MDCG 2025-9 Guidance: Breakthrough Devices (BtX)
Applicable regulations: MDR (EU) 2017/745, IVDR (EU) 2017/746
Guidance document: MDCG 2025-9 Guidance on Breakthrough Devices (BtX) (December 2025)
Introduction
Published in December 2025, MDCG 2025-9 is the first systematic EU guidance document providing comprehensive technical and procedural direction on "Breakthrough Devices (BtX)." The guidance does not create new legal obligations; within the existing MDR and IVDR framework, it provides a more predictable and proportionate regulatory pathway for highly innovative medical devices addressing serious conditions or unmet medical needs.
1. Concept and Regulatory Nature of BtX
BtX is not a new product classification, nor an independent compliance pathway under MDR or IVDR — it is a "status designation." Once designated as BtX, a device must still fully satisfy all essential safety and performance requirements, but may receive more flexible support in clinical evidence generation, regulatory communication, and review prioritisation.
BtX designation does not confer market exclusivity, nor does it restrict other products in the same disease area from obtaining similar designation.
2. Scope and Exclusions
The guidance applies in principle to all technology types and risk classes, including AI, nanotechnology, and advanced materials. Custom-made devices, in-house devices, and Annex XVI products without a medical purpose are excluded.
3. Dual Threshold for BtX Designation
BtX requires simultaneous satisfaction of two conditions:
High degree of innovation: Assessed across device technology, associated clinical practice, and application in medical practice. Typically manifests as fundamental changes in materials/design, new mechanisms of action, significantly different manufacturing/use methods, or existing technology in entirely new clinical scenarios. Incremental optimisation generally does not qualify.
Significant positive clinical impact: Must address life-threatening or irreversibly disabling conditions, and reasonably be expected to provide significant improvement over the current state of the art. Improvement may be at the individual patient level (survival, disease progression, treatment burden, quality of life) or public health level (care efficiency, resource utilisation). For unmet needs, the manufacturer must clearly demonstrate how the product fills the gap.
4. Clinical Evidence Strategy: Lifecycle Perspective
BtX does not reduce overall clinical evidence requirements — it distributes them more rationally across the lifecycle. BtX does not mean "low-evidence market access"; it allows certain confirmatory data to be systematically generated post-market under specific conditions.
Pre-market: Focus on demonstrating acceptable benefit-risk ratio and reasonable expectation of clinical performance. Some uncertainty is permitted, provided risks are identified, assessed, and controlled.
Post-market: Enhanced PMS systems and structured PMCF/PMPF activities must continuously confirm long-term safety, performance stability, and clinical benefit. Any strategy deferring evidence generation must be supported by adequate justification, clear milestones, and executable plans.
5. Role of Non-Clinical and Preclinical Evidence
Non-clinical and preclinical evidence plays a core function in reducing innovation uncertainty. The guidance sets higher expectations for bench testing, biocompatibility assessment, manufacturing process validation, and usability engineering. Validated in silico modelling and simulation are explicitly recognised as supporting evidence sources.
6. Clinical and Performance Study Design
Study design should serve the lifecycle evidence strategy. Short- or medium-term endpoints may support market access, with post-market studies confirming long-term outcomes. For BtIVD, composite reference standards, Bayesian methods, or real-world data may be used as supplements with adequate justification.
7. Post-Market Surveillance and PMCF/PMPF
Under the BtX framework, PMS is a core component of the overall evidence system. Enhanced PMS systems and structured PMCF/PMPF activities are required. For high-risk or implantable BtMD, registry systems are highly valuable; for BtIVD, external quality assessment and real-world use data are equally important.
8. Expert Panels and Notified Bodies
Manufacturers may apply for BtX designation opinions from expert panels at an early development stage, and reduce regulatory uncertainty through early scientific advice or clinical evaluation consultation. Notified bodies should prioritise BtX projects and may use conditional certification to balance innovation speed with evidence completeness.