Under EU MDR 2017/745, manufacturers must use post-market clinical follow-up, or PMCF, to identify possible systematic misuse or off-label use and verify whether the device’s intended purpose remains correct. When off-label use is identified, the resulting information must be considered within the device’s clinical evaluation, risk management and post-market documentation.
However, off-label data does not automatically provide sufficient clinical evidence to support a new indication or expanded intended purpose. The Team-NB position paper on data generated from off-label device use explains how manufacturers and Notified Bodies should assess its relevance, quality and regulatory implications.
Understanding “Off-Label” Use Under MDR
The term off-label use is not explicitly defined in the MDR. However, Annex XIV, Part B—which outlines requirements for Post-Market Clinical Follow-Up (PMCF)—expects manufacturers to identify misuse or off-label use of their devices proactively as part of their ongoing data collection and analysis.
This is because off-label use, intentional or unintentional, can influence a device’s safety, performance, and benefit–risk profile.
Unlike the pharmaceutical sector—where “off-label use” is well established and tied to product labeling and authorized indications—the concept for medical devices remains less formally defined. In practice, off-label use refers broadly to a device being used outside its intended purpose as described in the manufacturer’s instructions for use (IFU) or technical documentation.
The methodology used to identify, appraise and analyse this evidence should be defined in the device’s Clinical Evaluation Plan and reflected in the corresponding MDR Clinical Evaluation Report
Why It Matters: Data Relevance and Clinical Evidence
The Team-NB position paper emphasizes that data generated from off-label use can sometimes offer valuable safety and performance insights—but such data cannot be directly used to support the intended purpose of a device unless carefully analyzed and justified.
Manufacturers should therefore:
- Identify and record instances of off-label use through PMCF and Post-Market Surveillance (PMS) systems.
- Assess relevance and scientific validity of such data when considering it in the clinical evaluation or trend reporting.
- Differentiate between misuse due to human factors and genuine clinical necessity or innovation.
Any insights drawn from off-label data must be clearly documented, and the rationale for inclusion or exclusion in the device’s clinical evaluation report (CER) should be justified according to MDR Annex XIV, Part A.
Implications for Manufacturers and Notified Bodies
For manufacturers, this position paper serves as a reminder that off-label use is both a risk management consideration and a potential data source. It requires active monitoring, not passive recording.
Notified Bodies, for their part, are expected to evaluate how manufacturers:
- Capture and categorize off-label usage events.
- Integrate off-label findings into PMCF and PMS activities.
- Apply conclusions from such data to risk–benefit assessments and updates to labeling or IFUs.
When recurring off-label use indicates a systematic clinical need not covered by the original intended purpose, manufacturers may need to initiate a design or labeling review and consider regulatory reassessment.
By formalizing its view, Team-NB and the participating Mirror-MDCG Clinical Working Group aim to improve consistency and transparency across Notified Bodies when reviewing PMCF and CER documentation that includes off-label data.
This harmonization will help reduce uncertainty for manufacturers and contribute to more robust post-market evidence across the EU.
Can Off-Label Data Support a New Intended Purpose?
Not automatically. Systematic off-label use identified through PMCF may generate clinical data that must be considered as part of the clinical evaluation. Both favourable and unfavourable findings should be assessed and documented.
However, off-label data is often collected without a predefined protocol, controlled conditions or an appropriate statistical analysis plan. It may therefore lack the quality, quantity or methodological strength needed to support an expanded intended purpose or new indication.
If recurring off-label use reveals a genuine clinical need, the manufacturer should assess whether a formal clinical investigation is required. Under MDR Article 74(2), an investigation conducted to assess a CE-marked device outside its existing intended purpose is subject to the requirements applicable to pre-market clinical investigations.
- The manufacturer should document:
- How the off-label use was identified.
- Whether the use is isolated or systematic.
- The quality, relevance and limitations of the resulting data.
- Its impact on the clinical evaluation and benefit-risk assessment.
- Any necessary changes to risk management, labelling or the instructions for use.
- Whether further clinical evidence must be generated under a formal protocol.
Frequently Asked Questions
Off-label use generally means using a medical device outside the intended purpose, indications, patient population or conditions described by the manufacturer in its instructions for use and technical documentation.
The EU MDR mentions misuse and off-label use but does not provide a specific definition. Annex XIV, Part B requires PMCF activities to identify possible systematic misuse or off-label use and verify whether the device’s intended purpose remains correct.
Yes. Manufacturers should use PMCF, PMS, literature monitoring, complaints, registries, user feedback and other relevant data sources to identify possible systematic off-label use. The findings and their regulatory significance should be documented.
Yes. Clinically relevant data generated through off-label use should be considered during the clinical evaluation. Manufacturers must assess its relevance, scientific validity, limitations and impact on the device’s safety, performance and benefit-risk profile.
Off-label data may indicate a genuine clinical need, but it is not automatically sufficient to support a new indication. Because this data is often collected without a formal protocol or controlled methodology, additional clinical evidence or a formal clinical investigation may be required.
How MDx CRO Supports Manufacturers
MDx CRO assists manufacturers in integrating off-label monitoring into PMCF and PMS plans, ensuring that data handling and reporting align with MDR expectations.
Our team supports clinical evaluation, PMCF study design, and Notified Body submission strategy, helping you interpret real-world data responsibly—whether it originates from intended or off-label use.
MDx CRO supports manufacturers with clinical evaluation, PMCF planning, risk assessment and the regulatory interpretation of post-market data. Learn more about our Regulatory Affairs and Technical Documentation services or contact our team to discuss your MDR evidence strategy.
