Risk management shall be understood as a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating. In carrying out risk management manufacturers shall:
establish and document a risk management plan for each device;
identify and analyse the known and foreseeable hazards associated with each device;
estimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;
eliminate or control the risks referred to in point (c) in accordance with the requirements of Section 4;
evaluate the impact of information from the production phase and, in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their associated risks, as well as on the overall risk, the benefit-risk ratio and risk acceptability; and
based on the evaluation of the impact of the information referred to in point (e), if necessary amend control measures in line with the requirements of Section 4.
eliminate or reduce risks as far as possible through safe design and manufacture;
where appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and
provide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users.
Manufacturers shall inform users of any residual risks.
reduce as far as possible the risks related to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and
give consideration to the technical knowledge, experience, education, training and use environment, where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users).
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
the clinical performance, such as diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, likelihood ratio, expected values in normal and affected populations.
for devices for self-testing, performances obtained by laypersons;
for devices for near-patient testing, performances obtained in relevant environments (for example, patient home, emergency units, ambulances).
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.
allow easy and safe handling;
reduce as far as possible any microbial leakage from the device and/or microbial exposure during use;
and, where necessary
prevent microbial contamination of the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen.
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.
the risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;
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;
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;
the risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;
the risks of accidental ingress of substances into the device;
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;
the risks of any foreseeable interference with other devices.
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
fitted with visual displays and/or audible warnings of such emissions.
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.
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.
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
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.
can verify that, at the time of use, the device will perform as intended by the manufacturer; and
be warned if the device has failed to provide a valid result.
Each device shall be accompanied by the information needed to identify the device and its manufacturer, and by any safety and performance information relevant to the user or any other person, as appropriate. Such information may appear on the device itself, on the packaging or in the instructions for use, and shall, if the manufacturer has a website, be made available and kept up to date on the website, taking into account the following:
The medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.
The information required on the label shall be provided on the device itself. If this is not practicable or appropriate, some or all of the information may appear on the packaging for each unit. If individual full labelling of each unit is not practicable, the information shall be set out on the packaging of multiple devices.
Labels shall be provided in a human-readable format and may be supplemented by machine-readable information, such as radio-frequency identification or bar codes.
Instructions for use shall be provided together with devices. However, in duly justified and exceptional cases instructions for use shall not be required or may be abbreviated if the device can be used safely and as intended by the manufacturer without any such instructions for use.
Where multiple devices, with the exception of devices intended for self-testing or near-patient testing, are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.
When the device is intended for professional use only, instructions for use may be provided to the user in non-paper format (e.g. electronic), except when the device is intended for near-patient testing.
Residual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.
Where appropriate, the information supplied by the manufacturer shall take the form of internationally recognised symbols, taking into account the intended users. Any symbol or identification colour used shall conform to the harmonised standards or CS. In areas for which no harmonised standards or CS exist, the symbols and colours shall be described in the documentation supplied with the device.
In the case of devices containing a substance or a mixture which may be considered as being dangerous, taking account of the nature and quantity of its constituents and the form under which they are present, relevant hazard pictograms and labelling requirements of Regulation (EC) No 1272/2008 shall apply. Where there is insufficient space to put all the information on the device itself or on its label, the relevant hazard pictograms shall be put on the label and the other information required by Regulation (EC) No 1272/2008 shall be given in the instructions for use.
The provisions of Regulation (EC) No 1907/2006 on the safety data sheet shall apply, unless all relevant information, as appropriate, is already made available in the instructions for use.
