Passport to Europe for Medical Devices
1. EUROPEAN TECHNICAL HARMONIZATION AND CE-MARKING
In line with the European Union’s policy to establish a free trade zone among its member states, a New Approach to technical harmonization was adopted in 1985. This New Approach means that the European Union sets minimum requirements to industrially manufactured products for ensuring the necessary level of protection with respect to safety, health and environment.
These so-called essential requirements are specified in EC directives. Where these requirements have been formulated in general terms, they refer to harmonized technical standards. The European Commission has given mandates to CEN and CENELEC, the European standardization bodies, to establish the technical standards. If a product conforms to the relevant standards, it produces a presumption of conformity to the essential requirements.
The CE Mark demonstrates that the relevant product conforms with the essential requirements set within the European Union. This means that the product is safe and fit for the purpose for which it was made. Moreover, the CE Mark shows that the manufacturer has complied with the legal conformity requirements and that the product may be freely sold within the European Union and the European Free Trade Association (except for Switzerland).
2. THE MEDICAL DEVICE DIRECTIVES
As part of the New Approach to technical harmonization in the European Union, directives have also been established for medical devices. These directives specify conditions to be met before permission is granted to apply the CE Mark and cover all medical devices and accessories.
A medical device is any instrument, apparatus, appliance, material or other article, whether used alone or in combination, including the software necessary for its proper application intended by the manufacturer to be used for human beings for the purpose of:
– diagnosis, prevention, monitoring, treatment or alleviation of disease,
– diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,
– investigation, replacement or modification of the anatomy or of a physiological process,
– control of conception
and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.
Three Directives have been drawn up.
2.1 Active Implantable Medical Device Directive (90/385/EEC)
This directive covers all medical devices, which rely for its functioning on a power supply and are left in the human body. Examples of AIMD’s are implantable cardiac pacemakers, implantable nerve stimulators and implantable drug administration devices with or without catheter. As of January 1, 1995 all medical devices covered by this Directive require a CE marking.
2.2 Medical Device Directive (93/42/EEC)
The Medical Device Directive covers most other medical devices (active and non-active) and their accessories that are not covered by the first or the third directive. This concerns a large number of products ranging from walking aids to prosthetic heart valves. As of June 14, 1998, all medical devices placed on the market or put into service and covered by this directive must have a CE marking.
2.3 In Vitro Diagnostic Medical Device Directive (98/79/EEC)
The In Vitro Diagnostic Medical Device Directive covers any reagent, reagent product, control material, kit, medical device, instrument, apparatus or system which is intended to be used in-vitro for the examination of substances derived from the human body. As of December 7, 2003 all IVD medical devices covered by this Directive require a CE marking.
Note: these 3 main Directives mentioned above have been supplemented over time by several modifying and implementing directives, including the last technical revision brought about by Directive 98/79/EEC.
The subsequent sections of this “Passport” will deal with the Medical Device Directive (93/42/EEC) only
CLASSIFICATION OF MEDICAL DEVICES
A classification system has been developed for the Medical Device Directive, dividing the related devices into four classes based on the risk factor involved and the intended use to be made of the product. This classification is based on the following principles:
1. the duration of contact between the device and the patient
2. the degree and manner of the device penetrating the human body
3. the degree of the device’s impact on the human anatomy.
Classification Rules
Based on the above-mentioned principles, 18 classification rules have been developed; Annex IX to the Directive contains a list of these rules.
Rules 1 through 4 apply to devices that do not penetrate the human body (non-invasive devices), whereas rules 5 through 8 apply to devices that do penetrate the human body (invasive devices). A distinction is made between the manner of penetration the body (through a natural or an artificially created orifice) and the duration of contact between the device and the patient.
For powered devices (active devices) supplementary rules 9 through 12 are also applicable. A distinction is made between therapeutic and diagnostic devices, devices administering or removing medicines, devices administering or exchanging energy to the human body from it, and other devices.
Rules 13 through 18 are special rules for specifically defined devices used for special applications.
Classification
According to the classification rules given in Annex IX to the directive, devices are classified as follows:
– Class 1 for low-risk devices
This includes hospital beds, incontinence diapers, ordinary band-aids, external splints, spectacle glasses, examination gloves, reusable surgical tools, non-invasive electrodes etc.
– Class IIa for medium-risk devices
This includes catheters, ultrasound equipment, blood filtration equipment, standard contact lenses, surgical gloves, dental fillings, hearing aids etc.
– Class IIb for medium-risk devices
This includes haemodialysis equipment, standard intra-ocular lenses, drug administration devices, anaesthetic apparatus, contact lens fluids, blood bags, X-ray equipment etc.
– Class III for high-risk devices
This includes cardiac valves, neurological catheters, implants with a biologically active coating etc.
3 ESSENTIAL REQUIREMENTS
Each medical device must – regardless of its classification – comply with the essential requirements specified in Annex I to the directive. The essential requirements consist of general requirements and a number of more specific requirements.
