The control of the chain of distribution of medicines, from their manufacture or their import to their dispensing, is an essential element to guarantee the quality of the drugs and to guarantee that the conditions of conservation, transport and supply are appropriate.

Since the publication of Royal Decree 2259/1994 of 25 November 1994 regulating the pharmaceutical stores and wholesale distribution of medicinal products for human use and pharmaceutical products, the framework and the The characteristics of the establishments covered by this royal decree have been modified. In addition, the royal decree referred to the incorporation into the Spanish legal order of Council Directive 92/25/EEC of 31 March 1992 on the wholesale distribution of medicinal products for human use, which was repealed by the Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, subject to transposition by Law 29/2006 of 26 July, guarantees and the rational use of medicines and medical devices, which has been the emergence of new figures in the field of distribution.

In turn, the Directive of the European Parliament and of the Council of 2011 /62/EU of 8 June 2011 amending Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 on the on the prevention of the entry of counterfeit medicinal products into the legal supply chain, which incorporates additional measures to strengthen the guarantees in the distribution of medicinal products which are also incorporated in this standard.

The increased complexity of the supply chain, which requires greater control in each of its links, the inclusion of requirements for new agents involved in the distribution but which were not previously submitted to no control, as is the case with the intermediary of medicines or brokers, who participate in the sale or purchase of medicines without selling them or buying them themselves and without being the owners of the medicines or having contact physical with them, or the extension of the authorization requirements to the distribution stores located in customs areas, including free zones and free warehouses, are some of the aspects included in the aforementioned directive.

And Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012 amending Directive 2001 /83/EC of the European Parliament and of the Council of 6 November 2001 on the on pharmacovigilance which includes an amendment to Article 85a in relation to the precise controls on the operations carried out by the distribution entities with third countries.

All this requires that the existing regulations be adapted to the current requirements, which is why this royal decree is dictated in order to replace the aforementioned, in order to regulate the distribution of medicines. with the ultimate goal of safeguarding public health.

For its part, the enactment of Law 29/2006, of July 26, updated the legal framework in all aspects related to medicines and in particular regarding the distribution of medicines, established certain guarantees for the accessibility and availability of medicinal products and introduced the figure of third parties in the distribution of medicinal products, which carry out distribution activities for which they can be hired by a wholesaler or by a laboratory operator and that needs to be developed.

The above European legislation provides that all persons engaged in the distribution of medicinal products must have a distribution authorisation. In Spain, since the entry into force of Royal Decree 2259/1994 of 25 November, the distribution activities are mainly carried out by the wholesale warehouses. However, Law 29/2006, of July 26, already includes the distribution activity of the pharmaceutical laboratories and also introduces the figure of the third in the distribution, which, is pending development. They are now incorporated as a new figure in the distribution of medicines: distribution stores located in customs areas, including free zones and free warehouses. For all this in this royal decree dealing with the authorizations, requirements and obligations of all these figures who carry out some of the activities included in the definition of wholesale distribution of medicines, proceeds to the use of the term "distribution entities" where all these figures can be considered.

This royal decree also includes a chapter devoted to the good distribution practices that the European Commission is responsible for. The monitoring of these guidelines ensures that the quality of the medicinal products is maintained from the manufacturer to the place of supply. These practices are regularly updated to match technical, scientific and new developments that are incorporated in the pharmaceutical supply chain.

It should be mentioned that Directive 2011 /62/EU of 8 June 2011 also provides for increased controls for the active substances, both in their manufacture and in their distribution and also includes certain requirements. for the use of excipients in the manufacture of medicinal products.

Counterfeit active substances and active substances that do not comply with the applicable requirements in accordance with current regulations pose serious risks to public health. In order to address these risks, the requirements for verification of compliance with the correct manufacturing standards of manufacturers and importers of active substances are reinforced and new requirements for distributors of the products are also included. same.

This is why it is also necessary to amend the Royal Decree 824/2010 of 25 June, which regulates the pharmaceutical laboratories, the manufacturers of active principles of pharmaceutical use and the foreign trade of medicines and medicines in research, to include these new requirements. Consequently, a final provision has been included with the corresponding amendments.

In this royal decree, the third additional provision on the direct sale of medicinal products to healthcare professionals has been incorporated as the development of Article 2.5 of Law 29/2006, of July 26. In this sense, it is available that such sale or supply will be carried out by the pharmacy offices, in line with the functions assigned to them by the aforementioned law, although some medicines which, on the basis of their special characteristics will determine the The Spanish Agency for Medicines and Health Products by resolution, may be sold to professionals by pharmaceutical laboratories and wholesale warehouses.

In the elaboration of this royal decree, the autonomous communities and the cities with autonomy status have been consulted, having submitted to the prior report of the Advisory Committee of the National Health System and to the Interterritorial Council of the National Health System. The sectors concerned have been heard and have also been subject to a report from the Consumers and Users Council and the Spanish Data Protection Agency.

This rule is dictated by the development of the provisions of Law 29/2006 of 26 July, and under the provisions of Article 149.1.16. of the Constitution which gives the State exclusive competence in the field of bases and general coordination of health, having therefore a basic rule of law, with the exception of Chapter IV, Article 19 thereof, and its final provision, which are dealt with under exclusive jurisdiction in the field of legislation on pharmaceutical products, attributed to the State in that same constitutional precept.

In its virtue, on the proposal of the Minister of Health, Social Services and Equality, and the Minister of Agriculture, Food and Environment, with the prior approval of the Minister of Finance and Public Administrations, with the Council of State and after deliberation by the Council of Ministers at its meeting on 11 October 2013,

DISPONGO:

CHAPTER I

General provisions

Article 1. Object and scope of application.

1. This royal decree is intended to regulate the activities related to the distribution and intermediation of medicinal products for human use, in accordance with the definitions set out in Article 8 of Law 29/2006 of 26 July.

2. This royal decree will apply, provided they are located in Spain, to:

a) Drug distribution entities, which are:

1. The distribution wholesale stores, hereinafter the wholesale warehouses.

2. The contract stores.

3. Drug stores under control or customs surveillance.

b) Entities engaged in the intermediation of medicines, also known as brokers.

