Slides

Medical Devices

Definition of Medical Devices

  • New Medical Device Regulation (MDR): Defines a medical device as any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent, calibrator, software, material, or similar article intended by the manufacturer for use in humans for one or more of the following purposes:

    • Diagnosis, prevention, monitoring, treatment, or alleviation of disease.

    • Diagnosis, monitoring, treatment, alleviation, or compensation for an injury.

    • Investigation, replacement, modification, or support of anatomy or physiological processes.

    • Supporting or sustaining life.

    • Control of conception.

    • Disinfection of medical devices.

    • Providing information for medical purposes by means of in vitro examination of specimens derived from the human body.

  • Notably, medical devices do not achieve their primary intended action in or on the human body through pharmacological, immunological, or metabolic means, but may be assisted in their function by such means.

Harmonization and Regulatory Bodies

  • International Medical Device Regulators Forum (IMDRF): A voluntary group of medical device regulators from around the world aiming to accelerate international medical device regulatory harmonization and convergence, building upon the work of the Global Harmonization Task Force on Medical Devices (GHTF).

    • IMDRF Management Committee consists of representatives from:

    • Australia - Therapeutic Goods Administration

    • Brazil - National Health Surveillance Agency (ANVISA)

    • Canada - Health Canada

    • China - China Food and Drug Administration

    • Europe - European Commission Directorate General Health and Consumers

    • Japan - MHLWQ

    • Russia - Russian Ministry of Health

    • USA - US Food and Drug Administration

EU Medical Devices Regulation Timelines and Transitional Provisions

  • Regulation Adoption Dates:

    • 5 April 2017: Adoption of two new regulations on medical devices, which came into force on 25 May 2017:

    • Regulation (EU) 2017/745: Amends several directives related to medical devices.

    • Regulation (EU) 2017/746: Pertains to in vitro diagnostic medical devices, repealing Directive 98/79/EC and others.

  • Transition Period for Compliance:

    • 3 years for medical devices (MDR): Compliance deadline around Dec 2019/Jan 2020.

    • 5 years for in vitro diagnostics (IVDR): Compliance deadline around Dec 2021/Jan 2022.

    • Certificates issued under the current Medical Device Directive are valid until they expire (maximum of 5 years).

    • Devices legally placed on the market before the end of the transition period can be sold until 5 years after that date.

Key Facts of EU Medical Devices Regulation (1/2)

  • The new regulations implement important improvements to modernize the existing system, including:

    • Stricter Control for High-Risk Devices: Introduction of a new pre-market scrutiny mechanism involving EU-level expert pool.

    • Reinforcement of Designation Criteria for Notified Bodies: More stringent processes for oversight.

    • Inclusion of Aesthetic Devices: Devices with similar risk profiles as medical devices are included under these regulations.

    • New Risk Classification System: Standardized for in vitro diagnostic medical devices aligning with international guidance.

    • Improved Transparency: Establishment of a comprehensive EU database on medical devices and an enhanced device traceability system based on Unique Device Identification (UDI).

    • Introduction of an Implant Card: Contains information about implanted medical devices for patients.

    • Strengthened Clinical Evidence Rules: Introduction of a coordinated procedure for authorization of multi-center clinical investigations.

    • Enhanced Post-Market Surveillance Requirements: Manufacturers must comply with improved mechanisms for post-market vigilance.

    • Better Coordination among EU Countries: Mechanisms in place for vigilance and market surveillance.

Key Facts of EU Medical Devices Regulation (2/2)

  • Raised Expectations and Additional Scrutiny in all areas:

    • Design and Development

    • Vigilance

    • Post-market Surveillance (PMS)

    • Technical Documentation (TD)

    • Clinical studies

  • Regulatory Approval Process: Requires interaction among stakeholders (EMA, Notified Body, Sponsor) for combination products where a drug is the primary mode of action but must comply with device safety and performance.

  • Shift in Emphasis: Regulatory focus has transitioned from the pre-approval stage (path to CE Marking) to a life-cycle approach encompassing PMS, vigilance, and distribution.

  • Granularity in Device Definitions: Inclusion of:

    • Stand-alone software.

    • Systems – combinations of products aimed to achieve a specific medical purpose.

Summary of Requirements under EU MDR (1/3)

  • Device Classification: Most products follow a similar classification but inhalation devices will now be classified as Class IIa or IIb based on associated risk.

  • Unique Device Identifier (UDI): Compliance with UDI labeling and registration requirements is mandatory for manufacturers.

  • EUDAMED: A medical device database to store UDI, device, manufacturer information, adverse event reporting, clinical trial results, and annual reports.

  • Legal Responsibilities of Economic Operators: Defined for manufacturers, contract manufacturers, distributors, Authorized Representatives, etc., who become liable for vigilance and labeling compliance.

  • Person Responsible for Regulatory Compliance (PRRC): New role responsible for supervision and compliance of manufactured products, technical files, and post-market surveillance.

    • Most responsibilities will likely reside within Quality Assurance (QA) departments, ensuring daily compliance with regulatory requirements related to Quality Management Systems (QMS).

