Law 25/1990, of 20 December, of the Medicamento, regulates the pharmacovigilance in Chapter VI of its Title II, contemplating the Spanish System of Pharmacovigilance as a decentralized structure that integrates the activities of Health administrations in this field and coordinates the Ministry of Health and Consumer Affairs. It also lays down the obligation for healthcare professionals to collaborate with the system.

The primary purpose of pharmacovigilance is to continuously provide the best possible information on the safety of medicinal products, thereby enabling appropriate measures to be taken and thus to ensure that Medicinal products available on the market present a favourable benefit-risk ratio for the population under the authorised conditions of use.

Pharmacovigilance is a responsibility shared by the competent authorities, marketing authorisation holders and healthcare professionals. It is therefore essential to have a regulatory framework that defines the obligations of each of the actors involved and ensures effective communication between them, taking into account the administrative structure of the State and the membership of the State. European Union.

In this regard, Royal Decree 767/1993 of 21 May, regulating the evaluation, authorization, registration and conditions for dispensing of proprietary medicinal products and other medicinal products for human use On the other hand, the Commission has taken the view that the Commission's proposal for a directive on the approximation of the laws, regulations and administrative provisions relating to proprietary medicinal products, as well as its successive amendments.

The abovementioned Directives have been amended in turn by Commission Directive 2000 /38/EC of 5 June amending Chapter Va "Pharmacovigilance" of Directive 75 /319/EEC, resulting from the application of the Directive for the interpretation of the definitions and principles of that and, therefore, of this Royal Decree, the guidelines of the European Commission on the collection, verification and reporting of adverse reactions published in the Volume 9 of the European Union's Rules of Procedure. The incorporation of that Directive into national law, together with the development of the provisions of Chapter VI of Title II of Law 25/1990 of 20 December 1990 concerning the Spanish Pharmacovigilance System, It is necessary to regulate them in a single text by means of this standard, with the consequent repeal of the provisions contained in Royal Decree 767/1993 of 21 May 1993, as amended by Royal Decree 2000/1995 of 7 June 1993. The Court of State held that the Court of State held that the Court of authorization, registration and conditions for dispensing of proprietary medicinal products and other industrially manufactured medicinal products.

For its part, the Royal Decree 520/1999 of 26 March, approving the Statute of the Spanish Medicines Agency, partly develops the functions of that autonomous body in the field of pharmacovigilance, and those of the Committee for the Safety of Medicinal Products for Human Use as a collegiate body dependent on it.

This Royal Decree, which has the status of legislation on pharmaceutical products according to

as established in article 149.1.16.a of the Constitution, it develops Chapter VI of Title II of Law 25/1990 of 20 December of the Medicamento, finding its normative enablement in the final disposition of the said Law, and incorporates into national law the Commission Directive 2000 /38/EC of 5 June amending Chapter Va 'Pharmacovigilance' of Council Directive 75 /319/EEC on the approximation of the laws of the Member States relating to the approximation of the laws of the Member States relating to the legal, regulatory and administrative on proprietary medicinal products.

In its virtue, on the proposal of the Minister of Health and Consumer Affairs, after the approval of the Minister of Public Administration, heard the Autonomous Communities and the sectors affected, according to the State Council and previous deliberation of the Council of Ministers at its meeting on 19 July 2002,

D I S P O N G O:

CHAPTER I

General provisions

Article 1. Scope of application.

The provisions of this Royal Decree apply to the pharmacovigilance of medicinal products for human use, as a public health activity aimed at the identification, quantification, evaluation and prevention of risks associated with the use of such medicinal products.

Article 2. Definitions.

For the purposes of this Royal Decree, it shall be understood as:

(a) "Spanish Pharmacovigilance System for Medicinal Products for Human Use": a decentralised structure that integrates the activities that the health administrations undertake to collect and develop information on reactions adverse drug use, coordinated by the Ministry of Health and Consumer Affairs, through the Spanish Medicines Agency.

(b) "Spontaneous Reporting Scheme or System" means a pharmacovigilance method based on the communication, collection and assessment of reports of suspected adverse drug reactions, carried out by a professional health, including those derived from drug dependence, abuse and misuse of drugs.

(c) "adverse reaction" means any response to a medicinal product which is harmful and unintended and which occurs at doses normally applied in the human being for the prophylaxis, diagnosis or treatment of diseases; or for the restoration, correction or modification of physiological functions.