3. In turn, Articles 2, 3, 8, except Article 20 (1) (b) thereof and the provisions of Article 20 of this royal decree shall apply, in addition to their specific rules, to the laboratories holding the marketing authorization, regulated in Chapter V of Royal Decree 824/2010 of 25 June 2010 on the control of pharmaceutical laboratories, the manufacturers of active substances for pharmaceutical use and the external trade in investigational medicinal products and medicinal products.

4. Marketing authorisation holders established in another Member State or their local representatives in Spain, who carry out any wholesale distribution activity, shall carry out such marketing authorisation through entities which are authorized for the realization of the same according to the established in this royal decree.

5. Pharmaceutical laboratories manufacturers or importers which carry out distribution activities for medicinal products falling within the scope of their authorisation shall not require authorisation as a distribution entity, but must comply with the requirements laid down in Article 1 (1). paragraphs of the good distribution practices of the European Union that are applicable to the activities they develop.

Article 2. General principles.

1. Good practice for the distribution of medicinal products in the European Union will be mandatory both for the distribution entities for medicinal products for human use and for pharmaceutical laboratories carrying out activities in the European Union. distribution. Entities engaged in the intermediation of medicinal products shall comply with those aspects of the good distribution practices that are applicable to them.

2. Pharmaceutical laboratories which distribute their medicines and wholesale stores directly will have to ensure, within the limits of their responsibilities, adequate and continuous supply of medicines to respond to the needs of the pharmacy offices and pharmaceutical services of the national territory. To this end, they must have minimum stocks of medicinal products, as provided for in Article 70.1 of Law 29/2006 of 26 July on guarantees and the rational use of medicinal products and medical devices to ensure continuity. of the distribution.

3. In the distribution of medicinal products subject to special rules on conservation, distribution and control, it must be observed in addition to the provisions of this royal decree, the obligations specified in its special legislation and, in (a) special treatment for narcotic drugs and psychotropic drugs, as well as for blood products, immunological medicinal products and radiopharmaceuticals.

4. Wholesale warehouses may only carry out intra-Community consignments of medicinal products to persons holding a distribution authorisation or who are authorised or authorised in the Member State concerned to dispense medicinal products to the public. These activities will apply to the prior notification to the Spanish Agency for Medicines and Health Products provided for in Article 54 of Royal Decree 824/2010 of 25 June, in accordance with the instructions given by the Spanish Agency.

5. In the event that the distribution activities are carried out with third countries, it will be ensured that the medicinal products are obtained only from persons who are authorised or authorised to supply medicinal products, in accordance with the applicable legal and administrative provisions of the third country concerned. Also where wholesalers supply medicinal products to persons in third countries, they shall ensure that such supplies are made only to persons who are authorised or authorised to receive medicinal products for wholesale distribution or supply to the public, in accordance with the applicable legal and administrative provisions of the third country concerned.

6. Wholesale warehouses and pharmaceutical laboratories may only accept refunds from the pharmacy and pharmacy services to which they have supplied the medicinal products covered by the refund, without prejudice to any refund which may be awarded exclusively for destruction in the field of integrated waste management systems, as well as the application, where appropriate, of the provisions of Royal Decree 726/1982 of 17 March 2001 on the expiry and return of proprietary medicinal products to pharmaceutical laboratories.

7. A wholesale warehouse or a pharmaceutical laboratory may use a third party, or contract warehouse, for the distribution of medicinal products. This third party shall be included in the corresponding authorisation in accordance with the provisions of Article 68.3 of Law 29/2006 of 26 July, Article 17 of this royal decree and Article 39a of Royal Decree 824/2010 of 25 June 2010.

8. Wholesale warehouses and pharmaceutical laboratories may provide the sponsor of an approved clinical trial with medicinal products included in that test, on presentation by the same of the authorisation issued by the Spanish Agency of Medicines and Healthcare products for the same.

Article 3. Security of supply.

1. In accordance with Article 68.2 of Law 29/2006 of 26 July, the primary and essential function of the distribution of medicinal products is the supply to the pharmacy and pharmacy services offices legally. authorised in the national territory.

2. Wholesale warehouses and laboratories holding authorisation for the placing on the market of medicinal products must ensure, within the limits of their liability, and within the agreed time-limits, adequate and continued supply of medicinal products. medicines to legally authorised pharmacy offices and services in the national territory, so that the needs of patients are met.

3. In cases where there are problems with the supply of medicinal products whose supply may have an impact on the care given that:

(a) is a medicinal product which, due to its active substance, dosage or route of administration, is the only one registered in Spain for a given pathology and its lack generates a therapeutic lagoon or,

(b) in the case of a medicinal product which is not subject to a change in the prescription, in accordance with Order SCO/2874/2007 of 28 September 2007 laying down medicinal products which are the exception of the replacement by the pharmacist, or provision to replace it, in accordance with Article 86.4 of Law 29/2006 of 26 July.

The Spanish Agency for Medicines and Health Products, in collaboration with the competent authorities of the autonomous communities, will adopt the measures it deems necessary to resolve this situation. limit the departure of the national territory of medicinal products on the basis of the need for the protection of public health.

CHAPTER II

Material and personnel requirements for drug delivery entities

Article 4. Premises and warehouses.

1. Distribution entities shall have adequate and sufficient premises, facilities and equipment in such a way as to ensure the proper conservation and distribution of medicinal products, including transport to their customers.

2. The facilities must allow for the proper development of the activities of the distribution, in accordance with the provisions of the good distribution practices. They shall have at least the following duly separated areas:

a) Reception and compliance control.

b) Storage and preparation of orders.

c) Expedition.

d) Administrative.

3. The following special areas, duly identified, should be defined to store:

a) Narcotic Drugs. In addition, this area should be maintained with security measures to ensure the safekeeping of them.

(b) Medicines requiring special storage conditions.

c) Medicines returned.

(d) Non-compliant medicinal products, such as expired, counterfeit, withdrawn or frozen for destruction.

