Medical Device Approval. European Regulatory Process.
Information & Training. | Medical Devices.There is a standardized approach to Medical Device regulation & approval across the European Union (EU) and the European Free Trade Area (EFTA). There are three foundation standards which determine the medical device approval requirements, namely the:
MDD, Medical Devices Directive 93/42/EEC, plus Directive updates,
AIMD, Active Implantable Medical Devices Directive 90/385/EEC, and
IVMD, In Vitro Diagnostics Directive 98/79/EC.
There are also a broad range of related directives which may need to be considered when seeking medical device approval per the European Directives. Examples of such directives are the:
Hip, Knee, Shoulder Joint Replacement Reclassification Directive 2005/50/EC,
Breast Implants Reclassification Directive 2003/12/EC,
Electromagnetic Compatibility Directive 2004/108/EC,
Low Voltage 2006/95/EC, the Blood Product Directive 2002/98/EC,
When a medical device meets all the required regulations, a “CE” label may be applied to the device, which indicates to the purchaser or user that the device meets the necessary standards and directive requirements.
Where a Notified Body has involvement in the conformity assessment process, the identification number of the Notified Body must be affixed to the product alongside the CE marking.
Example of Notified Body numbers:0123 TÜV SÜD Product Service GmbH, Germany
0050 NSAI: – National Standards Authority of Ireland.
0086 BSI- British Standards Institute.
0094 Lloyd’s – Lloyd’s register Espana, S.A., Spain
All medical devices to be marketed throughout the European Union and European Free Trade Area need a “CE” mark. The initials “CE” is a declaration by the manufacturer that a product meets the requirements of the applicable European Directive(s). The letters “CE’ are the abbreviation of French phrase “Conformité Européene”.
Note: The CE mark applies to a wide range of products, not just medical devices, however, when applied to a medical device, indicates conformance with the relevant medical device directives and standards.
The only medical devices which do not require the CE label are devices for clinical trials or custom-made devices.
Structure of the European Regulatory regime for Medical Device Approval.There are a number of agencies and terms unique to the European regulatory process, the key being the:
The role of the European Commission in Medical Device Approval:This is the executive body within the European Union which has responsibility for proposing legislation. The Commission determines the requirements for medical device regulation and seeks approval at a European level from the European Parliament and the European Council of Ministers. Once approval is obtained, a Directive become binding across the European Union and by agreement the EFTA (European Free Trade Area).
Competent Authorities:Are the regulatory bodies, appointed by the respective governments within each European State, with the purpose of monitoring compliance with the relevant European directives as applied into national laws, i.e. the Competent Authority will seek to ensure that the medical device directives are fully implemented within their own country.
It is important to understand that the European Commission will determine the directives which apply across the full European Union and European Free Trade area. For example the Medical Devices Directive MDD 93/42/EEC equally applies to all European markets. The directives are not legally binding, therefore in order to enforce in law, each individual country will transpose the directive into their national laws. In this process, due at times to language and historical reasons some variations between the national laws of countries may arise. This can result in some variations in requirements between European countries for the medical device regulations. Note however, the substantive requirements are essentially the same across the EU and EFTA.
Notified Bodies and Medical Device Approval:Are third party non-governmental agencies involved in conformity assessment. Notified Bodies are and must remain third parties, independent of their clients and other interested parties. All medical devices need the employment of a Notified Body to certify the product except those that fall into Class I.
Note: The exception to this rule are Class I devices that are sterile or have a measuring function, in which case such medical devices need Notified Body input into the approval process,
The Notified Body may audit the quality system of a manufacturer and may perform relevant testing of devices where necessary to confirm conformance to regulations.
Authorized representatives:Where a medical device is manufactured outside the European Union, then an authorized representative that is based within the EU must be appointed. There should only be a single authorized representative for non-EU / EFTA manufacturers, i.e. there should not be different authorized representative for the various EU countries (reference Article 14.2* of Council Directive 93/42/EEC amended by Directive 2007/47/EC).
