A new position paper from the Mirror-MDCG Clinical Working Group, composed of representatives from 11 Notified Bodies and approved by Team-NB, clarifies how data from off-label medical device use should be viewed and handled under the EU Medical Device Regulation (MDR) 2017/745. Distributed through the CIRCABC platform, the paper aims to harmonize understanding across Notified Bodies and manufacturers when such data emerge during clinical evaluation or post-market surveillance.
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.
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.
Moving Toward Harmonized Practice
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.
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.
Learn more about our Regulatory Affairs Services and Clinical Research Solutions, or contact us to discuss compliance strategies for MDR Annex XIV requirements.