(d) "Serious adverse reaction": any adverse reaction that causes death, may endanger life, requires hospitalization of the patient or prolongation of the existing hospitalization, causes a disability or Significant or persistent disability or a birth defect or birth defect. For the purposes of their notification, serious suspected adverse reactions which are considered to be important from the medical point of view shall also be treated as serious, even if they do not meet the above criteria.

(e) "Unexpected adverse reaction" means any adverse reaction whose nature, severity or consequences are not consistent with the information described in the technical fiche.

(f) "Periodic Safety Report" means the report containing the records referred to in Article 8.g of this Royal Decree.

g) "Post-authorisation study" means any study carried out during the marketing of a medicinal product according to the conditions of its authorised technical information or under normal conditions of use.

h) "Post-authorisation safety study" means a pharmacoepidemiological study or clinical trial carried out in accordance with the provisions of the marketing authorisation and carried out for the purpose of identifying or quantifying the risks associated with authorised medicinal products.

i) "Abuse of a medicinal product": the intentional, persistent or sporadic use of a medicinal product which is accompanied by physical or psychological harmful effects.

(j) "Yellow card" means a form for the notification of suspected adverse reactions, distributed by the competent authorities in the field of pharmacovigilance of the Autonomous Communities to health professionals.

k) "Good pharmacovigilance practices":

set of rules or recommendations to ensure the authenticity and quality of data collected in pharmacovigilance, which allow the risk attributable to the medicinal product to be assessed at any time; information on the identity of persons who have submitted or reported adverse reactions; and the use of uniform criteria in the assessment of notifications and in the generation of alert signals.

Article 3. Sources of information in pharmacovigilance.

Information about the risks associated with medicines can come from the following sources:

a) Spontaneous reporting of individual cases of suspected adverse reactions by healthcare professionals.

b) Post-authorisation studies, including pharmacoepidemiological studies.

c) Databases of computerised health data.

d) Pre-clinical animal testing information and clinical trial information for a medicinal product.

e) Information related to the manufacture, preservation, sale, distribution, dispensing and habits of use, prescription and administration to patients of a medicinal product.

f) Publications of the medical literature.

g) Other sources of information, such as those relating to the misuse and abuse of medicinal products, which may have an impact on the assessment of the benefits and risks of medicinal products.

h) Other health authorities and international health agencies.

CHAPTER II

The Spanish Pharmacovigilance System for Medicinal Products for Human Use

Article 4. Agents of the Spanish Pharmacovigilance System for medicinal products for human use.

1. The Spanish Pharmacovigilance System for medicinal products for human use consists of:

a) The Spanish Medicines Agency.

(b) The pharmacovigilance bodies of the Autonomous Communities.

c) Healthcare professionals.

2. The Technical Committee of the Spanish Pharmacovigilance System, as an organ consisting of the Spanish Medicines Agency and the pharmacovigilance bodies of the Autonomous Communities, shall unify the operating criteria and evaluate the signals generated by the Spanish Pharmacovigilance System for medicinal products for human use.

Article 5. Duties of the Spanish Medicines Agency for pharmacovigilance.

They are functions of the Spanish Medicines Agency:

a) Plan, coordinate, evaluate and develop the Spanish Pharmacovigilance System for medicinal products for human use, as well as the tasks of its Technical Committee, in accordance with the "good practices of pharmacovigilance of the Spanish System" Pharmacovigilance " developed by the Technical Committee and published by the Ministry of Health and Consumer Affairs.

b) Establish, in collaboration with the Autonomous Communities, a data processing network that allows the competent authorities in the field of pharmacovigilance of the Autonomous Communities to have access to the whole of the information collected by the Spanish Pharmacovigilance System.

c) Administer the database of the Spanish Pharmacovigilance System for medicinal products for human use, ensuring at all times their availability and updating, monitoring their safety and ensuring the confidentiality of the data and its integrity during data transfer processes.

d) Act as a reference centre for the Spanish Pharmacovigilance System with the holders of marketing authorisations for medicinal products.

(e) To make available to the marketing authorisation holder immediately, and in any event within 15 calendar days following receipt, notifications of suspected adverse reactions which are serious in Spain and in which medicinal products from which they are the subject are involved.

Any other pharmacovigilance information not provided for in the preceding paragraph shall be expressly requested by the person concerned in accordance with the procedure provided for in this case.

(f) to transmit to the European Agency for the Evaluation of Medicinal Products and to the Member States immediately, and in any event within 15 calendar days of receipt, the notifications on suspicion of serious adverse reactions that have occurred in Spain.

