Chapter II: Requirements regarding performance, design and manufacture
9. Performance characteristics
9.1. Devices shall be designed and manufactured in such a way that they are suitable for the purposes referred to in point (2) of Article 2, as specified by the manufacturer, and suitable with regard to the performance they are intended to achieve, taking account of the generally acknowledged state of the art. They shall achieve the performances, as stated by the manufacturer and in particular, where applicable:
(a) the analytical performance, such as, analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability and reproducibility), accuracy (resulting from trueness and precision), limits of detection and quantitation, measuring range, linearity, cut-off, including determination of appropriate criteria for specimen collection and handling and control of known relevant endogenous and exogenous interference, cross-reactions; and
(b) the clinical performance, such as diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, likelihood ratio, expected values in normal and affected populations.
9.2. The performance characteristics of the device shall be maintained during the lifetime of the device as indicated by the manufacturer.
9.3. Where the performance of devices depends on the use of calibrators and/or control materials, the metrological traceability of values assigned to calibrators and/or control materials shall be assured through suitable reference measurement procedures and/or suitable reference materials of a higher metrological order. Where available, metrological traceability of values assigned to calibrators and control materials shall be assured to certified reference materials or reference measurement procedures.
9.4. The characteristics and performances of the device shall be specifically checked in the event that they may be affected when the device is used for the intended use under normal conditions:
(a) for devices for self-testing, performances obtained by laypersons;
(b) for devices for near-patient testing, performances obtained in relevant environments (for example, patient home, emergency units, ambulances).
10. Chemical, physical and biological properties
10.1. Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled.
Particular attention shall be paid to the possibility of impairment of analytical performance due to physical and/or chemical incompatibility between the materials used and the specimens, analyte or marker to be detected (such as biological tissues, cells, body fluids and micro-organisms), taking account of the intended purpose of the device.
10.2. Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure.
10.3. Devices shall be designed and manufactured in such a way as to reduce to a level as low as reasonably practicable the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device. Special attention shall be given to substances which are carcinogenic, mutagenic or toxic to reproduction (‘CMR’), in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council, and to substances having endocrine disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified in accordance with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council.
10.4. Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device, taking into account the device and the nature of the environment in which it is intended to be used.
11. Infection and microbial contamination
11.1. Devices and their manufacturing processes shall be designed in such a way as to eliminate or reduce as far as possible the risk of infection to the user or, where applicable, other persons. The design shall:
(a) allow easy and safe handling;
(b) reduce as far as possible any microbial leakage from the device and/or microbial exposure during use;
and, where necessary
(c) prevent microbial contamination of the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen.
11.2. Devices labelled either as sterile or as having a specific microbial state shall be designed, manufactured and packaged to ensure that their sterile condition or microbial state is maintained under the transport and storage conditions specified by the manufacturer until that packaging is opened at the point of use, unless the packaging which maintains their sterile condition or microbial state is damaged.
11.3. Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.
11.4. Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.
11.5. Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer.
11.6. The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile.
12. Devices incorporating materials of biological origin
Where devices include tissues, cells and substances of animal, human or microbial origin, the selection of sources, the processing, preservation, testing and handling of tissues, cells and substances of such origin and control procedures shall be carried out so as to provide safety for user or other person.
In particular, safety with regard to microbial and other transmissible agents shall be addressed by implementation of validated methods of elimination or inactivation in the course of the manufacturing process. This might not apply to certain devices if the activity of the microbial and other transmissible agent are integral to the intended purpose of the device or when such elimination or inactivation process would compromise the performance of the device.
13. Construction of devices and interaction with their environment
13.1. If the device is intended for use in combination with other devices or equipment, the whole combination, including the connection system, shall be safe and shall not impair the specified performances of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use.
13.2. Devices shall be designed and manufactured in such a way as to remove or reduce as far as possible:
(a) the risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;
(b) risks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, temperature, variations in pressure and acceleration or radio signal interferences;
(c) the risks associated with the use of the device when it comes into contact with materials, liquids, and substances, including gases, to which it is exposed during normal conditions of use;
(d) the risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;
(e) the risks of accidental ingress of substances into the device;
(f) the risk of incorrect identification of specimens and the risk of erroneous results due to, for example, confusing colour and/or numeric and/or character codings on specimen receptacles, removable parts and/or accessories used with devices in order to perform the test or assay as intended;
(g) the risks of any foreseeable interference with other devices.
13.3. Devices shall be designed and manufactured in such a way as to minimise the risks of fire or explosion during normal use and in single fault condition. Particular attention shall be paid to devices the intended use of which includes exposure to or use in association with flammable or explosive substances or substances which could cause combustion.
13.4. Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.
13.5. Devices that are intended to be operated together with other devices or products shall be designed and manufactured in such a way that the interoperability and compatibility are reliable and safe.
13.6. Devices shall be designed and manufactured in such a way as to facilitate their safe disposal and the safe disposal of related waste substances by users, or other person. To that end, manufacturers shall identify and test procedures and measures as a result of which their devices can be safely disposed after use. Such procedures shall be described in the instructions for use.
