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. )

• — where applicable, an indication that the device contains or incorporates a medicinal substance, including a human blood or plasma derivative, or tissues or cells of human origin, or of animal origin as referred to in Regulation (EU) No 722/2012.

• 2.The manufacturer shall undertake to keep available for the competent national authorities documentation that indicates its manufacturing site or sites and allows an understanding to be formed of the design, manufacture and performance of the device, including the expected performance, so as to allow assessment of conformity with the requirements of this Regulation.

• 3.The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which are manufactured in accordance with the documentation referred to in Section 2.

• 4.The statement referred to in the introductory part of Section 1 shall be kept for a period of at least 10 years after the device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.

• Section 8 of Annex IX shall apply.

• 5.The manufacturer shall review and document experience gained in the post-production phase, including from PMCF as referred to in Part B of Annex XIV, and implement appropriate means to apply any necessary corrective action, In that context, it shall report in accordance with Article 87(1) to the competent authorities any serious incidents or field safety corrective actions or both as soon as it learns of them.

ANNEX XIV

CLINICAL EVALUATION AND POST-MARKET CLINICAL FOLLOW-UP

PART A

CLINICAL EVALUATION

• 1. To plan, continuously conduct and document a clinical evaluation, manufacturers shall:

• (a) establish and update a clinical evaluation plan, which shall include at least:
• — an identification of the general safety and performance requirements that require support from relevant clinical data;
• — a specification of the intended purpose of the device;
• — a clear specification of intended target groups with clear indications and contra-indications;
• — a detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;
• — a specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;
• — an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;
• — an indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed; and
• — a clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF as referred to in Part B of this Annex with an indication of milestones and a description of potential acceptance criteria;

• (b) identify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;

• (c) appraise all relevant clinical data by evaluating their suitability for establishing the safety and performance of the device;

• (d) generate, through properly designed clinical investigations in accordance with the clinical development plan, any new or additional clinical data necessary to address outstanding issues; and

• (e) analyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits.

• 1. The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device.

• 1. A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:

• — Technical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements;

• — Biological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables;

• — Clinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.

The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification. It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.

• 1. The results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a clinical evaluation report which shall support the assessment of the conformity of the device.

The clinical evidence together with non-clinical data generated from non-clinical testing methods and other relevant documentation shall allow the manufacturer to demonstrate conformity with the general safety and performance requirements and shall be part of the technical documentation for the device in question.

Both favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation.

PART B

POST-MARKET CLINICAL FOLLOW-UP

• 1. PMCF shall be understood to be a continuous process that updates the clinical evaluation referred to in Article 61 and Part A of this Annex and shall be addressed in the manufacturer's post-market surveillance plan. When conducting PMCF, the manufacturer shall proactively collect and evaluate clinical data from the use in or on humans of a device which bears the CE marking and is placed on the market or put into service within its intended purpose as referred to in the relevant conformity assessment procedure, with the aim of confirming the safety and performance throughout the expected lifetime of the device, of ensuring the continued acceptability of identified risks and of detecting emerging risks on the basis of factual evidence.

• 1. PMCF shall be performed pursuant to a documented method laid down in a PMCF plan.

• 6.1. The PMCF plan shall specify the methods and procedures for proactively collecting and evaluating clinical data with the aim of:

• (a) confirming the safety and performance of the device throughout its expected lifetime,

• (b) identifying previously unknown side-effects and monitoring the identified side-effects and contraindications,

• (c) identifying and analysing emergent risks on the basis of factual evidence,

• (d) ensuring the continued acceptability of the benefit-risk ratio referred to in Sections 1 and 9 of Annex I, and

• (e) identifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct.

• 6.2. The PMCF plan shall include at least:

• (a) the general methods and procedures of the PMCF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data;

• (b) the specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;

• (c) a rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);

• (d) a reference to the relevant parts of the clinical evaluation report referred to in Section 4 and to the risk management referred to in Section 3 of Annex I;

• (e) the specific objectives to be addressed by the PMCF;

• (f) an evaluation of the clinical data relating to equivalent or similar devices;

• (g) reference to any relevant CS, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and

• (h) a detailed and adequately justified time schedule for PMCF activities (e.g. analysis of PMCF data and reporting) to be undertaken by the manufacturer.