This communication will be carried out through the data processing network which the European Agency for the Evaluation of Medicinal Products will establish in collaboration with the Member States and the European Commission.

g) Promote the creation of computerized health data bases that serve as a source of information for the conduct of pharmacologic studies.

(h) The plans, in this field, by Royal Decree 520/1999, of 26 March, approving the Statute of the Spanish Medicines Agency.

i) Any other function which may be necessary in the field of pharmacovigilance, and which must be exercised by the Spanish Medicines Agency.

Article 6. Functions of the competent authorities in the field of pharmacovigilance of the Autonomous Communities.

1. The competent authorities in the field of pharmacovigilance of the Autonomous Communities are responsible for implementing, developing and strengthening the Spontaneous Notification Programme, as well as other programmes, in their territorial scope, in accordance with the "good pharmacovigilance practices of the Spanish Pharmacovigilance System".

2. In particular, it is up to them to receive, evaluate and process the suspected adverse reactions produced in their territorial scope and communicated by healthcare professionals or the pharmaceutical industry, as well as those from the scientific literature and post-authorisation studies, where appropriate. Suspected serious adverse reactions should be recorded in the database of the Spanish Pharmacovigilance System within the maximum period of 10 calendar days from its receipt.

Article 7. Obligations of healthcare professionals.

Doctors, pharmacists, nurses and other healthcare professionals have an obligation to:

(a) Notify any suspected adverse reaction of those who are aware during their normal practice and send it as quickly as possible to the pharmacovigilance body of the Autonomous Community on the form of suspected adverse reactions ("yellow card").

b) Keep clinical documentation of suspected adverse drug reactions, in order to complete or follow up, if necessary.

c) Cooperate with the technicians of the Spanish Pharmacovigilance System for medicinal products for human use, providing the necessary information that they request to extend or complete the information on the suspicion of reaction adverse.

d) Stay informed on safety data relating to medicinal products that are usually prescribed, dispensed or administered.

e) Collaborate with the pharmacovigilance officers of the marketing authorisation holders in case of a suspected adverse reaction to one of their proprietary medicinal products, providing the information that is For further notification to the Spanish Pharmacovigilance System.

f) To collaborate, as experts, with the Spanish Medicines Agency and the competent bodies of the Autonomous Communities, in the evaluation of the safety problems of medicinal products for human use.

CHAPTER III

From marketing authorization holders

Article 8. Obligations of the marketing authorisation holder.

The marketing authorisation holder, in accordance with the "Good Pharmacovigilance Practice for Pharmaceutical Industry", published by the Ministry of Health and Consumer Affairs, shall:

(a) Carry a detailed record of all suspected adverse reactions occurring in Spain, in the European Union or in a third country.

(b) Register and communicate to the Spanish Medicines Agency and the competent authority in the field of pharmacovigilance of the Autonomous Community immediately, and in any case within 15 calendar days following receipt of the information, all suspicions of reactions

serious adverse events that occur in Spain and have been reported to you by healthcare professionals, or any other suspected serious adverse reaction occurring in Spain and reasonably expected You have knowledge.

c) Ensure that all suspicions of serious and at the same time unexpected adverse reactions of medicinal products authorised in Spain which occur outside the European Economic Area, of which he has knowledge through a Professional health services, be communicated to the Spanish Medicines Agency immediately, and in any case within the fifteen calendar days following the receipt of the information.

d) Track the global scientific literature, in order to identify published cases of adverse reactions where there is a reasonable suspicion that the causative is an active substance in a medicinal product of whose marketing authorisation in Spain is a holder. These cases shall be reported in accordance with the criteria specified in paragraphs (b) and (c) of this Article.

e) Ensure that all suspicions of serious adverse reactions occurring during the course of a post-authorisation study, and of which they can be reasonably expected to be known, are reported using the criteria specified in paragraphs (b) and (c) of this Article and in accordance with the conditions laid down by the health authorities in accordance with the provisions of Article 18.2 of this Royal Decree.

(f) Guarantee, in the case of medicinal products for human use, the reference Member State of which is Spain, assessed within the scope of the Community concertation procedure, or which have been authorised by the the procedure for mutual recognition, or which have been the subject of a Community decision in accordance with the provisions of Article 56 of Royal Decree 767/1993 of 21 May 1993 governing the assessment, authorisation, registration and dispensing of medicinal products and other medicinal products for human use manufactured industrially, that all suspicions of serious adverse reactions occurring within the territory of the European Union are reported in the format and intervals indicated by the Spanish Medicines Agency.

g) To present to the Spanish Medicines Agency the records of all suspected adverse reactions in the form of a periodic safety report.

