Law 29/2006 of 26 July on the guarantees and rational use of medicinal products and medical devices sets out, in particular in Chapter VI of Title II, guarantees for the monitoring of the risk-benefit ratio in the medicines and therefore regulates the Spanish pharmacovigilance system and the pharmacovigilance system for medicinal products for human use.

Royal Decree 1344/2007 of 11 October 2007 regulating the pharmacovigilance of medicinal products for human use, regulated in detail the law, regulating in detail: The agents involved in the Spanish System of Pharmacovigilance of medicinal products for human use, as well as the obligations of each of the agents involved in this activity, the aim of which is to provide on a continuous basis the best possible information on the safety of medicinal products, to make it possible to take appropriate measures and to ensure that the On the other hand, medicinal products available on the market have a favourable benefit-risk ratio for the population under the authorised conditions of use; the administrative consequences for safety reasons may affect the conditions of the authorisation for the placing on the market of medicinal products for human use, as well as post-authorisation studies to ensure that the risk-benefit assessment of the authorised medicinal product is ongoing.

This royal decree constituted the transposition into national law of Directive 2001 /83/EC of the European Parliament and of the Council of 6 November establishing a Community code for medicinal products for human use, following the developments introduced by Directive 2004 /27/EC of the European Parliament and of the Council of 31 March 2004.

However, in view of the experience gained and following an evaluation by the European Commission of the pharmacovigilance system of the European Union, the need for measures to improve the functioning of the system has been highlighted. European Union law on the pharmacovigilance of medicinal products, as amended by Directive 2001 /83/EC, which has been carried out by Directive 2010 /84/EU of the European Parliament and of the Council of 15 December 2001 on the protection of medicinal products December 2010, and Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2010 2012, amending in respect of pharmacovigilance, Directive 2001 /83/EC establishing a Community code on medicinal products for human use.

Also, Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15 December 2010 and Regulation (EU) No 1027/2012 of the European Parliament and of the Council of 25 October 2012, which were adopted, have been adopted. amend, as regards pharmacovigilance for medicinal products for human use, Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation of medicinal products for human use and the monitoring of medicinal products for human and veterinary use and for which the European Agency is established Medicinal products, and Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products, all with a view to adopting measures to improve the functioning of Union law on the pharmacovigilance of medicinal products for human use.

Consequently, with this royal decree is updated and adapted to the technical progress the regulation so far in force in this matter, collected in Royal Decree 1344/2007, of 11 October, for which the pharmacovigilance of medicinal products for human use, which are now repealed, and the new developments introduced by Directive 2010 /84/EU of the European Parliament and of the Council of 15 December 2010 and Directive 2012/26/EU of the European Parliament and of the Council of 15 December 2010 are incorporated into national law. European Parliament and the Council of 25 October 2012. These developments are numerous and of great relevance.

Among the novelties introduced by the new European legislation and which makes this real decree, they stand out: the extension of the definition of adverse reaction, in such a way that it includes any harmful and unintended response to a medicinal product, including thus adverse reactions resulting from any use outside the terms of the marketing authorisation, abuse and medication errors; the establishment of clear criteria for the obligations and the role of the responsible parties involved; the strengthening of the obligations of the holders of the marketing authorisation aimed at identifying potential safety issues in a proactive manner, which will be reflected in a risk management plan which will become part of the marketing authorisation, and to collect all the data that is being generated and may have an impact on the benefit-risk balance of the medicinal products, which must be brought to the attention of the Spanish Agency for Medicines and Health Products.

It is also important to note the incorporation of new measures to improve transparency and communication on the safety of medicinal products, which serve the right to information for patients and healthcare professionals, and the increase in their participation and confidence in the health system; in this sense, the participation of citizens in the notification of suspected adverse drug reactions is also possible.

The monitoring of new drugs and those in which a potential safety problem is identified is enhanced, leading to the need for specific studies or measures to minimise the risk. These medicinal products under additional follow-up will have a distinctive feature in the Summary of Product Characteristics and Package Leaflet for both the health care professional and the citizen to give priority to the reporting of suspected adverse reactions. under additional monitoring will be public. For the first time, the need to assess the impact of measures taken to minimise the risks of medicines is incorporated into the legislation.

It is also important to stress the importance of the creation of a new committee, the Committee for the Evaluation of Risks in Pharmacovigilance, in the decision-making process on the risks of medicinal products. The aim of the programme is to rationalise and harmonise decision-making after the assessment of the risks associated with medicinal products in order to implement in a fair, complete and simultaneous manner decisions in all Member States. The current administrative procedures are simplified and the telematic transmission of the periodic safety reports produced by the marketing authorisation holder is made possible; these reports will be accessible to all agencies In the light of the Commission's proposals, the Commission has been in charge of the regulation of medicinal products in the Member States, which will carry out their assessment in accordance with new procedures aimed at improving the efficiency of the system. Member States in the assessment of the risks of medicinal products and decision-making and clarifies the coordinating role of the European Medicines Agency.

The pharmacovigilance activities of the countries of the European Union will be reviewed by the European Commission in a biennial manner, to ensure that the established functions are fulfilled. This review includes both the functions of the Spanish Agency for Medicines and Health Products and the Autonomous Communities. In addition, the Spanish Agency for Medicinal Products and Health Products shall meet the minimum quality requirements laid down in the implementing measures of the European Commission, Commission Implementing Regulation (EU) No 520/2012 of 19 December 2012. Council Regulation (EC) No 726/2004 of the European Parliament and of the Council of 16 June 2012 on the conduct of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001 /83/EC of the European Parliament and of the Council.

For the exercise of pharmacovigilance for medicinal products for human use, the European Medicines Agency, in coordination with the countries of the European Union, has developed guidelines on good pharmacovigilance practices. which will be applicable, as well as its successive updates. In addition, Directive 2010 /84/EU, which is transposed into this royal decree, provides for a number of implementing measures to be implemented by the European Commission in the relevant regulation in its Article 108.

Finally, it should be noted that Directive 2010 /84/EC of the European Parliament and of the Council of 15 December 2010 incorporates Article 105, imposing the permanent control of the authorities on the management of the funds for the activity of pharmacovigilance, the functioning of the communication networks and market surveillance, as a fundamental guarantee for the preservation of their independence. Although this is already working in Spain, it must also be transferred to the field of pharmacoepidemiology, so that, with the necessary independence, studies that are of particular interest to protect health are carried out from the public sector. public.

Given this background, in this royal decree the responsibilities of the Spanish Agency for Medicines and Health Products, the autonomous communities, health professionals and citizens and the obligations of the marketing authorisation holders. All of them are designed to provide the best possible information on the safety of medicinal products on a continuous basis, enabling appropriate measures to be taken and thus to ensure that the medicines available in the the market presents a favourable benefit-risk ratio for the population under the authorised conditions of use.

The publication of all the recommendations of the European Pharmacovigilance Risk Assessment Committee is included, as well as a summary of the risk management plans that the holding laboratories have to carry out. The The option of conducting public hearings in the process of assessing safety issues of particular relevance is also contemplated.

In addition, this royal decree provides for the possibility of imposing on the laboratories holding the marketing authorization obligations for the conduct of post-authorisation studies on the safety or efficacy in the Common medical practice of medicinal products as a condition of the marketing authorisation, and the health authorities may suspend the marketing of the medicinal product in the event of non-compliance with those obligations. These obligations shall be included in the risk management plan.

Also indicated are the administrative consequences that for safety reasons may affect the conditions of authorization to place the medicinal products for human use on the market, incorporating a new urgent procedure for the assessment of safety problems in Europe. Finally, post-authorisation studies with medicinal products are regulated.

In addition, it is necessary to adapt the content of some of the committees attached to the Spanish Agency for Medicines and Health Products, in particular the Committee on the Safety of Medicinal Products for Human Use and the Committee of Coordination of Studies Poseauthorization.

In accordance with the provisions of Article 149.1.16 of the Constitution, this royal decree is dictated in accordance with the competence of the State to regulate the legislation of pharmaceutical products, and incorporates in part to the internal legal order Directive 2010 /84/EU of the European Parliament and of the Council of 15 December 2010, guaranteeing, as regards the processing of personal data, compliance with the Organic Law 15/1999 of 13 December, the Protection of Personal Data, and its development regulations.

According to the provisions of Article 24.3 of Law 50/1997 of 27 November of the Government, this rule has been submitted to the Ministry of Finance and Public Administration. Likewise, in accordance with the provisions of Articles 67.2 and 71 of Law 16/2003 of 28 May, of the cohesion and quality of the National Health System, this royal decree has been the subject of prior report by the Advisory Committee and the Plenary Assembly. of the Interterritorial Council of the National Health System.