13.. The measuring, monitoring or display scale (including colour change and other visual indicators) shall be designed and manufactured in line with ergonomic principles, taking account of the intended purpose, users and the environmental conditions in which the devices are intended to be used.
14. Devices with a measuring function
14.1. Devices having a primary analytical measuring function shall be designed and manufactured in such a way as to provide appropriate analytical performance in accordance with point (a) of Section 9.1 of Annex I, taking into account the intended purpose of the device.
14.2. The measurements made by devices with a measuring function shall be expressed in legal units conforming to the provisions of Council Directive 80/181/EEC.
15. Protection against radiation
15.1. Devices shall be designed, manufactured and packaged in such a way that exposure of users or other persons to radiation (intended, unintended, stray or scattered) is reduced as far as possible and in a manner that is compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for diagnostic purposes.
15.2. When devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall as far as possible be:
(a) designed and manufactured in such a way as to ensure that the characteristics and the quantity of radiation emitted can be controlled and/or adjusted; and
(b) fitted with visual displays and/or audible warnings of such emissions.
15.3. The operating instructions for devices emitting hazardous or potentially hazardous radiation shall contain detailed information as to the nature of the emitted radiation, the means of protecting the user, and on ways of avoiding misuse and of reducing the risks inherent to installation as far as possible and appropriate. Information regarding the acceptance and performance testing, the acceptance criteria, and the maintenance procedure shall also be specified.
16. Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves
16.1. Devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, shall be designed to ensure repeatability, reliability and performance in line with their intended use. In the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks or impairment of performance.
16.2. For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation.
16.3. Software referred to in this Section that is intended to be used in combination with mobile computing platforms shall be designed and manufactured taking into account the specific features of the mobile platform (e.g. size and contrast ratio of the screen) and the external factors related to their use (varying environment as regards level of light or noise).
16.4. Manufacturers shall set out minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.
17. Devices connected to or equipped with an energy source
17.1. For devices connected to or equipped with an energy source, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.
17.2. Devices where the safety of the patient depends on an internal power supply shall be equipped with a means of determining the state of the power supply and an appropriate warning or indication for when the capacity of the power supply becomes critical. If necessary, such warning or indication shall be given prior to the power supply becoming critical.
17.3. Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks of creating electromagnetic interference which could impair the operation of the device in question or other devices or equipment in the intended environment.
17.4. Devices shall be designed and manufactured in such a way as to provide a level of intrinsic immunity to electromagnetic interference such that is adequate to enable them to operate as intended.
17.5. Devices shall be designed and manufactured in such a way as to avoid as far as possible the risk of accidental electric shocks to the user, or other person both during normal use of the device and in the event of a single fault condition in the device, provided the device is installed and maintained as indicated by the manufacturer.
18. Protection against mechanical and thermal risks
18.1. Devices shall be designed and manufactured in such a way as to protect users and other persons against mechanical risks.
18.2. Devices shall be sufficiently stable under the foreseen operating conditions. They shall be suitable to withstand stresses inherent to the foreseen working environment, and to retain this resistance during the expected lifetime of the devices, subject to any inspection and maintenance requirements as indicated by the manufacturer.
18.3. Where there are risks due to the presence of moving parts, risks due to break-up or detachment, or leakage of substances, then appropriate protection means shall be incorporated.
Any guards or other means included with the device to provide protection, in particular against moving parts, shall be secure and shall not interfere with access for the normal operation of the device, or restrict routine maintenance of the device as intended by the manufacturer.
18.4. Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance.
18.5. Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance.
18.6. Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user or other person has to handle, shall be designed and constructed in such a way as to minimise all possible risks.
18.7. Errors likely to be made when fitting or refitting certain parts which could be a source of risk shall be made impossible by the design and construction of such parts or, failing this, by information given on the parts themselves and/or their housings.
The same information shall be given on moving parts and/or their housings where the direction of movement needs to be known in order to avoid a risk.
18.8. Accessible parts of devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings shall not attain potentially dangerous temperatures under normal conditions of use.
19. Protection against the risks posed by devices intended for self-testing or near-patient testing
19.1. Devices intended for self-testing or near-patient testing shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to the intended user and the influence resulting from variation that can be reasonably anticipated in the intended user's technique and environment. The information and instructions provided by the manufacturer shall be easy for the intended user to understand and apply in order to correctly interpret the result provided by the device and to avoid misleading information. In the case of near-patient testing, the information and the instructions provided by the manufacturer shall make clear the level of training, qualifications and/or experience required by the user.
19.2. Devices intended for self-testing or near-patient testing shall be designed and manufactured in such a way as to:
(a) ensure that the device can be used safely and accurately by the intended user at all stages of the procedure if necessary after appropriate training and/or information; and
(b) reduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, the specimen, and also in the interpretation of the results.
19.3. Devices intended for self-testing and near-patient testing shall, where feasible, include a procedure by which the intended user:
(a) can verify that, at the time of use, the device will perform as intended by the manufacturer; and
(b) be warned if the device has failed to provide a valid result.