Medical Device - Spain

For research involving medical devices, the contact email address is psinvclinic@aemps.es .The head of this area is Mª Concepción Rodríguez Mateos.

To follow the instructions from the AEMPS for conducting clinical investigations with medical devices review them here.

To review the  Spanish national law, this is the website where the AEMPS updates everything related to it. Law in effect:

Royal Decree 192/2023, Art 30-34

Royal Decree 1591/2009, Art 30

Royal Decree 1090/2015

CE-marked MD used within label only require approval from EC!

Combination studies:
(1) MD with CE-marked used outside label or without label + MP: Submission to SGMUH (General Subdirection of Human Medicinal Products') in 2 copies. Evaluation by SGMUH and SGPS (General Subdirection of Medical Devices). Single unified opinion after evaluation process.
(2) MP (not authorized in any EU country) integrated in a MD (e.g. insulin pre-filled pens): Submission to SGMUH (evaluation process like IMP trial)
(3) Comparing MP vs MD with CE mark used within label: Submission to SGMUH (evaluation process like IMP trial)
(4) Comparing MP vs MD without CE mark and/or with CE- mark used outside label: 2 applications (to SGMUH and SGPS). Sponsor notifies the Subdirections of application dates. Evaluation by both the Subdirections. Single unified opinion after evaluation process.

Observational studies: Submission obligation depends on authorisation status of the IMP and the MD (CE mark and use within or outside label). In case of required authorisation, the trial has to be submitted to both local + national CA. For any other types of clinical research only submission to national CA is required. (see: Orden SAS/3470/2009)

Documentation related to the application for authorization of a clinical investigation with a medical device, as well as any subsequent communications during its processing, should be submitted through the General Electronic Register of the General State Administration addressed to the AEMPS until the Eudamed electronic system is available. This applies when the applicant is required to interact electronically with the Administration (Article 14 of Law 39/2015 of October 1).

Everything related to how to apply is provided here, including the annex with important documentation.

Authorization for the clinical investigation must be requested through a written application from the sponsor addressed to the Director of the AEMPS, accompanied by the documentation described in Chapter II of Annex XV of Regulation 2017/745 on medical devices, as listed in Annex A of the below website, along with proof of payment of the corresponding fee (code 8.19).

1) Submission to AEMPS/ Dept. Medical Devices- SGPS:
• email to psinvclinic@aemps.es,
• CD-ROM with the information dissected into separate files and a paper version of the form B (by ordinary mail)

2) Submission to AEMPS/ Dpt. for Medicinal Products for Human Use - SGMUH:
Online submission via Portal ECM (Ensayos Clínicos con Medicamentos)
The AEMPS website (Section Clinical Trials) provides practical guidance and manuals on the use of the portal ECM and the application modality.
The submission portal is also accessible via "sede electrónica” to upload the xml file with the protocol.

Authorization of MD studies: € 824.24 - (Cat II-III)

Authorization of combined (MD+MP) studies: € 824.24 + €1508.22 for the evaluation of the active substance incorporated into the MD (Cat IV-VI)

The current fees (Tasas del Grupo VIII) and payment modalities (Instrucciones para el pago de las tasks por residentes/ no residentes en España) are provided on the AEMPS website in section Clinical research with Medical Devices>Tasas/Fees

Art 30.2-4 of Royal Decree 1591/2009
Art 127.2-4 of Royal Decree 1616/2009

The CA validates the correctness and completeness of the application and notifies the applicant on the decision. In case of any deficiencies the sponsor has a maximum time span of 10 days to correct them.

For Type III MD or active implantable type IIa-IIb MD the period for approval (by affirmative administrative silence) is reduced to 15 days. If clarifications are requested by the AEMPS, the Sponsor will have to submit a reply within 15 days.

Refer to Royal Decree 1090/2015.

The standard application form to be used for the submission of substantial amendments is provided on the AEMPS website in section “Aclaraciones sobre la aplicación de la normativa de ensayos clínicos”: Anexo 1C.
The application must be in writing, dated and signed by the sponsor and investigator.

Royal Decree 1090/2015

(1) SAE reporting form MEDDEV 2.7/3
(2) For combination studies: SUSAR reporting form CIOMS-I (provided on the AEMPS website in section “Aclaraciones sobre la aplicación de la normativa de ensayos clínicos”)

Combination studies: Detailed guidance and practical instructions are given in the document "Aclaraciones sobre la aplicación de la normativa de ensayos clínicos", published on the AEMPS website.

Royal Decree 1090/2015

The standard reporting form to be used is provided on the AEMPS website in section “Aclaraciones sobre la aplicación de la normativa de ensayos clínicos”: Anexo 1D: Notificación del fin del ensayo.

Royal decree 1090/2015
Art 30 Royal Decree 1591/2009

In case of premature trial termination, the notification must include the study data obtained until the study termination as well as the reasons for this and the measures taken relating to the study participants

The accreditation process for research centres is covered by Law 16/2003, regulating the cohesion and quality of the National Health System.

On the Health Ministry website MSSSI (Ministerio de Sanidad, Servicios Sociales e Igualdad) there is a register of the accredited RECs with functional and organizational aspects (Home>Professionals >Pharmacy>Directory of the accredited CIECs in Spain) .

There is no central Ethics Committee in Spain.
The Coordinator Centre for CEICs (Centro Coordinador de CEIC) is the contact point of the CEIC network and collaborates with the Health Authorities in the Autonomous Regions in Spain (17 all over the country).

According to the law, submission to the EC and CA can be done in any order or simultaneously, depending on the sponsor’s preference (pursuant to Art 15 Circular 7/2004)
NB! Approval by the EC is a necessary requirement for CA authorization!

