Beyond Implantation: Clinical Evaluation of Total Knee Replacement in the EU MDR Era

Author: Feral Ravi Daruwala, Regulatory & Compliance, Biorad Medisys

Under EU MDR, approval is not the end of clinical evaluation — it is the point from which evidence must continuously prove its value.

For Total Knee Replacement (TKR) devices, the EU MDR 2017/745 shifts clinical evaluation from a one-time regulatory requirement to a continuous, evidence-driven process. For Class III implants, the expectation is not just to generate clinical data but to maintain a clear and scientifically justified benefit–risk profile throughout the device lifecycle, while demonstrating performance in line with the current state of the art.

A key regulatory challenge lies in Article 61, particularly the stricter requirements for demonstrating equivalence. Equivalence must be demonstrated across clinical, technical, and biological characteristics, and in TKR systems, even small variations in design, materials, or fixation methods can impact clinical outcomes. As a result, reliance on legacy or similar device data is increasingly limited. Manufacturers are therefore required to generate device-specific clinical evidence, including for products that were historically approved under earlier frameworks. Under EU MDR, clinical investigations are generally expected for Class III devices unless a robust scientific justification is provided, further increasing the need for prospective, device-specific clinical data.

Annex XIV (Part A) defines a structured approach to clinical evaluation, beginning with a Clinical Evaluation Plan (CEP). The Clinical Evaluation Report (CER) must go beyond summarizing available data and instead provide a critical assessment of its quality, relevance, and limitations. For TKR devices, this is challenging due to variability in published studies, including differences in endpoints, patient populations, and follow-up durations. To manage this, manufacturers are adopting systematic literature review methods and clearly identifying data gaps to ensure transparency and regulatory acceptance. Where gaps cannot be adequately addressed through literature or existing data, clinical investigations conducted in accordance with Annex XV and ISO 14155 become a key component of evidence generation.

Another important consideration is the gap between the duration of pre-market studies and the expected lifespan of TKR implants. While clinical studies often provide short- to mid-term data, implants are expected to function for decades. To address this, Annex XIV (Part B) mandates Post-Market Clinical Follow-up (PMCF). PMCF plays a critical role in generating long-term evidence through registry data, post-market studies, and real-world clinical use, and is defined through a PMCF Plan, with outcomes documented in a PMCF Evaluation Report (PMCF ER). In many cases, PMCF includes post-market clinical investigations designed to generate long-term safety and performance data.

However, real-world data sources such as joint registries come with limitations, including variability in data quality and limited device-specific traceability. Manufacturers are addressing these challenges through improved data strategies, including the use of Unique Device Identification (UDI) systems and targeted PMCF studies designed to generate relevant and reliable data, often complementing or extending findings from pre-market clinical investigations.

In addition, Articles 83–86 link clinical evaluation with post-market surveillance, requiring ongoing updates through Periodic Safety Update Reports (PSURs), along with trend reporting where applicable. This ensures that new clinical information is continuously evaluated and that the benefit–risk profile remains current.

In summary, under EU MDR, clinical evaluation for TKR is an ongoing regulatory responsibility rather than a static submission. It requires continuous planning, data generation, and reassessment to ensure sustained safety and performance, with clinical investigations and PMCF activities forming an integrated, lifecycle-based evidence-generation strategy.