Law 14/1986, of 25 April, General of Health, attributes to the State Administration, in its Article 40.5, the regulation, authorization and registration or approval, as appropriate, of those products and sanitary articles that by affecting the human being they may pose a risk to the health of the people. Article 110 of the same law entrusts the State Health Administration to assess the safety, efficacy and efficiency of health and health care technologies.

On the other hand, Law 25/1990 of 20 December of the Medicamento, in its article 1.3, states that, inter alia, the regulation of principles, standards, criteria and basic requirements on efficiency, safety and quality of medical devices, since, as stated in their explanatory statement, they must be achieved for the same purposes as those which the Law seeks for medicinal products. That Law empowers the Government, in its third subparagraph, paragraph 2, to determine those medical devices to be approved, approved or certified by the State, in view of their particular risk or importance for the health. In addition, in Article 8.12, it contains the definition of a health product, which corresponds literally to that laid down in Community legislation.

Among the different kinds of medical devices are the active implantables, whose two fundamental characteristics consist, of a part, in that they are intended to be introduced totally or partially into the human body. to remain in the implanted, and of another, in which its functioning depends on the electricity or any other source of energy other than that generated by the human body or by gravity.

With regard to these products, the Council of the European Communities has adopted Directive 90 /385/EEC of 20 June on the approximation of the laws of the Member States relating to medical devices active implantable, with the objectives of ensuring their free movement within the Community territory and at the same time offering a high level of protection for patients, users and third parties, achieving the assigned performance when they are implanted in the human body. These objectives are achieved through the fulfilment of certain essential requirements.

To facilitate compliance with such essential requirements, reference to the harmonised standards developed by the European Committee for Standardisation (CEN) and the European Committee for Electrotechnical Standardisation is useful. (CENELEC), after the Commission's term of office, nevertheless retaining these rules as non-compulsory texts, with national rules being adopted by the State in application of these harmonised rules.

This Directive is incorporated into the national legal order by this Royal Decree, thus fulfilling the obligation laid down in Article 16.1 of the said Community provision.

This Royal Decree is dictated by the provisions of Article 149.1.10. and 16. of the Spanish Constitution and pursuant to Articles 40.5 and 6, 95 and 110 of Law 14/1986, of 25 April, General of Health, and in Articles 1.3, 2.2 and the third additional provision of Law 25/1990 of 20 December of the Medicinal product.

In its virtue, on the proposal of the Minister of Health and Consumer Affairs, the sectors affected, prior to the favorable report of the Interterritorial Council of the National Health System, according to the State Council deliberation of the Council of Ministers at its meeting of 30 April 1993,

D I S P O N G O:

Chapter I

General provisions

Article 1. Scope of application.

1. This Royal Decree lays down the conditions to be met by the active implantable medical devices for placing on the market and/or service, as well as the conformity assessment procedures applicable to them.

The conditions for their use in clinical research are also determined.

2. Where an active implantable medical device is intended for the administration of a medicinal product, it is necessary that the medicinal product has been authorised in accordance with the provisions of Law 25/1990 of 20 December 1990 on the medicinal product, and develop.

3. Where an active implantable medical device incorporates as an integral part a substance which may be used separately as a medicinal product, that product shall be assessed and authorised in accordance with the provisions of this Regulation. Royal Decree.

Article 2. Definitions.

For the purposes of this provision,

following definitions shall apply:

(a) : any instrument, device, equipment, material or other article, including accessories and software which are involved in the proper functioning of the device, intended by the manufacturer to be used in beings human, alone or in combination with others, for the purposes of:

1. Diagnosis, prevention, control, treatment or relief of a disease or injury.

2. Research, replacement or modification of the anatomy or a physiological process.

3. Regulation of conception.

And whose main action to obtain is not reached by pharmacological, chemical or immunological means, nor by metabolism, but whose function can be used by such means.

(b) : any sanitary product that is dependent on electricity or any other source of energy other than that generated directly by the human body or by gravity, to function appropriately.

(c) : any active medical device intended to be placed in whole or in part, by surgical or medical intervention, in the human body, or by medical intervention, in a natural orifice, and intended to remain after such intervention.

(d) : an active implantable medical device manufactured specifically according to the written prescription of a specialist practitioner, in which the characteristics are recorded under his/her responsibility; specific to the design and that is intended only for a particular patient.

e)

: any active implantable medical device intended to be made available to an optional specialist to be the subject of human research carried out in a suitable clinical setting and for whose experimentation is complied with the provisions of this Royal Decree and Title III of Law 25/1990 of 20 December, of the Medicamento, and provisions that develop it.

(f) : the use to be given to the medical device and for which the product is suitable, as indicated by the manufacturer in the instructions for use.

g) : making optional staff available for deployment.

Chapter II

Sanitary guarantees for products

Article 3. Health and safety guarantees.

1. Active implantable medical devices and bespoke medical devices can only be placed on the market and put into service if, implanted and properly maintained and used in accordance with their destination, they do not compromise safety or health of patients, users and, where appropriate, third parties.

2. In accordance with Article 100 of Law 14/1986 of 25 April 1986, General Health, the manufacture of the implantable medical devices active on national territory will require a prior operating licence of the installation, granted by the Directorate-General for Pharmacy and Health Products.

Article 4. Essential requirements.

1. The medical devices referred to in Article 2 (c), (d) and (e) of this Royal Decree, hereinafter to as 'the medical devices', shall be designed and constructed in such a way that their use does not compromise the clinical condition or safety of the patients, when they are put in place under the conditions and for the intended purposes. They shall not present any risks to persons who implement them or, where appropriate, third parties.

2. The products shall provide the services assigned to them by the manufacturer, that is to say, designed and manufactured in such a way as to enable them to perform one or more of the functions referred to in Article 2 (a), and such as the manufacturer has specified them.

3. The general requirements referred to in paragraphs 1 and 2 of this Article shall not be altered to such a degree as to be compromised by the clinical status and safety of patients and, where appropriate, third parties, for the duration of the period of the validity provided for by the manufacturer, and even if the product is subject to the limit situations resulting from the normal conditions of use.

4. Products must be designed, manufactured and conditioned in such a way that their characteristics and performance are not altered by the storage and transport conditions provided for by the manufacturer (temperature, humidity, etc.).

5. The relationship between benefit and risk must be assessed, so that any undesirable side effects are acceptable risks in relation to the benefits attributed.

6. The products shall meet the essential requirements laid down in Annex I which apply to them, taking into account the destination of the products concerned.

7. Compliance with the requirements set out in this Article, under normal conditions of use, shall be demonstrated by clinical data obtained in accordance with Annex VII.

Article 5. .

1. Only active implantable medical devices bearing the marking may be placed on the market and put into service, and the conformity assessment procedures referred to in Article 6 of this provision have been followed.

The health products to be measured and those intended for clinical investigation shall be governed by the provisions of Article 7.

