?
  3. Have you selected an IVD notified body with CDx experience and started the queue conversation?
  4. Do you have a performance evaluation plan that ties analytical performance, clinical performance, and scientific validity to the specific medicinal product?
  5. Have you planned the EMA consultation as a named work package with time and cost?
  6. Is your QMS built around EN ISO 13485:2016+A11:2021 with CDx-specific procedures?
  7. Are the CDx CE mark target date and the drug's marketing authorisation target date aligned in your project plan?
  8. Does your runway reflect a 24 to 36 month CDx path rather than a 12 month standard IVD path?

If any of these answers is "no," that is the next work item. CDx projects punish ambiguity more than most regulatory paths.

Frequently Asked Questions

What is the exact IVDR definition of a companion diagnostic? The definition is in IVDR Article 2 and identifies a companion diagnostic as a device essential for the safe and effective use of a specific medicinal product. The exact wording should always be quoted from the consolidated text of Regulation (EU) 2017/746 .

What class are companion diagnostics under IVDR? Class C, assigned by a specific rule in IVDR Annex VIII .

Is EMA consultation mandatory for every companion diagnostic? Yes, consultation with EMA or a national competent authority for medicinal products is required when a notified body assesses a companion diagnostic. The exact article and procedure should be verified in the consolidated IVDR text .

Can a single CDx serve multiple medicinal products? A CDx is defined by its essential role for a specific medicinal product. If the same assay is essential for multiple medicinal products, each one is a separate CDx relationship and each typically requires its own consultation and labelling link.

Who owns the technical documentation, the IVD startup or the pharma sponsor? The legal manufacturer of the IVD owns the technical documentation. In practice, data ownership and access rights should be set out explicitly in the collaboration agreement before clinical trials begin.

How long does the CDx path take? A realistic timeline from serious regulatory work starting to CE mark is 24 to 36 months, depending on the complexity of the assay, the drug's clinical development timeline, and the notified body and EMA consultation queues.

Sources

  1. Regulation (EU) 2017/746 on in vitro diagnostic medical devices, consolidated text. Article 2 definition of companion diagnostic, Annex VIII classification rules, EMA consultation article.
  2. EN ISO 13485:2016+A11:2021 – Medical devices, quality management systems.
  3. EN ISO 14971:2019+A11:2021 – Medical devices, application of risk management.
  4. European Medicines Agency, guidance on companion diagnostics consultation procedure. .
  5. Tibor Zechmeister follow-up interview, April 2026. Section 5, IVDR classification and performance evaluation observations.