In the process of drafting this standard, the autonomous communities and the cities of Ceuta and Melilla have been consulted, and the sectors affected have been heard. It has also been submitted to the report of the Spanish Data Protection Agency and has obtained the mandatory report from the Consumers and Users Council.

In its virtue, on the proposal of the Minister of Health, Social Services and Equality, with the prior approval of the Minister of Finance and Public Administrations, in agreement with the Council of State and after deliberation of the Council of Ministers at their meeting on 26 July 2013,

DISPONGO:

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 that aims to identify, quantify, evaluate and prevent risks associated with the use of the medicinal products once authorised.

These provisions, in turn, will be in line with the provisions of the European Commission Regulation on enforcement measures and the provisions of the European guidelines on good pharmacovigilance practices.

Article 2. Definitions.

For the purposes of this royal decree, it is understood by:

1. Spanish System of Pharmacovigilance of Medicinal Products for Human Use: Decentralized structure, coordinated by the Spanish Agency for Medicines and Health Products, which integrates the activities that the health administrations carry out in a way permanent and continuous to collect, elaborate and, where appropriate, process information on suspected adverse drug reactions in order to identify previously unknown risks or known risk changes, as well as for the performance of all studies deemed necessary to confirm and/or to quantify these risks. It is composed of the pharmacovigilance bodies responsible for the pharmacovigilance of the autonomous communities and the pharmacovigilance units or centres of pharmacovigilance to them, the Spanish Agency for Medicines and Health Products, the health professionals and citizens.

2. Spontaneous Notification Programme: Pharmacovigilance method based on the communication, collection, recording and evaluation of reports of suspected adverse drug reactions.

3. Pharmacovigilance Autonomous Centre: Unit responsible for implementing the spontaneous notification programme and any other pharmacovigilance tasks entrusted to it by the relevant autonomous community, without prejudice to the name of the receive in each of them.

4. Adverse reaction: Any harmful and unintended response to a drug.

5. 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 significant disability or disability or persistent, or constitutes 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, even if they do not meet the above criteria, such as those at risk to the patient or require an intervention to prevent any of the previous outcomes and all suspicions of transmission of an infectious agent through a drug.

6. Unexpected adverse reaction: Any adverse reaction whose nature, severity or consequences are not consistent with the information described in the technical information sheet of the medicinal product.

7. Medication error: Unintended failure in the process of prescribing, dispensing or administering a drug under the control of the healthcare professional or the citizen who consumes the medication. Medication errors that cause damage to the patient are considered to be adverse reactions, except for those derived from the treatment failure by default.

8. Pharmacovigilance system master file: Detailed description of the pharmacovigilance system used by the marketing authorisation holder in relation to one or more authorised medicinal products.

9. Signal: Pharmacovigilance information from one or more sources suggesting a possible new causal association or a new aspect of a known association between a medicinal product and an event or grouping of adverse events, which is deemed to be credible enough to justify actions for verification.

10. Yellow card: Form for notification of suspected adverse reactions. Its format can be on paper or electronic.

11. Medicinal products subject to further monitoring: Medicines included in the list to be prepared and maintained by the European Medicines Agency in accordance with the criteria laid down in Article 23 of Regulation (EC) No 726/2004 of the European Parliament and the Council of 31 March 2004 laying down Community procedures for the authorisation and control of medicinal products for human and veterinary use and establishing a European Medicines Agency. That list shall be drawn up after consultation of the European Pharmacovigilance Risk Assessment Committee and shall contain all medicinal products containing new active substances and biological medicinal products, including biosimilars. The list may also contain medicinal products subject to the obligation to carry out a post-authorisation study, or to conditions or restrictions on the safe and effective use of the medicinal product.

12. Good Practice of the Spanish Pharmacovigilance System: Set of standards and recommendations developed by the Technical Committee of the Spanish Pharmacovigilance System, taking into account the European guidelines on good practice in the field of pharmacovigilance pharmacovigilance, intended to ensure:

(a) The authenticity and quality of the suspected adverse reaction data collected by the Spanish Pharmacovigilance System.

b) The confidentiality of information regarding the identity of patients and healthcare professionals.

c) The use of homogeneous criteria in the management of information collected through the spontaneous reporting program.

13. Good Pharmacovigilance Practices for the Pharmaceutical Industry: Set of quality standards for the organisation and operation of marketing authorisation holders for medicinal products intended to guarantee authenticity and the quality of the safety data for the continued assessment of the risks associated with the medicinal products for which it is a holder.

14. Risks associated with the use of the medicinal product: Any risk to the health of the patient or public health related to the quality, safety or efficacy of the medicinal product, as well as any risk of undesirable effects in the medium environment.

15. Periodic Safety Report: Document prepared by the marketing authorisation holder in accordance with the rules and guidelines established in this respect in the European Union, the purpose of which is to update the new information which is know about the medicine in the reference period, including a scientific assessment of the benefit-risk balance of the medicine.

16. Post-authorisation study: Any clinical or epidemiological study carried out during the marketing of a medicinal product in accordance with the conditions authorised in its technical file, or under normal conditions of use, in which the medicinal product or Medicinal products of interest are the fundamental exposure factor investigated. This study may take the form of a clinical trial or an observational study.

17. Post-authorisation safety study: Any post-authorisation study carried out for the purpose of identifying, characterizing or quantifying a safety risk, confirming the safety profile of an authorised medicinal product or measuring the effectiveness of risk management measures.

18. Prospective follow-up study: All this post-authorisation study in which patients are followed over time in relation to the event of interest, being all or part of the period under investigation after the event. start date of the study.

19. Balance or benefit-risk ratio of the medicinal product: Valuation of the favourable therapeutic effects of the medicinal product in relation to the risks associated with its use.

20. Risk management system: A set of pharmacovigilance activities and interventions aimed at determining, characterizing, preventing or minimising risks related to a medicinal product, including the assessment of the effectiveness of such activities and interventions.

21. Risk Management Plan: Detailed description of the risk management system.

Article 3. Sources of information in pharmacovigilance.

1. Information on the risks associated with the use of medicinal products may come from the following sources:

(a) Results of studies provided by applicants or holders of marketing authorisations for medicinal products, or by independent researchers, be they quality, preclinical (pharmacological and toxicological) studies, pre-authorisation studies, post-authorisation studies, or meta-analysis.

b) Individual cases of suspected adverse reactions in Spontaneous Reporting Programs.

c) Informatised health data bases.

d) Records of patients selected on the basis of pathologies or pharmacological treatments and any other type of systematic collection of information on safety aspects of medicinal products.

e) Data related to the manufacture, preservation, sale, distribution, dispensing, prescribing and use of the medicinal products, including the use of medicinal products.

f) Data regarding the misuse and abuse of medication, medication errors, or occupational exposure, which are relevant to the assessment of the benefits and risks of the medications.

g) Scientific case publications, case series, pharmacological and toxicological studies, clinical trials, pharmacoepidemiological studies and meta-analysis.

h) Information from other health authorities and international health agencies.

i) Any other source of information that may provide data on the risks associated with the use of the medicinal products.

2. The Spanish Agency for Medicinal Products and Sanitary Products will establish the necessary agreements with the competent agencies of the General Administration of the State and the Autonomous Communities to facilitate the shared use of the information that they are dependent on as referred to in paragraphs (c), (d), (e) and (f) of the previous paragraph.

CHAPTER II

From health administrations

Article 4. Duties of the Spanish Agency for Medicinal Products and Sanitary Products for the pharmacovigilance of medicinal products for human use.

1. They are the functions of the Spanish Agency for Medicines and Health Products:

a) Coordinate and evaluate the functioning of the Spanish Pharmacovigilance System for medicinal products for human use, hereinafter the Spanish Pharmacovigilance System, taking into account the Good Practices of the Spanish System of Pharmacovigilance.

In the exercise of its coordination powers, the Spanish Agency for Medicines and Health Products will monitor the continuity and quality of the spontaneous notification program in the respective autonomous communities, and present an annual report on the activities of the Spanish Pharmacovigilance System to the Committee for the Safety of Medicinal Products for Human Use. It shall inform the competent authorities of the pharmacovigilance of the autonomous communities of any deviation from its proper functioning, in order to ensure that they provide for the necessary corrective measures. Report to the Committee on the Safety of Medicinal Products for Human Use.

b) To carry out the duties of the Secretariat of the Committee on the Safety of Medicinal Products for Human Use, the Technical Committee of the Spanish Pharmacovigilance System and the Committee for the Coordination of Possession Studies. The objectives, functions and composition of these committees are set out in Royal Decree 1275/2011 of 16 September 2011 establishing the State Agency for the Spanish Agency for Medicines and Health Products and approving its Statute.

