When Your Equivalence Route Was Never an Option
I reviewed a CER last month where the manufacturer spent eighteen months building an equivalence claim. The Notified Body rejected it in the opening review. Not because the literature was weak. Not because the comparison was poorly structured. But because the device should have had clinical investigation from day one.
In This Article
This scenario repeats across files I review. Teams invest heavily in equivalence demonstrations, only to discover late in the process that their device was never eligible for that pathway. The decision point comes early, but the consequences appear late.
The question is not whether you can build an equivalence argument. The question is whether the regulation allows you to avoid clinical investigation in the first place.
The Baseline Under MDR
MDR Article 61 establishes the foundation. Clinical investigation is the default for demonstrating safety and performance. Equivalence is not a right. It is an exception that must be earned through specific demonstrations.
This represents a fundamental shift from the Directive era. Under MDD, equivalence was broadly accessible. Under MDR, the entry criteria became substantially narrower.
The regulation does not say “you may use equivalence unless there are concerns.” It says you must conduct clinical investigation unless you can demonstrate equivalence to a device with sufficient clinical evidence.
That “unless” carries the entire weight of your clinical strategy.
The decision to pursue equivalence is not a strategic choice. It is a regulatory determination based on whether your device meets specific technical, biological, and clinical criteria defined in MDCG 2020-5.
When Equivalence Is Not Available
MDCG 2020-5 lays out the criteria for demonstrating equivalence. Most manufacturers read it as guidance on how to build the comparison. But it functions more as a filter. If your device does not pass through cleanly, you conduct clinical investigation.
The first filter is technical. If your device uses a different technology, a different mechanism of action, or operates on different engineering principles, equivalence is not available. This is not about similarity. It is about sameness at the level of function.
I see manufacturers try to bridge differences through literature or bench testing. That does not work. If the devices are not technically equivalent, no amount of clinical data on similar devices will close the gap.
The second filter is biological. If the materials contacting tissue differ, if the duration of contact differs, if the site of contact differs in ways that alter the biological interaction, equivalence breaks down.
The regulation does not allow you to say “both are biocompatible.” You must demonstrate that the biological interaction is the same.
Manufacturers claim equivalence based on similar indications and general technical similarity, without demonstrating that the devices are technically, biologically, and clinically equivalent according to MDCG 2020-5 criteria. The claim fails at first review.
The Clinical Characteristics Test
Even if technical and biological equivalence hold, the clinical characteristics must align. This means same clinical condition, same site of use, same patient population, same intended outcome.
Small differences matter here. If your device treats the same condition but in a different anatomical location, equivalence may not hold. If it targets the same site but in a different severity of disease, equivalence weakens.
The standard is whether clinical data from the equivalent device directly informs the risk-benefit assessment of your device. If it does not, you need your own data.
The Sufficiency of Evidence on the Equivalent Device
Let us assume your device passes all three equivalence criteria. That does not mean you avoid clinical investigation. You must now demonstrate that sufficient clinical evidence exists for the equivalent device.
Sufficient does not mean “some published studies.” It means the equivalent device has robust, long-term clinical data covering the full scope of your intended use, in representative populations, with adequate follow-up.
If the equivalent device was cleared under MDD with minimal clinical data, that evidence is unlikely to meet MDR requirements. You inherit the clinical gaps of the equivalent device.
This creates a circular problem. If the equivalent device does not have sufficient evidence under MDR standards, you cannot rely on equivalence. You must generate your own data. Which means clinical investigation.
Equivalence transfers both the evidence and the gaps. If the equivalent device lacks long-term data, lacks data in your specific population, or lacks data on specific risks, you must fill those gaps. Often through clinical investigation.
When the Regulation Requires Investigation
Beyond the equivalence pathway, MDR Annex XV Part A explicitly requires clinical investigation for certain device categories.
Devices containing a substance that, if used separately, would be a medicinal product require clinical investigation. Devices made of viable tissues or cells require investigation. Class III implantable devices and Class IIb devices that administer medicinal products require investigation unless equivalence can be demonstrated.
These requirements are absolute unless you meet the equivalence criteria. There is no third option.
I see manufacturers try to argue that literature alone should suffice for these devices. The regulation does not allow it. If your device falls into these categories and equivalence is not available, you conduct clinical investigation.
The Notified Body Position
Notified Bodies do not grant exceptions. They assess whether you meet the criteria. If the criteria for avoiding clinical investigation are not met, the file stops.
This is where timing becomes critical. If you discover at submission that clinical investigation was required, you face a two-to-three-year delay. The investigation must be designed, approved by ethics committees, conducted, and reported before the file can progress.
