ANNEX I – General safety and performance requirements

Chapter II

Requirements regarding design and manufacture

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:

(a)the choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;
(b)the compatibility between the materials and substances used and
biological tissues, cells and body fluids, taking account of the
intended purpose of the device and, where relevant, absorption,
distribution, metabolism and excretion;
(c)the compatibility between the different parts of a device which
consists of more than one implantable part;
(d)the impact of processes on material properties;
(e)where appropriate, the results of biophysical or modelling research
the validity of which has been demonstrated beforehand;
(f)the mechanical properties of the materials used, reflecting, where
appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;
(g)surface properties; and
(h)the confirmation that the device meets any defined chemical and/orphysical specifications.

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 that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use.

10.4. Substances

10.4.1. Design and manufacture of devices

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

Devices, or those parts thereof or those materials used therein that:

are invasive and come into direct contact with the human body,
(re)administer medicines, body liquids or other substances, including gases, to/from the body, or
transport or store such medicines, body fluids or substances,
including gases, to be (re)administered to the body,

shall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section 10.4.2:

(a)substances which are carcinogenic, mutagenic or toxic to
reproduction (‘CMR’), of category 1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European
Parliament and of the Council (1), or
(b)substances having endocrine-disrupting properties for which there
is scientific evidence of probable serious effects to human health
and which are identified either in accordance with the procedure
set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council (2) or, once a delegated act has been
adopted by the Commission pursuant to the first subparagraph of
Article 5(3) of Regulation (EU) No 528/2012 of the European
Parliament and the Council (3), in accordance with the criteria that
are relevant to human health amongst the criteria established
therein.

(1) 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).

(2) 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 396, 30.12.2006, p. 1).

(3) Regulation (EU) No 528/2012 of the European Parliament and the Council of 22 May 2012 concerning the making available on the market of and use of biocidal products (OJ L 167, 27.6.2012, p. 1).

10.4.2. Justification regarding the presence of CMR and/or endocrine-disrupting substances

(a)an analysis and estimation of potential patient or user exposure to
the substance;
(b)an analysis of possible alternative substances, materials or designs,
including, where available, information about independent
research, peer-reviewed studies, scientific opinions from relevant
scientific committees and an analysis of the availability of such
alternatives;
(c)argumentation as to why possible substance and/ or material
substitutes, if available, or design changes, if feasible, are
inappropriate in relation to maintaining the functionality,
performance and the benefit-risk ratios of the product; including
taking into account if the intended use of such devices includes
treatment of children or treatment of pregnant or breastfeeding
women or treatment of other patient groups considered particularlyvulnerable to such substances and/or materials; and
(d)where applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4.

10.4.3. Guidelines on phthalates

For the purposes of Section 10.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section 10.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated.

10.4.4. Guidelines on other CMR and endocrine-disrupting substances

Subsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section 10.4.3. also for other substances referred to in points (a) and (b) of Section 10.4.1., where appropriate.

10.4.5. Labelling

Where devices, parts thereof or materials used therein as referred to in Section 10.4.1. contain substances referred to in points (a) or (b) of Section 10.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.

10.5. 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.

10.6. Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient’s or user’s body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials.

11. Infection and microbial contamination

11.1. Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:

(a)reduce as far as possible and appropriate the risks from unintendedcuts and pricks, such as needle stick injuries,
(b)allow easy and safe handling,
(c)reduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and
(d)prevent microbial contamination of the device or its content such asspecimens or fluids.

11.2. Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation.

11.3. Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer.

11.4. Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user.

11.5. Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.

11.6. Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.

11.7. 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.

11.8. 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 a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.

12.1. In the case of devices referred to in the first subparagraph of Article 1(8), the quality, safety and usefulness of the substance which, if used separately, would be considered to be a medicinal product within the meaning of point (2) of Article 1 of Directive 2001/83/EC, shall be verified by analogy with the methods specified in Annex I to Directive 2001/83/EC, as required by the applicable conformity assessment procedure under this Regulation.