3.1 The general requirements are:
1 The devices must be designed and manufactured in such a way that, when used under the conditions and for the purposes intended, they will not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patients and are compatible with a high level of protection of health and safety.
2 The solutions adopted by the manufacturer for the design and construction of the devices must conform to safety principles, taking account of the generally acknowledged state of the art. In selecting the most appropriate solutions, the manufacturer must apply the following principles in the following order:
– eliminate or reduce risks as far as possible (inherently safe design and construction)
– where appropriate, take adequate protection measures including alarms, if necessary, in relation to risks that cannot be eliminated
– inform users of the residual risks due to any shortcomings of the protection measures adopted.
3 The devices must achieve the performances intended by the manufacturer and be designed, manufactured and packaged in such a way that they are suitable for one or more of the functions referred to in Article 1 (2) (a), as specified by the manufacturer.
4 The characteristics and performances referred to in Sections, 1, 2 and 3 must not be adversely affected to such a degree that the clinical conditions and safety of the patients and, where applicable, of other persons are compromised during the lifetime of the device as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use.
5 The devices must be designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected during transport and storage, taking account of the instructions and information provided by the manufacturer.
6 Any undesirable side-effect must constitute an acceptable risk when weighed against the performances intended.
3.2 Specific requirements relate to:
a. chemical, physical and biological properties
b. infection and microbial contamination
c. construction and environmental properties
d. devices with a measuring function
e. protection against radiation
f. medical devices connected to or equipped with an energy source
g. information supplied by the manufacturer
h. clinical data
4 PRODUCT QUALITY ASSURANCE
Generally speaking, the manufacturer’s quality system should ensure that the design and/or manufacture of a medical device is in compliance with the requirements of the directive. If the relevant harmonized standards are implemented in the quality system, it is presumed to conform to the directive.
A selection can be made of several quality assurance methods, depending on the classification of the products and the corresponding conformity procedure in accordance with the directive. The manufacturer can apply a `full quality assurance system’ or e.g. a `product quality assurance system’ if this is applicable to the products concerned. The different options are listed in Annex I to this brochure.
4.1 Post-Market Surveillance
The manufacturer’s responsibility for product quality continues after utilization of the product has started. The directive therefore stipulates that the manufacturer shall implement and maintain a systematic procedure based on which the experiences gained with products during their utilization can be evaluated, so as to be able to make improvements to these products where necessary.
4.2 Vigilance System
The manufacturer shall notify the competent authorities of any incidents involving products in use that have or could have seriously compromised the patient’s or user’s health.
Furthermore, the manufacturer shall notify the competent authorities when, following complaints or incidents, products of similar type are systematically taken from the market. The quality system must therefore incorporate procedures relating to these activities.
5 THE NOTIFIED BODY
A so-called notified body plays an important role in the procedure for obtaining a CE marking for devices in classes IIa, IIb and III and for class I products placed on the market in sterile condition (Is) and/or with a measuring function (Im).
The notified body is a certification organization designated by the national authority of any EC country (Competent Authority = CA), which is authorized to conduct conformity assessments in accordance with the procedures in the directive. The notified body offers its services to the manufacturer with the aim to have the manufacturer’s product put on the European market in conformity with the directives. The notified body performs its activities in a competent, neutral, independent and non-discriminatory manner.
Obtaining the CE Marking
Before being permitted to apply a CE marking, the manufacturer must demonstrate that his product satisfies the essential requirements of the directive and that he has an operational vigilance system for it. Moreover, one of the procedures specified in the directive is to be observed. The selection of a procedure depends among others on the classification of the product. Annex 1 contains a diagram of the options.
For Class I products the procedure given in Annex VII to the directive should be observed. Moreover, for class I products placed on the market in sterile condition and/or with a measuring function, one of the procedures referred to in Annexes IV, V or VI should also be observed. The notified body should assess the manufacturing aspects related to the sterile condition or associated with the metrological requirements.
For Class IIa products the procedure stated in Annex II, or the procedure of Annex VII in combination with one of the procedures described in Annexes IV, V or VI, should be observed.
For Class IIb products it is also possible to observe the procedure given in Annex II, or the procedure described in Annex III in combination with one of the procedures stated in Annexes IV, V or VI.
For Class III products the procedure of Annex II should be observed, or the procedure given in Annex III in combination with one of the procedures of Annexes IV or V.
Tasks of a Notified Body in the procedures of the directive
The tasks of the notified body in the conformity assessment procedures to be observed are described in the annexes to the directive. This section will outline the major tasks for each procedure.
Full quality assurance system (Annex II)
The notified body audits the quality system to determine that the products conform to the provisions of the directive which apply at every stage, from design to final inspection. It is assumed that quality systems which implement all relevant harmonized standards conform to these requirements.
The assessment procedure must include an inspection on the manufacturer’s premises and if necessary, an inspection on the premises of the manufacturer’s suppliers and/or subcontractors. The manufacturer is subsequently notified of the results and findings of the audit team.