4. The premises must meet hygienic and sanitary conditions relating to cleanliness, temperature, humidity, ventilation and lighting, appropriate to ensure the correct preservation of the medicinal products.

5. Such facilities must be properly separated and independent from any other party belonging to the same entity, who are not engaged in the distribution of medicinal products whether commercial, industrial or professional.

Article 5. Pharmaceutical technical director and additional staff.

1. Each drug distribution entity must have a pharmaceutical technical director for each facility, as well as the additional staff needed to ensure quality and safety in the distribution activities included in the scope of your authorization.

2. The technical director shall carry out his duties in person and must be accessible on a continuous basis. One or more alternate technical directors may be appointed, with the same requirements as the holder, which they shall replace in their absence.

3. The tasks of staff responsible for the implementation of good distribution practices shall be defined in the description of their duties. This staff must have sufficient qualifications and receive initial and continuing training to be able to perform them properly.

Article 6. Requirements of the Technical Technical Director.

1. The pharmaceutical technical director of these entities must be in possession of an official university degree in Pharmacy or Degree in Pharmacy and possess adequate training and experience in good distribution practices.

2. This position of technical director shall be incompatible with the exercise of other activities of a health nature which involve direct interests with the supply or manufacture of medicinal products or which are detrimental to the proper performance of their products. functions, as provided for in Article 71 of Law 29/2006 of 26 July. In the case of wholesale warehouses which are also authorised as a contract warehouse, the technical director shall be solely responsible for the activities to be carried out as a wholesale warehouse and as a contract warehouse.

3. For the acceptance of the appointment of a pharmaceutical technical director and his alternates, the procedure to be established by the competent health authority shall be followed.

Article 7. Duties of the Technical Technical Director.

1. The Technical Technical Director shall carry out his duties to ensure the implementation and enforcement of the good distribution practices established in the European Union as well as the applicable rules that are applicable.

2. These functions include:

a) Ensure the operation of a quality assurance system and have the necessary procedures for the proper development of its activities.

b) Verify the legality of your drug suppliers as well as the clients you supply them with.

(c) Control the correct compliance with the procedure for the withdrawal of the medicinal products, which must ensure the effective execution, and with the appropriate urgency, of any order of withdrawal issued by the Spanish Agency of Medicines and Health Products. Control in the correct application of any other precautionary measure ordered by the competent health authority.

d) Be informed of the complaints received, monitor their proper investigation, and take the measures in each case.

e) Monitor compliance with special legislation on narcotic drugs, psychotropic drugs and other medicinal products subject to special control.

f) Evaluate and approve, where appropriate, the returns of medicinal products that occur to the stock, after verifying that they correspond to medications previously supplied to the entity that returns them.

g) Serve as a partner with the health authorities and collaborate with them in the implementation of the measures that they take.

h) Save and safeguard all technical documentation relating to the authorization of the distribution establishment, as well as that established in good distribution practices.

i) Any other that imposes the current regulations or the good distribution practices established in the European Union.

CHAPTER III

Obligations of the holders of a distribution authorization

Article 8. General obligations of wholesale warehouses.

1. Without prejudice to Article 70.1 of Law 29/2006 of 26 July, the holder of the authorisation of a wholesale warehouse shall:

(a) Provide at any time the access of the inspectors to the premises, facilities, equipment and documents that are necessary for the verification of compliance with their obligations.

b) Get medicines from pharmaceutical laboratories only, or from other properly licensed wholesale stores that comply with current regulations, as well as with good distribution practices.

(c) Supply the medicinal products only to other wholesale stores or to pharmacy offices and legally authorized pharmaceutical services, without prejudice to the provisions of Article 2.8, ensuring that delivery is performs exclusively at the premises, which are authorised for the wholesale, own or contract warehouse, or for the office of pharmacy or pharmaceutical service to which these medicinal products are intended.

d) Ensure proper preservation of the medicinal products in accordance with the specifications approved for the medicinal products from the time of their receipt to their supply.

e) Ensuring that the transport of medicinal products is carried out under appropriate conditions as well as delivery times and a minimum frequency of deliveries, which ensures that orders are delivered to the offices and services of pharmacy, in less than 24 hours since they are performed and in the event that they mediate some non-working day, this will not be taken into consideration for the calculation of the term.

(f) Communicate immediately to the competent health authorities and, where appropriate, the holder of the marketing authorisation for the medicinal products, the medicinal products they receive or which they are suspected of having may be falsified.

g) Communicate to the competent health authorities any facts or suspicions they may know about an improper use of medication or their diversion to illicit trafficking.

(h) To present to the competent health authorities information on movements of medicinal products that are required.

i) Keep the documentation in which they are, in the form of purchases and sales invoices, in computerised form or in any other form, at least the following data from any inbound or outbound transaction:

1. Date.

2. Name of the medicine.

3. Number received or supplied.

4. The name and address of the provider or recipient, as appropriate.

5. Lote received or supplied.

j) Attach to all drug supplies a document that consists of:

1. Date.

2. Name of the medicine.

3. Quantity requested and supplied.

4. The name and address of the requester.

5. Lote supplied.

k) Provide the necessary means to the technical director for the performance of his/her duties.

(l) to provide for an emergency plan to ensure the effective implementation of any market withdrawal ordered by the competent authorities or initiated in cooperation with the manufacturer of the medicinal product concerned or with the holder of the marketing authorisation for that medicinal product.

m) Maintain a quality system that establishes risk management responsibilities, processes and measures with respect to their activities.

n) Keep your authorization up to date in accordance with the facilities and equipment you have and activities you develop.

n) Meet the current regulations, as well as the good distribution practices established in the European Union.

2. The documentation referred to in paragraph 1 (i) shall be kept for at least five years at the disposal of the health authorities, counted from the date on which it was generated, in an appropriate format for analysis and assessment.

3. Where the wholesale warehouse obtains medicinal products from another wholesale distributor, it shall, in addition to the provisions of paragraph 1 (b), verify compliance by the supplier of the principles and guidelines of good practice of distribution. This verification shall include the verification of whether the wholesale distributor has a wholesale distribution authorisation.