Summary of Requirements under EU MDR (2/3)

  • Clinical Trials: Greater emphasis will be placed on clinical information; Specific requirements:

    • Class IIb implants and Class III devices will necessitate specific clinical trials.

    • Use of clinical evidence from equivalent devices is significantly reduced.

    • Performance/safety quality aspects of devices are crucial in clinical assessments.

  • Equivalence Standards: The determination of equivalence will require:

    • Consideration of technical, biological, and clinical characteristics (e.g., intended use, materials).

    • Devices with similar specifications, properties, and intended uses may reference the same clinical trial data to support Technical Documentation.

    • Transition of equivalence requirements from MEDDEV guidance to MDR.

  • Vigilance: The MDR integrates the guidelines on Medical Device Vigilance System (MEDDEV) for reporting.

    • Reporting durations for serious incidents have decreased to 15 days from 30 days under the preceding MDR.

Summary of Requirements under EU MDR (3/3)

  • Post-Market Surveillance (PMS) activities and reporting must correspond with:

    • Risk/device classification, focusing on quality, performance, and safety monitoring.

    • Responsibilities outlined for different classes of devices:

    • Class I: Based on adverse events and corrective actions; part of Technical Documentation.

    • Class II and III: Post-market safety reports (PSUR) need to be part of compliance assessment.

      • Class IIa: Report every 2 years.

      • Class IIb: Annual reports required.

      • Implantable and Class III: Annual submission to Notified Body via EUDAMED database.

  • Quality Management System (QMS): Documentation strategies and supporting Standard Operating Procedures (SOPs) must cover:

    • Legal requirement identification.

    • Classification handling.

    • Clinical evaluation strategy.

    • UDI compliance for labeling updates.

  • Notified Body Audits: Audits by Notified Bodies can occur unannounced across the product lifecycle and may include physical tests or evaluations.

Regulatory Players in Medical Devices

  • Competent Authority: Enforces Medical Device Directives at national levels in each EU member state.

  • Notified Bodies: Responsible for advising on device classification and conformity assessment, conducting device pre-assessments, evaluating products and quality systems, and issuing necessary certifications.

  • Authorized Representative: Acts as liaison between manufacturers and competent authorities, managing technical files and participating in vigilance and post-market surveillance procedures.

Steps for Compliance in the EU

  1. Identify the Directives and Regulations applicable to your device.

  2. Classify your device according to MDD Annex IX or via MDR Annex VIII.

  3. Implement a Quality Management System compliant with ISO 13485.

  4. Prepare Technical Files or Design Dossiers demonstrating compliance with MDD 93/42/EEC.

  5. Appoint an Authorized Representative.

  6. Undergo a Notified Body audit for your Quality System and Technical File.

  7. Register your device with Competent Authorities, if applicable.

  8. Prepare a Declaration of Conformity and affix CE Mark on your device.

Medical Device Classification

  • US Classification: Divides devices into three classes based on risk assessment recommendations from a panel of specialists.

  • EU and Canada Classification: Predominantly rule-based, categorizing medical devices based on perceived hazards.

    • Canada: Four classes of devices.

    • EU: Three classes with Class II subdivided into IIa and IIb.

Medical Device Classification Criteria

  • Classification determines compliance requirements:

    • Rules are specified in Annex VIII (22 rules) based on:

    • Intended device use (active vs. non-active).

    • Duration of contact with the patient.

    • Degree of invasiveness.

    • Specific situations.

  • Classification based on:

    • Duration of Use:

    • < 60 minutes = Transient.

    • > 60 minutes and < 30 days = Short-term.

    • > 30 days = Long-term.

    • Degree of Invasiveness:

    • Surface application vs. orifice application.

    • Surgical invasiveness (invasive vs. non-invasive).

    • Implantable.

Classes of Medical Devices

  • Class III: Highest-risk devices including all active implantable devices.

  • Class IIb: Higher-risk, longer-term, potentially implantable devices.

  • Class IIa: Medium-risk, short-term invasive devices.

  • Class I: Non-sterile/non-measuring, sterile, and measuring; low-risk, non-invasive devices.

Medical Device Safety

  • Essential Elements:

    • Absolute safety cannot be guaranteed.

    • Medical device safety closely correlates with device effectiveness and performance.

    • Safety considerations must encompass the product's entire lifespan.

    • Shared responsibilities among all stakeholders are crucial.

Risk Assessment in Medical Devices

  • Risk Assessment: Estimation of medical device safety through:

    • Hazard: Potential for an adverse event, defined as a source of danger.

    • Risk: Evaluated by estimating:

    • Likelihood of the adverse event.

    • Severity or overall impact of the event.

  • The risk assessment process starts with risk analysis (identifying hazards) followed by risk evaluation (estimating risks).

  • Complexity involves personal perceptions and various external influences (cultural, economic, political).

  • Consideration must also be given to device design and manufacturing processes.

Regulatory Controls for Medical Devices

  • Regulatory bodies are responsible for ensuring public health and safety through adequate regulations matching the level of control with the risk associated with devices.