2. The marking of conformity, as reproduced in Annex IX, must be affixed to the packaging of the product which ensures sterility, in a visible, legible and indelible manner; it shall also be placed on the outer packaging, if any, and on the package leaflet.

3. The marking shall be accompanied by the identification of the notified body responsible for the implementation of the assessment procedures set out in the Annexes, as appropriate.

4. No other marking may be affixed to the product which may lead to confusion with the marking of conformity.

Article 6. Conditions for the placement of the markup.

The manufacturer, for the purposes of affixing the marking , shall opt for any of the following conformity assessment procedures, which shall be developed by any of the listed organisms which are This effect is published in the :

(a) EC declaration of conformity, as set out in Annex II.

(b) EC model examination, as set out in Annex III. This procedure will be complemented by any of the following procedures:

1. EC verification, as set out in Annex IV.

2. EC declaration of conformity with the model, set out in Annex V.

Article 7. Special purpose products.

1. At fairs, exhibitions and demonstrations, products which do not comply with the provisions of this Royal Decree may be presented, provided that they are shown in a sufficiently visible sign, placed on or next to the products themselves, clearly that such products cannot be placed on the market or put into service until their conformity is declared.

2. Custom products and products intended for clinical research shall be considered as products of special use, for the purposes of this provision, and shall not be provided with the marking , nor shall the communication provided for in this Article be applied. Article 9.

3. The products shall comply with the requirements set out in Annex VI as a precondition for placing on the market and/or in service.

4. Products intended for clinical research may only be made available to medical practitioners if this research has the favourable opinion of the Ethical Committee referred to in Article 64 of Law 25/1990 of 20 December 1990. Medicinal product and its development provisions. This forecast will be extended to changes in ongoing clinical investigations that may lead to increased risk for the subjects involved in the trial.

5. The conduct of the clinical investigations shall be in accordance with Annex VII. At least 60 days before the start of the same, the sponsor shall inform the General Directorate of Pharmacy and Health Products, accompanying the documentation set out in Annex VI. This communication shall be carried out without prejudice to the communication required by the health authority of the Autonomous Community concerned.

6. The clinical investigation in question may be initiated after a period of 60 days from the date of entry of the communication in the Directorate-General for Pharmacy and Health Products, except where the latter has communicated within this period a a decision to the contrary based on public or public health considerations.

7. If the documentation submitted is not complete or additional information is required, it shall be requested in writing from the sponsor. In this case, the period of sixty days shall be interrupted on the date of issue of the written document and shall be reinitiated from the date of entry into the General Directorate of Pharmacy and Health Products of the last information requested.

8. Any modification of a clinical investigation shall be communicated in accordance with the above procedure.

9. The Directorate General of Pharmacy and Health Products will keep an updated register, with all the clinical investigations reported.

Article 8. Presumption of conformity with the essential requirements.

1. Active implantable medical devices bearing the marking and having followed the conformity assessment procedures referred to in Article 6 shall be considered to be in conformity with the essential requirements, with the exception of indications reasonable against.

2. Where products comply with the relevant national rules which lay down harmonised standards, which satisfy certain essential requirements, they shall be presumed to comply with the essential requirements in question.

3. For the purposes of the preceding paragraph, the national rules and the harmonised standards are those whose reference numbers have been published in the Official Journal of the State and in the , respectively.

Chapter III

On the product market

Article 9. Communication of placing on the market and putting into service.

1. Any natural or legal person who, for the first time, makes available for distribution and/or use on national territory an active implantable medical device, whether for consideration or free of charge, shall direct a communication to the competent health authorities within a maximum of one month of the date on which they are made available.

2. The communication of active implantable medical devices from third countries and the communication of products from another Member State of the European Economic Community shall be carried out by means of the presentation of the documentation. directly in the Directorate-General of Pharmacy and Health Products.

3. The communication of active implantable medical devices manufactured in national territory shall be made by the presentation of the relevant documentation, in duplicate, to the body designated by the health authority of the Corresponding Autonomous Community, who shall immediately forward a copy thereof to the Directorate-General for Pharmacy and Health Products.

4. The Directorate-General for Pharmacy and Health Products shall keep up to date a register with all the communications referred to in the preceding paragraphs.

Article 10. Content of the communication.

1. The communication shall be made by means of the forms to be drawn up, which shall be completed, at least, in the official Spanish language of the State.

2. The following data shall be included in the following data:

a) Name and address of the person making the communication.

b) Category of the products in question.

c) Commercial name of the product.

d) Presentation and possible variants.

e) Description and destination of the product.

(f) Name and address or social reason of the manufacturer or his authorised representative and the place of manufacture.

g) The notified body/s that have/n intervened in the assessment for the purposes of marking the marking .

h) Labelling and instructions for use certified by the notified body.

(i) Labelling and instructions for use with which the product is to be marketed in Spain, in so far as the version in the official Spanish language of the State has not been certified by the notified body.

j) Date on which the product is placed on the market or in service in Spain.

3. Any modification of the data referred to in the preceding paragraph shall be communicated in accordance with the procedure laid down in Article 9 (2) and (3).

Article 11. Obligations of the person responsible for marketing.

1. The natural or legal person referred to in Article 9 shall keep a documented record of the products he or she distributes for use on national territory.

This record must contain at least the following data: product trade name, model, string, batch number, ship date, or customer supply and identification.

2. Whenever required, the person responsible shall provide the health authorities, for the exercise of their respective powers, with the documentation that guarantees the conformity of the products with the provisions of this Royal Decree. If the person responsible is not available for access to this documentation, it must be provided by the manufacturer.

3. If there is a reasoned doubt as to the conformity of a product, those health authorities may require the official Spanish language of the State of any information to be deemed necessary for the purpose of judging such conformity.

4. Refusal to provide the documentation referred to in this Article may be considered as a presumption of non-compliance with the essential requirements.

5. Where the affixing of the CE marking is established, the person responsible shall take the corrective or protective measures provided by the competent health authority.

6. In the event of suspicion or evidence of health risk, the person responsible shall implement any measure of restriction or monitoring of the use of the appropriate products, as well as those which, where appropriate, may be determined by such health authorities.

Article 12. Information to the Autonomous Communities.

The recording of the placing on the market, as provided for in Article 9 (4), shall be kept at the disposal of the competent health authorities of the Autonomous Communities.

Chapter IV

Distribution and Selling

Article 13. Distribution and sale.

1. The distribution and sale of the active implantable products, when carried out by different operators of the manufacturer established in Spanish territory, shall be carried out under the supervision of a responsible technician whose certification is adequate qualification, through the establishments which guarantee the proper storage and preservation of the products. Only products complying with this Royal Decree will be sold and distributed.

2. The distribution and sale establishments shall be subject to the supervision and inspection of the health authorities of the Autonomous Community concerned.

