Regulatory Submissions

What is a conformity assessment

A conformity assessment for medical devices is a comprehensive evaluation process to ensure that a medical device meets the essential safety and performance requirements specified by relevant regulations.

Medical device manufacturers compile technical documentation and submit it for review by the relevant regulatory authority. Manufacturers must also establish and implement a Quality Management System (QMS), which is audited as part of the regulatory approval process.

The conformity assessment process differs depending on:

• The geographic markets where the device will be placed on the market
• The risk classification of the medical device based on its intended purpose

US FDA Regulatory Submissions

In the USA, the Food and Drug Administration (US FDA) provides different conformity assessment routes for medical devices based on their risk classification (Class I, II, or III), reflecting the risk level they pose. The primary routes include:

Exemptions and General Controls:

• Applicable for: Most Class I devices and some Class II devices deemed to pose minimal risk.
• Process: These devices are generally exempt from premarket notification (510(k)) but must comply with general controls such as good manufacturing practices, labelling, and record-keeping requirements.
• Outcome: Devices can be marketed without prior FDA review, provided they meet all applicable regulatory requirements.

510(k) Premarket Notification:

• Applicable for: Most Class II devices and some Class I devices.
• Process: Manufacturers must demonstrate that their device is substantially equivalent to a legally marketed predicate device. This involves comparing the new device’s intended use, technological characteristics, and performance data with the predicate.
• Outcome: The device can be marketed if the FDA agrees with the substantial equivalence claim.

De Novo Classification Request:

• Applicable for: New or novel devices for which there is no legally marketed predicate but are determined to be low to moderate risk.
• Process: Manufacturers submit a De Novo request to classify their device as Class I or II, providing robust evidence of safety and effectiveness.
• Outcome: If granted, the device can be marketed and may serve as a predicate for future 510(k) submissions.

Premarket Approval (PMA):

• Applicable for most Class III devices, which pose the highest risk and usually support or sustain life, are implanted, or present potential unreasonable risk of illness or injury.
• Process: Manufacturers must provide extensive scientific evidence demonstrating the device’s safety and effectiveness through clinical trials and laboratory testing.
• Outcome: If the FDA determines that the benefits outweigh the risks, the device receives PMA approval, allowing it to be marketed.

Humanitarian Device Exemption (HDE):

• Applicable for: Devices intended to benefit patients with rare conditions (affecting fewer than 8,000 individuals annually in the USA).
• Process: Manufacturers must demonstrate that the device does not pose an unreasonable or significant risk of illness or injury and that no comparable device is available.
• Outcome: The device can be marketed if approved, but its use is restricted to specific conditions.

These routes ensure that medical devices introduced to the USA market are safe, effective, and appropriately classified based on their risk profiles.

EU CE Marking

The European Union (EU) Medical Device Regulation 2017/745 (MDR) process involves several key steps, including:

1. Classification: Determining the risk class of the medical device, which dictates the conformity assessment route and level of assessment required.
2. Technical Documentation: Compiling detailed information about the device, including design, manufacturing processes, clinical data, risk management, and labelling.
3. Quality Management System (QMS): Implementing a QMS, such as ISO 13485, to ensure consistent manufacturing and quality control processes. The QMS is audited during the conformity assessment process but may be independently audited and certified before submitting technical documentation. One important step that is sometimes overlooked is establishing a physical location in an EU member state or appointing an EU-based authorised representative.
4. Declaration of Conformity: A formal statement by the manufacturer declaring that the device complies with all relevant regulations.
5. Notified Body Review: Engaging a Notified Body, an independent certification organisation, to review the technical documentation and QMS. The extent of the review depends on the device’s risk classification. Conducting necessary tests and inspections to verify that the device complies with applicable standards and regulations.
6. CE Marking: The Notified Body reviews the submission and, if the device meets all regulatory requirements, issues a CE marking certification, enabling the device to be placed on the EU market. The manufacturer affixes the CE mark to the device, indicating it meets EU regulatory requirements.
7. Post-Market Surveillance: Implementing ongoing monitoring of the device’s performance and safety after placing it on the market. Additionally, manufacturers must register their devices with the European Database on Medical Devices (EUDAMED).

The EU Medical Device Regulation (MDR) outlines several conformity assessment routes tailored to the risk classification and complexity of the medical device. These routes ensure that devices meet stringent safety and performance standards. The main conformity assessment routes under the MDR are:

Self-Certification (Class I Non-Sterile, Non-Measuring Devices):

• Manufacturers of low-risk devices (Class I) that are not sterile, reprocessable or do not have a measuring function can perform a self-assessment.
• They must compile technical documentation and a Declaration of Conformity but do not require Notified Body involvement.

Class I Sterile, Class I Measuring, and Class I Reusable Surgical Instruments:

• These devices require a Notified Body to assess the aspects related to sterility, measuring function, or reusability.
• The Notified Body reviews the technical documentation and manufacturing processes related to these aspects.

Class IIa Devices:

• A Notified Body reviews the technical documentation and the QMS.
• The Notified Body issues a certificate of conformity if the device meets regulatory requirements.

Class IIb Devices

• A more rigorous assessment than Class IIa.
• Involves a comprehensive review of the QMS and complete technical documentation by a Notified Body.
• The Notified Body also inspects the manufacturer’s facilities and production processes.

Class III Devices:

• The highest risk class requires the most stringent assessment.
• A Notified Body must review full technical documentation and clinical evaluation.
• The Notified Body performs detailed manufacturing process inspections and conducts batch verification if applicable.
• Additional scrutiny is applied for implantable Class III devices, including a possible expert panel consultation.

Custom-Made Devices:

• Custom-made devices (tailored to individual patients) follow a specific assessment route.
• Manufacturers must prepare technical documentation and issue a statement that the device complies with the general safety and performance requirements.
• A Notified Body may assess certain aspects depending on the device’s risk classification.

Each conformity assessment route ensures that medical devices are rigorously evaluated for safety and performance, with the involvement of Notified Bodies increasing with the device’s risk classification. This structured approach helps maintain high standards for medical devices in the EU market.

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