(c) to establish and maintain, in coordination with the autonomous communities, a data processing network enabling the competent health authorities in the field of pharmacovigilance to provide for the telematic form of the whole of the information on suspected adverse reactions occurring in Spain from which knowledge has been known. This information will be integrated into the database called "Spanish Pharmacovigilance, Adverse Reactions Data", hereinafter FEDRA.

d) Administer the FEDRA database, ensuring its availability and updating at all times, ensuring its security, as well as the protection of personal data, and the integrity of the data during the process of transfer of the same. The Spanish Agency for Medicinal Products and Sanitary Products will establish, in collaboration with the Technical Committee of the Spanish Pharmacovigilance System, the terms in which this information will be made available to the public.

(e) Act as a reference centre for the Spanish Pharmacovigilance System with the holders of marketing authorisations for medicinal products and with international organisations, without prejudice to the powers of the pharmacovigilance of the autonomous communities.

(f) To transmit to the database of the European Medicines Agency, Eudravigilance, the notifications of suspected serious adverse reactions reported by healthcare professionals or citizens to the The Spanish Pharmacovigilance System, within the fifteen calendar days following its receipt.

g) To transmit to Eudravigilance the reports of suspected non-serious adverse reactions reported by healthcare professionals or citizens to the Spanish Pharmacovigilance System, within 90 days natural following their receipt.

h) Establish, in coordination with the Pharmacovigilance Autonomic Centres, a system that allows notification via electronic forms on websites of suspected adverse reactions by the health professionals and citizens.

i) To provide the European Commission with biennial information on pharmacovigilance activities, including those that are the responsibility of the Spanish Pharmacovigilance System.

j) Promote the creation and facilitate the use of computerized health data bases that serve as a source of information for the conduct of pharmacologic studies with the participation of health administrations of the Autonomous Communities and healthcare professionals, as well as to stimulate the creation and maintenance of a unified registry of the available databases.

k) Promote the creation of independent records that provide information on the safety of authorised medicinal products, in collaboration with the Autonomous Communities and healthcare professionals.

l) Promote and conduct pharmacoepidemiology studies aimed at assessing the benefit-risk ratio of authorised medicinal products.

m) Evaluate the information received from the Spanish Pharmacovigilance System, as well as other sources of information.

n) Assess the occurrence of new risks or changes in existing risks, periodic safety reports, risk management plans, results of post-authorisation studies that may change the relationship benefit-risk of the medicinal products and any other report on the safety of medicinal products, in coordination with the competent authorities of the Member States. In this regard, it shall draw up the reports for the network of national agencies of the European Union where it is determined by referring those reports to the Member States and the European Medicines Agency within the time limits laid down.

n) Establish appropriate measures to minimize or prevent identified risks, including necessary training and information, and assess the impact of such measures.

o) Publish, through its web portal, the summaries of risk management plans, the list of drugs subject to additional monitoring and information on the means to report suspected adverse reactions by part of healthcare professionals and citizens along with the web form for their communication, as well as any other information that is relevant to minimise the risks associated with medicines.

p) Spread information deemed relevant for the protection of public health including, where relevant, data submitted by marketing authorisation holders or by any other entity or person.

q) Collaborate in the European Pharmacovigilance Risk Assessment Committee of the European Medicines Agency and perform the tasks entrusted to it.

r) Establish, in conjunction with the Autonomous Communities within the Technical Inspection Committee, the relevant inspection procedures to ensure compliance with the obligations of the authorisation holders (a) to be placed on the market, as indicated in Chapter IV, and to carry out the necessary inspections to verify compliance within its field of competence.

s) Any other function which may be necessary in the field of pharmacovigilance, and which should be exercised by the Spanish Agency for Medicines and Health Products.

2. The Spanish Agency for Medicinal Products and Sanitary Products will ensure, in its field of competence, the means necessary to carry out the tasks above, meeting the minimum requirements of the quality system established by the European Commission in implementing measures, as well as the conduct of independent studies aimed at assessing the safety of medicinal products.

Article 5. Functions of the Autonomous Communities.

They are the functions of the autonomous communities, through their competent bodies or the units in which they delegate:

1. Permanently and continuously establish a spontaneous reporting program in line with the Good Practices of the Spanish Pharmacovigilance System, and communicate to the Spanish Agency for Medicines and Health Products the responsible unit to run this task on the stand-alone community.

2. Promote and carry out the pharmacovigilance actions, studies or programmes to be agreed within the Technical Committee of the Spanish Pharmacovigilance System.

3. To enable the reporting of suspected adverse reactions by healthcare professionals and citizens through various means, including electronic means, taking into account the agreed upon within the Technical Committee of the Spanish System of Pharmacovigilance.

4. Implement different strategies to facilitate the reporting of suspected adverse reactions to physicians, pharmacists and other healthcare professionals and citizens. The design of these strategies will be carried out in coordination with the Spanish Agency for Medicines and Health Products within the Technical Committee of the Spanish Pharmacovigilance System, with the participation of organizations of consumers and patients, scientific societies and professional organisations.

5. To record in the FEDRA database the suspicions of the adverse reactions received. The maximum period for this registration shall be ten calendar days from the receipt of the information for serious cases and eighty calendar days from receipt for non-serious cases.

6. To provide the Spanish Agency for Medicines and Health Products with the information required to assess the benefit-risk ratio of the medicinal products or the impact of the regulatory measures implemented for safety reasons.

7. Evaluate the information contained in the FEDRA database and other databases of suspected adverse reactions to detect signals.

8. Cooperate with the Spanish Agency for Medicines and Health Products and the marketing authorisation holders in the detection of possible duplication of reports of suspected adverse reactions.

9. Cooperate with the Spanish Agency for Medicines and Health Products for the implementation and development of programmes and studies on the evaluation and management of the risks of medicinal products, in accordance with the agreements adopted by the Committee of Safety of Medicinal Products for Human Use.

10. Cooperate with the Spanish Agency for Medicines and Health Products in the dissemination of knowledge on the safety of medicines.

11. Establish systems of collaboration with the patient safety units, so that the suspected adverse reactions resulting from medication errors are integrated into the FEDRA database, informing them in turn. units of cases that directly reach the Pharmacovigilance Autonomous Centres.

12. Implement the appropriate measures agreed in the Technical Committee of the Spanish Pharmacovigilance System, aimed at identifying the name of the medicinal product and the batch number in those notifications involving medicinal products of origin biological or biotechnological.

13. Implement appropriate measures to obtain the necessary information for the appropriate scientific assessment of the notifications of suspected adverse reactions, involving the marketing authorisation holders, to the health professionals or citizens, as appropriate, in obtaining follow-up information.

14. Carry out and submit to the Spanish Agency for Medicines and Health Products an annual activity report and carry out biennial internal audits of its Pharmacovigilance Autonomic Center, issuing a report to the Spanish Agency of Medicines and Healthcare products.

15. Perform the functions related to the post-authorisation studies referred to in Chapter VI.

16. Carry out the necessary inspections to verify compliance with the provisions of Chapter V, within its scope of competence and notify the Spanish Agency of Medicines and Health Products the result of the inspections, both the favorable as the unfavorable ones, including in the latter case the defaults they detect.

17. Contribute to scientific progress by improving pharmacovigilance methods, as well as knowledge and understanding of the nature and mechanisms of adverse reactions, and the safety profile of medicinal products.

18. Any other function which may be necessary in the field of pharmacovigilance, and which should be exercised by the Autonomous Communities.

19. The autonomous communities shall ensure the means necessary to carry out the tasks above.

CHAPTER III

From healthcare professionals and citizens

Article 6. Participation of healthcare professionals.

Healthcare professionals have an obligation to:

1. To report suspected adverse reactions to authorised medicinal products, including those used under conditions other than those authorised. These notifications shall be sent as soon as possible to the Pharmacovigilance Autonomic Centre corresponding to its care, by means of any of the routes available to it. The web address for your electronic notification will be available in the medical records of the medicines.

Priority should be given to reporting suspected serious or unexpected adverse reactions of any medicinal product and those related to medicinal products subject to further monitoring. The latter shall be identified by a symbol, common to the whole of the European Union, which shall be included in the information on the medicinal product in accordance with Article 12 (5

.