This presentation must be made immediately upon request by the Spanish Medicines Agency, and also on a regular basis in accordance with the following timetable, unless other requirements have been established such as: condition for granting the marketing authorisation for the medicinal product: Semestrally for the first two years following the authorisation, annually for the following two years and at the time of application for the first revalidation five-year From that point on, the periodic safety report shall be submitted at intervals of five years, together with the request for revalidation of the authorisation.

The periodic safety report should include a scientific assessment of the benefits and risks associated with the medicinal product.

Once the marketing authorisation has been granted, the holder may request the modification of the periods referred to in the preceding subparagraph in accordance with the procedure laid down in Commission Regulation (EC) 541/95 of 10 March, concerning the examination of the amendments to the terms of the marketing authorisations granted by the competent authority of a Member State.

This calendar will also start from the date of authorization of changes in the composition, new therapeutic indications, new management formats or substantial changes in the conditions of the authorisation.

h) Make, when necessary, post-authorisation studies to confirm, quantify or characterize potential risks, or to provide new scientific information on the benefit-risk ratio of authorised medicinal products in Spain.

i) Carry out a continuous evaluation of the benefit-risk ratio of the medicines you have authorised in Spain and immediately communicate to the Spanish Medicines Agency all new information that may influence in the overall assessment of the risk-benefit balance or may require the modification of the technical sheet, package leaflet or both.

Article 9. Person responsible for pharmacovigilance.

1. The holder of the authorisation to place a medicinal product for human use on the market must have a suitably qualified person responsible for pharmacovigilance in Spain, permanently and continuously. The marketing authorisation holder shall communicate to the Spanish Medicines Agency, as well as to the pharmacovigilance bodies of the Autonomous Community where he is based, the name of the person responsible. The Spanish Medicines Agency will keep a record of these responsible.

2. The person responsible for pharmacovigilance shall have the following functions:

a) Create and maintain a system to collect, treat and evaluate information on all suspected adverse reactions reported to the company's staff and medical visitors, in order to make it accessible at least in one place in the European Union.

(b) Prepare and submit to the Spanish Agency of the Medicines the periodic safety reports referred to in Article 8.g) of this provision.

c) Ensure that a rapid and complete response to any request for additional information from the Spanish Medicines Agency is required to be able to assess the benefits and risks of a medicinal product, including information on the volume of sales or prescriptions of the medicinal product concerned.

d) To provide the Spanish Medicines Agency with any other information of interest for the assessment of the benefits and risks associated with a medicinal product, including information on post-authorisation safety studies.

Article 10. Information and modification of the conditions of authorisation, at the request of the holder, for security reasons.

1. The holder of the marketing authorization is obliged to disseminate to the health professionals at least the technical information sheet, together with the information provided for in Article 19 (5) of Law 25/1990 of 20 December 1990. December, of the Medication. In addition, you must send to the Autonomous Communities the technical card authorized by the Spanish Medicines Agency.

2. Where, at the discretion of the Spanish Medicines Agency, it is deemed necessary for the marketing authorisation holder to inform healthcare professionals of new data relating to safety aspects of a medicinal product, and submit

individual letter to each healthcare professional concerned, the text must be agreed in advance with the Spanish Medicines Agency, and incorporated in it on a flag indicating the nature of the information it contains.

3. In accordance with Article 33 of Law 25/1990 of 20 December 1990, when the holder of a marketing authorisation for a medicinal product is aware of new relevant information affecting the safety of that medicinal product, including their knowledge by means of circular or individualized notification from the Spanish Medicines Agency, must update the authorisation and registration file in accordance with scientific and technical progress, through the procedures of modification of the conditions for the authorisation of medicinal products for use human, including the payment of the corresponding fee.

Failure to comply with this duty may be caused by suspension or revocation, in accordance with the provisions of Article 13 of this Royal Decree.

4. Without prejudice to paragraph 3, whenever it is considered appropriate by the Spanish Medicines Agency, a report may be requested from the marketing authorisation holder, through its pharmacovigilance officer, for a report. updated assessment of the benefit-risk ratio.

CHAPTER IV

From administrative intervention

Article 11. Advisory body and participation of experts in the evaluation of the safety of medicinal products.

1. In accordance with the provisions of Royal Decree 520/1999, of 26 March, approving the Statute of the Spanish Medicines Agency, the latter will have the Committee on the Safety of Medicinal Products for Human Use for advice on the subject of pharmacovigilance.