4. Where the medicinal product is obtained from pharmaceutical laboratories, the wholesale warehouse shall verify that they are holders of the relevant authorisations.

5. Where medicinal products are obtained through intermediary entities, as referred to in Article 11, the wholesale warehouse shall verify that the intermediary concerned complies with the requirements set out in this royal decree.

6. The hiring of a third party shall not exempt the titular laboratory or the wholesale warehouse from its responsibility for compliance with the good distribution practices and other obligations established in this royal decree in respect of the activities contracted.

7. The wholesale stores must also notify the Spanish Agency for Medicinal Products and Health Products, the importation of medicinal products not authorised in Spain from other Member States, 15 days before carrying out this activity. including the following data and documents:

1. The name and address of the supplier's supplier wholesale warehouse.

2. Name and presentation of the medication.

3. Number of drives.

4. Number Batch Number.

5. The minutes of control of the medicinal product signed by the qualified person referred to in Article 18 of Royal Decree 824/2010, of 25 June, or another document certifying their release to the market.

These medicines, which are not authorized in Spain, will in no case be distributed to pharmacy offices and services.

Article 9. Obligations of the warehouses by contract.

Contract stores shall comply with the obligations laid down in Article 8 (1) and (2), in accordance with their authorisation and with the activities for which they have been engaged.

Article 10. Obligations of the warehouses of medicinal products under control or customs supervision.

The warehouses of medicinal products under customs supervision or surveillance shall comply with the obligations laid down in Article 8, with the exception of paragraph 1 (e), and paragraphs 6 and 7 of the said Articles. authorization and with the activities for which they have been hired.

CHAPTER IV

Medication intermediation

Article 11. Requirements.

1. Any drug broker, also called a broker, located in Spain must:

(a) Notify the Spanish Agency of Medicines and Health Products of the contact details, including the first and last names, the social reason, as well as a permanent address, through the electronic procedure established to this effect.

(b) Ensure that all medicinal products under intermediation are covered by a marketing authorisation granted in accordance with Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 December March 2004, establishing Community procedures for the authorisation and control of medicinal products for human and veterinary use and establishing the European Medicines Agency, or by a Member State.

c) Maintain a quality system that establishes risk management responsibilities, processes and measures with respect to their activities.

d) comply with the provisions of the current regulations, as well as with the good distribution practices established in the European Union, that apply to it.

e) Dispose of staff with appropriate training in national and European regulations in relation to the activities it develops as well as in the issues related to the counterfeiting of medicines.

f) Keep the documentation in which, in computerised form or in any other form, for each of the transactions made, at least the following data:

1. Date.

2. Name of the medicine.

3. Number of intermediation object.

4. The name and address of the provider or recipient, as appropriate.

5. Drug Lot.

g) To communicate immediately to the competent health authorities and, if appropriate, to the holder of the authorization to place the medicinal products on the market, any suspicion of falsification of the medicinal products concerned brokering or being offered, or their diversion to illicit trafficking.

(h) To provide for an emergency plan to ensure the effective implementation of any market withdrawal ordered by the competent authorities or initiated in cooperation with the manufacturer of the medicinal product concerned or the marketing authorisation holder for that medicinal product.

2. The documentation referred to in point (f) of the preceding paragraph shall be kept for at least five years at the disposal of the health authorities, counted from the date on which it was generated, in an appropriate format to enable its analysis and evaluation.

3. In addition, these entities must be registered in the register provided for in Article 12 and communicate without delay any changes in the data provided.

Article 12. Registration of drug intermediation entities.

1. The Spanish Agency for Medicinal Products and Sanitary Products shall maintain a register of drug intermediation entities, as provided for in Article 71a of Law 29/2006 of 26 July.

2. This register will be published and your access will be made through the website of the Spanish Agency for Medicines and Health Products.

3. The following data shall be published for each intermediation entity:

a) Name and last name.

b) Social reason.

c) Permanent address.

d) Identification code to be assigned to you by the Spanish Agency for Medicines and Health Products.

CHAPTER V

Authorization of drug distribution entities

Article 13. Prior authorisation for the distribution of medicinal products.

1. Each of the distribution entities regulated in this royal decree must have prior authorization, in accordance with the provisions of Article 69 of Law 29/2006, of July 26. For this purpose, wholesale warehouses and contract warehouses shall be authorised by the corresponding autonomous community and the warehouses of medicinal products under the control or customs supervision by the Spanish Agency for Medicinal Products and Products. Sanitary.

2. This authorisation shall include details of the distribution activities for which the entity is authorised in accordance with the European format of these authorisations.

3. For the inclusion of a third party in the authorisation of a wholesale warehouse or of a marketing authorisation holder, this third party shall have prior authorisation as a contract warehouse, in accordance with the established in this royal decree.

Article 14. Pre-authorization evaluation.

1. The assessment prior to the authorisation of these entities is intended to verify that they have the appropriate personal, material and operating means to ensure the correct development of their activity and that the entity is capable of to provide a quality service in its field of action, in accordance with the obligations set out in this standard.

2. During the instruction of the administrative file, the legally established requirements shall be verified by means of the relevant inspection visit.

Article 15. General principles in relation to the granting of authorisations and their amendments.

1. Each facility will require an independent health authorisation. In the case of wholesale warehouses operating in the same facility, a single authorisation covering both activities shall also be issued as a contract warehouse.

2. The procedure for authorisation shall be that laid down by the health authorities responsible for issuing the authorisation. These authorisations must conform to the format agreed at Community level. Any relevant changes affecting the premises, equipment or activities, as well as the transfer to other facilities, shall be subject to prior authorisation.

3. The granting of such authorisations shall be without prejudice to the issue, where appropriate, of the certificates of good distribution practice as referred to in Article 21 (4

.

4. The maximum period for the notification of the decision of the authorisation procedure of a distribution entity shall be 90 days from the date of receipt of the request by the competent health authority. After the 90-day period laid down for the resolution of the procedure, without having been notified, the applicant may understand his application.