2. To report suspected adverse reactions of medicinal products not marketed in Spain that have been obtained through the procedures set out in Royal Decree 1015/2009 of 19 June, which regulates the availability of medicines in special situations, as set out in the same.

3. When suspected adverse reactions are caused by a medication error, they will specify this circumstance on the yellow card. For this purpose, special procedures shall be established to be collected in the Good Practice document of the Spanish Pharmacovigilance System.

4. Keep clinical documentation of suspected adverse drug reactions for at least five years in order to complete or follow up, if necessary.

5. Cooperate with the Spanish Pharmacovigilance System, providing the necessary information to enable them to expand or complete the information on suspected adverse reactions reported.

6. Where a suspected adverse reaction has been reported to the marketing authorisation holder, collaborate with the marketing authorisation holder by providing the information necessary for its proper scientific assessment.

7. To be kept informed of safety data relating to medicinal products which are normally prescribed, dispensed or administered, and to carry out the risk prevention measures set out in the technical fiche of the medicinal product and how many procedures are agreed to facilitate compliance with these measures, including training and information measures for users.

8. Collaborate with the Spanish Agency for Medicines and Health Products and the Autonomous Communities in any request for the systematic collection of information aimed at assessing the risks of the drugs or the impact of the measures administrative implementation to minimize them, including what is established in risk management plans.

9. Collaborate, as experts, with the Spanish Agency for Medicines and Health Products and with the Pharmacovigilance Autonomic Centres on what they are asked to do.

Article 7. Participation of citizens.

Citizens will be able to report suspected adverse drug reactions, or by placing them in the knowledge of healthcare professionals who, after their clinical assessment, will bring them to the attention of the The Spanish Pharmacovigilance System, or directly to the Spanish Pharmacovigilance System. The latter shall be provided via an electronic form on a website, the access of which shall be indicated in the package leaflet for each medicinal product.

CHAPTER IV

From marketing authorization holders

Article 8. Pharmacovigilance system of the marketing authorisation holder.

The marketing authorisation holder must have an appropriate system for the performance of its pharmacovigilance functions, aimed at monitoring the safety of authorised medicinal products and identifying any changes to your benefit-risk ratio. A summary of the same should be included in the marketing authorisation application.

For this purpose, the Marketing Authorisation Holder shall:

1. Develop a pharmacovigilance system master file. The Spanish Agency for Medicinal Products and Sanitary Products may at all times require the holder of the marketing authorization to submit a copy of this file, which must be submitted no later than seven days. natural since the reception of the requirement. The pharmacovigilance system master file will also be available for inspection purposes.

2. Perform an independent and periodic audit of your pharmacovigilance system, collecting the main results in the master file. Based on them, you will ensure that an appropriate corrective action plan is drawn up and implemented, and you can remove the reference to the audit results after the corrective actions have been completed.

3. To have at its disposal permanently and continuously a duly qualified person responsible for pharmacovigilance in the European Union. This person will reside and carry out his activities in the European Union and will be responsible for the establishment and maintenance of the pharmacovigilance system. The marketing authorisation holder shall communicate to the Spanish Agency for Medicinal Products and Health Products and to the European Medicines Agency the name and contact details of the responsible person.

4. Scientifically evaluate all information, consider options to minimize and prevent risks, and adopt, if necessary, appropriate measures.

5. Comply with the standards of Pharmacovigilance Good Practice for the pharmaceutical industry published by the Spanish Agency for Medicines and Health Products.

Article 9. Obligations in relation to suspected adverse reactions.

For suspected adverse reactions, the holder of a marketing authorisation shall:

1. To record electronically the suspected adverse reactions occurring in Spain, in the European Union or in a third country of which they are aware, both spontaneously reported by healthcare professionals or citizens as the ones collected during a post-authorization study.

2. To communicate by electronic means the suspicions of individual cases of adverse reactions on the basis of the requirements set out in the European Union reflected in the documents referred to in the second paragraph of Article 1.

3. Send by electronic means to the Eudravigilance database:

(a) All suspected serious adverse reactions occurring in the European Union and in third countries, in the 15 calendar days following the day on which they were aware of these.

(b) All suspicions of non-serious adverse reactions occurring in the European Union in the 90 calendar days following the day on which they were aware of these.

For suspected adverse reactions reported by healthcare professionals exercising their professional activity in Spain, or by citizens who are in Spain, the marketing authorisation holder must include information to enable knowledge of the autonomous community where the health care professional is active or where the citizen who has reported the case resides, respectively.

The suspicion of adverse reactions collected in the course of a clinical trial shall be reported in accordance with the relevant regulations.

4. Notify the Spanish Agency of Medicines and Health Products of suspected adverse reactions to investigational medicinal products obtained through compassionate use of which they are aware.

5. Properly identify suspected adverse reactions whose notifier has explicitly reported that they are the result of a medication error.

6. To monitor the global scientific literature, in order to identify cases of suspected adverse reactions associated with an active substance in a medicinal product that is a holder in Spain occurring in the European Union, as well as in third countries where the holder has the marketing authorisation for a medicinal product containing that active substance. Such cases shall be communicated by electronic means on the basis of the European requirements set out in the documents referred to in the second paragraph of Article 1. However, for medicinal products with the active substances included in the list supervised by the European Medicines Agency in accordance with Article 27 of Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, the marketing authorisation holders shall not be required to notify the Eudravigilance database of suspected adverse reactions in the medical literature which is included in the list of publications supervised by the European Medicines Agency.

7. Establish procedures for accurate and verifiable information to allow for the scientific evaluation of reports of suspected adverse reactions. For this purpose, they shall collect monitoring information on notifications where it is deemed necessary by the marketing authorisation holder, or by the Spanish Pharmacovigilance System and shall communicate the updates. of that information in accordance with paragraph 3 of this Article.

8. Collaborate with the Spanish Pharmacovigilance System to detect duplicate reports of suspected adverse reactions.

9. Include in the reporting of suspected adverse reactions exposures of descriptive and textual type integras in Spanish as reported, as well as a summary in English.

10. Marketing authorisation holders for homeopathic medicinal products authorised under Article 57 of Royal Decree 1345/2007 of 11 October 2007 are exempted from the establishment of a system of pharmacovigilance, but they shall in any case inform immediately to the Spanish Pharmacovigilance System according to the usual channels established for this purpose, of any incident that has caused damage to the patient.

Article 10. Obligations in relation to periodic safety reports.

1. The marketing authorisation holder shall submit the periodic safety update reports to the file set up for that purpose in the European Medicines Agency pursuant to Article 25a of Regulation (EC) No 1225/2009. 726/2004 of the Parliament and of the Council of 31 March 2004.

2. Periodic safety reports will be in the format agreed in the European Union. These will include summaries of relevant data on the benefits and risks of the medicinal product, taking into account the results of all studies, with an assessment of their potential impact on marketing authorisation and an assessment. Scientific evidence of the benefit-risk ratio of the medicinal product, in addition to all data relating to the volume of sales of the medicinal product, as well as any data on the number of prescriptions held by the marketing authorisation holder, together with an estimate of the number of people exposed to the drug.

3. With regard to the frequency and date of submission of periodic safety reports:

(a) The frequency and date of submission of periodic safety update reports shall be established under the conditions for the marketing authorisation of the medicinal product and may be amended after authorisation has been granted. marketing.

b) The date of submission of periodic safety reports is calculated from the date of the authorization of the medicinal product.

(c) The presentation shall be made immediately at the request of the Spanish Agency for Medicinal Products and Sanitary Products, and also on a regular basis in accordance with the time limits laid down in this paragraph, provided that there is no established another frequency as a condition for the marketing authorisation of the medicinal product. The frequency of submission of the reports shall be half-yearly from the authorisation and until the marketing year. Once they are placed on the market, they shall be submitted semi-annually for the first two years after first placing on the market in any country of the European Union and annually for the following two years. From that point on, the periodic safety report shall be submitted at intervals of three years.

4. Without prejudice to paragraph 3 and in order to carry out a harmonised single assessment of periodic safety reports for medicinal products containing the same active substance or the same combination of active substances, authorised in more than one Member State of the European Union, the frequency and dates of submission may be amended and harmonised according to a reference date of the European Union. This date shall be agreed by the competent European authorities on the basis of the date of authorisation of the first medicinal product containing that active substance or the same combination of active substances in the European Union. In this regard:

(a) The frequency, reference date and dates of submission shall be published on the website of the Spanish Agency for Medicines and Health Products and on the European medicines web-portal.

