European regulatory framework

Medical devices in the European community are subjected to a common regulatory framework designed to ensure that the essential requirements for placing a device on the market are the same in all member countries. This framework defines these essential requirements as well as the modalities of conformity assessment.

Overview

Key regulatory texts

Depending of their nature, medical devices are regulated by one of three directives:

• Directive 90/325/EEC applies to Active Implantable Medical Devices,
• Directive 98/37/EC applies to In Vitro Diagnosis Medical Devices,
• Directive 93/42/EEC covers all other medical devices.

The scope of Directive 90/385/EEC is defined as follows.

Active medical device

Any medical device relying for its functioning on a source of electrical energy or any source of power other than that directly generated by the human body or gravity.

Active implantable medical device

Any active medical device which is intended to be totally or partially introduced, surgically or medically, into human body or by medical intervention into a natural orifice, and which is intended to remain after the procedure.

Directives 90/385/EEC and 93/42/EEC were recently amended by directive 2007/47/EC. These changes (see below) apply since March 2010. These directives as well as various guidance and interpretative documents are available on the The European Commission portal for medical devices.

Device classification and conformity assessment

Conformity assessment, often referred to as CE Marking, is the process of ensuring and certifying that a device fulfils the essential requirements defined by the relevant directive. That is, it performs as claimed by the manufacturer and does not present any unacceptable risk in the context of its intended use.

The modalities of conformity assessment depend on the device characteristics and class. Devices are divided into four classes, according to their level of risk: I (low risk), IIa (moderate risk), IIb (increased potential for risk), and III (very significant potential for risk. Class III includes all active implantable medical devices.

Non-sterile class I devices with no measurement function are certified by the manufacturer.

All other devices must be submitted to a Notified Body, which is a public or private organisation appointed by national authorities to assess and certify conformity of medical devices. The manufacturer may choose any Notified Body from the European list.

In all cases a technical documentation should be provided by the manufacturer. However, this documentation will systematically analysed only for class III medical devices. For these devices, an audit of the manufacturer quality system will also be performed. For class IIa and IIb devices, only a representative sample of submitted devices will be assessed.

What has changed since 2010

Multiple changes were introduced by directive 2007/47/EC, for instance in device classification rules. Another noticeable change is that conformity certificates are now issued for a maximum duration of five years and must be renewed.

However, one of the most important changes is the requirement for clinical evidence of the performance and safety of medical devices. This evidence should be provided in a clinical evaluation report that is now a mandatory part of the technical documentation of the device, at certification time.

Principles of clinical evaluation

Definitions

Clinical evaluation

An assessment of the benefit/risk ratio of the device, based on clinical data.

Clinical data

The safety and/or performance information that is generated from the use of a device. Clinical data may be obtained from clinical investigation, relevant scientific literature or post-market surveillance.

Clinical investigation

A scientific assessment of the efficacy and safety of the device, performed in the conditions of its intended normal use, according to a state of the art and documented methodology, and conforming to applicable ethical and legal provisions.

When should Clinical evaluation be performed?

1. During the conformity assessment process leading to the marketing of an active implantable medical device.
2. Throughout the life cycle of the device as a part of the post-marketing surveillance.

How should clinical evaluation be performed?

Clinical evaluation may be performed by clinical investigation, by a critical review of scientific literature on the device or an equivalent device, or by a combination of both.

Choosing the literature route implies due justification that the existing literature is indeed relevant and sufficient to establish the benefit/risk ratio of the device.

Clinical Investigation

Clinical investigation is no longer optional for new devices nor for existing devices whose functionalities are extended or otherwise modified.

When should Clinical Investigation be performed?

• When the clinical effectiveness of a completely new device has to be demonstrated.
• When the clinical safety and performance of an existing device, that has been modified, is unknown.
• When the clinical effectiveness of an existing device has to be demonstrated for a new indication.

How should Clinical Investigation be performed?

Clinical investigation consists of one or more clinical studies. Performing a clinical study usually involves the following steps.

1. Determine the primary objective of the study. Optionally, secondary objectives may also be defined.
2. The study should be designed to accurately define the positive benefit/risk profile of the device for the indications and limitations of use.
3. The Investigation should be performed under the responsibility of a duly qualified medical practitioner. In accordance with this requirement, current CVs of the clinical investigators must be provided.
4. Investigator’s brochure, confirmation insurance of patients, document used to obtain informed consent, intended use statement for device should be provided.
5. All serious Adverse Events must be fully recorded and immediately notified to all competent authorities of the Member States in which the clinical investigation is being performed.
6. The end of clinical investigation should be notified to the competent authorities of the Member States.

What should be included in Clinical investigation documentation?

1. Clinical investigation plan that contains the aim and methodology of the study (selection criteria, type of design, efficacy criteria, approaches to statistical analyses and methods for recording outcomes).
2. Ethical and regulatory approval.
3. Case report forms, monitoring and audit records
4. The final report that comprises a critical analysis of all the data collected during the clinical investigation including the evaluation of the deviation from the original plan.