3. To this end, the establishments shall inform the health authorities of the Autonomous Community in advance of their existence and activity, by means of a written statement:

a) Identification of the establishment and its activity.

b) Identification of the responsible technician.

4. The establishment shall have the right organisation and means to take any measure that is appropriate in cases of potential risks related to the products.

Chapter V

Foreign trade

Article 14. Import.

Products imported from third countries may only be marketed and put into service in Spain if they comply with the requirements set out in this Royal Decree.

Article 15. Export.

Products that are manufactured for export to non-Community countries and do not comply with the requirements set out in this provision must be packaged and labelled in such a way that they are identified as (i) in order to prevent their use on the Community territory.

Chapter VI

Performances of Public Administrations

Article 16. Notified bodies.

1. The Ministry of Health and Consumer Affairs, heard by the Interterritorial Council of the National Health System, shall designate the bodies to carry out the conformity assessment procedures referred to in Article 6 and the specific tasks assigned to each body and shall notify the Commission of the European Communities and the other Member States thereof.

2. Notified bodies shall comply with the minimum requirements set out in Annex VIII. Bodies meeting the criteria laid down in the relevant harmonised standards shall be presumed to comply with the above minimum requirements.

3. Where a body has been designated and it is established that such a body no longer satisfies the minimum requirements listed in Annex VIII, the Ministry of Health and Consumer Affairs shall withdraw the authorisation, subject to the appropriate administrative procedure. with a hearing of the person concerned, and shall inform the Commission of the European Communities and the other Member States thereof.

4. In the event of the cessation of duties of a notified body, the Ministry of Health and Consumer Affairs shall take appropriate measures to ensure continuity in the management of conformity assessment procedures.

Article 17. Actions of the notified body.

1. The notified body shall verify that the product satisfies the essential requirements referred to in this Royal Decree and shall carry out the tasks provided for in the conformity assessment procedures chosen by the manufacturers.

2. The notified body and the manufacturer or his authorised representative established within the Community shall establish by common agreement the time limits for the completion of the conformity assessment procedures to which the products are to be submitted.

The documentation corresponding to these evaluation procedures will be drawn up, at least, in the official Spanish language of the State.

3. Where the notified body refuses any of the certificates or authorisations provided for in Annexes II and V, it shall forward a copy of the refusals to the Directorate-General for Pharmacy and Health Products.

4. Where it is found that the CE marking has been affixed unduly, the notified body concerned shall withdraw or temporarily suspend the relevant authorisation or certificate, informing the Directorate-General of the Pharmacy and Healthcare products.

5. Against the decisions taken by the notified body, in accordance with paragraphs 3 and 4 of this Article, the person concerned may express his disagreement with the body itself and, in the event of the disagreement, the General Secretariat of Health, which, after having been given the appropriate procedure with a hearing of the person concerned, shall decide within the maximum period of three months. An ordinary appeal may be brought against that decision within one month, in accordance with Article 114 of the Law on the Legal Regime of Public Administrations and the Common Administrative Procedure.

Article 18. Inspection.

1. The health authorities of the Autonomous Communities shall carry out periodic inspections to verify that the active implantable medical devices placed on the market and put into service are in conformity with this provision.

The infringement of the presentations provided for by this Royal Decree will result in the adoption by these authorities of the precise corrective measures, regardless of the penalties they have taken.

2. The Directorate-General for Pharmacy and Health Products may carry out inspection and control activities in respect of products intended for external trade and of establishments in which they are manufactured, provided that they are located in national territory. It may also carry out, without prejudice to the powers of other health authorities, the inspection and monitoring of clinical investigations of products which do not bear the CE marking.

3. The staff at the service of the Public Administrations who carry out the inspection functions shall proceed as laid down in Article 105 (3) of Law 25/1990 of 20 December of the Medication and may also request the responsible for the placing on the market of information on the documentation of products marketed in Spain and those submitted to clinical research.

Article 19. Surveillance system.

1. Where, on the occasion of their activity, the health professionals, the inspection authorities, the manufacturers or the persons responsible for the products warn of any dysfunction, alteration of the characteristics or performance of the product, as any inadequacy of the prospectus which may or may have resulted in the death or deterioration of a patient's health condition, shall inform the Directorate-General of Pharmacy and Health Products, where such data shall be evaluated and record. This communication shall be carried out without prejudice to the communication required by the health authority of the Autonomous Community concerned.

2. Similarly, the manufacturer or any other person responsible for the product shall notify the withdrawal of the market of a product caused by technical or health reasons related to one of the circumstances mentioned in the previous paragraph.

3. These facts and the measures taken shall be communicated to the Commission of the European Communities and to the other Member States by the Directorate-General for Pharmacy and Health Products.

Article 20. Precautionary measures.

1. As a guarantee of the health and safety of persons, the competent health authorities shall, when they consider an active implantable medical device or a tailor-made medical device, once put into service and used correctly. in accordance with its destination, it may compromise the health and/or safety of patients or third persons, it shall take the appropriate precautionary measures provided for in Article 26 of Law 14/1986 of 25 April, General of Health, and in the Article 106 of Law 25/1990 of 20 December of the Medication.

2. The Directorate-General for Pharmacy and Health Products shall be informed immediately by the health authority which adopted the measure, indicating the reasons for the precautionary measure.

3. The Directorate-General for Pharmacy and Health Products shall immediately inform the Commission of the European Communities of the measures taken.

4. Where a non-compliant product is marked , the health authorities of the Autonomous Community concerned shall take the appropriate measures against those who have placed the mark and shall inform the Directorate-General of Pharmacy and Sanitary Products. It shall be notified by the management centre to the Commission of the European Communities.

Article 21. Confidentiality.

The health authorities, without prejudice to the existing provisions on professional secrecy, shall ensure that all the parties to which the application of this Royal Decree is concerned maintain the confidentiality of any information obtained in the exercise of its function. This shall not affect the obligations of the notified bodies with regard to reciprocal information and the dissemination of warnings, or the reporting obligations incumbent upon the persons concerned, both before the health authority and before the courts.

Chapter VII

Advertising

Article 22. Advertising.

1. Advertising directed at the promotion of the products covered by this provision shall be governed by the general principles laid down in Law 34/1988 of 11 November 1988, General of Advertising, as well as in Article 102 of Law 14/1986, of 25 April, General of Health.

2. The means of information and promotion used as support, whether audiovisual or otherwise, will be basically scientific in character and will be directed and distributed exclusively to healthcare professionals.

3. In particular, advertising or promotional texts must indicate the contraindications and any possible side effects which may arise from the use of these products.

Chapter VIII

Violations and penalties

Article 23. Infringements.

The actions and omissions provided for in Article 35 of Law 14/1986 of 25 April, General of Health, and specifically the following shall be taken into consideration for violations of the provisions of this Royal Decree:

1. Minor infractions:

1. The presentation at fairs, exhibitions and demonstrations of products not suitable for placing on the market or in service, without the corresponding indication of their non-conformity or impossibility of putting into service.

