FantasticSearch

1. Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall 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 patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art.

2. The requirement in this Annex to reduce risks as far as possible means the reduction of risks as far as possible without adversely affecting the benefit-risk ratio.

3. Manufacturers shall establish, implement, document and maintain a risk management system. 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:

(a) establish and document a risk management plan for each device;

(b) identify and analyse the known and foreseeable hazards associated with each device;

(c) estimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;

(d) eliminate or control the risks referred to in point (c) in accordance with the requirements of Section 4;

(e) 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 (f) 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.

4. Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, the manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:

(a) eliminate or reduce risks as far as possible through safe design and manufacture;

(b) where appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and (c) provide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users. Manufacturers shall inform users of any residual risks.

5. In eliminating or reducing risks related to use error, the manufacturer shall:

(a) 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 (b) 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).

6. The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user 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 and has been properly maintained in accordance with the manufacturer's instructions.

7. Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.

8. All known and foreseeable risks, and any undesirable effects shall be minimised and be acceptable when weighed against the evaluated potential benefits to the patients and/or the user arising from the intended performance of the device during normal conditions of use. 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.