The label shall bear all of the following particulars:
the name or trade name of the device;
the details strictly necessary for a user to identify the device and, where it is not obvious for the user, the intended purpose of the device;
the name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business;
if the manufacturer has its registered place of business outside the Union, the name of its authorised representative and the address of the registered place of business of the authorised representative;
an indication that the device is an in vitro diagnostic medical device, or if the device is a ‘device for performance study’, an indication of that fact;
the lot number or the serial number of the device preceded by the words LOT NUMBER or SERIAL NUMBER or an equivalent symbol, as appropriate;
the UDI carrier as referred to in Article 24 and Part C of Annex VI;
an unambiguous indication of the time limit for using the device safely, without degradation of performance, expressed at least in terms of year and month and, where relevant, the day, in that order;
where there is no indication of the date until when it may be used safely, the date of manufacture. This date of manufacture may be included as part of the lot number or serial number, provided the date is clearly identifiable;
where relevant, an indication of the net quantity of contents, expressed in terms of weight or volume, numerical count, or any combination of thereof, or other terms which accurately reflect the contents of the package;
an indication of any special storage and/or handling condition that applies;
where appropriate, an indication of the sterile state of the device and the sterilisation method, or a statement indicating any special microbial state or state of cleanliness;
warnings or precautions to be taken that need to be brought to the immediate attention of the user of the device or to any other person. This information may be kept to a minimum in which case more detailed information shall appear in the instructions for use, taking into account the intended users;
if the instructions for use are not provided in paper form in accordance with point (f) of Section 20.1, a reference to their accessibility (or availability), and where applicable the website address where they can be consulted;
where applicable, any particular operating instructions;
if the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union;
if the device is intended for self-testing or near-patient testing, an indication of that fact;
where rapid assays are not intended for self-testing or near-patient testing, the explicit exclusion hereof;
where device kits include individual reagents and articles that are made available as separate devices, each of those devices shall comply with the labelling requirements contained in this Section and with the requirements of this Regulation;
the devices and separate components shall be identified, where applicable in terms of batches, to allow all appropriate action to detect any potential risk posed by the devices and detachable components. As far as practicable and appropriate, the information shall be set out on the device itself and/or, where appropriate, on the sales packaging;
the label for devices for self-testing shall bear the following particulars:
the type of specimen(s) required to perform the test (e.g. blood, urine or saliva);
the need for additional materials for the test to function properly;
contact details for further advice and assistance.
The name of devices for self-testing shall not reflect an intended purpose other than that specified by the manufacturer.
The following particulars shall appear on the sterile packaging:
an indication permitting the sterile packaging to be recognised as such,
a declaration that the device is in a sterile condition,
the method of sterilisation,
the name and address of the manufacturer,
a description of the device,
the month and year of manufacture,
an unambiguous indication of the time limit for using the device safely, expressed at least in terms of year and month and, where relevant, the day, in that order,
an instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.
the name or trade name of the device;
the details strictly necessary for the user to uniquely identify the device;
the device's intended purpose:
what is detected and/or measured;
its function (e.g. screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction, companion diagnostic);
the specific information that is intended to be provided in the context of:
a physiological or pathological state;
congenital physical or mental impairments;
the predisposition to a medical condition or a disease;
the determination of the safety and compatibility with potential recipients;
the prediction of treatment response or reactions;
the definition or monitoring of therapeutic measures;
whether it is automated or not;
whether it is qualitative, semi-quantitative or quantitative;
the type of specimen(s) required;
where applicable, the testing population; and
for companion diagnostics, the International Non-proprietary Name (INN) of the associated medicinal product for which it is a companion test.
an indication that the device is an in vitro diagnostic medical device, or, if the device is a ‘device for performance study’, an indication of that fact;
the intended user, as appropriate (e.g. self-testing, near patient and laboratory professional use, healthcare professionals);
the test principle;
a description of the calibrators and controls and any limitation upon their use (e.g. suitable for a dedicated instrument only);
a description of the reagents and any limitation upon their use (e.g. suitable for a dedicated instrument only) and the composition of the reagent product by nature and amount or concentration of the active ingredient(s) of the reagent(s) or kit as well as a statement, where appropriate, that the device contains other ingredients which might influence the measurement;
a list of materials provided and a list of special materials required but not provided;
for devices intended for use in combination with or installed with or connected to other devices and/or general purpose equipment:
information to identify such devices or equipment, in order to obtain a validated and safe combination, including key performance characteristics, and/or
information on any known restrictions to combinations of devices and equipment.
