EU has a new approach of Risk Management for clinical trials
Risk management plays now a pivotal role in the lifecycle of medical product development within organizations dedicated to the field. From the initial stages of development to manufacturing and the subsequent commercial distribution of medical products, adhering to robust risk management practices is a fundamental requirement.
In recent times, the European health sector has witnessed substantial regulatory changes. The transition from the EU Medical Device Directive (MDD) to the EU Medical Device Regulation (MDR) signifies a noteworthy shift toward a more universally risk-based approach. This transition places explicit and stringent requirements on manufacturers, outlining the necessity for maintaining a comprehensive risk management program throughout the entire life cycle of a medical product.
Notably, the EU MDR introduces significant changes compared to its predecessor, the MDD (93/42/EEC). Unlike the MDD, the EU MDR explicitly mandates manufacturers to establish, document, implement, and maintain a systematic approach to risk management. This includes the obligation to address and communicate residual risks to users, emphasizing a proactive stance in risk reduction. Keep reading and learn more about the new approach of Risk Management for clinical trials.
MDR defines risk as the following
“The combination of the probability of occurrence of harm and the severity of that harm” and benefit-risk determination is defined as “the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer.”
EU MDR requirements for Risk Management plans
Within the framework of the EU Medical Device Regulation (MDR), manufacturers must develop a comprehensive risk management plan for each device in their scope. This entails a meticulous process of identifying and analysing both known and foreseeable hazards associated with the device, followed by a thorough estimation and evaluation of the corresponding risks throughout the entire product’s life cycle.
This emphasis on ongoing evaluation and adaptation underscores the dynamic nature of risk management within the life cycle of medical devices, ensuring that manufacturers remain vigilant and responsive to evolving information and potential risks.
Risk-Benefit Ratio
EU MDR Annex I Chapter I (2) mandates risks reduction while maintaining the benefit-risk ratio. Requirements for each device include:
- Establishing and documenting a risk management plan.
- Identifying and analysing possible hazards.
- Estimating and evaluating risks related to intended use and misuse.
- Implementing risk mitigation strategies.
- Assessing production and post-market information on the documents
- Modifying control measures based on assessments.
Risk Management During Design and After
Annex I provide detailed instructions for risk management during design. Priority order for manufacturers includes:
- Eliminating or reducing risks through safe design.
- Implementing protection measures for unavoidable risks (e.g., alarms).
- Providing information or user training for safety and disclosing residual risks.
The EU MDR states that the manufacturer is ultimately responsible for the disclosure of any residual risks.
Requirement for Acceptable Benefit/Risk
Evaluation criteria include:
- Description of the device’s intended purpose.
- Assessment of benefits to the patient.
- Quantification of patient benefits.
- Probability and duration of experiencing benefits.
- Evaluation of clinical risks, addressing severity, number, and rates of harmful events.
- Consideration of harmful event probability and duration.
- Assessment of risks from false-positive or false-negative results (for diagnostic medical devices).
- Overall evaluation of the acceptability of the benefit/risk profile.
Clinical Investigations and PMCF
The symbiotic relationship between risk management and clinical evaluation is integral, necessitating continuous cross-referencing and simultaneous updates. Post-market surveillance data becomes a crucial resource for refining benefit-risk assessments and enhancing risk management strategies. This wealth of information contributes to the ongoing improvement of technical documentation related to risk assessment and clinical evaluation, creating a dynamic loop of refinement.
Beyond the standard PMCF requirement, manufacturers of class IIa, class IIb, and class III devices face an additional requirement: the preparation of a Periodic Safety Update Report (PSUR) for each device or relevant device groups. The PSUR encapsulates post-market surveillance analyses, corrective or preventive actions taken, and updated benefit-risk determinations, all contextualized by sales volume or estimated device usage. The periodic updating of PSURs aligns with device risk class and involves careful consideration of ongoing risk activities.
Under the EU MDR 2017/745, implantable and Class III devices also require new an assessment —the Summary of Safety and Clinical Performance (SSCP). This comprehensive document includes residual risks, undesirable effects, warnings, and precautions, all compiled for submission to the Notified Body (NB) during conformity assessment. Strikingly, the NB uploads the SSCP to Eudamed, ensuring public accessibility to this critical information.
