Companion diagnostic consulting is the regulatory and clinical advisory work that takes a CDx from an intended-use statement to a CE-marked device under the IVDR. In practice it covers five things: qualification and classification of the device, the clinical performance study strategy under Annex XIV, the technical documentation, the Notified Body conformity assessment, and the EMA consultation procedure that runs alongside it.
It is not the same as a CRO, which executes studies, and not the same as a CDMO, which manufactures a device someone else has already defined. Most sponsors do not need all five workstreams. Knowing which ones you need, and at what point in the programme, is what this page is for.
What a companion diagnostic consultant actually does
The work divides into five workstreams. They do not run sequentially, the classification decision constrains the study design, and the study design constrains what the technical documentation can claim.
| Workstream | The question it answers | When it starts |
| Qualification & classification | Is this device a CDx under IVDR Article 2(7)? Which class, and which conformity assessment route follows? | Before assay design is locked |
| Clinical performance strategy | Does Annex XIV apply? Is a performance study application needed, and in which Member States? | At trial design, not after the CTA is filed |
| Technical documentation | Does the evidence package support the intended purpose as written? | From first analytical validation |
| Notified Body assessment | Is the dossier ready for submission, and which NB is designated for this device type? | 12-18 months before target CE date |
| EMA consultation | Does the CDx align with the medicinal product it is tied to? | Triggered by the NB, planned far earlier |
The most common structural failure is not doing any of this badly. It is doing the first workstream late, after decisions have already been made elsewhere in the programme that cannot easily be unwound.
When sponsors engage, and when they should have
There are four points at which sponsors typically pick up the phone. Only the first two are comfortable.
- At trial design, before the biomarker strategy is fixed. This is the cheapest possible moment to be told your classification assumption is wrong.
- At assay lock, when the version used in the clinical programme is being frozen and the bridging question becomes real.
- After a Notified Body request for information, when a dossier has already been submitted and the gap is now on the record.
- Nine months before database lock, when someone finally works out that a performance study application is required in three Member States and none of them wants the same documentation.
The fourth is the expensive one, and it is more common than it should be. The underlying cause is almost always the same misunderstanding about who owns the IVDR workstream.
“The most expensive assumption a pharmaceutical sponsor can make is that the IVDR side is the diagnostic manufacturer’s problem. It isn’t. Under Article 2(57), the sponsor is whichever entity initiates, manages and finances the performance study — and in early-phase combined programmes that is very often the pharma company itself. Sponsors who build the IVDR workstream into the trial timeline from day one avoid most of these problems. The ones who don’t are the ones calling us nine months before database lock.”
Carlos Galamba | CEO & Head of IVD
In-house, generalist CRO, IVD consultancy or CDMO?
Sponsors rarely choose between these four in the abstract. They usually already have one of them and are trying to work out what it does not cover. The honest answer is that each covers a genuinely different part of the problem.
| In-house RA | Generalist CRO | IVD consultancy | CDMO | |
| Owns regulatory strategy | If IVD experience exists | Rarely — drug-led | Yes | No |
| Annex XIV study design | Often first time | Partial | Core competence | No |
| Notified Body interaction | Limited | Limited | Ex-NB reviewers | No |
| EMA consultation support | Rare | Rare | Yes | No |
| Country-adapted submissions | Learned the hard way | One dossier, all countries | Country-specific from the outset | No |
| Assay development | Sometimes | No | Advisory only | Builds to spec |
| Manufacturing | No | No | No | Yes |
The distinction that matters most is the third row. A generalist CRO can run an excellent clinical trial and still have never seen an IVDR performance study dossier from the reviewer’s side. That is not a criticism of generalist CROs, it is a description of what they are built to do.
“Across more than 40 combined programmes, specialist IVDR expertise has saved an average of three to five months against in-house teams or generalist CROs approaching a combined study for the first time. Most of that saving isn’t clever work. It’s not making the classification mistake in the first place, not submitting an identical dossier to every Member State, and knowing which authority to resolve a borderline question with before anything is filed.”