5. The competent health authority may agree to suspend or revoke in whole or in part the authorisation of a distribution entity when it no longer meets the requirements for granting such authorisation or for failure to comply with the requirements. obligations set out in this royal decree, as well as, where appropriate, the specific rules governing the competent autonomous community.

In any event the adoption of these measures will not be considered as a sanction.

6. The authorisations granted to the distribution entities shall lose their validity, and shall be revoked in accordance with the provisions of the preceding paragraph if, after one year after their granting, the entity is found not to develop full, effective and continuous form, all distribution activities for which it has been authorised.

Article 16. Authorization of the warehouses of medicinal products under control or customs supervision.

1. The Spanish Agency for Medicines and Health Products shall be responsible for the authorisation of these entities.

2. Applications for authorisation shall be submitted through the IT application established for that purpose by the Spanish Agency for Medicines and Health Products and shall be accompanied by the following information and documentation:

(a) Name or social reason of the applicant and registered office or registered office, NIF or CIF, and, in the case of a legal person, certification of registration in the Commercial Registry, and must be collected in the social object the activity to be performed.

b) Name of the legal representative and accreditation of such representation.

(c) Technical memory describing the activities to be carried out and the premises in accordance with the provisions of Article 4 and the equipment at its disposal.

d) Proposal for a pharmaceutical technical director accompanied by the documentation certifying compliance with the requirements set out in Article 7.

(e) Justifying the payment of the corresponding fees, as set out in Article 111 of Law 29/2006, of 26 July.

3. The Spanish Agency for Medicinal Products and Health Products, after receipt of the documentation and within a maximum period of ten days, shall verify that the application meets the intended requirements and shall notify the applicant of its admission to the process.

4. Where the application does not meet the requirements laid down, the person concerned shall be required to submit the application within 10 days, with the indication that, if he does not do so, he shall be given the withdrawal of his request in accordance with the provisions of the provided for in Article 71.1 of Law No 30/1992 of 26 November 1992 on the Legal Regime of Public Administrations and of the Common Administrative Procedure, subject to a decision declaring that circumstance, with an indication of the facts produced and the applicable rules.

5. Once the Spanish Agency for Medicines and Health Products has been admitted to the process, the evaluation may be carried out and may require further documentation or clarification from the applicant on any extreme subject of the application, by setting a one-month deadline for submission of the additional information, with the time limit for notifying the resolution to be suspended until the required data are received or the time limit has elapsed.

6. The documentation presented in the application will be evaluated, the Spanish Agency for Medicines and Health Products will carry out the mandatory inspection at the appropriate facilities. In general, these inspections will be carried out through the Pharmaceutical Inspection Services of the Health and Social Policy Areas.

7. If the result of the assessment is unfavourable, the Spanish Agency for Medicinal Products and Sanitary Products shall notify the applicant of the reasons for which the requested authorisation is not applicable, so that, within 15 months of the days, you can make the allegations and present the documentation that you consider appropriate.

8. Where the results of the assessment are favourable, the Spanish Agency for Medicinal Products and Health Products shall issue the authorisation resolution.

9. After the procedure has been completed, a reasoned decision shall be taken to notify the person concerned. This decision shall put an end to the administrative procedure, and the person concerned may, in accordance with Articles 116 and 117 of Law No 30/1992 of 26 November of 26 November, or the administrative dispute, bring an action for replacement. in accordance with Law 29/1998 of 13 July of the Jurisdiction-Administrative Jurisdiction.

10. After the 90-day period laid down for the resolution of the procedure, without having been notified, the applicant may understand his application.

11. In the case of modifications or transfers of facilities, the corresponding application for modification and in its processing shall be required to apply the provisions of this article.

Article 17. Inclusion of a third party in the authorisation of a wholesale warehouse.

1. The procedure for the inclusion of a warehouse by contract in the authorisation of a wholesale warehouse shall be initiated with the application of the wholesale warehouse to the competent authority of the autonomous community which authorised it. The application shall include the distribution activities which the third party is to carry out and must be accompanied by the contract signed between the parties.

2. In turn, the contract between the parties must be accompanied by the necessary documentation to prove that the third party has the required authorization, granted by the autonomous community where the warehouse is located, according to the established in Article 13, for the activities for which it is contracted.

3. The contract shall specify the distribution activities, as well as any technical agreement relating to the subject matter of the contract, delimiting the tasks of each party. The technical aspects of the contract must be signed by the pharmaceutical technical directors of the parties.

4. The parties shall ensure the implementation of good distribution practices.

5. The pharmaceutical technical director of the wholesale warehouse shall monitor the correct performance of the activities contracted to the third party.

6. The maximum period for the notification of the decision of the said procedure shall be 30 days from the date of receipt of the request.

7. The competent health authority shall communicate the inclusion of a contract warehouse in the authorisation of a wholesale warehouse to the autonomous community where the contract warehouse is located.

Article 18. Notifications.

1. The new authorizations, suspensions and revocations of the authorization of any distribution entity, as well as the relevant modifications of the conditions of the authorization granted by the autonomous communities, will be notified to the Spanish Agency for Medicines and Health Products through the electronic procedure established for this purpose.

2. These notifications will enable the catalogue of distribution entities described in Article 19 to be kept up to date, as well as the fulfilment of the exchange of information set out in European legislation.

Article 19. Distribution entity catalog.

1. The Spanish Agency for Medicines and Health Products shall maintain a catalogue of authorised distribution entities which shall include both the authorisations notified by the autonomous communities and those granted by the Agency.

2. The registration in this catalog will be performed according to the data of the authorization resolution of the corresponding entity.

3. This catalogue will be published and accessed through the website of the Spanish Agency for Medicines and Health Products.

CHAPTER VI

Good distribution practices

Article 20. Good distribution practices.

1. For the purposes of this royal decree, 'Good distribution practices' means the part of the quality assurance which ensures that the quality of the medicinal products is maintained at all stages of the supply chain from the manufacturer's headquarters. up to the pharmacy or pharmacy service office.

2. Good distribution practices will be published by the Ministry of Health, Social Services and Equality.

3. The computerised systems that are used, related to compliance with such good practices, shall be properly validated.

4. The distribution entities must have a certificate of compliance with good practice of distribution in force issued by the competent health authority, in addition to the mandatory authorisation, in addition to the mandatory authorisation, set out in Article 21.