(b) Marketing authorisation holders shall request an amendment to the conditions of authorisation in order to present these periodic safety reports according to the Union reference date. European.

(c) In turn, marketing authorisation holders may request the competent European authorities to change the reference date of the European Union or the frequency of submission of the periodic reports. for the safety of a medicinal product in order to avoid duplication of assessment, to achieve international harmonisation or for reasons of public health.

(d) Any modification of the dates and frequency of submission of periodic safety reports, as a result of the application of this paragraph 4, shall enter into force six months after the date of publication.

e) The single assessment will be carried out in a harmonised manner between the countries of the European Union. The marketing authorisation holder shall have 30 calendar days, from the receipt of the assessment report, to issue his observations, which he shall send to the European Medicines Agency and to the country which is leading the marketing authorisation. evaluation. The final evaluation will be adopted within the Committee for the Evaluation of Risks in European Pharmacovigilance, which will issue a recommendation. The regulatory measures arising from that recommendation shall be made available to the marketing authorisation holder. If the conditions for authorisation are to be amended, the marketing authorisation holder shall request the modification of the marketing authorisation concerned on the basis of the timetable which is set.

5. Medicinal products authorised as generics, homeopathic medicinal products authorised through a simplified register, traditional herbal medicinal products or those for use are exempt from the submission of periodic safety reports. established, unless that obligation has been imposed as a condition of the marketing authorisation or where the Spanish Agency for Medicinal Products and Health Products so requests for pharmacovigilance or due reasons that periodic safety reports are no longer available for the active substance that contains the medicine.

Article 11. Obligations in relation to risk management systems and post-authorisation studies.

In relation to risk management systems and post-authorisation studies, the marketing authorisation holder shall:

1. To have a risk management system for each medicinal product for which marketing authorisation is sought after the entry into force of this royal decree. For medicinal products already authorised, the Spanish Agency for Medicinal Products and Sanitary Products may require the marketing authorisation holder to have a risk management system in the event of new risks appearing which may arise. affect the benefit-risk ratio of the medicinal product. In such cases, the marketing authorisation holder may submit claims within 30 calendar days of receipt of the application. If, once the claims have been made, the Spanish Agency for Medicinal Products and Sanitary Products ratifies the need for the risk management system, the risk management system shall be incorporated into the marketing authorisation. In this respect:

(a) The conditions required during the authorisation procedure of the medicinal product or subsequently shall be incorporated into the risk management system.

b) Monitor the outcome of risk minimisation measures included in the risk management system.

c) The risk management system will be updated.

(d) The risk management plan shall be submitted to the Spanish Agency for Medicines and Health Products together with a summary of the risk management plan in Spanish, according to the format to be established.

2. Carry out the post-authorisation studies required by the Member States or the European Commission:

a) As a condition of the marketing authorization. The marketing authorisation shall, where necessary, set the time limits for compliance.

(b) After the granting of a marketing authorisation, in the event of any doubt as to the safety of an authorised medicinal product. When this affects more than one medicinal product, the Spanish Agency for Medicinal Products and Sanitary Products, after consulting the Committee for the Evaluation of Risks in European Pharmacovigilance, will invite the marketing authorisation holders in order to jointly carry out a single study.

3. Carry out the post-authorisation studies required by the Member States or the European Commission in the following circumstances:

(a) As a condition of the marketing authorisation, when questions are raised about the efficacy of the medicinal product which can only be resolved after the marketing authorisation is made available. The marketing authorisation shall, where necessary, set the time limits for compliance.

(b) After the granting of a marketing authorisation, where knowledge of the disease or clinical methodology indicates that prior assessments of efficacy may have to be reviewed in a manner significant.

The requirement for such studies will be based on the situations stipulated by the European Commission.

Article 12. Obligations for continuous assessment of the benefit-risk and update of the conditions of authorisation.

The marketing authorization holder must:

1. Carry out a continuous evaluation of the benefit-risk ratio of the medicines you have authorized in Spain, immediately communicating to the Spanish Agency for Medicines and Health Products any new information that may influence in the overall assessment of the benefit-risk relationship or which may require the modification of the technical sheet, package leaflet or both.

You must also immediately notify the Spanish Medicines and Health Products Agency of any restrictions, suspension or prohibition imposed by the competent authorities of any country.

2. Provide a benefit-risk report when requested by the Spanish Medicines and Healthcare Products Agency, or any additional information deemed necessary by the Agency to be able to assess the risk-benefit ratio of a medicinal product, including information relating to the volume of sales or prescription of the medicinal product concerned. The marketing authorisation holder shall respond in full and within the required time limits to such requests.

3. Carry out in Spain regulatory measures taken for safety reasons, including those referred to in the risk management plan.

4. Assess the impact of regulatory measures taken for safety reasons, including, where appropriate, any studies deemed necessary.

5. For medicinal products that are included in the list of medicinal products subject to additional monitoring, published on the European medicines web-portal and on the website of the Spanish Agency for Medicines and Health Products, the holder will be required to include the symbol, followed by the phrase and explanation agreed by the competent authorities of the European Union, on the technical fiche and package leaflet; it shall also be required to include information on the additional monitoring status in any type of material for dissemination to healthcare professionals, including those for dissemination to patients through healthcare professionals.

Article 13. Information provided by the marketing authorisation holder for safety reasons.

1. The marketing authorisation holder shall inform the Spanish Agency for Medicinal Products and Sanitary Products in advance of any communication to the public on pharmacovigilance issues relating to its medicinal product. It shall ensure that the information is presented in an objective and non-misleading manner, without ignoring relevant security information. Dissemination of information without respecting the terms set out in this paragraph will be considered as a breach of the duty of pharmacovigilance provided for in Article 101.2.b.14 of Law 29/2006 of 26 July of guarantees and the rational use of medicines and medical devices.

2. Where, at the discretion of the marketing authorisation holder, the Spanish Agency for Medicinal Products and Sanitary Products or the European Medicines Agency, it is deemed necessary for the first report to be given to healthcare professionals on data relating to the safety of the medicinal product or the prevention of risks, and it is decided to forward information on an individual basis to the data, the holder shall:

a) Agreed previously with the Spanish Agency for Medicines and Health Products for the text and any other complementary material.

b) Agree on the communication strategy, which will include at least the distribution procedure, the calendar and the type of healthcare professional to which it should be addressed. The Spanish Agency for Medicines and Health Products shall also inform the marketing authorisation holders of the bodies or institutions to which the communication is to be sent in all cases.

c) Report to the Spanish Agency for Medicines and Health Products on the number of healthcare professionals to whom the communication has been made.

d) To properly identify in the communication that the text has been agreed with the Spanish Agency for Medicines and Health Products and incorporate a flag indicating the nature of the information contained therein.

The obligations set out in this paragraph will also apply to the material aimed at minimising risks included in the risk management plans to be made known to healthcare professionals and, through these, to the patients.

Article 14. Pharmacovigilance contact person.

1. The marketing authorisation holder shall have a permanent and continuous availability in Spain of a person of contact in the field of pharmacovigilance and shall communicate to the Spanish Agency for Medicinal Products and Medicinal Products the contact of the same through an electronic system that will be provided for this purpose. The designated person shall have the appropriate experience and training for the performance of his/her duties. The Spanish Agency for Medicines and Health Products will maintain a database of these people, which will be available to the competent bodies of the Autonomous Communities.

2. The pharmacovigilance contact person shall assist the qualified person responsible for European pharmacovigilance referred to in Article 8.3 in those tasks entrusted to him and shall collaborate in the following tasks:

(a) Collect, information on all suspected adverse reactions to which the staff of the undertaking is aware, in order for such information to be incorporated in the register referred to in paragraph 1 of the Article 9, ensuring that:

1. º accurate and verifiable information is obtained to allow for the scientific evaluation of reports of suspected adverse reactions.

2. º Tracking information about these notifications is collected.

3. In collaboration with the Spanish Pharmacovigilance System, duplicate cases of suspected adverse reactions are detected.

4. The suspicion of adverse reactions reported by the notifier as a result of a medication error is adequately identified.

(b) Transfer to the person responsible for pharmacovigilance of the European Union referred to in Article 8.3 any request for additional information from the Spanish Agency for Medicines and Health Products needed for be able to assess the benefits and risks of a medicinal product and to respond to any information which the Spanish Agency for Medicinal Products and Health Products requests concerning the volume of sales or prescriptions of the medicinal product concerned Spain.

c) Act as a point of contact to provide information to the Spanish Agency for Medicines and Health Products on the implementation in Spain of the regulatory measures taken for security reasons, as well as actions carried out in Spain relating to the provisions of the risk management plan.

d) Establish the necessary procedures to ensure the proper functioning of local pharmacovigilance activities.

e) Act as a contact person for pharmacovigilance inspections carried out in Spain.

f) Co-operate with the autonomic pharmacovigilance centres by providing all the information available to them in relation to reports of suspected adverse drug reactions.