Carlos Galamba | CEO & Head of IVD
The questions that separate a capable CDx consultancy from one that looks good on paper
Capability statements all read the same. These are the questions that do not have a comfortable generic answer.
- Has anyone on the team assigned to my programme sat on the Notified Body side of an IVDR assessment? Not the company, the named individuals who will do the work.
- Which Member States have you actually filed a performance study application in during the last 24 months? A list of countries you can ‘support’ is not the same thing.
- Do you own the regulatory strategy, or do you execute a strategy I provide? These are different commercial relationships and different levels of accountability.
- What happens to my timeline if the classification question is answered differently than we have assumed? A partner who has not modelled this has not thought about it.
- Who signs the documentation that goes to the Notified Body and, through it, to the EMA?
- When a Member State issues a request for information, does your response anticipate the same question arriving from the other authorities still reviewing?
If you are evaluating a partner to build and manufacture the assay itself rather than to own the regulatory pathway, the questions are different, see our guidance on choosing a CDx development partner.
Where the EMA consultation fits
For a CDx, IVDR conformity assessment is not purely a Notified Body matter. Once the NB has the application, it submits a letter of intent to the EMA — or in some cases to a national competent authority — together with a technical dossier. The EMA appoints a rapporteur, issues a scientific opinion on whether the device is suitable for use with the medicinal product, and returns that opinion to the NB, which then decides on the CE mark.
The procedure has short response windows and a documentation standard well above the instructions for use, particularly in the Summary of Safety and Performance. We have set out the full pathway, the timelines and the SSP requirements separately.
A product-specific example is the VENTANA PD-L1 (SP263) assay for Libtayo, where a clinical bridging study connected the commercial assay with evidence generated using another PD-L1 test.
Frequently Asked Questions
A CDx consultant owns the regulatory pathway for the diagnostic: qualification and classification under the IVDR, clinical performance study strategy under Annex XIV, technical documentation, Notified Body assessment and the EMA consultation. They advise on evidence generation rather than performing assay development or manufacturing.
At trial design, before the biomarker strategy and assay configuration are fixed. Classification and performance study requirements constrain study design, so decisions taken before the regulatory workstream exists frequently have to be revisited at significant cost.
A consultancy defines the regulatory strategy and evidence requirements. A CRO executes the clinical work. A CDMO manufactures a device that has already been specified by someone else. A CDMO cannot resolve an intended-use or classification question, because it does not own those decisions.
Often yes, but for a different reason than sponsors expect. Under IVDR Article 2(57) the sponsor of a performance study is whoever initiates, manages and finances it, which in early-phase combined programmes is frequently the pharmaceutical company, not the diagnostic manufacturer. The obligation may sit with you regardless of your partner’s capability.
Plan on 18 to 24 months from a complete technical dossier to CE certificate, and longer where the EMA consultation raises questions or the Notified Body has capacity constraints. Very few Notified Bodies are designated for companion diagnostics, and queue time is a real planning variable.
Yes, and there is a strong argument for it. The intended-use statement and much of the analytical validation package can be shared across both frameworks if they are aligned from the outset. Where the two diverge is in clinical evidence and population justification, data generated exclusively on EU samples requires justification of equivalence to the US population, and vice versa. If you are planning both routes, our FDA Companion Diagnostic Roadmap sets out the US pathway in full, classification, IDE, Q-Submission strategy and PMA content requirements.
Working with MDx CRO
MDx CRO is a regulatory CRO specialising in in vitro diagnostics and companion diagnostics. Our IVD team includes former Notified Body reviewers and an External Expert to the European Commission on IVDs. We have supported companion diagnostic programmes across EU IVDR, FDA and global markets, including more than 40 combined drug-and-diagnostic programmes.
If you are at trial design, at assay lock, or holding a request for information you were not expecting, a short scoping conversation will tell you which of the five workstreams you actually need.