CHAPTER VII

Inspection

Article 21. Inspection.

1. The verification of compliance with good distribution practices, as well as other legal requirements concerning the distribution of medicinal products, shall be carried out by means of periodic inspections by the authorities. competent health care.

2. At the end of each inspection, the inspectors shall draw up a regulatory inspection report, which shall be signed by the inspector or acting inspectors and by the technical director of the warehouse. It shall contain the most relevant facts and findings that have resulted from the inspection actions.

3. The inspectors will then draw up a report on compliance with good distribution practices which will be in line with the European format agreed at Community level. Before adopting the report, the competent authority shall give the relevant inspected entity the opportunity to submit comments to it. In the case of deficiencies in the report relating to breaches of good distribution practice or the applicable rules on the distribution of medicinal products, the inspected entity shall report on the measures taken. which it has adopted or intends to adopt for its correction, as well as the time limits for its implementation.

4. Once compliance with good distribution practices has been established, in the 90 days following the inspection visit, the health authorities acting shall issue an inspection of a certificate of compliance with these guidelines, which will be in line with the European format. The certificate shall include its period of validity.

5. In the event that the inspection has led to the adoption of the precautionary measures referred to in Article 99 of Law 29/2006 of 26 July, the health authority which adopted the precautionary measure must inform the health authority immediately. to the Spanish Agency for Medicines and Health Products.

6. The authorities of the General Administration of the State and the competent autonomous communities shall assist each other for the purpose of these inspections.

Article 22. Cooperation with the inspection authorities of the Member States of the European Union.

1. The Spanish Agency for Medicinal Products and Sanitary Products shall send to the European Medicines Agency the information contained in the authorisations referred to in Article 15 for registration in a Community database. In addition, the Spanish Agency for Medicinal Products and Sanitary Products shall enter the certificates of good distribution practice described in Article 21 (4) in the database administered by the European Medicines Agency in name of the European Union.

2. Where a health authority of a Member State of the European Union requests information relating to a reasoned written inspection, the Spanish Agency for Medicinal Products and Health Products shall transmit the relevant report. To this end, it shall request, where appropriate, the report in respect of the competent authorities of the autonomous community in which the distribution warehouse is situated.

3. Similarly, where it is necessary to request information from another Member State on a wholesale warehouse authorised therein, the Spanish Agency for Medicinal Products and Sanitary Products shall be addressed to the competent body of that Member State, by reasoned writing, and the relevant information shall be required.

Additional disposition first. Veterinary medicinal products.

Wholesale warehouses may also distribute veterinary medicinal products in the form set out in the implementing provisions.

Additional provision second. Other products.

Wholesale warehouses may also supply other products which may be distributed by the pharmaceutical channel in the form laid down in the implementing rules provided that this activity does not interfere with the negatively with compliance with good drug distribution practices.

Additional provision third. Direct sales to healthcare professionals.

1. The direct sale to professionals, provided for in Article 2.5 of Law 29/2006, of 26 July, will be carried out by the pharmacy offices, upon request of the professional of the precise medicines, by means of order sheet, capable of being realized by any means or telematic system that ensures a maintenance and file of the orders received, all without prejudice to the autonomous regulations applicable to the centers, services and sanitary establishments. The Spanish Agency for Medicines and Health Products will provide instructions for these waivers that will be agreed in advance in the Technical Inspection Committee.

2. The Spanish Agency for Medicines and Health Products will issue a resolution, which will be published on its website, with the list of medicinal products which may be sold directly to medical, dental, veterinary and medical professionals. podiology for the exercise of your professional activity. The list may include use or security requirements.

In such cases, the supplying entity must inform the health care professional both about the conditions for the preservation of the delivered medicinal products, and the quality alerts that might affect the units sold. and perform the checks that are established in relation to the security devices.

3. The delivery note shall include:

a) The personal and professional identification of the petitioner.

b) The identification of the centre, service or health establishment where the professional is engaged.

c) Data referring to the name, quantity, and batch of the drugs supplied.

d) The identification of the pharmacy, or the supplier of the pharmacy where appropriate, date and signature.

4. All documentation shall be kept both in the pharmacy office, or in the supply entity where appropriate, as in the health centre or service where the professional is engaged, at the disposal of the competent authority in whose field the activity is carried out. assistance.

5. In any case, in the case of narcotic drugs, their specific rules will apply to them.

Additional provision fourth. No increase in staff expenditure.

The application of this royal decree will not result in any increase in personnel expenditure.

Single transient arrangement. Period of adequacy.

Within six months, from the entry into force of this royal decree, the distribution and intermediation entities will adapt their operation to the forecasts in the included.

Single repeal provision. Regulatory repeal.

The entry into force of this royal decree is repealed by Royal Decree 2259/1994 of 25 November, which regulates the pharmaceutical stores and the wholesale distribution of medicinal products for human use and products. pharmacists and how many provisions of equal or lower rank are opposed to what was established in this royal decree.

Final disposition first. Amendment of Royal Decree 824/2010 of 25 June on the regulation of pharmaceutical laboratories, manufacturers of active substances of pharmaceutical use and the external trade of medicinal products and investigational medicinal products.

Royal Decree 824/2010 of 25 June on the control of pharmaceutical laboratories, manufacturers of active substances of pharmaceutical use and the external trade of medicinal products and medicines in research modified as follows:

One. Article 1 (1) (b) is worded as follows:

"b) The manufacture and distribution of active substances and excipients."

Two. Article 1 (2) (c) is worded as follows:

" Manufacturers of active substances used as raw materials in the manufacture of medicinal products, the activity of which consists in the complete or partial manufacture or the importation of an active substance used as material premium, as well as the processes of fractionation, conditioning and presentation prior to incorporation into a medicinal product, including reconditioning and relabelling, as well as the distribution thereof. '

Three. A point (e) is added to Article 1 (2), with the following wording:

"e) Manufacturers and importers of excipients."