2. Failure to fulfil the obligation to communicate the amendments relating to the information provided for in Article 10 of this Royal Decree.

3. Failure to comply with the requirements relating to the advertising and promotion of products.

2. Serious breaches:

1. The placing on the market or in service of products that do not meet all the essential requirements that apply to them, according to this Royal Decree.

2. The use of any other marking which may lead to confusion in the CE marking.

3. The placing on the market and/or in service of products which have not satisfied the conformity assessment procedures or which have not made the declarations which, if necessary, result from them being applied.

4. The conduct of clinical investigations without complying with the procedures and conditions provided for in this Royal Decree.

5. Failure to fulfil the obligation of communication of placing on the market and/or in service.

6. Failure to comply with the obligation to maintain the documented register provided for in Article 11.1 of this Royal Decree.

7. Failure to comply with the obligation to provide documentation as set out in Article 11 (2) and (3) of this Royal Decree.

8. Failure to comply with the conditions of distribution and sale set out in Article 13 of this Royal Decree.

9. Failure to fulfil the obligation of communication provided for in Article 19 of this Royal Decree.

10. The violation of the principle of confidentiality established in Article 21 of this Royal Decree.

3. Very serious breaches:

1. Placing on the market and/or in service of products that commit the following

or the health of patients, users, or third parties.

2. The misuse of the CE marking.

3. The conduct of clinical investigations without respect to the content of the protocols communicated, or without respecting the obligations relating to the consent of the persons subject to them or, where appropriate, their representative, or the substantial non-compliance with the duty of information on the clinical investigation in which it participates as a subject.

4. Failure to comply with the duty to implement the measures relating to Article 11.5 of this Royal Decree.

5. The incorrect execution, by the notified body, of the actions entrusted to it in Article 17 of this Royal Decree.

6. Failure to comply with the precautionary measures taken by the competent health authorities.

Article 24. Sanctions.

1. The actions and omissions constituting infringements, as provided for in Article 23 of this Royal Decree, shall be subject to the appropriate administrative penalties, subject to the appropriate procedure, without prejudice to the civil, criminal or other order responsibilities that may be present. The procedure for imposing sanctions shall be in accordance with the principles laid down in Title IX of the Law on the Legal Regime of Public Administrations and the Common Administrative Procedure.

2. The offences referred to in Article 23 of this Royal Decree shall be sanctioned by fine in accordance with the graduation laid down in Article 36 of Law 14/1986 of 25 April, General of Health.

Additional disposition first. Basic character.

1. They have the status of legislation on pharmaceutical products, in accordance with the provisions of Article 149.1.16 of the Constitution and Article 2.1 of Law 25/1990 of 20 December of the European Medicines, Article 1 (2) of the present Royal Decree.

2. They have the status of basic health standards, as set out in Articles 149.1.1. and 16. of the Constitution, 2.2 of Law 25/1990, of 20 December, of the Medicamento, and 40.5 and 110 of Law 14/1986, of 25 April, General of Health, all other articles, provisions and annexes of this Royal Decree. Articles 14 and 15 of this Royal Decree are issued under the exclusive and full jurisdiction of the State to regulate foreign trade, in accordance with Article 149.1.10. of the Constitution.

Additional provision second. Health Services planning criteria.

The provisions of this Royal Decree will not affect the planning criteria of the Health Services to be adopted by the competent health authorities.

Additional provision third. Evaluation procedures.

The implementation of the conformity assessment procedures referred to in Article 6 of this provision, which, on a binding basis, must be carried out for the affixing of the CE marking, shall be independent of the (i) certification that in the field of industrial quality is stated in Law 21/1992, of 16 July, of Industry.

Additional provision fourth. Rate application.

To the procedures referred to in Articles 7.5, 7.8 and 9 of this Royal Decree, the rate indicated in Section 3.3 of Group III of Title X of Law 25/1990, of 20 December, of the Medication is applicable.

Single transient arrangement. Validity of the Ministerial Order of 21 July 1978.

Until 31 December 1994, the placing on the market and the putting into service of products complying with the Ministerial Order of 21 July 1978 regulating the registration and control of implants will be permitted. therapeutic or correction clinical trials.

First repeal provision. Specific regulatory repeal.

As of 1 January 1995, the Order of 21 July 1978 is hereby repealed as soon as it is opposed to the provisions of this Royal Decree.

Repeal provision second. Generic regulatory repeal.

Likewise, any provisions of equal or lower rank shall be repealed with the provisions of this Royal Decree.

Final disposition first. Faculty of development.

The Minister of Health and Consumer Affairs is empowered to make any provisions necessary for the implementation and development of this Royal Decree.

Final disposition second. Entry into force.

This Royal Decree will enter into force on the day following its publication in the Official Journal of the State.

Given in Madrid on 3 May 1993.

JOHN CARLOS R.

The Minister of Health and Consumer Affairs,

JOSE ANTONIO GRINAN MARTINEZ

ANNEX I

Essential design and manufacturing requirements

I. Safety, efficacy and quality assurance

1. The specifications of the manufacturer as regards the design and manufacture of the products shall comply with the principles of safety integration, taking into account the generally recognised state of the art.

2. The products must be designed in such a way that they are removed or reduced as far as possible:

(a) The risks of injury linked to its physical characteristics or its dimensions.

(b) The risks associated with the use of energy sources, in the case of electricity, with particular attention to insulation, leakage currents and the heating of products.

(c) Risks linked to the reasonably foreseeable environment conditions, in particular those linked to magnetic fields, external electrical influences, electrostatic discharges, pressure or pressure variations, acceleration, etc.

d) The risks associated with medical interventions, particularly those derived from the use of defibrillators or high frequency surgical equipment.

e) the risks associated with ionising radiation from radioactive substances forming part of the product, in accordance with the requirements for protection against ionising radiation referred to in the Council Directive 80 /836/Euratom of 15 July 1980 amending the Directives laying down basic standards for the protection of the health of the public and workers against the dangers arising from the use of the ionising radiation, as amended by Directives 84 /4667/Euratom and 84 /466/Euratom.

f) The risks arising from the lack of maintenance and calibration related especially to:

1. The excessive increase in leakage currents.

2. The degradation of the materials used.

3. The excessive increase in heat generated by the product.

4. The deterioration of the accuracy of any measurement or control mechanism.

3. Products shall be designed and manufactured in such a way as to achieve the characteristics and performance attributed to the product, with the guarantees referred to in Article 3 of this Royal Decree, in particular:

1. The choice of the materials used, especially as regards the toxicity.

2. The reciprocal compatibility between the materials used and the tissues, biological cells and body fluids, taking into account the intended use of the product.