an indication of any special storage (e.g. temperature, light, humidity, etc.) and/or handling conditions which apply;
in-use stability which may include the storage conditions, and shelf life following the first opening of the primary container, together with the storage conditions and stability of working solutions, where this is relevant;
if the device is supplied as sterile, an indication of its sterile state, the sterilisation method and instructions in the event of the sterile packaging being damaged before use;
information that allows the user to be informed of any warnings, precautions, measures to be taken and limitations of use regarding the device. That information shall cover, where appropriate:
warnings, precautions and/or measures to be taken in the event of malfunction of the device or its degradation as suggested by changes in its appearance that may affect performance,
warnings, precautions and/or measures to be taken as regards the exposure to 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, or temperature,
warnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment,
precautions related to materials incorporated into the device that contain or consist of CMR substances, or endocrine disrupting substances or that could result in sensitisation or an allergic reaction by the patient or user,
if the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union,
if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, decontamination, packaging and, where appropriate, the validated method of re-sterilisation. Information shall be provided to identify when the device should no longer be reused, such as signs of material degradation or the maximum number of allowable reuses;
any warnings and/or precautions related to potentially infectious material that is included in the device;
where relevant, requirements for special facilities, such as a clean room environment, or special training, such as on radiation safety, or particular qualifications of the intended user;
conditions for collection, handling, and preparation of the specimen;
details of any preparatory treatment or handling of the device before it is ready for use, such as sterilisation, final assembly, calibration, etc., for the device to be used as intended by the manufacturer;
the information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:
details of the nature, and frequency, of preventive and regular maintenance, including cleaning and disinfection;
identification of any consumable components and how to replace them;
information on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime;
methods for mitigating the risks encountered by persons involved in installing, calibrating or servicing devices.
where applicable, recommendations for quality control procedures;
the metrological traceability of values assigned to calibrators and control materials, including identification of applied reference materials and/or reference measurement procedures of higher order and information regarding maximum (self-allowed) batch to batch variation provided with relevant figures and units of measure;
assay procedure including calculations and interpretation of results and where relevant if any confirmatory testing shall be considered; where applicable, the instructions for use shall be accompanied by information regarding batch to batch variation provided with relevant figures and units of measure;
analytical performance characteristics, such as analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability and reproducibility), accuracy (resulting from trueness and precision), limits of detection and measurement range, (information needed for the control of known relevant interferences, cross-reactions and limitations of the method), measuring range, linearity and information about the use of available reference measurement procedures and materials by the user;
clinical performance characteristics as defined in Section 9.1 of this Annex;
the mathematical approach upon which the calculation of the analytical result is made;
where relevant, clinical performance characteristics, such as threshold value, diagnostic sensitivity and diagnostic specificity, positive and negative predictive value;
where relevant, reference intervals in normal and affected populations;
information on interfering substances or limitations (e.g. visual evidence of hyperlipidaemia or haemolysis, age of specimen) that may affect the performance of the device;
warnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories, and the consumables used with it, if any. This information shall cover, where appropriate:
infection or microbial hazards, such as consumables contaminated with potentially infectious substances of human origin;
environmental hazards such as batteries or materials that emit potentially hazardous levels of radiation);
physical hazards such as explosion.
the name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business at which he can be contacted and its location be established, together with a telephone number and/or fax number and/or website address to obtain technical assistance;
date of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use, with a clear indication of the introduced modifications;
a notice to the user that any serious incident that has occurred in relation to the device shall be reported to the manufacturer and the competent authority of the Member State in which the user and/or the patient is established;
where device kits include individual reagents and articles that may be made available as separate devices, each of these devices shall comply with the instructions for use requirements contained in this Section and with the requirements of this Regulation;
for devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.
details of the test procedure shall be given, including any reagent preparation, specimen collection and/or preparation and information on how to run the test and interpret the results;
specific particulars may be omitted provided that the other information supplied by the manufacturer is sufficient to enable the user to use the device and to understand the result(s) produced by the device;
the device's intended purpose shall provide sufficient information to enable the user to understand the medical context and to allow the intended user to make a correct interpretation of the results;
the results shall be expressed and presented in a way that is readily understood by the intended user;
information shall be provided with advice to the user on action to be taken (in case of positive, negative or indeterminate result), on the test limitations and on the possibility of false positive or false negative result. Information shall also be provided as to any factors that can affect the test result such as age, gender, menstruation, infection, exercise, fasting, diet or medication;
the information provided shall include a statement clearly directing that the user should not take any decision of medical relevance without first consulting the appropriate healthcare professional, information on disease effects and prevalence, and, where available, information specific to the Member State(s) where the device is placed on the market on where a user can obtain further advice such as national helplines, websites;
for devices intended for self-testing used for the monitoring of a previously diagnosed existing disease or condition, the information shall specify that the patient should only adapt the treatment if he has received the appropriate training to do so.
Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 (OJ L 353, 31.12.2008, p. 1).
Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ L 136, 29.5.2007, p. 3).
Council Directive 80/181/EEC of 20 December 1979 on the approximation of the laws of the Member States relating to units of measurement and on the repeal of Directive 71/354/EEC (OJ L 39, 15.2.1980, p. 40).