CHAPTER V

From administrative intervention

Article 15. Advisory body and expert participation.

1. The Spanish Agency for Medicinal Products and Sanitary Products will have the Committee for the Safety of Medicinal Products for Human Use, a collegiate body provided for in the Statute of this approved by Royal Decree 1275/2011 of 16 September 2011. advice on pharmacovigilance matters.

2. The Spanish Agency for Medicines and Health Products will be able to request the advice of drug safety experts and in other medical and scientific areas, among which will be the technicians of the Spanish System of Pharmacovigilance.

Article 16. Amendment of the authorisation for reasons of pharmacovigilance.

1. In accordance with Article 17.9 of Law 29/2006 of 26 July, when the holder of a marketing authorisation for a medicinal product is aware of any relevant new information affecting the safety of that medicinal product, it shall update without procrastination of the authorisation and registration dossier, by means of the procedures for the modification of the conditions for the authorisation of medicinal products for human use, the failure to comply with the conditions for suspension or revocation of the authorisation. These modifications shall be subject to payment of the corresponding fee.

2. The marketing authorisation holder shall ensure that the information on the medicinal product is up to date, in the light of the latest scientific knowledge, including the conclusions of the evaluations and the recommendations published on the European medicines web-portal, established in accordance with Article 26 of Regulation 726/2004 of the European Parliament and of the Council of 31 March 2004, and on the website of the Spanish Medicines Agency and Sanitary Products.

The above conclusions will include those agreed in the Coordination Group or issued by the European Commission, as appropriate. These shall be based on the recommendations of the European Pharmacovigilance Risk Assessment Committee derived from periodic safety report assessments, post-authorisation studies, results of risk management plans and the following: any data on new risks or changes in the risks already known. In order to provide the holder of the marketing authorisation with the fulfilment of its obligations, the Spanish Agency for Medicinal Products and Sanitary Products shall include in its website an application timetable. It shall inform the data subject of any other measure aimed at reducing the risk.

3. Where the evaluation of pharmacovigilance data is based on reasons of public interest, protection of the health or safety of persons, the Spanish Agency for Medicinal Products and Health Products may restrict the conditions of authorisation. of a medicinal product, and to establish any of the reserves or restrictions of the scope of use listed below, as defined in the rules governing the procedure for the authorisation, registration and conditions of supply of medicinal products for human use industrially manufactured:

a) Medicament for hospital use (H).

b) Medical diagnosis or prescription by certain medical specialists (DH).

c) Special medical control medicine (ECM).

These reserves or restrictions of use may also be applied to medicinal products authorised by the European Commission subject to restricted medical prescription.

Article 17. Urgent amendments for reasons of security and applicable procedure.

1. Where new information is known to indicate an important public health risk associated with the use of a medicinal product or which has a relevant impact on the safety of the medicinal product, the Spanish Agency for Medicinal Products and Products Health care may agree to the temporary and urgent change in the information of the medicinal product which will affect in particular one of the following sections of the technical fiche: indications, posology, contraindications, adverse reactions, warnings and special precautions for use, including warnings concerning their use during pregnancy and breast-feeding.

2. Where the holder of the marketing authorisation considers it necessary to amend the conditions for the authorisation of a medicinal product for safety reasons as a matter of urgency, he shall request that amendment from the Spanish Medicines Agency and Sanitary Products, accompanying the following documentation:

a) Report on the detected risks that make the modification necessary.

b) Proposal for amendment of the Summary of Product Characteristics and Package Leaflet.

c) Proposal for information to healthcare professionals and, where appropriate, the provision of information to users.

d) Proposal for complementary actions, as well as any other information deemed necessary for the effective implementation of the amendment.

If the Spanish Agency for Medicinal Products and Sanitary Products does not raise any objection within the business day following receipt of the information, urgent amendments for safety reasons shall be deemed to be accepted. on a provisional basis and the marketing authorisation holder shall request the amendment of the technical information sheet within 15 calendar days from the date of acceptance. The Spanish Agency for Medicines and Health Products shall establish the specific procedures to be followed.

3. Where the urgent amendment for safety reasons is imposed by the Spanish Agency for Medicinal Products and Sanitary Products, the marketing authorisation holder shall be obliged to submit a request for amendment to the terms to be established by the Agency immediately and within a period not exceeding 15 calendar days following receipt of the Agency's notification.

4. In the cases referred to in paragraphs 2 and 3, the time limit and the terms of the information addressed to healthcare professionals, as well as the effective implementation of the amendment by the holder, including changes in the material packaging, will be agreed with the Spanish Agency for Medicines and Health Products.

5. In the case of products authorised under the mutual or decentralised recognition procedure, account shall be taken of the harmonisation mechanisms to be established for this purpose in the European Union through the relevant guidelines. For products authorised in accordance with the centralised procedure, the provisions specified in Commission Regulation (EC) No 1234/2008 of 24 November 2008 on the examination of amendments to the terms of the rules of procedure shall be followed. authorisations for the placing on the market of medicinal products for human use and veterinary medicinal products granted by the competent authority of a Member State, and the guidelines which develop it.

Article 18. Suspension or revocation of the authorisation for reasons of pharmacovigilance.

The Spanish Agency for Medicinal Products and Health Products, in accordance with the evaluation of pharmacovigilance data, may temporarily suspend or revoke the authorisation of a medicinal product when:

1. Have an unfavorable benefit-risk relationship.

2. Pose an unacceptable risk to people's health or safety.

3. The pharmacovigilance rules are not complied with, in accordance with the provisions of Article 22.1.d of Law 29/2006 of 26 July.

4. This is regulated in the current legislation.

Article 19. The urgency procedure of the European Union.

1. The Spanish Agency for Medicinal Products and Sanitary Products shall initiate the procedure laid down in this Article by informing the other Member States, the European Medicines Agency and the European Commission whether, as a result of the assessing a safety concern and providing advice from the Committee on the Safety of Medicinal Products for Human Use, considering suspending or revoking a marketing authorisation, prohibiting the supply of a medicinal product or refusing to provide it renewal of a marketing authorisation.

2. The Spanish Agency for Medicines and Health Products shall also assess the initiation of the procedure laid down in this Article by informing the other Member States, the European Medicines Agency and the European Commission whether, as Result of the evaluation of a security problem:

(a) considers necessary, after consulting the Committee on Safety of Medicinal Products for Human Use, a new contraindication, a reduction of the recommended dose, a restriction of the indications or any of the reservations or restrictions of the scope of use referred to in Article 16.3. or,

(b) the holder of a marketing authorisation has informed him that, on the basis of safety concerns, he has discontinued the placing on the market of a medicinal product or has taken measures for the withdrawal of a marketing authorisation marketing, or plans to do so, or has not requested the renewal of a marketing authorisation.

3. In the case of medicinal products containing active substances authorised in more than one Member State of the European Union, the matter shall be evaluated by the Committee for the Evaluation of Risks in European Pharmacovigilance, with the the aim of reaching a common decision at the level of the European Union. In this respect:

(a) The Spanish Agency for Medicinal Products and Health Products shall provide the Committee for the Evaluation of Risks in European Pharmacovigilance with any assessment carried out and scientific information available.

b) The Spanish Agency for Medicines and Health Products will be able to announce the start of the European evaluation procedure on its web portal, and in any case will be announced on the European medicines web portal planned in the article 26 of Regulation (EC)726/2004 of the European Parliament and of the Council of 31 March 2004, including the procedures by which the holder of the marketing authorisation, healthcare professionals and citizens can provide relevant information to the procedure.

(c) The Committee for the Evaluation of Risks in European Pharmacovigilance shall make recommendations in the 60 calendar days following the presentation of the information.

In addition, in the case of medicinal products authorised by the centralised procedure laid down in Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, when the Spanish Medicines Agency and Medical devices consider taking decisions or measures referred to in Article 20 of that Regulation on the basis of the pharmacovigilance data assessment, and shall refer the matter for evaluation by the Committee for Risk Assessment in European Pharmacovigilance, after consulting the Committee on Security Medicinal products for Human Use.