• 1. The manufacturer shall analyse the findings of the PMCF and document the results in a PMCF evaluation report that shall be part of the clinical evaluation report and the technical documentation.

• 1. The conclusions of the PMCF evaluation report shall be taken into account for the clinical evaluation referred to in Article 61 and Part A of this Annex and in the risk management referred to in Section 3 of Annex I. If, through the PMCF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them.

ANNEX XV

CLINICAL INVESTIGATIONS

CHAPTER I

GENERAL REQUIREMENTS

1. Ethical principles

Each step in the clinical investigation, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.

2. Methods

• 2.1. Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims regarding the safety, performance and aspects relating to benefit-risk of devices as referred to in Article 62(1); the clinical investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions. The rationale for the design and chosen statistical methodology shall be presented as further described in Section 3.6 of Chapter II of this Annex.

• 2.2. The procedures used to perform the clinical investigation shall be appropriate to the device under investigation.

• 2.3. The research methodologies used to perform the clinical investigation shall be appropriate to the device under investigation.

• 2.4. Clinical investigations shall be performed in accordance with the clinical investigation plan by a sufficient number of intended users and in a clinical environment that is representative of the intended normal conditions of use of the device in the target patient population. Clinical investigations shall be in line with the clinical evaluation plan as referred to in Part A of Annex XIV.

• 2.5. All the appropriate technical and functional features of the device, in particular those involving safety and performance, and their expected clinical outcomes shall be appropriately addressed in the investigational design. A list of the technical and functional features of the device and the related expected clinical outcomes shall be provided.

• 2.6. The endpoints of the clinical investigation shall address the intended purpose, clinical benefits, performance and safety of the device. The endpoints shall be determined and assessed using scientifically valid methodologies. The primary endpoint shall be appropriate to the device and clinically relevant.

• 2.7. Investigators shall have access to the technical and clinical data regarding the device. Personnel involved in the conduct of an investigation shall be adequately instructed and trained in the proper use of the investigational device, and as regards the clinical investigation plan and good clinical practice. This training shall be verified and where necessary arranged by the sponsor and documented appropriately.

• 2.8. The clinical investigation report, signed by the investigator, shall contain a critical evaluation of all the data collected during the clinical investigation, and shall include any negative findings.

CHAPTER II

DOCUMENTATION REGARDING THE APPLICATION FOR CLINICAL INVESTIGATION

For investigational devices covered by Article 62, the sponsor shall draw up and submit the application in accordance with Article 70 accompanied by the following documents:

1. Application form

The application form shall be duly filled in, containing information regarding:

• 1.1. name, address and contact details of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative in accordance with Article 62(2) established in the Union;

• 1.2. if different from those in Section 1.1, name, address and contact details of the manufacturer of the device intended for clinical investigation and, if applicable, of its authorised representative;

• 1.3. title of the clinical investigation;

• 1.4. status of the clinical investigation application (i.e. first submission, resubmission, significant amendment);

• 1.5. details and/or reference to the clinical evaluation plan;

• 1.6. If the application is a resubmission with regard to a device for which an application has been already submitted, the date or dates and reference number or numbers of the earlier application or in the case of significant amendment, reference to the original application. The sponsor shall identify all of the changes from the previous application together with a rationale for those changes, in particular, whether any changes have been made to address conclusions of previous competent authority or ethics committee reviews;

• 1.7. if the application is submitted in parallel with an application for a clinical trial in accordance with Regulation (EU) No 536/2014, reference to the official registration number of the clinical trial;

• 1.8. identification of the Member States and third countries in which the clinical investigation is to be conducted as part of a multicentre or multinational study at the time of application;

• 1.9. a brief description of the investigational device, its classification and other information necessary for the identification of the device and device type;

• 1.10. information as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;

• 1.11. summary of the clinical investigation plan including the objective or objectives of the clinical investigation, the number and gender of subjects, criteria for subject selection, whether there are subjects under 18 years of age, design of the investigation such as controlled and/or randomised studies, planned dates of commencement and of completion of the clinical investigation;

• 1.12. if applicable, information regarding a comparator device, its classification and other information necessary for the identification of the comparator device;

• 1.13. evidence from the sponsor that the clinical investigator and the investigational site are capable of conducting the clinical investigation in accordance with the clinical investigation plan;

• 1.14. details of the anticipated start date and duration of the investigation;

• 1.15. details to identify the notified body, if already involved at the stage of application for a clinical investigation;

• 1.16. confirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and

• 1.17. the statement referred to in Section 4.1.

