Decode and Conquer
Clinical evaluation translated for EU medical devices regulation transition
by Kamala Kodihally Nanjundeshaiah
Clinical evaluation is a hard nut to crack. But it’s the most important evidence for providing safety and performance data of medical devices. Currently, medical device companies are busy working to transition their Conformité Européenne (CE)-certified products on to the new medical devices regulation (MDR). They’re expected to spend much time and effort ensuring clinical evaluation conformity.
Clinical evaluation is a methodologically sound ongoing procedure to collect, appraise and analyze clinical data pertaining to a medical device. “Analyze” refers to whether there is enough clinical evidence to confirm and comply with relevant essential requirements for safety and performance when using the device according to the manufacturer’s instructions for use.
Sources for clinical evaluation can include published data on an equivalent device, clinical investigations, post-market surveillance data, scientific literature, public adverse event databases, and internal corrective and preventive actions.
European Medical Device Vigilance System (MEDDEV) 2.7/1 revision 4 is a guideline for clinical evaluation under directives 93/42/European Economic Community (EEC) (medical device directive) and 90/385/EEC (active implantable medical device directive).
The following are steps involved in performing a clinical evaluation:
- Step zero: Define the scope and plan of clinical evaluation.
- Step one: Identify the device’s pertinent safety and performance data.
- Step two: Appraise each individual data set in terms of its scientific validity, relevance and weight.
- Step three: Analyze the data to determine the device’s safety, performance and intended use, including any undesirable side effects that can be minimized and are within the acceptable benefits-risks ratio.
- Step four: Draw conclusions to show that the device is safe and performing as intended or corrective actions have been initiated to fulfill the gaps.
Even though MDR doesn’t specifically reference MEDDEV 2.7/1 clinical evaluation guidelines, it’s a stepping-stone to perform systematic clinical evaluations because MDR requires a formal clinical evaluation report (CER).
Elements to consider for clinical evaluation under MDR—assuming the existing clinical evaluation report complies with MEDDEV 2.7/1, rev. 4, include:
- MDR regulation (EU) 2017/745, Chapter VI, Article 61 (clinical evaluation), Article 62-82 (clinical investigations) and Annex XIV—part A outlines the clinical evaluation requirements, and Annex XV outlines the clinical investigations for MDR. It is important to understand them thoroughly and assess their applicability.
- Clinical evaluation is confirmation of compliance with relevant general safety and performance requirements established in Annex I under the normal conditions of the device’s intended use. Sections one and eight requirements are particularly relevant and to be supported with clinical evidence and pertinent data.
- An expert panel must consult on and review the strategy of all class III and IIb devices (as referred in Article 106) before the device’s clinical evaluation. The panel’s views must be considered during clinical evaluation.
- The manufacturer should specify and justify the level of clinical evidence necessary to demonstrate conformity relevant to general safety and performance requirements. The level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.
- The manufacturer should plan and establish a clinical evaluation plan identifying the scope, requirements, relevant data, methods, sources and selection criteria to perform clinical evaluation.
- Post-market clinical follow up is part of post-market surveillance (PMS), which continuously updates the clinical evaluation. Clinical evaluation should be addressed in the PMS plan.
- Appraise all relevant clinical data by evaluating their suitability for establishing the device’s safety and performance.
- Evaluate the scientific literature to review generally acknowledged information on the state of the device’s art, safety, performance, design characteristics and intended purpose.
- Analyze all relevant clinical data to reach conclusions about the device’s safety and performance.
- For any new or additional clinical evidence needed to support the device’s safety and performance, properly designed clinical investigations should be done in accordance with the clinical development plan.
- Article 2(49) MDR introduces a “sponsor,” or any individual or organization that takes the responsibility for the initiation, management and setting up of the clinical investigation’s financing. This requires a legal representative be appointed to ensure compliance with the sponsor’s obligations and requires the appointment of a monitor independent from the investigational site.
- To demonstrate equivalence with an already-marketed device, the device’s technical, biological and clinical characteristics must be considered.
- If the manufacturer did not make the demonstrated equivalent device, the manufacturer must have a contract to have full access to the technical documentation on an ongoing basis.
- The clinical evaluation shall be thorough and objective, considering favorable and unfavorable data.
- The clinical evaluation and its documentation shall be updated throughout the life cycle of the device. A clinical evaluation report must be updated annually for class III and implantable devices, and two to five years for low-risk devices.
- Clinical evaluation documents must be updated whenever new clinical data are available, and the design or intended use of the device is updated.
Ensuring clinical evaluation compliance can range from minimal work to performing clinical investigation. Executives should be informed of the importance of meeting increasingly stringent clinical data and evaluation requirements.
By proper planning and systematic execution, compliance can be met. Start the transition early and have continuous dialogue with the notified body to avoid any audit surprises. For legacy devices, review the MDR transitional provisions in Article 120 to determine the effect on existing devices and develop the clinical data policy for it.
European Commission, “MEDDEV 2.7/1 revision 4, Clinical Evaluation: A Guide for Manufacturers and Notified Bodies Under Directives 93/42/EEC and 90/385/EEC,” June 2016.
European Union Medical Device Regulation (Council Regulation 2017/745), https://tinyurl.com/EU-2017-745, April 5, 2017.
Kamala Kodihally Nanjundeshaiah is a quality and regulatory consultant based in Winnipeg, Manitoba. She received a bachelor’s engineering degree with specialties in electronics and communication from the University Visvesvaraya College of Engineering in Bangalore, India. She is an ASQ senior member and an ASQ-certified quality engineer and auditor.