3. Where appropriate, the compatibility with the substances intended to be administered.

4. The quality of the connections, in particular in the security plan.

5. The reliability of the power source.

6. If appropriate, the proper tightness.

7. The proper functioning of the control, programming and control systems, including software.

4. Where a product incorporates, as an integral part, a substance which, if used separately, is considered as a medicinal product in accordance with the provisions of Law 25/1990 of 20 December 1990, the action in combination with the the product may lead to its availability by the body, the safety, quality and usefulness of that substance, taking into account the destination of the product, shall be verified by analogy with the provisions laid down for medicinal products.

II. Guarantees of conditioning, identification and information

1. Conditioning.

Products must be designed, manufactured and conditioned in non-reusable packaging, and in accordance with appropriate procedures, which ensure their sterile condition at the time of their marketing. In the case of storage and transport conditions laid down by the manufacturer, the qualities laid down must be maintained until the packaging is opened for implantation.

2. Identification.

1. The products and, where appropriate, the components, must be identified in such a way as to make it possible to carry out any appropriate action which is necessary when potential risks arising from the products and their components are manifest.

2. The products shall bear a code allowing the product to be clearly identified (in particular the type of product and the year of manufacture) and the manufacturer. This code must be detectable, if necessary, without the need for a surgical intervention.

3. Information.

1. All the information contained in this paragraph 3 must be supplied at least in the official Spanish language of the State.

2. Where a product or its accessories are accompanied by instructions necessary for its operation to indicate operating parameters, or adjustment by means of a display system, such information must be comprehensible to the user and, if any, for the patient.

3. Each product must be legibly and indelibly present, where appropriate, by means of generally recognised symbols, the following indications on the packaging:

a) On immediate packaging that guarantees sterility:

1. The sterilization method.

2. The indications to allow this packaging to be recognised.

3. The name and address of the manufacturer.

4. The name of the product.

5. If this is a product intended for clinical research, the mention .

6. If this is a custom product, the mention .

7. The indication that the implantable product is in a sterile state.

8. The indication of the month and year of manufacture.

9. The indication of the deadline in which the product can be safely implanted.

b) On the outer carton:

1. The name and address of the manufacturer.

2. The name of the product.

3. The destination of the product.

4. The particular characteristics for correct use.

5. If this is a product intended for clinical research, the mention .

6. If this is a custom product, the mention .

7. The indication that the implantable product is in a sterile state.

8. The conditions of transport and storage of the product.

9. The indication of the month and year of manufacture.

10. Indication of the deadline in which the product can be safely implanted.

4. At the time of placing on the market, each product must be accompanied by a package leaflet containing at least the following elements:

1. The authorization year of the .

markup placement

2. The particulars referred to in paragraphs (a) and (b) of paragraph 3.3, with the exception of those set out in the last two numbers of subparagraph (b).

3. The performance attributed to them by the manufacturer as well as any unwanted side effects.

4. The necessary information to enable the optional product to be selected as well as the appropriate software and accessories.

5. Information on the method of use and those enabling the patient to use the product, his accessories and the software, as well as information relating to nature, scope and the use of the product, to the patient and, where appropriate, to the patient the time limits for the checks and tests and, where appropriate, the maintenance measures.

6. Information which, where appropriate, is necessary to avoid certain risks arising from the implementation of the product.

7. Information on the risks of reciprocal interations which may take place between the product, and other instruments present in specific research or treatment.

8. The necessary instructions in the event of a breakdown of the packaging to ensure sterility and, where appropriate, the indication of suitable resterilization methods.

9. The warning, if appropriate, that a product may only be used again, in case it has been reconditioned under the manufacturer's responsibility to meet the essential requirements.

5. The package leaflet must also contain the information to enable the patient to inform the patient about the contraindications and precautions to be observed. These indications shall be particularly relevant to:

1. Information enabling the life span of the energy source to be defined.

2. The precautions to be taken in case of changes in the performance of the product.

3. The precautions to be taken with regard to exposure, under reasonably foreseeable environmental conditions, to magnetic fields, external electrical influences, electrostatic discharges, pressure or pressure variations, acceleration, etc.

4. Appropriate information concerning medicinal products which the health product concerned is intended to be administered in accordance with the provisions of the legislation applicable to medicinal products.

ANNEX II

EC declaration of conformity. (Full Quality Assurance System)

1. The manufacturer shall apply the approved quality system for the design, manufacture and final inspection of the medical devices concerned, as provided for in paragraphs 3 and 4 of this Annex, and shall be subject to the EC control, as provided for in paragraph 5 of this Annex.

2. The declaration of conformity is the procedure whereby the manufacturer who fulfils the obligations of the preceding paragraph ensures and declares that the products in question comply with the provisions of this Royal Decree which are applicable.

The manufacturer shall affix the marking in accordance with Article 6 and make a written declaration of conformity. This declaration shall cover one or more identified specimens of the product and the manufacturer shall keep it. The marking shall be accompanied by the identification symbol of the notified body responsible.

3. Quality system.

1. The manufacturer shall submit an application for the assessment of his quality system to a notified body.

This request must contain:

(a) All relevant information for the category of products to be manufactured.

b) The documentation relating to the quality system.

c) Commitment to meet the obligations arising from the quality system to be approved.

d) Commitment to maintaining the approved quality system, in order to ensure its adequacy and effectiveness.

e) The manufacturer's commitment to install and update an after-sales control system. The undertaking shall include the obligation on the part of the manufacturer to inform the competent authorities of the following facts immediately after they have become aware of them:

1. Any dysfunction or alteration of the characteristics and performance, as well as any inadequacy of the package leaflet of a product that may give rise to or may have resulted in the death or deterioration of a patient's health status.

2. Any technical or sanitary reason which has led the manufacturer to withdraw a medical device from the market.

2. The application of the quality system shall ensure the conformity of the products with the provisions of this Royal Decree applicable to all phases, from the design to the final controls.

All the elements, requirements and provisions adopted by the manufacturer for its quality system shall appear in a systematic and orderly documentation in the form of written procedures. The documentation of the quality system should enable a uniform interpretation of quality procedures such as quality programmes, plans, manuals and quality records.

In particular, you must contain an appropriate description of:

a) The quality objectives of the manufacturer.

b) The organization of the company, and in particular:

1. Of the organizational structures, the responsibilities of the technicians and their authority in terms of quality of design and the manufacture of the products.

2. Means to monitor the effective functioning of the quality system, and in particular its ability to obtain the desired quality of design and products, including the control of non-compliant products.

c) Procedures for controlling and verifying the design of products, and in particular:

1. Of the design characteristics, including the rules to be applied and the descriptions of the solutions adopted for compliance with the essential requirements to be applied to products where the standards referred to in Article 3 of this Royal Decree do not apply in full.

2. Of the techniques of control and verification of the design, procedures and systematic actions to be used in the design phase of the products.

d) Of the quality assurance and control techniques in the manufacture and in particular:

1. Of the processes and procedures used, in particular in the field of sterilisation, procurement and relevant documents.