The authorized representative will be the contact for submitting the required regulatory requirements to the various Notified Bodies and Competent Authorities and for communicating with these bodies where questions arise, information is required, etc..
Stages in the European Medical Device Approval process.
1st stage in the medical device approval process.
The manufacturer, in preparing for CE marking, should first determine if their product falls within the scope of a relevant Directive either as a medical device or as an accessory to a medical device. Definitions of what constitutes a medical device will be defined in the relevant directive.
NOTE: as the vast majority of medical devices are governed by the Medical Devices Directive 93/42/EEC, throughout this document we will primarily make reference to this directive.
In order to be classified as a medical device, the product should have a medical purpose and its primary mode of action will typically be physical.
Having confirmed that the product under consideration is subject to a European Medical Device Directive, confirm which directive specifically applies, also confirm if the regulations see the medical device as a product within its own right, or as an accessory to a related medical device.
Identify other European Directives which may be impacting on the product. For example, if the medical device has an active power source, then the AIMD Directive (Active Implantable Medical Devices Directive) may apply, however, equally the medical device may have to comply with Directive 2004/108/EC which relates to electromagnetic compatibility.
3rd stage: Determining the level of risk.
General medical devices and related accessories must be classified into one of four classes, which are based on the perceived risk of the device to the patient or user. The classification of a device determines the conformity assessment options that are applicable to the device, with higher risk devices undergoing higher levels of assessment.
Devices are grouped into 4 classes as follows:
Class I – low risk
Class IIa – medium risk
Class IIb – medium risk
Class III – high risk
Duration of contact.
In determining the correct classification of a device the duration that the device is in continuous contact with the patient is defined as transient, short term or long term.
The longer the device is in contact with the patient or user, the greater the potential risk, and therefore contact duration needs to be taken into account when determining classification.
Continuous use is defined in MEDDEV 2.4/1 as the uninterrupted actual use for the intended purpose. Where use of a device is discontinued in order that the device is immediately replaced with an identical device (e.g. replacement of a urethral catheter) this shall be considered as continuous use of the device.
Duration of contact can be difficult in some instances to determine. For example, if a device requires a cream or ointment is applied to the body, the duration of effect of the cream or ointment may be considered as a factor when determining the duration of contact of a device itself.
Degree of invasiveness.
A device, which in whole or in part, penetrates inside the body either through a body orifice or through the skin surface, is invasive. Invasiveness is generally categorized as invasive of a body orifice (including the surface of the eye), surgically invasive devices and implantable devices.
An implantable device is one which is intended to be totally introduced into the human body or to replace an epithelial surface or the surface of the eye by surgical intervention and which is intended to remain in place after the procedure.
Any device intended to be partially introduced into the human body through surgical intervention and intended to remain in place after the procedure for at least 30 days is also considered an implantable device.
Is the device active or non- active?
A medical device is considered to be active if operation of the device depends on a source of electrical energy or any source of power other than that directly generated by the human body or gravity and which acts by converting this energy. Medical devices intended solely to transmit energy between an active medical device and the patient where there is no significant change in the energy (e.g. nature, density, level) are not considered to be active medical devices.
The concept ‘act by converting energy’ includes conversion of energy in the device and/or conversion at the interface between the device and the tissues or in the tissues of the human body.
Part of the body affected.
The anatomy affected by the use of the device must be considered. Devices in contact with the central nervous system or the central circulatory system are automatically placed in a higher risk category.
Examples of medical devices and their classifications:
Class I – Reusable surgical instruments. Walking aids. Wheelchair. Stethoscope.
Class I Measuring – Volumetric urine bag.
Class I Sterile – Sterile dressings. Non-medicated.
Class IIa – Hypodermic needles. Suction equipment.
Class IIb – Ventilators. Orthopedic implants.
Class III – Ophthalmic lasers. Drug eluting cardiac stents.
4th stage: Technical File, Design Dossier.
The device developer and manufacturer will need to maintain a Design File (Design Dossier) and ongoing Technical File which provides evidence of conformity to the essential requirements of the relevant Medical Device Directive. Clinical data or in the case of some lower risk devices, peer product review data will need to be available to assure the effective functioning of the device.