After the CE certificate has been granted, the notified body will conduct periodic inspections and audits to ascertain the proper implementation of the approved quality assurance system. Moreover, the notified body may also pay unannounced inspection visits, where, if necessary, tests to ascertain the proper operation of the implemented quality assurance system can be performed. Reports on the results of either type of inspection will be sent to the manufacturer.
Design dossier (Annex II)
For class III products the notified body must examine the design dossier of the product the manufacturer intends to produce. If the design conforms to the relevant provisions of the Directive, the notified body will issue an EC design examination certificate. The notified body may demand that supplementary tests be performed or additional evidence be submitted, to be able to assess whether the provisions of the directive are met.
EC Type Examination (Annex III)
The notified body examines and assesses the documentation submitted by the manufacturer and verifies that a representative sample of the product type has been manufactured in conformity with the documentation. The notified body also documents which product elements have and which elements have not been designed in accordance with the provisions of the relevant harmonized standards.
The notified body carries out the appropriate inspections and the testing necessary to verify whether solutions adopted by the manufacturer meet the essential requirements of the Directive for product elements that were not designed in accordance with the provisions of the relevant harmonized standards. Moreover, the notified body carries out the appropriate inspections and tests necessary to verify whether the relevant harmonized standards have actually been applied for the product elements which according to the documentation were designed according to these standards. The location where these inspections and tests will be performed is to be determined in consultation with the manufacturer.
If the type conforms to the provisions of the Directive, the notified body will issue an EC type examination certificate to the manufacturer.
EC Verification (Annex IV)
With products of Classes IIb and III, the notified body examines every product individually and appro¬priate tests are carried out in order to verify its conformity to the applicable requirements of the directive and with the EC type described in the type-examination certificate.
For Class IIa products the notified body examines the product and carries out appropriate tests in order to verify whether the product is manufactured in accordance with the technical documentation described in Annex VII and meets the relevant provisions of the directive.
For products to be placed on the market in sterile condition, the notified body will conduct an audit of the sterilization process in accordance with Annex V of the directive, in order to verify whether the implemented quality system ensures conformity of the sterilization process to the relevant harmonized standards.
The examination and the tests can be performed either on each product individually, or in a statistically justifiable manner, at the manufacturer’s discretion.
If a product or batch is accepted, the notified body affixes or has affixed its identification number to each product and issues a written certificate of conformity.
If a batch is rejected, the notified body must take appropriate measures to prevent the batch being placed on the market.
Production Quality Assurance System (Annex V)
For products of Classes IIb and III the notified body audits the quality system to determine whether it ensures that the products conform to the type described in the type-examination certificate.
For Class IIa products the notified body audits the quality system to determine whether it ensures that the products conform to the technical documentation described in Annex VII and that they are in accordance with the applicable provisions of the directive.
For products to be placed on the market in sterile condition, the notified body will conduct an audit of the sterilization process, regardless of the product classification, in order to verify whether the implemented quality system ensures conformity of the sterilization process to the relevant harmonized standards.
The assessment procedure must include an inspection on the manufacturer’s premises and if necessary, an inspection on the premises of the manufacturer’s suppliers and/or subcontractors. Conformity to the provisions of the directive is presumed if all relevant harmonized standards are implemented. The manufacturer is subsequently notified of the results and findings of the audit team.
After the CE certificate has been granted, the notified body will conduct periodic inspections and audits to ascertain the proper implementation of the approved quality assurance system. Moreover, the notified body may also pay unannounced inspection visits, if necessary performing tests to ascertain the proper operation of the implemented quality assurance system. Reports on the results of either type of inspection will be sent to the manufacturer.
Product quality assurance (Annex VI)
For products of Classes IIb and III the notified body audits the quality system to determine whether it ensures that the products conform to the type described in the type-examination certificate and that they are in accordance with the applicable provisions of the directive.
For Class IIa products the notified body audits the quality system to determine whether it ensures that the products conform to the technical documentation described in Annex VII and that they are in accordance with the applicable provisions of the directive. Conformity to the provisions of the directive is presumed if all relevant harmonized standards are implemented.
For products to be placed on the market in sterile condition, the notified body will conduct an audit of the sterilization process in accordance with Annex V of the directive, in order to verify whether the implemented quality system ensures conformity of the sterilization process to the relevant harmonized standards.
The assessment procedure must include an inspection on the manufacturer’s premises and if necessary, an inspection on the premises of the manufacturer’s suppliers and/or subcontractors. Conformity to the provisions of the directive is presumed if all relevant harmonized standards are implemented. The manufacturer is subsequently notified of the results and findings of the audit team.
After the CE certificate has been granted, the notified body will conduct periodic inspections and audits to ascertain the proper implementation of the approved quality assurance system. Moreover, the notified body may also pay unannounced inspection visits, if necessary performing tests to ascertain the proper operation of the implemented quality assurance system. Reports on the results of either type of inspection will be sent to the manufacturer.
EC Declaration of Conformity (Annex VII)
For Class IIa products the notified body assesses the technical documentation submitted by the manufacturer to ascertain whether the products conform to the provisions of the directive.