2. The Spanish Medicines Agency shall draw up a list of safety experts for medicinal products, which shall include, inter alia, the technicians of the Spanish Pharmacovigilance System for medicinal products for human use designated by the competent bodies in Each Autonomous Community. These experts, at the request of the Spanish Medicines Agency, may participate in the evaluation of safety problems, post-authorisation studies and requests for modification of the technical information sheet.

Article 12. Alteration of the authorisation scheme.

The Spanish Medicines Agency, when the evaluation of pharmacovigilance data is inferred for reasons of public interest, defence of the health or safety of persons, may restrict the conditions of authorisation of the a medicinal product, and to establish any of the reservations or restrictions of the scope of use listed below:

a) Hospital use.

b) Hospital diagnosis or prescription by medical specialists.

c) Drug of special control.

Article 13. Suspension or revocation of the authorisation.

1. The Spanish Medicines Agency, in accordance with the assessment of pharmacovigilance data, may temporarily suspend or revoke the authorisation of a medicinal product when:

a) Result in being harmful or unsafe under normal conditions of employment.

b) Result not being therapeutically effective.

c) For any other cause, there is a foreseeable risk to the health or safety of people.

(d) Show an unfavourable benefit-risk ratio, as provided for in Article 10.3 of Law 25/1990 of 20 December of the Medication.

2. For reasons of public health, and pending the termination of the suspension or revocation procedure, a preventive suspension may be imposed by a reasoned decision, even immediately before the opening of the procedure. In such cases, the person concerned must withdraw the product from the market, without prejudice to a performance by the Spanish Medicines Agency when the urgency of the case so requires. The costs incurred by such measures shall be borne by the person concerned, without, in any event, a penalty.

Article 14. Procedure for the alteration of the regime, suspension or revocation of the marketing authorisation.

1. The Spanish Medicines Agency may agree to the alteration of the system of authorisation of a medicinal product which involves a relevant restriction of its use or conditions of authorisation, or the suspension or revocation of such a medicinal product. authorisation, for the reasons provided for in Articles 12 or 13 of this Royal Decree, as appropriate, in accordance with the following procedure:

(a) The Spanish Medicines Agency shall ask the marketing authorisation holder for an expert report assessing the benefit-risk ratio of the medicinal product for the conditions of use authorised in Spain, including a proposal for measures to reduce the risk. This report shall be in accordance with the structure and issues specified in the application of the Spanish Medicines Agency.

The report must be sent within 60 days of receipt of the request.

(b) In the light of the expert report, the Spanish Medicines Agency shall draw up an assessment report on the safety problem within 30 days and forward it to the Committee on the Safety of Medicinal Products for Human Use.

c) The Committee on Safety of Medicinal Products for Human Use shall deliver a mandatory but non-binding opinion.

(d) The Spanish Medicines Agency, after hearing the person concerned, shall make a decision indicating the resources coming, and shall notify the person concerned within 30 days of the date of issue of the said opinion or, where appropriate, the notification of the Community decision referred to in the following subparagraph.

Without prejudice to the above, in the specific cases in which the interests of the European Union are at stake, and in advance of the resolution of the Spanish Medicines Agency, the matter may be referred to the Committee for Proprietary Medicinal Products for a Community Decision to be adopted.

This application may be made by the holder of the authorisation or by the Spanish Medicines Agency following the opinion of the Committee on the Safety of Medicinal Products for Human Use. In any case, the request shall be accompanied by all available information.

e) In the case of the procedure for altering the authorisation system, the resolution shall indicate the changes to be made to the technical information sheet, package leaflet, labelling and scope of use of the medicinal product, as well as other measures aimed at reducing risk and informing healthcare professionals and users.

In accordance with these indications, the marketing authorisation holder shall request the appropriate modification of the conditions for the authorisation of the medicinal product in accordance with the procedures laid down in Royal Decree 767/1993 of 21 May 1993 and the circular on the modification of the conditions for the authorisation of medicinal products for human use, including the payment of the corresponding fee.

(f) The resolutions of suspension, revocation and alteration of the authorisation regime, in so far as they may affect the public health of third countries, shall be brought to the attention of the World Health Organisation.

2. The procedure laid down in the preceding paragraph shall not apply to medicinal products authorised by the centralised procedure laid down in Council Regulation (EEC) 2309/93 of 22 July laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing the European Agency for the Evaluation of Medicinal Products, which shall be governed by their specific rules.

Article 15. Communications and precautionary measures.