2. Of the product identification procedures adopted and updated on the basis of drawings, specifications and other relevant documents throughout all stages of manufacture.

e) Of the appropriate studies and tests carried out before, during and after production, of the frequency with which they are carried out and of the test equipment used.

3. The notified body shall carry out an audit of the quality system to determine whether it meets the requirements referred to in paragraph 2. It shall, for alleged compliance with those requirements, determine whether the quality systems comply with the harmonised standards. corresponding.

The assessment team shall include at least one member who has experience in evaluations within the technological field concerned. The assessment procedure shall include a visit to the manufacturer's premises.

The decision will be notified to the manufacturer after the last visit. It shall contain the findings of the inspection and a reasoned assessment.

4. The manufacturer shall inform the notified body that he has approved the quality system of any proposed modification of that system.

The notified body shall evaluate the proposed amendments and check whether the quality system thus amended meets the requirements referred to in paragraph 2, notifying the manufacturer of its decision. That decision shall include the findings of the inspection and a reasoned assessment.

4. Examination of the design of the product.

1. The manufacturer shall, in addition to the obligations relating to it in accordance with paragraph 3, submit a request for a study of the design dossier for the product to be manufactured and which is part of the category referred to in paragraph 3. 3.1.

2. The application shall describe the design, manufacture and performance of the medical device concerned and shall include the necessary elements to enable the conformity with the requirements of this provision to be judged.

This request must contain, in particular:

1. The design characteristics, including the rules that have been applied.

2. A mandatory test showing its suitability, particularly where the relevant national rules have not been applied in full. This test shall include the results of the appropriate tests carried out by the manufacturer or under his responsibility.

3. The indication that the product incorporates or does not, as an integral part, a substance as referred to in Annex I, paragraph I. 4, the action of which in combination with the product may lead to its availability by the body, as well as the related data to the tests carried out in this respect.

4. The clinical data referred to in Annex VII.

5. The draft prospectus for instructions.

3. The notified body shall examine the application and, if the product complies with the requirements of this Royal Decree which apply to it, it shall issue an EC design examination certificate to the applicant. The notified body may require the application to be completed with additional tests, so that compliance with the requirements of this Royal Decree can be assessed. This certificate shall contain the conclusions of the examination, the conditions of validity, the data necessary for the identification of the approved design and, where appropriate, a description of the destination of the product.

4. The applicant shall inform the notified body which has issued the EC examination certificate of the design of any modification which has been introduced in the approved design. The modifications introduced shall be accompanied by an additional approval by the notified body which has issued the EC design examination certificate where such modifications may affect conformity with the requirements This additional approval shall be granted in the form of an annex to the EC design examination certificate, provided for in the Royal Decree or with the conditions laid down for the use of the product.

5. EC control.

1. The purpose of the EC control is to ensure that the manufacturer of the obligations arising from the approved quality system is properly complied with.

2. The manufacturer shall authorise the notified body to carry out all necessary inspections and shall provide it with all relevant information, in particular:

1. The documentation of the quality system.

2. The data foreseen in the part of the quality system relating to the design, such as the results of the analyses, the calculations, the tests, etc.

3. The data provided for in the part of the quality system relating to manufacturing, such as the reports for the inspections, the tests, the contracts and the qualification of the staff concerned, etc.

3. The notified body shall carry out regular inspections and assessments in order to ensure that the manufacturer applies the approved quality system and shall provide an assessment report to the manufacturer.

4. Inspections may also be carried out by the notified body by means of unannounced visits to the manufacturer, to which a report shall be delivered.

6. The notified body shall communicate to the other bodies the relevant information concerning the approvals of the quality systems issued, rejected and withdrawn.

ANNEX III

CE Model Review

1. The EC model examination is the procedure whereby a notified body determines and certifies that a representative copy of the intended production complies with the corresponding provisions of this Royal Decree.

2. The manufacturer, or his authorised representative established in the Community, shall submit the application for an EC model examination to a notified body.

This request must include:

1. Name and address of the manufacturer, as well as the name and address of the authorised representative in case the application is submitted.

2. A written declaration specifying that the application has not been submitted to another notified body.

3. The documentation referred to in paragraph 3 of this Annex, which is necessary to assess the conformity of the representative of the intended production, hereinafter referred to as , in accordance with the requirements of this Royal Decree.

The applicant shall make a model available to the notified body. The notified body may request other copies if necessary.

3. The documentation shall enable the design, manufacture and performance of the product to be understood. The documentation shall include, in particular, the following elements:

1. A general description of the model.

2. Design drawings, intended manufacturing methods, in particular for sterilisation, component schemes, sub-assemblies, circuits, etc.

3. The descriptions and explanations necessary for the understanding of the drawings and schemes mentioned and the operation of the product.

4. A list of the national rules adopted in application of the harmonised standards applied in whole or in part, as well as descriptions of the solutions adopted to meet the essential requirements where those standards are not applied.

5. The results of the design calculations performed, the examinations and technical tests performed, etc.

6. The indication that the product incorporates or does not, as an integral part, a substance as referred to in paragraph I (4) of Annex I, the action of which in combination with the product may lead to its availability by the body, as well as the data relating to the tests carried out in this respect.

7. The clinical data referred to in Annex VII.

8. The draft prospectus.

4. The notified body:

1. It shall examine and evaluate the documentation, verify that the model has been manufactured in accordance with it; it shall also identify the elements which have been designed in accordance with the applicable provisions of national rules, as well as elements whose design is not based on the relevant provisions of those rules.

2. It shall carry out or make appropriate checks and tests necessary to verify that the solutions adopted by the manufacturer comply with the essential requirements of this Royal Decree, where the national rules are not applied.

3. It shall carry out or make appropriate checks and tests to check whether, in the event that the manufacturer has decided to apply the relevant rules, they have actually been applied.

4. It shall agree with the applicant where the necessary checks and tests are to be carried out.

5. Where the model complies with the provisions of this Royal Decree, the notified body shall issue an EC model examination certificate to the applicant. The certificate shall contain the name and address of the manufacturer, the conclusions of the assessment, the conditions of validity of the certificate and the data necessary for the identification of the approved model.

To be attached to the certificate, the significant parts of the documentation; the notified body shall keep a copy of the certificate.

6. The applicant shall inform the notified body which issued the EC model examination certificate of any changes to the approved product.

When the modifications made to the approved product may affect their conformity with the basic requirements or with the intended conditions of use of the product, the notified body which has issued the The EC model examination certificate shall also approve those amendments. This new approval shall be issued, if appropriate, in the form of an Annex to the initial EC model examination certificate.

7. Each notified body shall communicate to the other notified bodies the relevant information on the EC model examination certificates and any corresponding additions which it has issued, refused or withdrawn.

8. The other bodies may obtain a copy of the EC model examination certificates and/or their additions. The annexes to the certificates shall be made available to the other notified bodies submitting a reasoned request and, after informing the manufacturer.