Notified Bodies will not debate the point. If the regulation requires investigation and you do not have it, the pathway forward is clear.
Manufacturers submit files with equivalence claims for Class III implants or drug-device combinations without demonstrating equivalence according to MDCG 2020-5. The Notified Body requests clinical investigation. The timeline extends by years.
Making the Decision Early
The decision on clinical investigation should happen before you write the clinical evaluation plan. It should happen before you initiate literature searches. It should happen as part of the initial classification and regulatory strategy.
Start by applying the MDCG 2020-5 criteria systematically. Document whether your device is technically equivalent to a device with sufficient clinical evidence. Document whether biological interactions are equivalent. Document whether clinical characteristics align.
If any criterion fails, plan for clinical investigation.
Next, assess whether your device falls into the categories that require investigation under Annex XV. If it does, and equivalence is not available, clinical investigation is mandatory.
Finally, evaluate the sufficiency of evidence on the equivalent device. If that device lacks robust clinical data, you must generate it.
The Cost of Getting It Wrong
The cost of a late discovery is not just time. It is the disruption of the entire regulatory timeline. Launch dates shift. Market entry delays. Competitive position erodes.
Worse, it undermines confidence with the Notified Body. If the fundamental regulatory strategy was based on an invalid assumption, reviewers question other aspects of the file.
The manufacturers who move efficiently through MDR are the ones who made the clinical investigation decision early, based on the regulation, not on preference.
When Investigation Becomes Strategy
If clinical investigation is required, it shapes everything downstream. The clinical evaluation plan must define the investigation objectives. The risk management process must identify what the investigation will address. The PMCF plan must build on the investigation data.
Clinical investigation is not a failure of the equivalence strategy. For many devices, it is the only compliant pathway. Recognizing that early turns investigation into a strategic advantage.
You control the study design. You control the endpoints. You generate data that directly addresses your device, your population, your risks. That evidence is stronger than borrowed data from an equivalent device.
The manufacturers who struggle are the ones who see investigation as a backup plan. The ones who succeed see it as the primary route when equivalence criteria are not met.
Clinical investigation is not a regulatory burden when it is required. It is the only pathway that generates evidence robust enough to support the full lifecycle of the device under MDR scrutiny.
What This Means for Your File
If you are building a clinical evaluation strategy now, start with the decision on clinical investigation. Do not start with literature searches. Do not start with drafting the CER. Start with the regulatory determination.
Apply MDCG 2020-5 criteria formally. Document the assessment. If equivalence holds, proceed. If it does not, plan investigation.
If you are uncertain, assume investigation is required. It is easier to cancel a planned study than to initiate one after Notified Body rejection.
The question is not whether you want to conduct clinical investigation. The question is whether the regulation allows you to avoid it. Most of the time, for most devices with any degree of novelty or risk, it does not.
That clarity early is what separates files that move efficiently from files that stall.
Peace,
Hatem
Clinical Evaluation Expert for Medical Devices
Follow me for more insights and practical advice.
Frequently Asked Questions
What is a Clinical Evaluation Report (CER)?
A CER is a mandatory document under MDR 2017/745 that demonstrates the safety and performance of a medical device through systematic analysis of clinical data. It must be updated throughout the device lifecycle based on PMCF findings.
How often should the CER be updated?
The CER should be updated whenever significant new clinical data becomes available, after PMCF activities, when there are changes to the device or intended purpose, and at minimum during annual reviews as part of post-market surveillance.
What causes CER rejection by Notified Bodies?
Common reasons include inadequate equivalence demonstration, insufficient clinical data for claims, poorly structured SOTA analysis, missing gap analysis, and lack of clear benefit-risk determination. Structure and logical flow are as important as the data itself.
Which MDCG guidance documents are most relevant for clinical evaluation?
Key documents include MDCG 2020-5 (Equivalence), MDCG 2020-6 (Sufficient Clinical Evidence), MDCG 2020-13 (CEAR Template), MDCG 2020-7 (PMCF Plan), and MDCG 2020-8 (PMCF Evaluation Report).
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Peace, Hatem
Your Clinical Evaluation Partner
Follow me for more insights and practical advice.
– MDR 2017/745 Article 61
– MDR 2017/745 Annex XV Part A
– MDCG 2020-5 Clinical Evaluation – Equivalence
Deepen Your Knowledge
Read Complete Guide to Clinical Evaluation under EU MDR for a comprehensive overview of clinical evaluation under EU MDR 2017/745.
