When Your Device Acts Like a Drug: The Borderline Trap
I reviewed a file last month where the manufacturer insisted their product was a device. The active substance delivered a pharmacological effect. The claim rested on drug delivery. Yet the classification remained device. The Notified Body stopped the review in the first audit cycle. This was not a grey area. This was a classification error that invalidated the entire conformity route.
In This Article
Borderline products occupy a strange regulatory position. They sit between medical device legislation and pharmaceutical legislation. The distinction is not always intuitive. And the consequences of getting it wrong are severe.
Most manufacturers understand the basic principle. A medical device achieves its principal intended action by physical means. A medicinal product achieves its effect through pharmacological, immunological, or metabolic action. The dividing line should be clear.
But in practice, it is not.
Where the Confusion Begins
The confusion arises when a product combines mechanical function with a substance that has biological activity. The manufacturer focuses on the delivery mechanism. The regulator focuses on the mode of action. These two perspectives do not always align.
I see this most often with drug-device combinations, wound care products with active ingredients, and diagnostic systems that use biological reagents. The manufacturer designs a clever delivery system and believes that makes it a device. The active substance, however, may be doing most of the therapeutic work.
The question is not what the product contains. The question is how the product achieves its principal intended action.
Classification depends on the principal mode of action, not on the technological sophistication of the delivery system. If the therapeutic effect comes primarily from pharmacological action, the product falls under pharmaceutical legislation regardless of how innovative the device component is.
MDR Article 1(6) addresses this directly. If a device incorporates a substance that, if used separately, would be considered a medicinal product, and that substance has an action ancillary to that of the device, it remains a device under specific conditions. But if that substance achieves the principal intended action, the product is a medicinal product.
The word “ancillary” is critical here. It means secondary. Supporting. Not primary.
The Principal Intended Action Test
Determining the principal intended action is not always straightforward. It requires looking at what the product actually does in the body, not what the manufacturer wants it to be classified as.
I worked on a wound healing product that contained a bioactive peptide. The manufacturer emphasized the occlusive dressing component. The peptide, they argued, merely supported the healing environment created by the dressing. When we examined the clinical data, the peptide was responsible for most of the healing acceleration. The dressing alone showed minimal effect. The principal action was pharmacological.
This changes everything. The clinical evaluation strategy, the conformity assessment route, the competent authority, the approval timeline—all of it shifts.
MDCG 2022-5 provides the qualification and classification framework. It walks through decision trees for borderline products. But even with guidance, the analysis requires careful judgment.
What Reviewers Look For
When a Notified Body or competent authority reviews a borderline case, they look at several elements:
First, they examine the intended purpose as stated by the manufacturer. What is the product supposed to do? What claims are being made?
Second, they review the mechanism of action. How does the product achieve that purpose? Is it through physical barrier, mechanical action, or chemical/pharmacological interaction?
Third, they assess the clinical evidence. What does the data actually show? Which component drives the clinical benefit?
If there is any doubt, they consult with the relevant competent authorities. And when authorities disagree on classification, the manufacturer ends up in a regulatory limbo that can last months.
Manufacturers describe the physical delivery mechanism in detail but fail to demonstrate that the mechanical component achieves the principal action. The clinical data shows pharmacological activity as the primary driver. The classification justification contradicts the evidence.
The Ancillary Substance Pathway
MDR Article 1(8) allows devices to incorporate an ancillary medicinal substance under specific conditions. This is not a simple exemption. It requires consultation with a medicines agency, additional testing, and specific approval steps.
Many manufacturers underestimate this requirement. They assume that because the product is classified as a device, the normal device pathway applies. It does not.
The ancillary substance must be assessed for quality, safety, and usefulness in combination with the device. This assessment follows pharmaceutical standards, not device standards. The manufacturer must demonstrate that the substance is integral to the device performance and cannot be replaced by a substance that does not fall under pharmaceutical legislation.
This means you cannot simply choose a pharmacologically active substance for convenience. You must show it is necessary for the device to achieve its intended purpose.
What This Means for Clinical Evaluation
The clinical evaluation for a device with an ancillary substance becomes more complex. You must address both the device component and the substance component separately and then in combination.
The literature review must cover both device-related clinical data and pharmaceutical data on the substance. The risk analysis must consider both mechanical risks and pharmacological risks. The clinical investigation plan, if needed, must assess both modes of action.