12.2. Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body, and that are absorbed by or locally dispersed in the human body shall comply, where applicable and in a manner limited to the aspects not covered by this Regulation, with the relevant requirements laid down in Annex I to Directive 2001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions, as required by the applicable conformity assessment procedure under this Regulation.

13. Devices incorporating materials of biological origin

13.1. For devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable covered by this Regulation in accordance with point (g) of Article 1(6), the following shall apply:

(a)donation, procurement and testing of the tissues and cells shall be
done in accordance with Directive 2004/23/EC;
(b)processing, preservation and any other handling of those tissues and cells or their derivatives shall be carried out so as to provide safety
for patients, users and, where applicable, other persons. In
particular, safety with regard to viruses and other transmissible
agents shall be addressed by appropriate methods of sourcing and
by implementation of validated methods of elimination or
inactivation in the course of the manufacturing process;
(c)the traceability system for those devices shall be complementary
and compatible with the traceability and data protection
requirements laid down in Directive 2004/23/EC and in Directive
2002/98/EC.

13.2. For devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply:

(a)where feasible taking into account the animal species, tissues and
cells of animal origin, or their derivatives, shall originate from
animals that have been subjected to veterinary controls that are
adapted to the intended use of the tissues. Information on the
geographical origin of the animals shall be retained by
manufacturers;
(b)sourcing, processing, preservation, testing and handling of tissues,
cells and substances of animal origin, or their derivatives, shall be
carried out so as to provide safety for patients, users and, where
applicable, other persons. In particular safety with regard to virusesand other transmissible agents shall be addressed by
implementation of validated methods of elimination or viral
inactivation in the course of the manufacturing process, except
when the use of such methods would lead to unacceptable
degradation compromising the clinical benefit of the device;
(c)in the case of devices manufactured utilising tissues or cells of
animal origin, or their derivatives, as referred to in Regulation (EU) No 722/2012 the particular requirements laid down in that
Regulation shall apply.

13.3. For devices manufactured utilising non-viable biological substances other than those referred to in Sections 13.1 and 13.2, the processing, preservation, testing and handling of those substances shall be carried out so as to provide safety for patients, users and, where applicable, other persons, including in the waste disposal chain. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process.

14. Construction of devices and interaction with their environment

14.1. 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 performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimise all possible risks, such as misconnection.

14.2. 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 risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; and
(g)risks arising where maintenance or calibration are not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism.

14.3. 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.

14.4. Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.

14.5. 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.

14.6. Any measurement, monitoring or display scale 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.

14.7. 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 the user, patient 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.

15. Devices with a diagnostic or measuring function

15.1. Diagnostic devices and devices with a measuring function, shall be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. The limits of accuracy shall be indicated by the manufacturer.

15.2. 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 (1).

(1) 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).

16. Protection against radiation

16.1. General

(a)Devices shall be designed, manufactured and packaged in such a
way that exposure of patients, users and other persons to radiation
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 therapeutic and diagnostic purposes.
(b)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 patient and 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.

16.1. Intended radiation

(a)Where devices are designed to emit hazardous, or potentially
hazardous, levels of ionizing and/or non- ionizing radiation
necessary for a specific medical purpose the benefit of which is
considered to outweigh the risks inherent to the emission, it shall bepossible for the user to control the emissions. Such devices shall be
designed and manufactured to ensure reproducibility of relevant
variable parameters within an acceptable tolerance.
(b)Where devices are intended to emit hazardous, or potentially
hazardous, ionizing and/or non-ionizing radiation, they shall be
fitted, where possible, with visual displays and/or audible warnings of such emissions.

16.3. Devices shall be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as possible. Where possible and appropriate, methods shall be selected which reduce the exposure to radiation of patients, users and other persons who may be affected.