Four. Point (g) is amended and three new letters are added to Article 15 (1), with the following wording:

" g) Meet the principles and guidelines of the correct manufacturing standards and use as raw materials only active principles, manufactured in accordance with the detailed guidelines of the correct manufacturing standards of active and distributed principles in accordance with good practices for the distribution of active principles.

m) Inform the competent authority and the marketing authorisation holder immediately if it obtains information that the medicinal products falling within the scope of its authorisation, as a manufacturer or importer, are, or they are suspected of being, falsified, irrespective of whether they are distributed through the legal distribution chain or by illegal means, including illegal sale through the provision of information society services.

n) Check that manufacturers, importers or distributors from which it obtains active substances are registered with the competent authority of the Member State where they are established.

n) Verify the authenticity and quality of the active substances and excipients. "

Five. The first subparagraph of Article 17 (2) shall be worded as follows:

" 2. The training cycle shall contain a theoretical and practical teaching covering at least the following basic subjects: "

Six. Article 23 (2) is worded as follows:

" 2. The manufacturers and importers of active substances do not require authorisation as a pharmaceutical laboratory, with the exception of the production activities of sterile or biological active substances, for which they must be have the relevant authorisation as a pharmaceutical manufacturer. '

Seven. Article 24 is worded as follows:

" Article 24. Obligations of the pharmaceutical laboratories in relation to the active substances and excipients.

1. Pharmaceutical laboratories manufacturers or importers have an obligation to:

(a) Ensure compliance with the standards of correct manufacturing by manufacturers and the good distribution practices by distributors of the active substances they use in the manufacture of the medicines. To this end, they shall be audited at regular intervals, to manufacturers and distributors of active substances, to confirm that they meet the requirements of the correct manufacturing standards and good practices for the distribution of active substances. The frequency of audits shall be at least once every three years, unless a longer period is justified on the basis of a risk analysis. The holder of the manufacturing authorization shall verify such compliance by himself or, without prejudice to his or her responsibility in accordance with the provisions of this royal decree, through an entity acting on behalf of him under a contract.

b) Document the supply chain of each starting material.

(c) The technical director shall issue, for each active principle, a declaration that the latter is manufactured and distributed in accordance with the principles of the correct manufacturing standards and good practice of distribution of principles assets, in accordance with the knowledge acquired through the conduct of audits.

2. In the case of the importing pharmaceutical laboratories, the audit referred to in paragraph 1 (a) may be delegated to the manufacturer of the medicinal product located in a third country, provided that the responsibilities of the each party to a contract in accordance with Article 22 (2).

3. Pharmaceutical laboratories manufacturers or importers shall ensure that the excipients are suitable for use in a medicinal product by determining the appropriate good manufacturing practice. Such determination shall be based on a formal risk assessment in accordance with the applicable guidelines referred to in the rules of correct manufacture of medicinal products. Such risk assessment shall take into account the requirements of other appropriate quality systems as well as the origin and intended use of the excipients and previous incidents of quality defects. The laboratories shall ensure that the relevant relevant manufacturing standards are applied and shall document the measures taken pursuant to this paragraph. '

Eight. Article 25 is worded as follows:

" Article 25. Registration of manufacturers, importers or distributors of active principles and annual declaration of activities.

1. The manufacturers, importers or distributors of active substances must be registered in the register established for this purpose in the Spanish Agency for Medicines and Health Products, which shall be public. These undertakings must notify by way of telematics, by completing the questionnaire set out for that purpose, the beginning of their activity at least 60 days before the date set for the commencement of the activity. The Spanish Agency for Medicinal Products and Health Products, on the basis of a risk assessment, may carry out an inspection in which case it shall report within 60 days of the submission of the notification, to the company, which must refrain from starting its activity until the visit is made and the corresponding certificate is issued, in the terms provided for in Article 46 of this royal decree. If within 60 days of receipt of the registration form, the competent authority has not notified the applicant that an inspection will be carried out, the applicant may initiate the activity.

2. In addition, before 31 January each year, these companies are obliged to make a statement of their activities to the Spanish Agency for Medicines and Health Products, also by means of telematics, by completing the questionnaire to this effect.

3. Without prejudice to the above paragraph, the companies registered in the register must immediately notify the Spanish Agency for Medicinal Products and Health Products, through the established telematic procedure, any change that may have an impact on the quality or safety of the active substances manufactured, imported or distributed.

4. The Spanish Agency for Medicinal Products and Health Products shall record the information contained in this register in the European Union database established by the European Medicines Agency. '

Nine. Article 26 (4) is worded as follows:

" 4. Manufacturers and importers of active substances used as raw materials for medicinal products are required to comply with the guidelines for raw materials, set out in Part II of the detailed guide to the correct manufacturing standards. establishing the European Commission, as well as the Annexes which apply to them. "

Ten. A new paragraph 5 is added to Article 26, with the following wording:

" 5. Distributors of active substances used as raw materials for medicinal products are obliged to comply with the good distribution practices of active principles adopted by the European Commission in the form of guidelines to be published. by the Ministry of Health, Social Services and Equality. '

Once. A new Article 39a is added, with the following wording:

" Article 39a. Inclusion of the third party in the authorisation of a marketing authorisation holder.

1. The application for the inclusion of a third party in the authorisation of a laboratory holder of the marketing authorisation shall be submitted by means of the computerised application established for that purpose by the Spanish Agency for Medicinal Products and Sanitary Products.

2. The application shall include the distribution activities which the third party is to carry out and must be accompanied by the contract signed between the parties.

3. In turn, the contract between the parties must be accompanied by the necessary documentation to prove that the third party has the required authorization, granted by the autonomous community where the warehouse is located, for the activities for the to be hired.

4. The contract shall specify the distribution activities, as well as any technical agreement relating to the subject matter of the contract, delimiting the tasks of each party. The technical aspects of the contract shall be signed by the pharmaceutical technical officers of the parties.