2. Investigator's Brochure

The investigator's brochure (IB) shall contain the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application. Any updates to the IB or other relevant information that is newly available shall be brought to the attention of the investigators in a timely manner. The IB shall be clearly identified and contain in particular the following information:

• 2.1. Identification and description of the device, including information on the intended purpose, the risk classification and applicable classification rule pursuant to Annex VIII, design and manufacturing of the device and reference to previous and similar generations of the device.

• 2.2. Manufacturer's instructions for installation, maintenance, maintaining hygiene standards and for use, including storage and handling requirements, as well as, to the extent that such information is available, information to be placed on the label, and instructions for use to be provided with the device when placed on the market. In addition, information relating to any relevant training required.

• 2.3. Pre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in-design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.

• 2.4. Existing clinical data, in particular:
• — from relevant scientific literature available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of the device and/or of equivalent or similar devices;
• — other relevant clinical data available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of equivalent or similar devices of the same manufacturer, including length of time on the market and a review of performance, clinical benefit and safety-related issues and any corrective actions taken.

• 2.5. Summary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks, any undesirable side-effects, contraindications and warnings.

• 2.6. In the case of devices that incorporate a medicinal substance, including a human blood or plasma derivative or devices manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives, detailed information on the medicinal substance or on the tissues, cells or their derivatives, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to the substance or tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the device.

• 2.7. A list detailing the fulfilment of the relevant general safety and performance requirements set out in Annex I, including the standards and CS applied, in full or in part, as well as a description of the solutions for fulfilling the relevant general safety and performance requirements, in so far as those standards and CS have not or have only been partly fulfilled or are lacking.

• 2.8. A detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation and in particular information on any deviation from normal clinical practice.

3. Clinical Investigation Plan

The clinical investigation plan (CIP) shall set out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation. It shall contain in particular the information as laid down in this Annex. If part of this information is submitted in a separate document, it shall be referenced in the CIP.

3.1.   General

• 3.1.1. Single identification number of the clinical investigation, as referred to in Article 70(1).

• 3.1.2. Identification of the sponsor — name, address and contact details of the sponsor and, where applicable, the name, address and contact details of the sponsor's contact person or legal representative in accordance with Article 62(2) established in the Union.

• 3.1.3. Information on the principal investigator at each investigational site, the coordinating investigator for the investigation, the address details for each investigational site and the emergency contact details for the principal investigator at each site. The roles, responsibilities and qualifications of the various kinds of investigators shall be specified in the CIP.

• 3.1.4. A brief description of how the clinical investigation is financed and a brief description of the agreement between the sponsor and the site.

• 3.1.5. Overall synopsis of the clinical investigation, in an official Union language determined by the Member State concerned.

• 3.2. Identification and description of the device, including its intended purpose, its manufacturer, its traceability, the target population, materials coming into contact with the human body, the medical or surgical procedures involved in its use and the necessary training and experience for its use, background literature review, the current state of the art in clinical care in the relevant field of application and the proposed benefits of the new device.

• 3.3. Risks and clinical benefits of the device to be examined, with justification of the corresponding expected clinical outcomes in the clinical investigation plan.

• 3.4. Description of the relevance of the clinical investigation in the context of the state of the art of clinical practice.

• 3.5. Objectives and hypotheses of the clinical investigation.

• 3.6. Design of the clinical investigation with evidence of its scientific robustness and validity.

• 3.6.1. General information such as type of investigation with rationale for choosing it, for its endpoints and for its variables as set out in the clinical evaluation plan.

• 3.6.2. Information on the investigational device, on any comparator and on any other device or medication to be used in the clinical investigation.

• 3.6.3. Information on subjects, selection criteria, size of investigation population, representativeness of investigation population in relation to target population and, if applicable, information on vulnerable subjects involved such as children, pregnant women, immuno-compromised or, elderly subjects.

• 3.6.4. Details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors.

• 3.6.5. Description of the clinical procedures and diagnostic methods relating to the clinical investigation and in particular highlighting any deviation from normal clinical practice.

• 3.6.6. Monitoring plan.