ANNEX IV

CE Verification

1. EC verification is the act by which a notified body verifies and certifies that the products manufactured are in conformity with the model described in the EC model examination certificate and that they meet the requirements of this Royal I decree to apply them.

2. Prior to the start of manufacture, the manufacturer shall draw up a documentation setting out the manufacturing procedures, in particular as regards sterilisation, as well as the set of pre-established provisions and The system shall be applied to ensure the homogeneity of the production and conformity of the products with the model described in the EC model examination certificate and with the requirements of this Royal Decree applicable to it.

3. The manufacturer shall undertake to establish and maintain an updated after-sales surveillance system. The undertaking shall involve the obligation of the manufacturer to immediately inform the competent authorities of the following facts, as soon as they are aware of them:

1. Any dysfunction or alteration of the characteristics and performance, as well as any inadequacy of the package leaflet of a product that may give rise to or may have resulted in the death or deterioration of a patient's health status.

2. Any technical or sanitary reason that has induced the manufacturer to withdraw a product from the market.

4. The notified body shall carry out the EC verification by means of controls and tests of the products on a statistical basis, as specified in paragraph 5 of this Annex. The manufacturer shall authorise the notified body to assess the effectiveness of the measures taken pursuant to paragraph 2 of this Annex, if applicable, by audit.

5. Statistical verification.

1. The manufacturer shall present the products manufactured in the form of homogeneous lots.

2. A random sample shall be taken from each batch. The products constituting the sample shall be individually examined and, in order to verify their conformity with the model described in the EC model examination certificate, the relevant tests as defined in the national or national standards shall be carried out. harmonised or equivalent tests, in order to determine the acceptance or rejection of the lot.

3. The statistical control of the products will be performed by properties, which will involve a sampling plan of the following characteristics:

1. A quality level corresponding to a probability of acceptance of 95 per 100, with a percentage of non-conformity between 0.29 and 1 per 100.

2. A limit quality corresponding to a probability of acceptance of 5 per 100, with a percentage of non-compliance comprised between 3 and 7 per 100.

4. If a lot is accepted, the notified body shall extend a written certificate of conformity. All products in the lot may be placed on the market, with the exception of non-compliant products.

If a lot is rejected, the competent notified body shall take appropriate measures to prevent its placing on the market.

Whenever justified for practical reasons, the manufacturer may, under the responsibility of the notified body, place the marking during manufacture accompanied by the identification symbol of the body responsible for statistical verification.

ANNEX V

EC declaration of compliance with the model

(Production Quality Assurance)

1. The manufacturer shall apply the approved quality system for the manufacture and final control of the products concerned as specified in paragraph 3, and shall be subject to the control referred to in paragraph 4, both of which are Annex.

2. This declaration of conformity is the procedure whereby the manufacturer who fulfils the obligations of paragraph 1 of this Annex ensures and declares that the products concerned are in conformity with the model described in the examination certificate EC model and comply with the provisions of this Royal Decree which apply to it.

The manufacturer will affix the marking and make a written declaration of compliance. The manufacturer shall keep this statement which may relate to one or more copies of the product identified. The marking shall be accompanied by the identification symbol of the notified body responsible.

3. Quality system.

1. The manufacturer shall submit an application for the approval of his quality system to a notified body.

This request must contain:

(a) All relevant information on the products to be manufactured.

b) The documentation relating to the quality system.

c) A commitment to meet the obligations arising from the quality system that is approved.

d) A commitment to the maintenance of the approved quality system in order to ensure its adequacy and effectiveness.

e) Where applicable, the technical documentation relating to the approved model and a copy of the EC model examination certificate.

f) A commitment on the part of the manufacturer to establish and maintain an after-sales surveillance system. The commitment shall involve the obligation of the manufacturer to inform the competent authorities of the following facts, as soon as they are aware of them:

1. Any dysfunction or alteration of the characteristics and performance, as well as any inadequacy of the package leaflet of a product that may give rise to or may have resulted in the death or deterioration of the patient's health status.

2. Any technical or sanitary reason that has induced the manufacturer to withdraw a product from the market.

2. The application of the quality system shall ensure the conformity of the products with the model described in the EC model examination certificate.

All the elements, requirements and provisions adopted by the manufacturer for its quality system shall appear in a systematic and orderly documentation in the form of written policies and procedures. The documentation of the quality system should enable a uniform interpretation of the policy and quality procedures applied, such as quality programmes, plans, manuals and records.

You must contain, in particular, an appropriate description of:

a) The quality objectives of the manufacturer.

b) The organization of the company, and in particular:

1. Of the organizational structures, the responsibility of the cadres and their authority for the organization as regards the manufacture of the products.

2. The means to monitor the effective functioning of the quality system, and in particular its ability to obtain the desired quality of the products, including the control of non-compliant products.

(c) Quality assurance and control techniques and, in particular:

1. Of the procedures to be used in relation, in particular, to sterilisation, purchases and relevant documents.

2. Of the product identification procedures, established and updated from drawings, specifications or other applicable documents, throughout all stages of manufacture.

(d) The appropriate examinations or tests to be carried out before, during and after production, the frequency with which they will be carried out and the test equipment used.

3. The notified body shall carry out an audit of the quality system to determine whether it meets the requirements referred to in paragraph 2. It shall, for alleged compliance with those requirements, determine whether the quality systems comply with the harmonised standards. corresponding.

At least one of the team members in charge of the assessment should have experience in evaluating the technology in question. The assessment procedure shall include a visit to the manufacturer's premises.

The decision will be communicated to the manufacturer after the last visit. It shall contain the findings of the inspection and a reasoned assessment.

4. The manufacturer shall communicate to the notified body that he has approved the quality system of any project for the adaptation of that system.

The notified body shall evaluate the proposed modifications and check whether the quality system thus amended meets the requirements set out in paragraph 2 of this Annex, the decision shall be notified to the manufacturer. The conclusions of the inspection and a justified assessment shall be set out therein.

4. Control.

1. The purpose of the control is to ensure the correct compliance by the manufacturer of the obligations arising from the approved quality system.

2. The manufacturer shall authorise the notified body to carry out all necessary inspections and shall provide it with all relevant information, in particular:

1. The documentation of the quality system.

2. The data provided for in the part of the quality system relating to manufacturing, such as the reports concerning inspections, tests, contrasts, the qualification of the staff concerned, etc.

3. The notified body shall carry out regular inspections and assessments in order to ensure that the manufacturer applies the approved quality system and shall provide an assessment report to the manufacturer.

4. On the part of the notified body, inspections may also be carried out by means of unannounced visits to the manufacturer, to which a report shall be delivered.

5. The notified body shall communicate to the other notified bodies the relevant information concerning the approvals of the quality systems issued, refused and withdrawn.

ANNEX VI

Statement regarding special purpose products

1. The manufacturer shall draw up the declaration with the elements specified in paragraph 2 of this Annex for the products to be measured and those intended for clinical investigation.