5. The parties shall ensure the implementation of good distribution practices.

6. The technician responsible for the marketing authorisation holder shall monitor the correct performance of the activities contracted to the third party. '

Twelve. Article 40 is worded as follows:

" 1. The marketing authorisation holder established in another Member State may designate his local representative in Spain for the performance of the distribution activities, in accordance with Article 1 (4) of the royal decree for which he is regulates the distribution of medicinal products for human use.

2. The designation of this representative shall not exonerate the marketing authorisation holder of his responsibilities in this field. '

Thirteen. Article 43 (4) is worded as follows:

" 4. After each inspection, the inspectors shall, where appropriate, draw up a report on compliance with the correct manufacturing standards, published by the Ministry of Health, Social Services and Equality, in accordance with the format established at the level of the " Before adopting the report, the competent authority shall give the relevant inspected entity the opportunity to submit comments. In the case of deficiencies in the report relating to breaches of the rules of good manufacturing or of the rules applicable to the manufacture of medicinal products, the inspected entity shall report on the measures it has taken. adopted or intends to adopt for its correction, as well as the time limits for its implementation.

When sampling is necessary, it shall be carried out in accordance with the provisions of Article 48. "

Fourteen. Article 45 is worded as follows:

" Article 45. Issuing certificates of compliance with the correct manufacturing standards.

Once the inspection visit has been carried out and the compliance with the correct manufacturing standards has been verified, in the ninety days following the inspection, the health authorities shall issue the inspection to the institution. a certificate of compliance with those standards, without prejudice to the issue, where appropriate, of the relevant authorisation by the Spanish Agency for Medicinal Products and Health Products. '

Fifteen. Article 46 is worded as follows:

" Article 46. Inspections of manufacturers and distributors of active substances or excipients.

1. Inspections of active ingredient manufacturers may be carried out in accordance with the processes involved in the manufacture of active substances, both in the production facilities and in the production, storage or distribution facilities in where handling, fractionation, packaging or relabelling activities are carried out. Inspections may also be carried out for distributors of active substances and for manufacturers, importers or distributors of excipients.

2. In order to ensure compliance with the correct manufacturing standards and the good practices for the distribution of active substances, the Spanish Agency for Medicines and Health Products and the Autonomous Communities, in the framework of their (a) a system of supervision, by means of inspections at a suitable frequency depending on the risk, of the facilities of the manufacturers, importers or distributors of active substances, as well as of a effective monitoring of them. The Spanish Agency for Medicinal Products and Sanitary Products may carry out inspections, in accordance with the instructions issued in this respect, on the premises, located both in the national territory and in a third country, in order to review the manufacturing or distribution process of one or more active substances related to a record of a medicinal product.

3. Once the inspection visit has been carried out and the conformity with the compliance with the correct manufacturing standards or the good distribution practices has been verified, in the ninety days following the inspection, the current health authorities they shall issue a certificate of compliance with these guidelines to the inspected entity.

4. However, that certificate, or other certificate issued by another competent health authority of the European Union or a country with a Mutual Recognition Agreement, shall not exempt the holders of the manufacturer's pharmaceutical laboratory approval. or importer of the obligation to ensure compliance with the correct manufacturing standards and good distribution practices by the manufacturers and distributors of active substances. '

Sixteen. A new Chapter IX is added, with the following wording:

" CHAPTER IX

Controls on the import of active substances used in the manufacture of medicinal products for human use

Article 57. Conditions for the import.

1. Only active substances that meet the following conditions will be imported:

(a) which have been manufactured in accordance with the provisions in force, in the exporting country, in the field of standards of good manufacturing, at least equivalent to those laid down in the framework of the European Union,

(b) which are accompanied by a written confirmation, in accordance with the characteristics agreed at European level, of the competent authority of the exporting third country that:

1. The provisions in force in the exporting country in respect of the correct manufacturing rules applicable to installations which manufacture the active substance exported are at least equivalent to those laid down in the the framework of the European Union;

2. The manufacturing facility in question is subject to periodic, strict and transparent controls and effective application of the correct manufacturing standards, which include repeated and unannounced inspections, in such a way as to ensure that public health protection is at least equivalent to that established in the European Union; and

3. If a non-compliance is found, the exporting third country shall without delay transmit to the European Union information on the non-compliance.

2. The document referred to in paragraph 1 (b) shall not be required where the exporting country is on the list drawn up by the European Commission after verification that it complies with the requirements for the production of active principles necessary to ensure a level of public health protection equivalent to that existing in the Community framework.

3. The written confirmation referred to in paragraph 1 (b) of this Article shall be without prejudice to the obligations of pharmaceutical laboratories arising from the provisions of Article 24.1 (a)

4. In exceptional cases and where necessary to ensure the availability of medicinal products, the Spanish Agency for Medicinal Products and Sanitary Products may dispense with the requirement laid down in paragraph 1 (b), if the installation in which it is The active principle has a certificate of good manufacturing standards issued by a Member State. This exemption may not exceed the period of validity of the said certificate. The Spanish Agency for Medicines and Health Products will communicate this to the European Commission. "

Final disposition second. Competence title.

This royal decree is issued in accordance with the provisions of Article 149.1.16. of the Constitution which attributes to the State exclusive competence in the field of bases and general coordination of health, having a character of legislation (a) the basic principle, with the exception of the provisions of Chapter IV, of Article 19, as well as its final provision, which are given in the field of competition in the field of pharmaceutical legislation, attributed exclusively to the State in the the same constitutional precept cited above.

Final disposition third. Incorporation of European Union law.

This royal decree partially incorporates into Spanish law Directive 2011 /62/EU of the European Parliament and of the Council of 8 June 2011 amending Directive 2001 /83/EC establishing a code of law (a) Community action on medicinal products for human use, with regard to the prevention of the entry of falsified medicinal products into the legal supply chain, and in particular the amendments to Articles 46 (f); new 46b; New 52a; new 52b, paragraph 1; 80, with the exception of paragraph a); new 85 b; and the new 85a, in the the wording of Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012.

Final disposition fourth. Faculty of development.

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. Entry into force.

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

Given in Madrid, on October 11, 2013.

JOHN CARLOS R.

The Vice President of the Government and Minister of the Presidency,

SORAYA SAENZ DE SANTAMARIA ANTON