• 3.7. Statistical considerations, with justification, including a power calculation for the sample size, if applicable.

• 3.8. Data management.

• 3.9. Information about any amendments to the CIP.

• 3.10. Policy regarding follow-up and management of any deviations from the CIP at the investigational site and clear prohibition of use of waivers from the CIP.

• 3.11. Accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices.

• 3.12. Statement of compliance with the recognised ethical principles for medical research involving humans, and the principles of good clinical practice in the field of clinical investigations of devices, as well as with the applicable regulatory requirements.

• 3.13. Description of the Informed consent process.

• 3.14. Safety reporting, including definitions of adverse events and serious adverse events, device deficiencies, procedures and timelines for reporting.

• 3.15. Criteria and procedures for follow-up of subjects following the end, temporary halt or early termination of an investigation, for follow-up of subjects who have withdrawn their consent and procedures for subjects lost to follow-up. Such procedures shall for implantable devices, cover as a minimum traceability.

• 3.16. A description of the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects' participation in the clinical investigation and where it differs from that normally expected for the medical condition in question.

• 3.17. Policy as regards the establishment of the clinical investigation report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section 1 of Chapter I.

• 3.18. List of the technical and functional features of the device, with specific mention of those covered by the investigation.

• 3.19. Bibliography.

4. Other information

• 4.1. A signed statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.

• 4.2. Where applicable according to national law, copy of the opinion or opinions of the ethics committee or committees concerned. Where according to national law the opinion or opinions of the ethics committee or committees is not required at the time of the submission of the application, a copy of the opinion or opinions shall be submitted as soon as available.

• 4.3. Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article 69 and the corresponding national law.

• 4.4. Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document.

• 4.5. Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:

• — organisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;

• — a description of measures that will be implemented to ensure confidentiality of records and personal data of subjects; and

• — a description of measures that will be implemented in case of a data security breach in order to mitigate the possible adverse effects.

• 4.6. Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports, shall, upon request, be submitted to the competent authority reviewing an application.

CHAPTER III

OTHER OBLIGATIONS OF THE SPONSOR

• 1. The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor.

• 1. The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article 80(2) are reported by the investigator or investigators to the sponsor in a timely manner.

• 1. The documentation mentioned in this Annex shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.

Each Member State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph in case the sponsor, or its contact person or legal representative as referred to in Article 62(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period.

• 1. The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation.

• 1. The Sponsor shall complete the follow-up of investigation subjects.

• 1. The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection.

• 1. The Sponsor shall prepare a clinical investigation report which includes at least the following:

• — Cover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.

• — Details of the author and date of the report.

• — A summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.

• — Investigational device description, in particular clearly defined intended purpose.

• — A summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.

• — Results of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.

• — Summary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.

• — Discussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.

ANNEX XVI

LIST OF GROUPS OF PRODUCTS WITHOUT AN INTENDED MEDICAL PURPOSE REFERRED TO IN ARTICLE 1(2)

• 1.Contact lenses or other items intended to be introduced into or onto the eye.

• 2.Products intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.

• 3.Substances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing.

• 4.Equipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.

• 5.High intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.

• 6.Equipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain.