4. In the case of only medicinal products containing active substances authorised only in Spain and not in other Member States of the European Union, the matter shall be assessed in accordance with the following procedure:

(a) The Spanish Agency for Medicinal Products and Sanitary Products shall ask the marketing authorisation holder for a report assessing the safety concern identified and, where appropriate, the risk-benefit ratio of the medicinal product for the conditions of use authorised in Spain, including a proposal for measures for the reduction of risk. This report shall be in accordance with the structure and issues specified in the application. The report shall be transmitted within the maximum period of 60 calendar days from the date of receipt of the request, unless the urgency of the problem provides for a shorter period, or in exceptional cases and at the request of the holder, to be agreed with the Spanish Agency for Medicines and Health Products an extension of this period.

b) In the light of the previous report, the Spanish Agency for Medicines and Health Products will produce a report evaluating the safety problem.

(c) In all cases where one of the restrictions of use referred to in Article 16 (3) may be derived, a suspension or revocation of the marketing authorisation, the Security Committee of the Medicinal products for Human Use shall deliver a mandatory opinion, giving the person concerned a hearing.

Article 20. Administrative measures arising from the urgency procedure of the European Union.

1. The administrative measures resulting from the assessment shall be agreed by the Spanish Agency for Medicines and Health Products within the Coordination Group, or by a decision of the European Commission communicated to the Member States and to the holder of the the marketing authorisation, as appropriate, and shall be accompanied by a timetable for its implementation.

2. Where, as a result of the procedures described in the previous Article, the marketing authorisation is to be amended, the changes to be made to the technical information sheet and the package leaflet shall be made available to the interested party. of the web portal of the Spanish Agency for Medicines and Health Products, together with the application calendar. The Spanish Agency for Medicines and Health Products shall inform the person concerned of any other measures aimed at reducing the risk.

In accordance with these indications, the marketing authorisation holder shall request the appropriate modification of the conditions for the authorisation of the medicinal product, taking into account the procedures laid down in the Royal Decree 1345/2007 of 11 October 2007 regulating the procedure for the authorisation, registration and dispensing of medicinal products for human use manufactured industrially.

3. Where, following the procedures described in the previous Article, the marketing of the medicinal product is to be suspended, the marketing authorisation shall be revoked or the conditions of authorisation should be amended accordingly, referred to in Article 16 (3), a decision shall be made indicating the resources and the time limit for implementation, which shall be notified to the person concerned.

4. These administrative measures shall not apply to medicinal products authorised by the centralised procedure laid down in Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, which shall be governed by specific regulations.

Article 21. Precautionary measures.

1. The Spanish Agency for Medicinal Products and Sanitary Products, in the light of pharmacovigilance data, may adopt the precautionary measures provided for in Article 99 of Law 29/2006 of 26 July. It may also adopt these measures at any stage of the procedure laid down in Article 19 on its own initiative or at the request of the European Commission.

The Spanish Agency for Medicinal Products and Sanitary Products shall inform the Member States, the European Commission and the Agency of the precautionary measures taken at the latest by the following working day at the latest. European Medicines.

2. The Spanish Agency for Medicinal Products and Sanitary Products may publish on its website the technical sheets and leaflets including information concerning the security changes decided upon in the emergency procedures of the Union. European, even if the holder has not yet submitted the relevant amendment. This publication shall in no case be exempted from the submission of the relevant modification application.

Article 22. Communications to the autonomous communities, healthcare professionals, citizens and international organizations.

1. The Spanish Agency for Medicines and Health Products shall inform the autonomous communities and other responsible bodies about the adoption of the measures provided for in this chapter which are relevant to public health.

2. The Spanish Agency for Medicines and Health Products and the Autonomous Communities will make it possible to reach health professionals and citizens, in an appropriate manner, information on the risks of the drugs. The information disseminated by the Spanish Agency for Medicines and Health Products will be available on its website.

3. The resolutions of suspension, revocation and relevant modification of the authorisation, in so far as they may affect the public health of third countries, shall be brought to the attention of the World Health Organisation.

Article 23. Pharmacovigilance inspections.

1. The Spanish Agency for Medicinal Products and Sanitary Products and the competent health authorities of the autonomous communities, within the scope of their respective powers, shall verify compliance with the provisions of Chapter IV, by means of inspections of the premises, archives, documents and the master file of the pharmacovigilance system of the marketing authorisation holder or of any undertaking contracted by the marketing authorisation holder for the development of the intended activities; in that chapter.

2. After each inspection, which shall be carried out in accordance with the procedures agreed in the Technical Inspection Committee, the inspectors shall draw up a report which shall conform to the format agreed in the European Union, giving the entity inspected the opportunity to submit comments.

3. If these inspections result in the conclusion that the marketing authorisation holder has not complied with the pharmacovigilance system described in his master file or any of the other obligations provided for, he shall communicate such non-compliance with the marketing authorisation holder for its purpose. The Spanish Agency for Medicinal Products and Sanitary Products or the competent health authorities of the Autonomous Communities shall impose appropriate penalties where appropriate.

4. The Spanish Agency for Medicines and Health Products shall communicate these non-compliances to the other Member States, the European Medicines Agency and the European Commission.

CHAPTER VI

From post-authorization studies

Article 24. Scope and general aspects.

1. Post-authorisation studies shall be intended to supplement the information obtained during the clinical development of medicinal products prior to their authorisation. The planning, performance or funding of post-authorisation studies is prohibited in order to promote the prescription of medicinal products.

2. The remuneration of healthcare professionals involved in post-authorisation studies shall be limited to compensation for the time spent and the costs incurred, without prejudice to the rules applicable to the remuneration received by the public employees, as well as the internal rules of the researchers ' employing entities on this issue.

3. In order to ensure the welfare and rights of the participants, the post-authorisation studies should, prior to their initiation, have the favourable opinion of a Research Ethics Committee. That opinion shall be unique and therefore recognised throughout the national territory.

4. Where the post-authorisation study, in accordance with the provisions of Law 29/2006 of 26 July, is of a clinical trial rather than an observational study, it shall not be governed by the provisions of this Chapter, but shall result from the application of the Royal Decree 223/2004 of 6 February on the regulation of clinical trials with medicinal products for human use.

Article 25. Of the administrative procedure.

1. Health administrations through the Committee for the Coordination of Posauthorization Studies will harmonise the criteria and requirements for post-authorisation studies with medicinal products, facilitating the performance of those who have the greatest scientific interest and may contribute to the knowledge of the medicinal product or to improve clinical practice.

2. The Spanish Agency for Medicinal Products and Sanitary Products, in collaboration and coordination with the autonomous communities, will provide the data subjects with a single access point for the processing of the applications for telematic post-authorisation studies, as well as the exchange for such information, documentation and trades. The competent bodies of the autonomous communities shall have access to the data recorded in the information system established by the Spanish Agency for Medicinal Products and Health Products and shall keep the data relating to the requests for authorization that they receive as well as the result of their assessments.

3. Prior to the start in Spain of the studies that meet the criteria that the Spanish Agency for Medicines and Health Products establishes, the promoter will have to ask for its classification. Such studies shall be included in the public register of clinical studies that the Spanish Agency for Medicines and Health Products establishes.

4. Without prejudice to their necessary approval by the service providers and health care providers in whose field they are to be carried out, post-authorisation studies shall require prior authorisation in accordance with the following:

(a) Post-authorisation studies complying with the requirements of Article 11.2 shall be evaluated by the European Pharmacovigilance Risk Assessment Committee, which shall decide in the following 60 calendar days: the presentation of the protocol project.

The Spanish Agency for Medicines and Health Products will be responsible for the evaluation of post-authorisation studies in the following cases:

1. Studies which are required by the Spanish Agency for Health Products and Medicines for safety reasons after the granting of the marketing authorization, and are intended to be carried out only in Spain.

2. Prospective follow-up post-authorisation studies that are included in the risk management plan for a drug and are intended to be performed in Spain, not referred to in the previous paragraphs.

b) The post-authorisation studies for prospective monitoring promoted by the health administrations or financed with public funds, will require the authorisation of the Spanish Agency for Medicines and Health Products who will request a mandatory report from the Committee for the Coordination of Possession Studies.

c) The competent bodies of the Autonomous Communities shall evaluate applications for the authorisation of post-authorisation follow-up studies which do not comply with the provisions of the preceding paragraphs. In order to harmonise these assessments and to authorise a common protocol, the Committee for the Coordination of Posauthorization Studies shall establish a system of mutual recognition between the Autonomous Communities.

5. The relevant modifications of a post-authorisation study which are intended to be incorporated once authorised shall have the prior authorisation of the bodies that initially assessed it.