The Technical File is a requirement for class I, IIa, IIb devices.
The Design Dossier is a requirement of class III devices.
The Technical File will provide information (or point to the location of information) on development and performance aspects of the device.
5th stage: Quality Management System.
The product manufacturing process will need to comply with basic quality management system requirements. For the majority of medical device manufacturers this will require compliance with the ISO 13485 standard. Specifically compliance with the ISO 13485 standard will be demanded for products which reside within the IIa, IIb, and III levels of risk, in addition to class I products with a sterile aspect or a measurement function.
Class I devices need a lower level of quality system elements, however compliance with all aspects of the ISO 13485 standard could be seen as good business practice even for Class I medical devices.
Certification to the ISO 13485 standard will require 3rd party Notified Body certification and on-going surveillance auditing.
6th Stage: Labelling.
Each European country may require labelling to be in their official language, or in a widely utilized language within their territory.
7th stage: Registration.
The following device classes must be registered with the Competent Authority where the manufacturer or their Authorized Representative is located. Most EU countries do not require registration for class IIa, class IIb, or Class III devices as these will require review via the independent Notified Bodies.
All class I devices.
All class I devices which may have been refurbished or re-labelled under a new name.
All system or procedure packs containing at least one medical device.
Custom-made medical devices.
All in vitro medical devices.
In vitro diagnostic medical devices (IVDs) undergoing performance evaluation.
8th stage: EC (European Community) Declaration of Conformity.
The EC declaration of conformity is a written document which states that the manufacturer of a medical device has complied with all relevant EU requirements relevant to the device i.e. completed the medical device approval process. The declaration may cover a single device or multiple devices, all of which will be clearly identified on the declaration via product name, product model, etc.. Also detailed where relevant will be the applicable directives, the EU Authorized Representative (where the manufacturer is not based in the EU), Notified Body engaged for audit and technical files review, key standards applied in meeting the requirements of the directive.
9th stage: Market vigilance. Post market surveillance.
All medical devices placed onto the European market need to be subject to an appropriate post market surveillance process. A medical device manufacturer needs to have a pro-active surveillance system in place, which will include monitoring customer feedback, identifying investigating and addressing complaints, complaint trending, the implementation of an effective and efficient corrective and preventative action process, for higher level risk devices maintenance of a database which links devices to customers, maintenance of records which will allow forward and reverse tracking of manufactured devices, i.e. if a problem is identified for example with a raw material after devices have been manufactured, then the manufacturer needs to be able to identify affected devices in the field, alternatively if a fault is identified with a device in the field, then the manufacturer needs to be able to track back to manufacturing data. The higher risk devices will need more comprehensive tracking records and processes.
10th stage: Medical Device Approval. Affixing the CE label.
Where all relevant directive requirements have been met (i.e. medical device approval), the Notified Body if applicable has confirmed that the quality system, technical file, design files are all to expectations, product labels meet individual country requirements, a market surveillance system is in place, then the CE label can be affixed to the product and the device placed onto the European market. Where the manufacturer is located outside the EU, an Authorized Representative will need to have been appointed.
Information & Training.
- Validation. Classification. Regulation. Requirements. Current best practices.
- FDA cGMP’s. EU MDR’s / MDD’s.
- FDA Medical Device Regulation. Outline of the FDA regulatory requirements.
- FDA Medical Device Classification. The FDA approach to Medical Device Classification.
- EU Medical Device Regulation and Classification (per MDD’s).
- NewEuropean Medical Device Regulations (MDR’s). MDR Classification. MDR General Safety requirements.
- Current Good Manufacturing Practices. QSR’s. General requirements of the QSR’s.
- Quality System requirements to maintain compliant Validations.
- Medical Device Process Validation. Validation requirements. Protocol development. IQ. OQ. PQ.
- Medical Device Software Validation.
- Medical Device Design Validation.
- Electronic Signature, Electronic Records.
- Life Cycle Approach to Validation.
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- Etc. Etc. …
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