Clinical Evaluation Challenges for Annex XVI Devices: – Navigating GSPRs without Clinical Benefit Claims 

19 Aug 2025

As Europe’s Medical Device Regulation (EU) 2017/745 (MDR) continues to shape the compliance landscape, manufacturers face a unique challenge: evaluating devices listed under Annex XVI that lack a direct medical purpose. These products—from aesthetic implants to electromagnetic stimulation tools—must still satisfy General Safety and Performance Requirements (GSPRs) without relying on traditional clinical benefit claims. It’s a regulatory paradox that demands precision, agility, and a deep understanding of performance-based compliance. 

At RAPS Euro Convergence 2025, Johanna Chesnel, Senior Medical Writer at NAMSA, outlined this nuanced evaluation process. Her insights offer both clarity and direction for navigating the Common Specifications (CS) laid out in Regulation (EU) 2022/2346, and interpreting Article 61(9) of the MDR. Her presentation emphasized two key pillars for Annex XVI evaluations: performance demonstration and risk management, supported by data from diverse sources such as clinical investigations, scientific literature, pre-clinical testing, and post-market surveillance. 

Understanding the Regulatory Shift 

Under Article 61(9), Annex XVI products are not expected to deliver clinical benefits, yet they must demonstrate performance through robust evidence. This creates a paradoxical demand: 

• ✅ Demonstrate performance: Prove that the device meets its defined performsnce criteria  

• ✅ Ensure risk mitigation: Show that safety risks are minimized in line with the product’s intended use 

This shift from benefit-based to performance-centric evaluation mirrors the two-step approach defined in the CS: 1) Performance Evaluation, and 2) Risk Management. This reframing of clinical evaluation—from benefit-based to performance-centric—requires manufacturers to shift their evidence strategy while still aligning with GSPRs. 

Acceptable Data Sources for Clinical Evaluation 

Even without medical benefits, manufacturers must build a convincing data dossier. Key sources include: 

• Clinical investigations (if available or feasible) 

• Scientific publications related to performance or comparable devices 

• Pre-clinical bench data supporting design intent 

• Post-market surveillance data, showing real-world performance and risk profiles 

For dual-purpose devices (e.g. aesthetic lasers with therapeutic indications), separate Clinical Evaluation Reports (CERs) must be prepared to delineate between medical and non-medical uses. This segregation aligns with CS guidance to avoid conflating clinical benefits with performance claims. 

Common Specifications (EU 2022/2346): The Backbone of Compliance 

To bring consistency to this new terrain, the European Commission issued Common Specifications (CSs) applicable to products listed in Annex XVI. These complement ISO 14971, the standard for risk management, with added stipulations such as: 

• Evaluation of residual risk without considering clinical benefits 

• User and consumer group classification based on risk exposure 

• Public accessibility of safety information, beyond just IFUs 

Let’s walk through some product-specific examples outlined in the CS: 

These classifications help manufacturers identify applicable compliance pathways and justify the exclusion of medical benefit claims. 

Risk Management without Clinical Benefits 

Here’s where things get especially nuanced. According to the CS: 

• Residual risks must be evaluated independently of benefit 

• If side effects are temporary and non-invasive, they may be deemed acceptable 

• For permanent alterations or impairments, the manufacturer must justify residual risk using scientific rationale and post-market data 

The CS further requires manufacturers to document acceptability of residual risks, particularly when adverse effects are more than transient. This places greater emphasis on risk acceptability thresholds defined in ISO 14971 and interpreted via the CS. 

User & Consumer Group Segmentation 

Annex XVI demands that manufacturers define: 

• Professional vs layperson users 

• Consumers based on anatomical variability, age, gender, or vulnerability 

• Exclusion criteria for high-risk groups 

This segmentation ensures that products are safely marketed to appropriate populations. For example, a brain stimulation device may be contraindicated in epileptic patients or children, even without medical claims. These categories must be explicitly stated in product documentation and labeling, with supporting rationale in the Technical File. 

Balancing Risk and Performance 

Manufacturers may find themselves needing to trade off certain performance aspects in order to reduce risk. According to Chesnel: 

“Risk control measures may impact device performance, provided the primary non-medical function is retained.” 

This is a subtle but powerful permission: regulators accept minor performance sacrifices if they improve user safety, as long as the device’s intended non-medical use is not compromised. 

Transparency of Safety Information 

Under CS guidance, safety and performance information must be accessible through: 

• Labeling and Instructions for Use (IFU) 

• Public portals or websites 

• Online databases or brochures targeted at consumers 

This extends beyond traditional medical disclosures—manufacturers must now proactively educate users, even when products are marketed purely for aesthetic or wellness reasons. 

✅ Strategic Guidance for Teams 

Here’s how your teams can stay ahead of Annex XVI compliance: 

1. Conduct Performance Mapping 

Clearly define performance criteria and test methods. For example, a skin resurfacing device may need to show reproducible laser depth profiles and thermal tolerances. 

2. Develop Risk-Focused Clinical Evaluation Reports (CERs) 

Shift the emphasis from outcomes to intended function and safety. Use observational data and simulate potential adverse scenarios. 

3. Optimize Labeling and Consumer Education 

Ensure clarity, accessibility, and completeness in IFUs and digital formats. Don’t assume users have medical literacy—safety messaging must be intuitive. 

4. Segment and Validate User Groups 

Use post-market feedback, usability studies, or simulations to define appropriate consumer profiles. Logically exclude high-risk populations based on scientific reasoning. 

5. Leverage CS Frameworks for Device Justification 

Integrate CS references into your Technical File, CERs, and marketing claims. This improves regulator trust and accelerates review timelines. 

Looking Forward: Regulatory Pragmatism Meets Scientific Rigor 

Evaluating Annex XVI devices without the anchor of clinical benefits is a challenge—but also an opportunity to redefine how performance is measured and risks are communicated. As Chesnel concludes, “By rigorously applying these requirements, manufacturers can ensure both regulatory compliance and user protection.” This approach transforms regulatory evaluation into a structured, evidence-based pathway for ensuring user safety, even when no medical benefit is claimed. 

QA teams must now embrace a dual lens of performance and pragmatism, building evaluation strategies that are as much about risk anticipation as they are about device capabilities. 

Let’s turn regulatory ambiguity into clarity—and compliance into confidence. Let us know how we can help.

Reference: Chesnel, J. (2025) ‘Clinical Evaluation Challenges for Annex XVI Devices: Navigating GSPRs without Clinical Benefit Claims’, RAPS Euro Convergence 2025. Available at: