Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance. )

Article 99

Good administrative practice

Where action has been taken without the economic operator having had the opportunity to make submissions as referred to in the first subparagraph, it shall be given the opportunity to make submissions as soon as possible and the action taken shall be reviewed promptly thereafter.

Article 100

Electronic system on market surveillance

• (a) summaries of the results of the surveillance activities referred to in Article 93(4);

• (b) the final inspection report referred to in Article 93(7);

• (c) information in relation to devices presenting an unacceptable risk to health and safety as referred to in Article 95(2), (4) and (6);

• (d) information in relation to non-compliance of products as referred to in Article 97(2);

• (e) information in relation to the preventive health protection measures referred to in Article 98(2);

• (f) summaries of the results of the reviews and assessments of the market surveillance activities of the Member States referred to in 93(8).

CHAPTER VIII COOPERATION BETWEEN MEMBER STATES, MEDICAL DEVICE COORDINATION GROUP, EXPERT LABORATORIES, EXPERT PANELS AND DEVICE REGISTERS

Article 101

Competent authorities

The Member States shall designate the competent authority or authorities responsible for the implementation of this Regulation. They shall entrust their authorities with the powers, resources, equipment and knowledge necessary for the proper performance of their tasks pursuant to this Regulation. The Member States shall communicate the names and contact details of the competent authorities to the Commission which shall publish a list of competent authorities.

Article 102

Cooperation

Article 103

Medical Device Coordination Group

The members of the MDCG shall be chosen for their competence and experience in the field of medical devices and in vitro diagnostic medical devices. They shall represent the competent authorities of the Member States. The names and affiliation of members shall be made public by the Commission.

The alternates shall represent and vote for the members in their absence.

• — the adoption of opinions or recommendations or other positions, including in cases of urgency;

• — the delegation of tasks to reporting and co-reporting members;

• — the implementation of Article 107 regarding conflict of interests;

• — the functioning of sub-groups.

Article 104

Support by the Commission

The Commission shall support the functioning of the cooperation between national competent authorities. It shall, in particular, provide for the organisation of exchanges of experience between the competent authorities and provide technical, scientific and logistic support to the MDCG and its sub-groups. It shall organise the meetings of the MDCG and its sub-groups, participate in those meetings and ensure the appropriate follow-up.

Article 105

Tasks of the MDCG

Under this Regulation, the MDCG shall have the following tasks:

• (a) to contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;

• (b) to advise the Commission, at its request, in matters concerning the coordination group of notified bodies as established pursuant to Article 49;

• (c) to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;

• (d) to contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation (EU) 2017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex I to this Regulation;

• (e) to contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;

• (f) to assist the competent authorities of the Member States in their coordination activities in particular in the fields of classification and the determination of the regulatory status of devices, clinical investigations, vigilance and market surveillance including the development and maintenance of a framework for a European market surveillance programme with the objective of achieving efficiency and harmonisation of market surveillance in the Union, in accordance with Article 93;

• (g) to provide advice, either on its own initiative or at request of the Commission, in the assessment of any issue related to the implementation of this Regulation;

• (h) to contribute to harmonised administrative practice with regard to devices in the Member States.

Article 106

Provision of scientific, technical and clinical opinions and advice

The members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.

The Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.

• — physico-chemical characterisation, or

• — microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical biological and toxicological testing

of specific devices, categories or groups of devices.

The Commission shall only designate expert laboratories for which a Member State or the Joint Research Centre has submitted an application for designation.

• (a) have adequate and appropriately qualified staff with adequate knowledge and experience in the field of the devices for which they are designated;

• (b) possess the necessary equipment to carry out the tasks assigned to them;

• (c) have the necessary knowledge of international standards and best practices;

• (d) have an appropriate administrative organisation and structure;

• (e) ensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.

• (a) to provide scientific, technical and clinical assistance to the Commission and the MDCG in relation to the implementation of this Regulation;

• (b) to contribute to the development and maintenance of appropriate guidance and CS for:
• — clinical investigations,
• — clinical evaluation and PMCF,
• — performance studies,
• — performance evaluation and post-market performance follow-up,
• — physico-chemical characterisation, and
• — microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing for specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;

• (c) to develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;

• (d) to contribute to the development of standards at international level, ensuring that such standards reflect the state of the art;

• (e) to provide opinions in response to consultations by manufacturers in accordance with Article 61(2), notified bodies and Member States in accordance with paragraphs 11 to 13 of this Article.

• (f) to contribute to identification of concerns and emerging issues on the safety and performance of medical devices;

• (g) to provide views in accordance with Article 48(4) of Regulation (EU) 2017/746 on the performance evaluation of certain in vitro diagnostic medical devices.

The Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article 109. The clinical evaluation guidance referred to in point (c) of paragraph 10 shall be published following consultation with the MDCG.

The fees related to the advice provided by expert panels are payable to EMA pursuant to Article 30, point (f), of Regulation (EU) 2022/123 of the European Parliament and of the Council ([^E0005]).

The fees related to the advice provided by expert laboratories are payable to the Commission.

Article 107

Conflict of interests

Article 108

Device registers and databanks

The Commission and the Member States shall take all appropriate measures to encourage the establishment of registers and databanks for specific types of devices setting common principles to collect comparable information. Such registers and databanks shall contribute to the independent evaluation of the long-term safety and performance of devices, or the traceability of implantable devices, or all of such characteristics.

CHAPTER IX CONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES

Article 109

Confidentiality

• (a) personal data, in accordance with Article 110;

• (b) commercially confidential information and trade secrets of a natural or legal person, including intellectual property rights; unless disclosure is in the public interest;

• (c) the effective implementation of this Regulation, in particular for the purpose of inspections, investigations or audits.

Article 110

Data protection

Article 111

Levying of fees

Article 112

Funding of activities related to designation and monitoring of notified bodies

The costs associated with joint assessment activities shall be covered by the Commission. The Commission shall, by means of implementing acts, lay down the scale and structure of recoverable costs and other necessary implementing rules. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).

Article 113

Penalties

The Member States shall lay down the rules on penalties applicable for infringement of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate, and dissuasive. The Member States shall notify the Commission of those rules and of those measures by  25 February 2021 and shall notify it, without delay, of any subsequent amendment affecting them.

CHAPTER X FINAL PROVISIONS

Article 114

Committee procedure

Where the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph of Article 5(4) of Regulation (EU) No 182/2011 shall apply.

Article 115

Exercise of the delegation

Article 116

Separate delegated acts for different delegated powers

The Commission shall adopt a separate delegated act in respect of each power delegated to it pursuant to this Regulation.

Article 117

Amendment to Directive 2001/83/EC

In Annex I to Directive 2001/83/EC, point 12 of Section 3.2. is replaced by the following:

‘(12)Where, in accordance with the second subparagraph of Article 1(8) or the second subparagraph of Article 1(9) of Regulation (EU) 2017/745 of the European Parliament and of the Council ([^E0006]), a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation contained in the manufacturer's EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE marking to the medical device.

If the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) 2017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.

Article 118

Amendment to Regulation (EC) No 178/2002

In the third paragraph of Article 2 of Regulation (EC) No 178/2002, the following point is added:

‘(i)medical devices within the meaning of Regulation (EU) 2017/745 of the European Parliament and of the Council ([^E0007]).

Article 119

Amendment to Regulation (EC) No 1223/2009

In Article 2 of Regulation (EC) No 1223/2009, the following paragraph is added:

‘4. The Commission may, at the request of a Member State or on its own initiative, adopt the necessary measures to determine whether or not a specific product or group of products falls within the definition ‘cosmetic product’. Those measures shall be adopted in accordance with the regulatory procedure referred to in Article 32(2).’.

Article 120

Transitional provisions

Certificates issued by notified bodies in accordance with Directives 90/385/EEC and 93/42/EEC from 25 May 2017 that were still valid on 26 May 2021 and that have not been withdrawn afterwards shall remain valid after the end of the period indicated on the certificate until the date set out in paragraph 3a of this Article applicable for the relevant risk class of the devices. Certificates issued by notified bodies in accordance with those Directives from 25 May 2017 that were still valid on 26 May 2021 and that have expired before 20 March 2023 shall be considered to be valid until the dates set out in paragraph 3a of this Article only if one of the following conditions is fulfilled:

• (a) before the date of expiry of the certificate, the manufacturer and a notified body have signed a written agreement in accordance with Section 4.3, second subparagraph, of Annex VII to this Regulation for the conformity assessment in respect of the device covered by the expired certificate or in respect of a device intended to substitute that device;

• (b) a competent authority of a Member State has granted a derogation from the applicable conformity assessment procedure in accordance with Article 59(1) of this Regulation or has required the manufacturer, in accordance with Article 97(1) of this Regulation, to carry out the applicable conformity assessment procedure.

3a. Devices which have a certificate that was issued in accordance with Directive 90/385/EEC or Directive 93/42/EEC and that is valid by virtue of paragraph 2 of this Article may be placed on the market or put into service until the following dates:

• (a) 31 December 2027, for all class III devices, and for class IIb implantable devices except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors;

• (b) 31 December 2028, for class IIb devices other than those covered by point (a) of this paragraph, for class IIa devices, and for class I devices placed on the market in sterile condition or having a measuring function.

3b. Devices for which the conformity assessment procedure pursuant to Directive 93/42/EEC did not require the involvement of a notified body, for which the declaration of conformity was drawn up prior to 26 May 2021 and for which the conformity assessment procedure pursuant to this Regulation requires the involvement of a notified body, may be placed on the market or put into service until 31 December 2028.

3c. Devices referred to in paragraphs 3a and 3b of this Article may be placed on the market or put into service until the dates referred to in those paragraphs only if the following conditions are met:

• (a) those devices continue to comply with Directive 90/385/EEC or Directive 93/42/EEC, as applicable;

• (b) there are no significant changes in the design and intended purpose;

• (c) the devices do not present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health;

• (d) no later than 26 May 2024, the manufacturer has put in place a quality management system in accordance with Article 10(9);

• (e) no later than 26 May 2024, the manufacturer or the authorised representative has lodged a formal application with a notified body in accordance with Section 4.3, first subparagraph, of Annex VII for conformity assessment in respect of a device referred to in paragraph 3a or 3b of this Article or in respect of a device intended to substitute that device, and, no later than 26 September 2024, the notified body and the manufacturer have signed a written agreement in accordance with Section 4.3, second subparagraph, of Annex VII.

3d. By way of derogation from paragraph 3 of this Article, the requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply to devices referred to in paragraphs 3a and 3b of this Article in place of the corresponding requirements in Directives 90/385/EEC and 93/42/EEC.

3e. Without prejudice to Chapter IV and paragraph 1 of this Article, the notified body that issued the certificate referred to in paragraph 3a of this Article shall continue to be responsible for the appropriate surveillance in respect of the applicable requirements relating to the devices it has certified, unless the manufacturer has agreed with a notified body designated in accordance with Article 42 that the latter shall carry out such surveillance.

No later than 26 September 2024, the notified body that has signed the written agreement referred to in paragraph 3c, point (e), of this Article shall be responsible for the surveillance in respect of the devices covered by the written agreement. Where the written agreement covers a device intended to substitute a device which has a certificate that was issued in accordance with Directive 90/385/EEC or Directive 93/42/EEC, the surveillance shall be conducted in respect of the device that is being substituted.

The arrangements for the transfer of the surveillance from the notified body that issued the certificate to the notified body designated in accordance with Article 42 shall be clearly defined in an agreement between the manufacturer and the notified body designated in accordance with Article 42 and, where practicable, the notified body that issued the certificate. The notified body designated in accordance with Article 42 shall not be responsible for conformity assessment activities carried out by the notified body that issued the certificate.

3f. By way of derogation from Article 5, class III custom-made implantable devices may be placed on the market or put into service until 26 May 2026 without a certificate issued by a notified body in accordance with the conformity assessment procedure referred to in Article 52(8), second subparagraph, provided that no later than 26 May 2024, the manufacturer or the authorised representative has lodged a formal application with a notified body in accordance with Section 4.3, first subparagraph, of Annex VII for conformity assessment, and, no later than 26 September 2024, the notified body and the manufacturer have signed a written agreement in accordance with Section 4.3, second subparagraph, of Annex VII.

Article 121

Evaluation

By 27 May 2027, the Commission shall assess the application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation. Special attention shall be given to the traceability of medical devices through the storage, pursuant to Article 27, of the UDI by economic operators, health institutions and health professionals.

Article 122

Repeal

Without prejudice to Article 120(3) to (3e) and (4) of this Regulation, and without prejudice to the obligations of the Member States and manufacturers as regards vigilance and to the obligations of manufacturers as regards the making available of documentation, under Directives 90/385/EEC and 93/42/EEC, those Directives are repealed with effect from 26 May 2021, with the exception of:

• — Articles 8 and 10, Article 10b(1), points (b) and (c), and Article 10b(2) and (3) of Directive 90/385/EEC, Article 10, Article 14a(1), points (c) and (d), Article 14a(2) and (3) and Article 15 of Directive 93/42/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes to those Directives, which are repealed, as applicable, with effect from the date referred to in Article 123(3), point (d), of this Regulation in respect of the application of the obligations and requirements that relate to the electronic systems referred to in Article 33(2), points (e) and (f), respectively, of this Regulation;

• — Article 10a, Article 10b(1), point (a), and Article 11(5) of Directive 90/385/EEC, Article 14(1) and (2), Article 14a(1), points (a) and (b), and Article 16(5) of Directive 93/42/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes to those Directives, which are repealed, as applicable, with effect from the date referred to in Article 123(3), point (d), of this Regulation in respect of the application of the obligations and requirements that relate to the electronic systems referred to in Article 33(2), points (a) to (d), respectively, of this Regulation;

• — Article 9(9) of Directive 90/385/EEC and Article 11(13) of Directive 93/42/EEC, which are repealed with effect from 24 April 2020.

As regards the devices referred to in Article 120(3) to (3e) and (4) of this Regulation, the Directives referred to in the first paragraph of this Article shall continue to apply to the extent necessary for the application of those paragraphs.

Notwithstanding the first paragraph, Regulations (EU) No 207/2012 and (EU) No 722/2012 shall remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.

References to the repealed Directives shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex XVII to this Regulation.

Article 123

Entry into force and date of application

• (a) Articles 35 to 50 shall apply from 26 November 2017. However, from that date until  26 May 2021, the obligations on notified bodies pursuant to Articles 35 to 50 shall apply only to those bodies which submit an application for designation in accordance with Article 38;

• (b) Articles 101 and 103 shall apply from 26 November 2017;

• (c) Article 102 shall apply from 26 May 2018;

• (d) without prejudice to the obligations of the Commission pursuant to Article 34, the obligations and requirements that relate to any of the electronic systems referred to in Article 33(2) shall apply from the date corresponding to 6 months from the date of publication of the notice referred to in Article 34(3), informing that the relevant electronic system is functional and meets the functional specifications drawn up pursuant to Article 34(1). The provisions referred to in the preceding sentence are:
• — Article 29,
• — Article 31,
• — Article 32,
• — Article 33(4),
• — the second sentence of Article 40(2),
• — Article 42(10),
• — Article 43(2),
• — the second subparagraph of Article 44(12),
• — points (d) and (e) of Article 46(7),
• — Article 53(2),
• — Article 54(3),
• — Article 55(1),
• — Article 56(5),
• — Articles 70 to 77,
• — Article 78(1) to (13), without prejudice to Article 78(14),
• — Articles 79 to 82,
• — Article 86(2),
• — Articles 87 and 88,
• — Article 89(5) and (7), and the third subparagraph of Article 89(8),
• — Article 90,
• — Article 93(4), (7) and (8),
• — Article 95(2) and (4),
• — the last sentence of Article 97(2),
• — Article 99(4),
• — Article 120(3d). Until the date of application of the provisions referred to in the first subparagraph of this point, the corresponding provisions of Directives 90/385/EEC and 93/42/EEC regarding information on vigilance reporting, clinical investigations, registration of devices and economic operators, and certificate notifications shall continue to apply.

• (e) no later than 12 months from the date of publication of the notice referred to in Article 34(3) in respect of the electronic system referred to in Article 33(2), points (a) and (b), manufacturers shall ensure that the information to be entered in Eudamed in accordance with Article 29 is entered in that electronic system, including regarding the following devices, provided that those devices are also placed on the market from 6 months from the date of publication of that notice:
• (i) devices, other than custom-made devices, for which the manufacturer has undertaken a conformity assessment in accordance with Article 52;
• (ii) devices, other than custom-made devices, placed on the market pursuant to Article 120(3), (3a) or (3b), unless the device, for which the manufacturer has undertaken a conformity assessment in accordance with Article 52, is already registered in Eudamed;

• (ea) no later than 18 months from the date of publication of the notice referred to in Article 34(3) in respect of the electronic system referred to in Article 33(2), point (d), notified bodies shall ensure that the information to be entered in Eudamed in accordance with Article 56(5) is entered in that electronic system, including regarding devices referred to in point (e)(i) of this paragraph; for those devices, only the latest relevant certificate and, where applicable, any subsequent decision taken by the notified body related to such certificate shall be entered;

• (eb) by way of derogation from point (d), first subparagraph, of this paragraph, the obligations to upload the summary of safety and clinical performance in accordance with Article 32(1) and to notify competent authorities in accordance with Article 55(1), through the electronic system referred in Article 33(2), point (d), shall apply to devices referred to in point (e) of this paragraph when the certificate is entered in Eudamed in accordance with point (ea) of this paragraph;

• (ec) without prejudice to point (d), first subparagraph, of this paragraph, when a manufacturer is to submit a PSUR in accordance with Article 86(2) of this Regulation, to report a serious incident or a field safety corrective action in accordance with Article 87 of this Regulation, or to submit a trend report in accordance with Article 88 of this Regulation through the electronic system referred to in Article 33(2), point (f), of this Regulation, it shall also register the device, which is the subject of the PSUR or the vigilance reporting, in the electronic system referred to in Article 33(2), points (a) and (b), of this Regulation, except if such device was placed on the market in accordance with Directive 90/385/EEC or 93/42/EEC;

• (f) for implantable devices and for class III devices Article 27(4) shall apply from 26 May 2021. For class IIa and class IIb devices Article 27(4) shall apply from 26 May 2023. For class I devices Article 27(4) shall apply from 26 May 2025;

• (g) with regard to reusable devices that are required to bear the UDI carrier on the device itself, Article 27(4) shall apply to:
• (i) implantable devices and class III devices from 26 May 2023;
• (ii) class IIa and class IIb devices from 26 May 2025;
• (iii) class I devices from 26 May 2027;

• (i) Article 120(12) shall apply from 26 May 2019;

• (j) Article 59 shall apply from 24 April 2020.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

ANNEXES

I	General safety and performance requirements
II	Technical documentation
III	Technical documentation on post-market surveillance
IV	EU declaration of conformity
V	CE marking of conformity
VI	Information to be submitted upon the registration of devices and economic operators in accordance with Articles 29(4) and 31; core data elements to be provided to the UDI database together with the UDI-DI in accordance with Articles 28 and 29;and the UDI system
VII	Requirements to be met by notified bodies
VIII	Classification rules
IX	Conformity assessment based on a quality management system and assessment of the technical documentation
X	Conformity assessment based on type examination
XI	Conformity assessment based on product conformity verification
XII	Certificates issued by a notified body
XIII	Procedure for custom-made devices
XIV	Clinical evaluation and post-market clinical follow-up
XV	Clinical investigations
XVI	List of groups of products without an intended medical purpose referred to in Article 1(2)
XVII	Correlation table

ANNEX I

GENERAL SAFETY AND PERFORMANCE REQUIREMENTS

CHAPTER I

GENERAL REQUIREMENTS

• 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.

• 1. 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.

• 1. 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, 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.

• 1. 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, 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.

• 1. 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).

• 1. 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.

• 1. 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.

• 1. All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use.

• 1. For the devices referred to in Annex XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product's use which is consistent with a high level of protection for the safety and health of persons.

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/or physical 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 ([^E0008]), or

• (b) substances which are classified as endocrine disruptors for human health, of Category 1, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council ([^E0009]) and 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 ([^E0010]) or substances having endocrine-disrupting properties relevant to human health identified in accordance with Regulation (EU) No 528/2012 of the European Parliament and the Council ([^E0011]).

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

The justification for the presence of such substances shall be based upon:

• (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 particularly vulnerable to such substances and/or materials; and

• (d) where applicable and available, the latest relevant guidelines in accordance with Sections 10.4.3 and 10.4.4.

10.4.3.   Guidelines on phthalates

When deemed appropriate based on the latest scientific evidence, but at least every 5 years, the Commission shall request the European Chemicals Agency (ECHA) to prepare and update guidelines on the benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in Section 10.4.1, points (a) and (b). The benefit-risk assessment shall consider 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 appropriate or when requested by the Commission, the ECHA shall consult the Committee for Risk Assessment and the Committee for Socio-economic Analysis.

10.4.4.   Guidelines on other CMR and endocrine-disrupting substances

In addition to the guidelines referred to in Section 10.4.3, the Commission shall request the ECHA to prepare such guidelines for other substances referred to in Section 10.4.1, points (a) and (b), where appropriate. Such guidelines shall be prepared in accordance with the process described in Section 10.4.3.

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 unintended cuts 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 as specimens 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.

• 1. 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.

• 1. 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 viruses and 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.

• 1. 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.