And here is where most files fail: they treat the substance as a material characteristic rather than as an active component requiring its own clinical evaluation.
I see clinical evaluation reports that mention the active substance in passing. One paragraph. No dedicated risk-benefit analysis. No assessment of systemic effects. No consideration of dose-response relationships. The reviewers reject these files immediately.
An ancillary substance is not a passive ingredient. It requires a dedicated clinical evaluation section addressing its quality, safety profile, interaction with the device component, and contribution to the overall risk-benefit balance. Treating it as a material specification is insufficient.
When the Classification Is Wrong
What happens when a product is incorrectly classified as a device when it should be a medicinal product?
The conformity assessment process stops. The Notified Body cannot issue a certificate for a product outside its scope of designation. The manufacturer must reclassify and start again under pharmaceutical legislation. This means a completely different regulatory pathway, different timelines, and different competent authorities.
I have seen manufacturers lose years because of initial misclassification. The device file was well-prepared. The clinical data was strong. But the classification was wrong from the start. Everything had to be rebuilt.
The risk is not just delay. If the product has already been placed on the market under the wrong classification, there are serious legal consequences. The CE mark is invalid. The product is non-compliant. Market surveillance authorities can issue corrective actions or withdrawals.
The Grey Zones
Some products genuinely sit in the grey zone. They have both significant mechanical and pharmacological actions. The principal mode of action is not obvious.
In these cases, early consultation with the competent authority is essential. Do not wait until the file is complete. Do not assume the Notified Body will make the call. Request an official classification opinion before investing in the full technical documentation.
This consultation takes time, but it prevents catastrophic rework later. The authority will review your intended purpose, mechanism of action, and preliminary data. They will provide a written opinion on classification. This opinion protects you during the conformity assessment.
Manufacturers rely on internal classification decisions without seeking competent authority consultation for borderline cases. When the Notified Body raises classification concerns during review, there is no official classification opinion to reference. The review halts while classification is resolved.
Practical Steps for Borderline Products
If you suspect your product might be borderline, take these steps early:
First, document a detailed analysis of the principal intended action. Do not just describe what the product does. Explain how it does it. Break down the contribution of each component to the overall effect. Use your preclinical and clinical data to support the analysis.
Second, review MDCG 2022-5 systematically. Follow the decision trees. Document your answers at each decision point. If the guidance points toward medicinal product classification, do not ignore it.
Third, consult with the competent authority before finalizing your classification. Submit a formal classification request with supporting documentation. Wait for the written response.
Fourth, if the classification confirms medical device status but with an ancillary substance, plan for the additional consultation and approval steps. Budget the time and resources for pharmaceutical-level substance assessment.
Fifth, structure your clinical evaluation to address both the device and the substance as distinct elements with a combined risk-benefit analysis. Do not merge them into a single generic discussion.
What the Notified Body Will Check
During conformity assessment, the Notified Body will verify your classification justification. They will ask for the competent authority opinion if the product is borderline. They will review the mechanism of action against your claims.
If your product includes an ancillary substance, they will check that the medicinal consultation was completed and that the substance was approved as ancillary. They will review the quality and safety data for that substance. They will assess whether the clinical evaluation addresses the substance adequately.
If any element is missing or unconvincing, the review stops. Classification disputes cannot be resolved at the Notified Body level. They escalate to the competent authority, which adds months to the timeline.
Final Considerations
Borderline classification is not a technicality. It determines your entire regulatory pathway. Getting it wrong invalidates everything that follows.
The distinction between device and medicinal product rests on the principal mode of action, not on the manufacturer’s preference or the product’s design elegance. If the therapeutic effect comes primarily from pharmacological action, the product is a medicinal product. If the pharmacological action is truly ancillary, the device classification may hold, but only with additional regulatory steps.
When in doubt, consult early. Do not build a complete file on an assumption. One wrong classification decision can unravel years of work.
In the next part of this series, I will address software as a medical device in combination products and when the algorithm becomes the primary therapeutic component.
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). MDCG 2022-5, MDR Article 1
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Peace, Hatem
Your Clinical Evaluation Partner
Follow me for more insights and practical advice.
– Regulation (EU) 2017/745 Article 1(6) and Article 1(8)
– MDCG 2022-5 Guidance on Classification of Medical Devices
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Read Complete Guide to Clinical Evaluation under EU MDR for a comprehensive overview of clinical evaluation under EU MDR 2017/745.
