RAC Study Group Week 15: Post Market / Compliance (US / EU)

US Compliance (Chapter 9)

Objective #1: FDA Medical Device Regulations Compliance

• Establishment Registration and Product Listing:
  • Establishments involved in medical device activities (production, distribution, manufacturing, preparation, etc.) must list their commercial devices (21 CFR 807). Updates are required annually.
  • FDA mandates electronic submission of all registration and listing information unless a waiver is granted.

Objective #2: US Post Marketing Requirements

• Postapproval Studies (PAS):
  • FDA may require PAS at the time of PMA, HDE approval, or PDP application.
  • Can be clinical or nonclinical.
• 522 Postmarket Surveillance Study (PMS):
  • Under FD&C Act Section 522, FDA may require a manufacturer to conduct a PMS for Class II or Class III devices if certain criteria are met.
• Unique Device Identification (UDI):
  • Final rule established in 2013.

Objective #3: US Postmarketing Requirements - MDR, Recalls, Tracking

• Medical Device Reporting (MDR):
  • Regulation 21 CFR 803 provides a mechanism to monitor adverse events and device malfunctions.
  • Aims to identify and correct device problems promptly.
• Medical Device Recalls, Corrections, and Removals:
  • Recall Definition: Removal or correction of a marketed product that FDA considers to be in violation of the law, subject to legal action.
  • Correction: Repair, modification, adjustment, relabeling, destruction, or inspection without physical removal.
  • Removal: Repair, modification, adjustment, relabeling, destruction, or inspection by physically removing to other location to reduce device-related risks or correct device violations.
  • Market Withdrawal: Removal or correction of a marketed product involving minor violations not subject to legal action or involving no violation.
  • Routine Servicing: Regularly scheduled maintenance, including replacing parts at the end of their normal life expectancy.
  • Stock Recovery: Removal or correction of a product that has not been marketed or has not left the firm’s direct control; intended to improve device quality or performance.
  • Manufacturers or importers typically conduct recalls voluntarily.
  • If a manufacturer/importer doesn't initiate a recall for a device posing a risk, the FDA may issue a recall order under 21 CFR 810.
  • Health hazard evaluation is critical in the recall decision-making process.
    • Class I: Serious adverse health consequences or death.
    • Class II: Temporary or medically reversible adverse health consequences.
    • Class III: Not likely to cause adverse health consequences.
  • Firms must notify the FDA immediately if a product is violative; the removal/correction will be classified as a recall.
  • Recall strategy must address health hazard evaluation, degree of risk, and continued product availability, and should address level of effectiveness.
  • Recall status reports must be submitted to the DRC until the FDA terminates the recall.
  • DRC will issue a written notification of recall termination once the FDA determines the firm has made all reasonable efforts to correct the product.
• Medical Device Tracking:
  • Ensures devices can be traced from manufacturing to the patient.
  • Allows manufacturers to address dangerous/defective devices by removing them from the market or issuing notifications.

Objective #4: US Requirements for Importing and Exporting

• Exporting Medical Devices From the US (without FDA notification/approval):
  • The manufacturer's facility must be registered with the FDA.
  • The device must be listed with the FDA.
  • The device must be cleared/approved/exempted, meet labeling requirements, and comply with QSR.
  • The exported device must also meet the importing country's applicable laws/regulations.
  • Devices not FDA approved or cleared can be exported if they meet the export requirements set in the FD&C Act.

EU Compliance (Chapter 2 and Chapter 11)

Objective #1: Role of Authorities & Enforcement

• Competent Authorities:
  • Each member state (27) has regulatory bodies for market oversight/enforcement.
  • Have specific national powers based on their countries’ legislation.
  • Powers vary among member states.
  • Some can impose fines directly; others refer cases to a national court.
  • National variations require regulatory professionals to understand which entity enforces regulations.
  • In most Member States, competent authorities for MD operate under the Ministry of Health.

Objective #2: Coordination Among EU Commission & Member States

• Clinical Investigations:
  • Subject to competent authority monitoring and control.
  • Aims to protect human subjects' health and safety.
  • Competent authority permission is needed before the start of an investigation.
  • Competent authorities can intervene and stop the investigation.
• Coordination and Cooperation:
  • Coordination and cooperation among involved entities are required for effective enforcement.
  • Competent Authorities and the EU Commission are obligated to cooperate and exchange information.
  • Obligated to share market surveillance reports with other member states via EUDAMED.
  • Review and assess market surveillance activities every 4 years and share results.
  • For coordination of notified bodies, EU MDR established the Notify Body Combination Group.
  • Medical Device Coordination Group (MDCG) has delegated specific tasks to 13 subgroups.
  • Member State 2 Members: EU MDR , EU IVDR Alternative Members

Objective #2: Manufacturer Postmarket Surveillance Procedure

• Market Surveillance: Activities and measures by competent authorities to check devices comply with requirements.
• Post-Market Surveillance: A systematic process to collect and review experience gained from devices on the market.
• Vigilance Reporting: Requires manufacturers to notify competent authorities of serious incidents and field safety corrective actions.
• EUDAMED: A centralized database for information exchange among competent authorities.
• Notified Bodies' Specific Enforcement Role:
  • Primary responsibility is to check manufacturers' premarket conformity assessments.
  • MDD Article 16 gives NBs the power to withdraw or suspend certificates for noncompliance.
  • Member States ensure devices do not endanger health, safety, or public health.
  • Member States ensure devices can be placed on the market only if they comply with the Directive (MDD Article 2).

Objective #3: Manufacturer Postmarket Surveillance Procedure

• Medical Device Manufacturers must implement a systematic procedure to review device experience in the post-production phase.
• Risk Assessment, Risk Analysis, Risk Management:
  • Critical components in all phases of the product lifecycle.
  • When new/revised standards are implemented, maintain a comprehensive risk management file as a living document reflecting all known product issues.
  • Manufacturers should have proactive and reactive strategies for managing risks throughout the product lifecycle.

Objective #4: EU Medical Device Vigilance System

• Aims to improve health and safety by reducing the likelihood of incidents related to medical device use.
• Competent Authorities are responsible for establishing and operating a vigilance system within Member States.
• They record and evaluate incident information centrally (AIMDD Article 8, MDD article 10, IVDD article 11).
• Under EU MDR, Article 87 & 89, manufacturers report to Component Authorities through the EUDAMED database.
• MEDDEV 2.12/1 describes the vigilance system as a vehicle for adverse incident notification and evaluation, clarifying actions to be taken.
• Vigilance system procedures are the same for all three directives and refer to incidents within EU Member States, EEA, Switzerland, Turkey, regarding CE-marked devices.
• Also applies to incidents involving non-CE-marked devices when they lead to an FSCA relevant to CE-marked devices.
• Types of Incidents to be Reported:
  • Incidents resulting in death of a patient, user, or other person.
  • Incidents resulting in serious deterioration in a patient, user, or other person's state of health.
  • Events that might have led to death or serious deterioration but did not due to fortunate circumstances or intervention.