ANNEX XVII

CORRELATION TABLE

Council Directive 90/385/EEC	Council Directive 93/42/EEC	This Regulation
Article 1(1)	Article 1(1)	Article 1(1)
Article 1(2)	Article 1(2)	Article 2
Article 1(3)	Article 1(3) first subparagraph	Article 1(9) first subparagraph
—	Article 1(3) second subparagraph	Article 1(9) second subparagraph
Article 1(4) and (4a)	Article 1(4) and (4a)	Article 1(8) first subparagraph
Article 1(5)	Article 1(7)	Article 1(11)
Article 1(6)	Article 1(5)	Article 1(6)
—	Article 1(6)	—
—	Article 1(8)	Article 1(13)
Article 2	Article 2	Article 5(1)
Article 3 first paragraph	Article 3 first paragraph	Article 5(2)
Article 3 second paragraph	Article 3 second paragraph	Article 1(12)
Article 4(1)	Article 4(1)	Article 24
Article 4(2)	Article 4(2)	Article 21(1) and (2)
Article 4(3)	Article 4(3)	Article 21(3)
Article 4(4)	Article 4(4)	Article 10(11)
Article 4(5)(a)	Article 4(5) first subparagraph	Article 20(6)
Article 4(5)(b)	Article 4(5) second subparagraph	—
Article 5(1)	Article 5(1)	Article 8(1)
Article 5(2)	Article 5(2)	Article 8(2)
Article 6(1)	Articles 5(3) and 6	—
Article 6(2)	Article 7(1)	Article 114
Article 7	Article 8	Articles 94 to 97
—	Article 9	Article 51
Article 8(1)	Article 10(1)	Articles 87(1) and 89 (2)
Article 8(2)	Article 10(2)	Article 87(10) and Article 87(11) first subparagraph
Article 8(3)	Article 10(3)	Article 89(7)
Article 8(4)	Article 10(4)	Article 91
Article 9(1)	Article 11(1)	Article 52(3)
—	Article 11(2)	Article 52(6)
—	Article 11(3)	Article 52(4) and (5)
—	Article 11(4)	—
—	Article 11(5)	Article 52(7)
Article 9(2)	Article 11 (6)	Article 52(8)
Article 9(3)	Article 11(8)	Article 11(3)
Article 9(4)	Article 11(12)	Article 52(12)
Article 9(5)	Article 11(7)	—
Article 9(6)	Article 11(9)	Article 53(1)
Article 9(7)	Article 11(10)	Article 53(4)
Article 9(8)	Article 11(11)	Article 56(2)
Article 9(9)	Article 11(13)	Article 59
Article 9(10)	Article 11(14)	Article 4(5) and Article 122 third paragraph
—	Article 12	Article 22
—	Article 12a	Article 17
Article 9a(1) first indent	Article 13(1)(c)	—
Article 9a(1) second indent	Article 13(1)(d)	Article 4(1)
—	Article 13(1)(a)	Article 51(3)(a) and Article 51(6)
—	Article 13(1)(b)	Article 51(3)(b) and Article 51(6)
Article 10	Article 15	Articles 62 to 82
Article 10a(1), second sentence of Article 10a(2) and Article 10a(3)	Article 14(1), second sentence of Article 14(2) and Article 14(3)	Articles 29(4), 30 and 31
Article 10a(2), first sentence	Article 14(2) first sentence	Article 11(1)
Article 10b	Article 14a	Articles 33 and 34
Article 10c	Article 14b	Article 98
Article 11(1)	Article 16(1)	Articles 42 and 43
Article 11(2)	Article 16(2)	Article 36
Article 11(3)	Article 16(3)	Article 46(4)
Article 11(4)	Article 16(4)	—
Article 11(5)	Article 16(5)	Article 56(5)
Article 11(6)	Article 16(6)	Article 56(4)
Article 11(7)	Article 16(7)	Articles 38(2) and 44(2)
Article 12	Article 17	Article 20
Article 13	Article 18	Articles 94 to 97
Article 14	Article 19	Article 99
Article 15	Article 20	Article 109
Article 15a	Article 20a	Article 102
Article 16	Article 22	—
Article 17	Article 23	—
—	Article 21	—

[^E0001]: Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ L 136, 30.4.2004, p. 1).

[^E0002]: Directive 2006/42/EC of the European Parliament and of the Council of 17 May 2006 on machinery, and amending Directive 95/16/EC (OJ L 157, 9.6.2006, p. 24).

[^E0003]: Commission Recommendation 2003/361/ΕC of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises (OJ L 124, 20.5.2003, p. 36).

[^E0004]: Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 27.5.2014, p. 1).

[^E0005]: Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a reinforced role for the European Medicines Agency in crisis preparedness and management for medicinal products and medical devices (OJ L 20, 31.1.2022, p. 1).

[^E0006]: 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 (OJ L 117, 5.5.2017, p. 1).’.

[^E0007]: 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 (OJ L 117, 5.5.2017, p. 1).’.

[^E0008]: 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).

[^E0009]: 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, ELI: http://data.europa.eu/eli/reg/2008/1272/oj).

[^E0010]: 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), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (OJ L 396, 30.12.2006, p. 1, ELI: http://data.europa.eu/eli/reg/2006/1907/oj).

[^E0011]: 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, ELI: http://data.europa.eu/eli/reg/2012/528/oj).

[^E0012]: 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).

[^E0013]: Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ L 50, 20.2.2004, p. 44).