16.4. Ionising radiation

(a)Devices intended to emit ionizing radiation shall be designed and
manufactured taking into account the requirements of the Directive2013/59/Euratom laying down basic safety standards for protection
against the dangers arising from exposure to ionising radiation.
(b)Devices intended to emit ionising radiation shall be designed and
manufactured in such a way as to ensure that, where possible,
taking into account the intended use, the quantity, geometry and
quality of the radiation emitted can be varied and controlled, and, ifpossible, monitored during treatment.
(c)Devices emitting ionising radiation intended for diagnostic radiology shall be designed and manufactured in such a way as to achieve an
image and/or output quality that are appropriate to the intended
medical purpose whilst minimising radiation exposure of the patient and user.
(d)Devices that emit ionising radiation and are intended for
therapeutic radiology shall be designed and manufactured in such
a way as to enable reliable monitoring and control of the delivered
dose, the beam type, energy and, where appropriate, the quality of
radiation.

17. Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves

17.1. 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.

17.2. 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.

17.3. 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).

17.4. 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.

18. Active devices and devices connected to them

18.1. For non-implantable active devices, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.

18.2. 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.

18.3. Devices where the safety of the patient depends on an external power supply shall include an alarm system to signal any power failure.

18.4. Devices intended to monitor one or more clinical parameters of a patient shall be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient’s state of health.

18.5. 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.

18.6. 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.

18.7. 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 patient, user or any 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.

18.8. Devices shall be designed and manufactured in such a way as to protect, as far as possible, against unauthorised access that could hamper the device from functioning as intended.

19. Particular requirements for active implantable devices

19.1. Active implantable devices shall be designed and manufactured in such a way as to remove or minimize as far as possible:

(a)risks connected with the use of energy sources with particular
reference, where electricity is used, to insulation, leakage currents
and overheating of the devices,
(b)risks connected with medical treatment, in particular those
resulting from the use of defibrillators or high- frequency surgical
equipment, and
(c)risks which may arise where maintenance and calibration are
impossible, including:
— excessive increase of leakage currents,
— ageing of the materials used,
— excess heat generated by the device,
— decreased accuracy of any measuring or control mechanism.

19.2. Active implantable devices shall be designed and manufactured in such a way as to ensure

if applicable, the compatibility of the devices with the substances
they are intended to administer, and
the reliability of the source of energy.

19.3. Active implantable devices and, if appropriate, their component parts shall be identifiable to allow any necessary measure to be taken following the discovery of a potential risk in connection with the devices or their component parts.

19.4. Active implantable devices shall bear a code by which they and their manufacturer can be unequivocally identified (particularly with regard to the type of device and its year of manufacture); it shall be possible to read this code, if necessary, without the need for a surgical operation.

20. Protection against mechanical and thermal risks

20.1. Devices shall be designed and manufactured in such a way as to protect patients and users against mechanical risks connected with, for example, resistance to movement, instability and moving parts.

20.2. 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.

20.3. 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.

20.4. 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.

20.5. 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.

20.6 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.

21. Protection against the risks posed to the patient or user by devices supplying energy or substances

21.1. Devices for supplying the patient with energy or substances shall be designed and constructed in such a way that the amount to be delivered can be set and maintained accurately enough to ensure the safety of the patient and of the user.

21.2. Devices shall be fitted with the means of preventing and/or indicating any inadequacies in the amount of energy delivered or substances delivered which could pose a danger. Devices shall incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy or substances from an energy and/or substance source.

21.3. The function of the controls and indicators shall be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information shall be understandable to the user and, as appropriate, the patient.

22. Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons

22.1. Devices for use by lay persons 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 lay persons and the influence resulting from variation that can be reasonably anticipated in the lay person’s technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply.

22.2. Devices for use by lay persons shall be designed and manufactured in such a way as to:

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,
reduce, as far as possible and appropriate, the risk from unintended cuts and pricks such as needle stick injuries, and
reduce as far as possible the risk of error by the intended user in thehandling of the device and, if applicable, in the interpretation of the
results.

22.3. Devices for use by lay persons shall, where appropriate, include a procedure by which the lay person:

can verify that, at the time of use, the device will perform as
intended by the manufacturer, and
if applicable, is warned if the device has failed to provide a valid
result.

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