2. The declaration will contain the following data:

1. For custom products:

(a) Data to identify the product in question.

b) The claim that the product is intended for the exclusive use of a patient indicating his or her first and last names.

(c) Name and surname of the optional person who has made this prescription and, if applicable, name of the health centre concerned.

(d) The specific characteristics of the product in relation to the medical prescription in question.

(e) The statement that the product is in conformity with the essential requirements set out in Annex I and, where applicable, an indication of the essential requirements which do not fully comply with the grounds.

2. For products intended for clinical research:

a) The approval of the conduct of the trial by a duly accredited Clinical Research Ethics Committee.

(b) The approval of the address of the centre in which the test shall be carried out.

(c) Data to identify the product in question.

(d) The research programme, including, in particular, the object, scope and number of the products concerned.

e) Name of the physician and the institution responsible for the investigations.

(f) Place, date of commencement and expected duration of the investigations.

g) The data shown in the preceding paragraphs shall be contained in a protocol, the document setting out the reason for the study, its objectives, design, methodology and the intended analysis of its results, as well as the conditions under which the test will be performed and developed.

Any clinical trial protocol should be written in Spanish and include the following basic sections:

1. Summary.

2. Index.

3. General information.

4. Justification and objectives.

5. Type of clinical trial and design of the same.

6. Selection of subjects.

7. Description of the treatment or procedure of use of the medical device, as appropriate.

8. Development of the test and assessment of the response. 9. Adverse events.

10. Ethical aspects. Informed consent of the patient.

11. Practical considerations.

12. Statistical analysis.

h) The statement that the product concerned complies with the essential requirements, with the exception of the aspects covered by the investigation, and, as regards the latter, declare that all precautions have been taken necessary to protect the health and safety of the patient.

3. The manufacturer shall undertake to make available to the competent national authorities:

1. With regard to custom-made products, the documentation to enable the design, manufacture and performance of the product, including the intended performance, to be understood, which will enable the assessment of its conformity with the requirements of this Royal Decree.

The manufacturer shall take all necessary measures to ensure that the manufacturing process ensures conformity of the products manufactured with the documentation referred to in the first subparagraph.

2. As regards products intended for use in clinical investigations, the documentation shall also include:

a) A general description of the product.

b) Design drawings, methods of manufacture, in particular, in the field of sterilisation, as well as schemes of components, sub-assemblies, circuits, etc.

c) The descriptions and explanations necessary for the understanding of such drawings and schemes and the operation of the product.

(d) A list of the harmonised national rules, applied in full or in part, as well as the description of the solutions adopted to meet the essential requirements of this Royal Decree when these are not applied rules.

e) The results of the design calculations made, of the controls and technical tests carried out, etc.

(f) The commitment to submit to the Directorate-General for Pharmacy and Health Products the evaluation report of the results of the investigation, including the report referred to in paragraph 3.f) of Annex VII to this Royal Decree.

The manufacturer shall take all necessary measures to ensure that the manufacturing process ensures conformity of the products manufactured with the documentation referred to in paragraph 3.1 and in the first paragraph of this paragraph. paragraph.

The manufacturer may authorise the assessment, where appropriate, by an audit, of the effectiveness of those measures.

ANNEX VII

Clinical Assessment

1. General provisions.

1. The adequacy of the clinical data presented shall be based, taking into account, where appropriate, the relevant harmonised standards:

(a) Well in a sufficiently up-to-date bibliographic documentation covering the use to which the product is intended and its mode of use, accompanied, where appropriate, by a written report containing an assessment of the documentation.

(b) Well in the results of all clinical trials performed, including those performed in accordance with the provisions laid down in paragraph 2 of this Annex.

2. The documentation submitted shall be confidential unless its disclosure is essential for public health reasons.

2. Clinical trials.

1. Objectives: The objectives of the clinical trials shall be:

(a) Check if, under normal conditions of use, the performance of the product corresponds to those attributed by the manufacturer, and

(b) To determine, under normal conditions of employment, the possible undesirable side effects and to assess whether they generate acceptable risks with respect to the expected benefits of the product.

2. Ethical considerations.

Clinical research will be conducted in accordance with the ethical principles set out in Law 25/1990 of 20 December of the Medication and its development provisions.

3. Methods.

(a) Clinical investigations shall be conducted in accordance with an appropriate research plan, corresponding to the state of science and technology, defined in such a way as to confirm or refute the manufacturer's claims. with respect to the product; such investigations shall include a sufficient number of observations to ensure the scientific validity of the findings.

(b) The procedures used to carry out the investigations shall be adapted to the product under examination.

(c) Investigations must be carried out in circumstances equivalent to those which would be found under normal conditions of use of the product.

d) All adverse events shall be recorded in full.

e) The investigations will be carried out under the supervision of a responsible physician, specialist in the corresponding pathology, in a suitable environment.

The responsible physician will have access to the product's technical data.

f) The written report, signed by the responsible physician will include a critical judgment of all information collected throughout the clinical investigations.

ANNEX VIII

Minimum requirements to be collected by notified bodies for designation

1. The body, its director and the staff responsible for carrying out the assessment and verification operations shall be persons other than the designer, the manufacturer, the supplier or the installer of the product under control, and different of the authorised representative of any of these parties. They shall not be directly involved in the design, construction, marketing or maintenance of the product or represent any of the parties involved in these activities. This, however, does not preclude the possibility for the manufacturer and the body to exchange technical information.

2. The body and the staff responsible for the control shall carry out the assessment and verification operations with the highest degree of professional integrity and technical competence; they shall not be subjected to any pressure, or it shall provide for no incentive, in particular economic, which may influence its judgment or the results of the inspection, in particular by persons or groups of persons who are interested in the outcome of the verifications.

3. The body must be able to carry out all the tasks listed in one of the Annexes to the V, which have been assigned to it and for which it has been accredited, either the same designated body or the body is carried out under its own responsibility. In particular, they shall have at their disposal the necessary personnel and possess the necessary means to be able to carry out the technical and administrative tasks relating to the assessment and verification properly; they shall also have access to the equipment required for the necessary verifications.

4. The staff responsible for the control must have:

(a) A sound professional training on the set of assessment and verification operations for which the notified body has been designated.

b) A satisfactory knowledge of the requirements of the controls they carry out and an adequate experience in such controls.

c) The aptitude required to write the certificates, record, and reports that are required to authenticate the execution of the controls.

5. The independence of the inspection staff shall be ensured. Their remuneration should not be established on the basis of the number of checks carried out or on the results of such checks.

6. The body shall be covered by a liability insurance covering the risks arising from the exercise of the functions provided for in this Royal Decree.

7. The staff of the body shall be obliged to observe the professional secrecy in relation to all the information to which it accesses during the performance of its tasks under this provision.

ANNEX IX

CE Conformity Marking

(GRAPHIC OMITTED)