    • The overarching goal is to ensure appropriate controls commensurate with the risk level.

    • Regulatory methods vary by geographic regions, and regulations follow market presence regardless of manufacturing location (e.g., products made in the US but sold in the EU must adhere to EU regulations).

Relationships Among Regulatory Participants

  • Member State: Responsible for the notification process and the evaluation of potential notified bodies.

  • Notified Body: Assists manufacturers by providing services like classification advice, pre-assessments, and maintaining surveillance on devices sold in the EU.

  • Manufacturer: Responsible for placing the product on the market and ensuring compliance with applicable regulations.

  • Customer: The end-user or purchaser of the medical device.

Quality System Requirements for Medical Devices

  • Manufacturers of Class I sterile/measuring devices, Class IIa, IIb, and Class III devices must implement Quality Management Systems (QMS), often based on ISO 13485.

  • System Requirements:

    • Phase I: Preparation and Development:

    • Management buy-in (assigning resources, conducting analyses).

    • Development of a quality manual and documentation control.

    • Phase II: Implementation:

    • Employee training and internal auditing.

    • Implementation of corrective and preventative actions.

    • Phase III: Registration:

    • Conducting registration audits by notified bodies leading to final ISO 13485 certification.

Responsibilities of Authorized Representatives

  • Manufacturers without EU offices must appoint Authorized Representatives (EC REPs) to act on their behalf.

  • Core Responsibilities include:

    • Registering devices with Competent Authorities prior to commercialization.

    • Liaising with all EU Competent Authorities on behalf of the manufacturer.

    • Ensuring availability of Technical Files for inspections by Competent Authorities.

    • Authorizing representation on device labels and packaging.

    • Managing incident reporting and corrective actions with Competent Authorities.

    • Ensuring confidentiality of product information and maintaining clinical evaluation data for review.

Declaration of Conformity Process

  • Manufacturers can place a CE mark on a medical device once conformity assessment is passed, involving:

    • Audit of the manufacturer’s QMS, and review of technical documentation regarding device safety and performance.

  • EU Member States designate notified bodies to carry out conformity assessments, sometimes requiring expert panel opinions for high-risk devices.

Notified Body Audit Process

  • After appointing the EC REP, manufacturers’ QMS and technical files/design dossiers must be audited by a notified body.

  • Upon successful audit completion, the notified body issues a CE certificate. For Class I devices, manufacturers must register with the competent authority of the country their EC REP is based in.

Post-Marketing Surveillance (PMS)

  • PMS is mandatory for all medical devices sold in the EU; manufacturers must develop proactive PMS plans including:

    • Continuous reviews of market and field data, complaints, and corrective measures.

    • Maintenance of systematic records of PMS findings.

  • Vigilance Requirements:

    • Establishing systematic procedures to analyze experiences from the post-production phase.

    • Implementing necessary corrective actions based on review findings.

Medical Device Product Development Lifecycle

  • Stages include:

    • Design and Feasibility Review: Assessing regulations, conducting technology evaluations, and defining product specifications.

    • Manufacturing and Launch: Encompassing quality control/assurance, regulatory filing processes, and compliance assurance.

    • Post-Market Surveillance: Involves ongoing safety and performance assessments, identifying safety issues, and managing corrective actions.

Importance of Risk Management in Medical Devices

  • Integral to product development and lifecycle management, involving:

    • Data analysis to ensure compliance with evolving safety standards.

    • Continuous monitoring through post-market surveillance to respond effectively to identified risks and maintain device safety standards.


Similarities and Differences between the Development of Medical Devices and Drugs:

Similarities:

  • Regulatory Oversight: Both medical devices and drugs must comply with regulatory requirements established by authorities like the FDA (USA) and EMA (Europe).

  • Clinical Testing: Both go through rigorous testing phases, including preclinical studies and clinical trials, to ensure efficacy and safety.

  • Risk Management: Both fields utilize risk assessment and management practices to identify hazards, assess risks, and implement controls throughout development.

Differences:

  • Nature of Testing:

    • Drugs: Typically require extensive randomized controlled trials to establish safety and efficacy based on pharmacodynamics and pharmacokinetics.

    • Devices: Often focus more on technical performance and usability, with trials concentrated on specific design aspects.

  • Approval Pathways:

    • Drugs: Generally follow a more linear pathway consisting of phases (Preclinical, Phase I, II, and III trials).

    • Devices: Can follow different pathways such as 510(k) or PMA (Pre-Market Approval), depending on their classification and risk level.

  • Post-Market Surveillance:

    • Drugs: Monitoring continues via pharmacovigilance for adverse effects.

    • Devices: Involves vigilance systems focusing on device performance and durability post-launch, including mandatory post-market surveillance (PMS).

  • Lifecycle Management:

    • Drugs: Lifespans can be prolonged with patent protections but must go through complete re-evaluation for generics.

    • Devices: Can adapt or improve rapidly based on feedback and advancements in technology without complete re-evaluation, focusing more on iterative design changes.