Medical Device Regulation
Overview and Legal Framework of Regulation (EU) 2017/745
General Purpose: The Regulation aims to establish a robust, transparent, and sustainable regulatory framework for medical devices to ensure a high level of safety and health whilst supporting innovation. It replaces Council Directives 90/385/EEC (Active Implantable Medical Devices) and 93/42/EEC (Medical Devices).
Dual Objectives:
Smooth functioning of the internal market regarding medical devices.
High level of protection of health for patients and users, including high standards of quality and safety.
Key Amendments: It amends Directive 2001/83/EC, Regulation (EC) No 178/2002, and Regulation (EC) No 1223/2009. It clarifies that medical devices are excluded from the scope of food law (Regulation (EC) No 178/2002).
Scope and Key Definitions (Article 1 & 2)
Medical Device Definition: Any instrument, apparatus, appliance, software, implant, reagent, material, or other article intended for human use (diagnosis, prevention, monitoring, treatment, alleviation of disease/injury/disability, or investigation of anatomy/physiology) that does not achieve its principal action by pharmacological, immunological, or metabolic means.
Included Products:
Devices for control or support of conception.
Products for cleaning, disinfection, or sterilization of medical devices.
Products without an intended medical purpose as listed in Annex XVI (e.g., contact lenses, dermal fillers, liposuction equipment).
Exclusions:
In vitro diagnostic devices (regulated by Regulation (EU) 2017/746).
Medicinal products (Directive 2001/83/EC).
Cosmetic products (Regulation (EC) No 1223/2009).
Viable biological materials or organisms.
Active Device: Operation depends on an energy source other than the human body or gravity. Software is also deemed an active device.
Implantable Device: Intended to be totally introduced or to replace an epithelial surface/surface of the eye by clinical intervention, remaining for at least days.
Nanomaterial: Material containing particles where or more have one or more external dimensions in the range to nm.
Obligations of Economic Operators (Chapter II)
Manufacturers (Article 10):
Must ensure devices are designed and manufactured per Regulation requirements.
Establish and maintain a Quality Management System (QMS) and a Risk Management System.
Conduct clinical evaluation and maintain technical documentation.
Draw up an EU Declaration of Conformity and affix the CE marking.
Responsible for the Unique Device Identification (UDI) system assignment.
Financial Coverage: Must have measures (proportional to risk class) to provide sufficient financial coverage for potential liability.
Authorised Representatives (Article 11): Mandatory for manufacturers located outside the EU. They are legally liable for defective devices on the same basis as the manufacturer if the manufacturer fails to comply with obligations.
Importers (Article 13): Must verify CE marking, identification of manufacturer/representative, and UDI assignment. They must ensure storage and transport conditions do not jeopardize compliance.
Distributors (Article 14): Must act with due care and verify compliance (CE mark, instructions, labels) before making devices available.
Person Responsible for Regulatory Compliance (Article 15): Manufacturers and Authorised Representatives must have at least one person with requisite expertise (e.g., degree + year experience or years' experience) available at all times.
Classification and Conformity Assessment (Chapter V)
Classification (Article 51): Devices are divided into Classes I, IIa, IIb, and III based on intended purpose and inherent risks. Class III represents the highest risk.
Conformity Procedures (Article 52):
Class III: Requires assessment per Annex IX (QMS and Technical Documentation) or Annex X (Type-examination) + Annex XI (Product verification).
Class IIb: Assessment of QMS and technical documentation for at least one representative device per generic group.
Class IIa: Assessment of QMS and technical documentation for at least one representative device per category.
Class I: Manufacturer's responsibility to declare conformity, except for sterile, measuring, or reusable surgical instruments (where a Notified Body is involved).
Clinical Evaluation Consultation (Article 54): Certain Class III and IIb devices require a consultation with expert panels on the clinical evaluation report.
Identification, Traceability, and Eudamed (Chapter III)
UDI System (Article 27): Consists of a UDI-DI (device identifier) and UDI-PI (production identifier). It must be placed on labels and all higher levels of packaging.
Eudamed (Article 33): The European database on medical devices integrates systems for registration, UDI, certificates, clinical investigations, vigilance, and market surveillance. It aims to increase transparency and facilitate info flow.
Summary of Safety and Clinical Performance (SSCP): Required for Class III and implantable devices. It must be clear to intended users/patients and accessible via Eudamed.
Clinical Evaluation and Investigations (Chapter VI)
Clinical Evaluation (Article 61): Confirmation of conformity must be based on clinical data providing sufficient clinical evidence. Evaluation must be updated throughout the lifecycle with post-market clinical follow-up (PMCF) data.
Clinical Investigations (Article 62): Must protect the rights, safety, and well-being of subjects. Requires authorization by Member States and a positive opinion from an ethics committee. Informed consent is mandatory.
Vulnerable Populations: Specific protection measures are required for incapacitated subjects, minors, and pregnant/breastfeeding women.
Vigilance and Market Surveillance (Chapter VII)
Post-Market Surveillance (PMS): Manufacturers must proactively collect and review experience from devices to identify corrective/preventive actions.
Periodic Safety Update Report (PSUR): Required for Class IIa, IIb, and III devices. Class IIb and III must update at least annually.
Reporting Serious Incidents (Article 87):
Immediate reporting of serious public health threats within days.
Reporting of death or unanticipated deterioration within days.
General serious incidents must be reported within days.
Field Safety Corrective Action (FSCA): Manufacturer must bring actions to the attention of users via a Field Safety Notice.
Notified Bodies (Chapter IV)
Criteria: Must be independent, impartial third-party bodies with competent personnel and a quality management system. Requirements are detailed in Annex VII.
Oversight: Member States appoint an authority responsible for assessing, designating, and monitoring notified bodies.
Joint Assessment Team: Includes representatives from the Commission and other Member States to review applications for notification.
Annex I: General Safety and Performance Requirements
Design for Safety: Manufacturers must eliminate/reduce risks through safe design, then protection measures (alarms), then info for safety (warnings).
Chemical/Biological Properties: Special attention to toxicity, flammability, and CMR (Carcinogenic, Mutagenic, or toxic to Reproduction) substances. Concentration of CMR/Endocrine-disruptors above weight by weight () must be justified.
Labeling and IFU: Requirements for indelible labels and instructions for use (IFU) in official Union languages. IFUs are generally required except for Class I and IIa where safe use is possible without them.
Similarities in the development of medical devices and drugs include:
Both require extensive research and development to ensure safety and efficacy.
Each undergoes regulatory scrutiny and must comply with health and safety standards before market entry.
Both typically involve preclinical studies followed by clinical trials to assess their effects on human subjects.
They require extensive documentation and reporting to regulatory bodies to demonstrate compliance and gain approval.
Differences include:
Regulatory Pathways: Medical devices are often regulated under different frameworks (e.g., Regulation (EU) 2017/745) than drugs (Directive 2001/83/EC).
Approval Process: The approval process for drugs tends to be more rigorous and time-consuming, focusing heavily on clinical trial data, while some lower-risk medical devices may follow a more streamlined process (like the CE marking for Class I devices).
Variability in Testing: The testing protocols differ; drugs are tested for pharmacological effects, while devices are evaluated for safety, performance, and adherence to regulatory specifications.
Market Surveillance: Post-market surveillance and monitoring might differ, with distinct requirements for clinical evaluations and post-market clinical follow-ups for medical devices compared to drugs.