6. The sponsor shall communicate to the Spanish Agency for Medicinal Products and Health Products the effective date of initiation of the study, transmit the annual monitoring reports when it is established and, within 12 months of the end of the the collection of the data, the final report. This information shall be available to the Autonomous Communities through the information system referred to in paragraph 2.

Additional disposition first. Data protection.

The regulation contained in this Royal Decree must be understood without prejudice to the provisions of the Organic Law 15/1999 of 13 December, the Protection of Personal Data and its implementing regulations, in such a way as to processing of data derived from the development of pharmacovigilance activities as well as their electronic process, should be ensured, in accordance with specific rules of application, confidentiality, privacy personal and family members of the public and the protection of their personal data.

Additional provision second. Cities of Ceuta and Melilla.

The references to the competent authorities in the field of pharmacovigilance of the autonomous communities will be understood also to the cities of Ceuta and Melilla, with the scope provided for in their respective Statutes of Autonomy and real decrees for the transfer of functions and services.

Additional provision third. No increase in staff expenditure.

The application of this royal decree will not result in any increase in personnel spending. The new human resources needs that may arise as a result of the regulatory obligations set out in this royal decree must be met through the redistribution of places.

Additional provision fourth. Health Centers of the Ministry of Defense.

The General Inspection of Defence Health shall notify the Spanish Agency for Medicinal Products and Sanitary Products, through the Spanish Pharmacovigilance System and in the manner determined, of any information on suspected adverse reactions occurring in Spain, of which knowledge has been known.

The Inspection will notify the Spanish Agency of Medicines and Health Products directly of any information related to hospitals or Spanish health units of the Armed Forces that are on missions.

First transient disposition. Electronic reporting of suspected adverse reactions.

As referred to in Article 9 (3), it shall apply from the six months following the date on which the functionalities of the Eudravigilance database have been established. Until that time, the marketing authorisation holders shall send electronically to the Spanish Pharmacovigilance System only the suspected serious adverse reactions reported by healthcare professionals or the citizens to the Spanish Pharmacovigilance System. Suspicions of reported serious reactions will be sent electronically to Eudravigilance by the Spanish Agency for Medicines and Health Products.

However, suspicions of serious adverse reactions to which the marketing authorisation holder is aware, which have occurred outside the European Union, shall be sent electronically to Eudravigilance by the marketing authorisation holder.

In relation to the suspicion of non-serious adverse reactions, during this transitional period Eudravigilance and the Spanish Pharmacovigilance System will not be sent.

Once the functionalities of the database of suspected adverse reactions have been established, the Spanish Agency for Medicinal Products and Sanitary Products shall report on the date on which Article 9 (3) of the relationship with the referral of suspected adverse reactions to the Eudravigilance database will take effect.

Second transient disposition. Electronic submission of periodic safety reports.

Article 10 (1) shall apply from the 12 months after the date of the establishment of the functionalities of the periodic safety update report file. Until that time, the marketing authorisation holders shall send the periodic safety reports to the Spanish Agency for Medicinal Products and Health Products in an electronic form and through the application set up for that purpose, complying with the requirements laid down in the previous legislation in force.

Once the functionalities of the periodic safety update report file have been established, the Spanish Agency for Medicines and Health Products shall report on the date on which Article 10 (1) shall enter into force.

Transitional provision third. Updating the contact person's identifying data.

The recording and updating of the data identifying the pharmacovigilance contact person referred to in Article 14 (1) shall be carried out by means of telematics once the Spanish Medicines Agency and Sanitary Products make public the enablement of an application for this purpose. Until that time, the marketing authorisation holders shall communicate this information to the Spanish Agency for Medicinal Products and Sanitary Products and to the competent bodies of the autonomous communities concerned.

Transitional disposition fourth. Pharmacovigilance master file.

For medicinal products authorized prior to the entry into force of this royal decree, the obligation on the marketing authorization holder to dispose and maintain a master file of the pharmacovigilance and to present the summary of the same set out in Article 8 shall be made at the time of the renewal of the marketing authorisation or in any case before 21 July 2015.

Transient disposition fifth. Amendment of the Summary of Product Characteristics and Package Leaflet.

The amendments to the prospectus and the technical information provided for in Articles 6.1, 7 and 12.5 of this royal decree will be incorporated at the time when, by means of an information note published on their website, they are communicated by the Spanish Agency for Medicinal Products and Sanitary Products, resulting from the application of the exceptions and reductions provided for in Articles 109.4 and 111.6 of Law 29/2006 of 26 July.

Single repeal provision. Regulatory repeal.

As many provisions of the same or lower rank are repealed, they oppose the provisions of this royal decree, and in particular, Royal Decree 1344/2007 of 11 October, which regulates the pharmacovigilance of medicinal products. human use.

Final disposition first. Amendment of Royal Decree 1015/2009 of 19 June on the availability of medicinal products in special situations.

The Royal Decree 1015/2009 of 19 June, which regulates the availability of medicinal products in special situations, is amended in such a way that Article 11 (1) (c) is worded as follows:

"c) Immediately report suspected adverse reactions to the Spanish Agency for Medicines and Health Products."

Final disposition second. Amendment of the Statute of the Spanish Agency for Medicines and Health Products approved by Royal Decree 1275/2011 of 16 September 2011 establishing the State Agency for the Spanish Agency for Medicinal Products and Health Products their Staff Regulations.

The Statute of the Spanish Agency for Medicines and Health Products approved by Royal Decree 1275/2011 of 16 September 2011 establishing the State Agency for the Spanish Agency for Medicines and Health Products approves its Staff Regulations, is amended as follows:

One. Article 19 (3) (c) and (d) shall be worded as follows:

" (c) Inform precept in the procedure for the suspension or revocation of a marketing authorisation for medicinal products for human use in the cases covered by the rules in force in the field of pharmacovigilance of medicinal products for human use.

d) Provide technical advice to the Spanish representatives at the European Pharmacovigilance Risk Assessment Committee. "

Two. Two new paragraphs (f) and (g) are inserted in Article 19 (3) with the following wording:

" (f) Develop the recommendations for use described in Article 13 (2) of Royal Decree 1015/2009 of 19 June, which regulates the availability of medicinal products in special situations.

g) Recommend conducting studies to assess the impact of measures taken to minimize the risks of medication. "

Three. Article 23 (3) and (4) are worded as follows:

" 3. The Committee for the Coordination of Posauthorization Studies shall be composed of the following members:

a) Two vowels due to their position:

1. The Head of the Agency's Department of Medicinal Products for Human Use.

2. The Head of the Pharmacoepidemiology and Pharmacovigilance Division of the Department of Medicinal Products for Human Use.

b) Seventeen vowels representing each other to a competent body in the field of studies Poseauthorization of the autonomous communities, officially designated by that body.

c) A vowel representing the General Secretariat of Prison Institutions of the Ministry of the Interior.

4. The President and the Vice-Chair of the Committee for the Coordination of Posauthorization Studies shall be elected by their members from among the representatives of the Autonomous Communities and the General Secretariat of Penitentiary Institutions. The Head of the Division of Pharmacoepidemiology and Pharmacovigilance of the Department of Medicinal Products for Human Use shall act as Secretary of the Coordination Committee for Studies. '

Four. A new paragraph 5 is inserted in Article 29, with the following wording:

" 5. The functioning of the Committees shall be addressed with the personal, technical and budgetary resources allocated to the Spanish Agency for Medicines and Health Products. "

Final disposition third. Competence title.

This royal decree is issued under article 149.1.16 of the Spanish Constitution, which attributes exclusive competence to the State in the field of pharmaceutical legislation.

Final disposition fourth. Regulatory enablement.

The head of the Ministry of Health, Social Services and Equality is empowered to make the necessary provisions for the correct application and development of this royal decree.

Final disposition fifth. Incorporation of European Union law.

By this royal decree, paragraphs 1, 20 and 21 of Article 1 and Article 2 of Directive 2010 /84/EU of the European Parliament and of the Council of 15 December 2010 are incorporated into national law. amend, as regards pharmacovigilance, Directive 2001 /83/EC establishing a Community code on medicinal products for human use. As well as Directive 2012/26/EU of the European Parliament and of the Council of 25 October amending Directive 2001 /83/EC as regards pharmacovigilance.

Final disposition sixth. Entry into force.

This royal decree will enter into force on the day following its publication in the "Official State Gazette".

Given in Madrid, July 26, 2013.

JOHN CARLOS R.

The Minister of Health, Social Services and Equality,

ANA MATO ADROVER