1. If the Spanish Medicines Agency, in the light of the pharmacovigilance data, considers that a marketing authorisation should be subject to suspension, revocation or amendment involving a relevant restriction on the use of the It shall immediately inform the Health Council of the Autonomous Communities, the European Agency for the Evaluation of Medicinal Products, the other Member States and the marketing authorisation holder.

2. In cases of urgency, the Spanish Medicines Agency may suspend the authorization to place a medicinal product on the market by informing the Council of Health of the Autonomous Communities at the latest by the following first working day at the latest. European Commission, the European Agency for the Evaluation of Medicinal Products, the other Member States and the marketing authorisation holder.

Article 16. Alteration of the system of authorisation, suspension and revocation of medicinal products authorised by mutual recognition procedures and by the former Community conciliation procedure defined in Royal Decree 767/1993 of 21 May 1993.

1. Without prejudice to the provisions of Article 14 of this provision, where the Spanish Medicines Agency, in accordance with the assessment of pharmacovigilance data, considers it necessary for reasons of public health to alter the arrangements, suspension or revocation of the authorization to place medicinal products on the market authorized by mutual recognition procedures and by the old Community conciliation procedure, the matter must be referred to the Committee of Pharmaceutical specialities for a Community decision to be taken.

2. Notified of the Community decision, without further processing than the hearing of the person concerned, the Spanish Medicines Agency shall adopt and notify the appropriate resolution, with an indication of the resources obtained, within 30 days of the date of the notification of the Community decision.

3. Where a preventive suspension of the medicinal product is justified, the provisions of Article 13.2 of this Royal Decree shall apply and the reasons for such suspension shall be reported no later than the working day following that of the adoption of the measure, the Health Ministry of the Autonomous Communities, the European Commission, the European Agency for the Evaluation of Medicinal Products, the other Member States, and the marketing authorisation holder.

Article 17. Communication to the Autonomous Communities, health professionals and citizens.

1. The Spanish Medicines Agency shall inform the Autonomous Communities and other bodies responsible for the adoption of the measures provided for in this Chapter which, due to their relevance to public health, should be made known to the health professionals.

The Autonomous Communities will disseminate this information among healthcare professionals who, both in the public and private sectors, exercise their activity in their territorial scope.

2. The Spanish Medicines Agency and the Autonomous Communities will make it possible to reach the citizens, in an appropriate manner, information on the risks of the drugs that may have relevant implications for their health.

CHAPTER V

From post-authorization studies

Article 18. Applicable regime.

1. Post-authorisation studies shall be intended to supplement the information obtained during the clinical development of medicinal products prior to their authorisation. Post-authorisation studies will not be planned, carried out or funded in order to promote the prescription of medicines.

2. Post-authorisation studies of an observational type shall be carried out in accordance with the conditions laid down by the health authorities in the field of their competence.

3. Without prejudice to the provisions of the previous paragraph, the Spanish Medicines Agency shall keep a record of the post-authorisation proposals of an observational type which, in accordance with paragraph 2, require a prior authorisation. To this end, the study promoter should send a copy of the study protocol to the Spanish Medicines Agency and, where appropriate, report the effective start of the study and report the follow-up reports and the final report.

4. Where the post-authorisation study, in accordance with the provisions of Article 59 of Law 25/1990 of 20 December 1990, of the Medicamento, is of a clinical trial rather than an observational study, it shall not be governed by the provisions of the present chapter, but will result in the application of the specific rules on clinical trials.

Single additional disposition. Character of legislation.

This Royal Decree is adopted in the development of Law 25/1990 of 20 December of the Medication and has the character of legislation of pharmaceutical products for the purposes provided for in Article 149.1.16.a of the Constitution.

Single repeal provision. Regulatory repeal.

Articles 37 and 37a of Royal Decree 767/1993 of 21 May 1993, as amended by Royal Decree 2000/1995 of 7 December 1993 amending Royal Decree 767/1993 of 21 May 1993, which regulates the assessment, authorisation, registration and conditions for the supply of medicinal products and other medicinal products for human use manufactured industrially, as well as any provisions of equal or lower rank shall be contrary to the provisions of the Royal Decree.

Final disposition first. Faculty of development.

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

Final disposition second. Entry into force.

This Royal Decree shall enter into force on the day following that of its publication in the "Official Gazette of the State".

Given in Madrid on July 19, 2002.

JOHN CARLOS R.

The Minister of Health and Consumer Affairs, ANA MARIA PASTOR JULIAN