The competent REC (Research Ethics Committee), selected by the sponsor, evaluates the clinical trial as well as any modifications/ amendments of authorized clinical trials and issues its reasonable opinion.

The application of MD studies (with randomization) has to be submitted to and approved by all local RECs of the participating sites (Art 18 & 19 Circular 7/2004).
For observational studies with no randomization, the protocol has to be submitted to all participating EC (for the evaluation of local issues), but it is only required the approval from one EC.

Art 18 & 19 Circular 7/2004

The sponsor is responsible for the submission to the concerned Research ECs of all sites involved in the trial

(1) Portal ECM (Ensayos Clínicos con Medicamentos)
It also provides further guidance on the use of the portal and the application procedure.
(2) CD-ROM, e-mail or paper by attaching the specific documentation required by the EC. Online submission is compulsory for all ECs. Additionally, there are specific requirements for each EC the Sponsor has to fulfil.

There is no standard application form for all RECs (each EC has its own specific forms).

The application must include the documentation according to Art 16 of Circular 7/2004. A list of required documents (including practical examples) is available on the MSSSI website in section "Documentación del ensayo clínico para presentar a los CEIC"

Fees are mandatory for all clinical investigation of MD (interventional and observational) and vary according to the EC concerned.
Fees are provided on the corresponding EC website or requested by phone.

Royal Decree 1090/2015

Contacts of ECs are provided on the MSSSI website in section Directorios de los CEIC's acreditados en España.

Art 18 Circular 7/2004
Royal Decree 1090/2015

Formal evaluation of application dossier for both mono-centre and multicentre trials: The REC(s) has/have 10 days to validate the application documentation and to notify the sponsor on the decision.

There are different submission deadlines for each of the RECs. The corresponding meeting schedules are provided on the MSSSI website in section "Calendario de los CEIC's".

There is no standard form, unlike CT with IMPs. Only required information and documents have to be sent.
The application must be in writing, dated and signed by the sponsor and investigator.

Royal Decree 1090/2015 (Article 22)
Art 25 Circular 7/2004

Formal validation of application dossier: The EC has 10 days to validate the application of the substantial amendment.
A reasonable opinion is communicated to the sponsor and the national CA within the given timeline.

Royal Decree 1090/2015

For Combination studies (MD+MP) when the AE is associated to the MP, only SUSARs (Suspected Unexpected Adverse Reaction) are reported (in compliance with the reporting timelines).

There is no standard form available for investigations of MD

Art 27 Circular 7/2004 & Royal Decree 1090/2015

In case of premature trial termination, the notification must include the study data obtained so far as well as the reasons for early study termination and the measures taken relating to the study participants,

Promotor (pursuant to Art 2e) Circular 07/2004)
Individuo u organización que asume la responsabilidad de la iniciación y/o puesta en práctica de una investigación clínica.
NOTA: Cuando un investigador clínico de forma independiente inicia, pone y práctica y asume la total responsabilidad de una investigación clínica, el investigador clínico asume también el papel de promotor.

It is mandatory to have a sponsor in clinical investigations of MD (interventional and observational).

There are no specific requirements/regulations for GCP training of the investigators
Qualification and Adequacy of IPs: they must be qualified in clinical research and in the specific field of the MD.

The provisions related to the informed consent form and the patient information sheet is provided in Article 7 Circular 7/2004 & Royal Decree 1090/2015 (articles,4 ,5, 6)

The aspects on ethical principles, methodologies and protection of trial subjects are also applicable to clinical investigations with MD (pursuant to Art 30.1. RD 1591/2009) (refer to Royal Decree 1090/2015).

Informed consent obtained from vulnerable subjects (e.g. minors and incapacitated adults) who are potentially involved in the clinical investigation is specifically covered in Royal Decree 1090/2015.

Law 29/2006
Royal Decree 1090/2015 (Articles 4, 5, 6, 7)
Art 3, 4, 6.2 and 7.3 of Circular 7/2004

Art 3, 5, 6.2 and 7.3 Circular 7/2004

Art 7.4 Circular 7/2004

Art 3, 6.3 Circular 7/2004

The European Guideline "Ethical considerations for clinical trials on medicinal products conducted with the paediatric population" contains further helpful recommendations concerning minors.

Compensations are compulsory when there is no direct clinical benefit for the patient. Otherwise, compensations are not mandatory and are only paid to compensate for expenses (e.g. transport tickets) or potential inconveniences (like extra visits) (see Art 3 Circular 7/2004/ Royal Decree 1090/2015).

The sponsor is obliged to inform the patients on the outcome of the clinical trial and to publish the results of the investigation (pursuant to Art 38 Circular 7/2004)

The protection of the data of study subjects is mentioned in Art 3.2, 3.6, 38.3 of Circular 7/2004) and safeguarded by Ley Orgánica 15/1999, de 13 de diciembre, de Protección de Datos de Carácter Personal.

Royal Decree 1090/2015
Art 39 Circular 7/2004

A list of International standards as well as European and Spanish legislation applicable to clinical trials with MDs is also available on the AEMPS website in section Investigaciones clínicas con productos sanitarios (in Spanish only).

The Spanish regulations and ordinances can be found on the official website of the State Agency Official Gazette within the Ministry of the Presidency BOE (Boletín Oficial del Estado).

Note: Currently, the Spanish Law regarding medical devices is not as fully characterized as it is regarding medicinal products.
In the event of doubts concerning the classification of the study, required documents or on the submission process itself, the Subdivision of Medical Devices at the Spanish Agency may be contacted for further clarifications:
Email: psinvclinic@agemed.es
FAX: +34 91 822 52 89

(1) Law 29/2006 on Medicinal Products and MD
(2) Royal Decree 1090/2015
(2) Royal Decree 1591/2009, on Medical Devices (Real Decreto 1591/2009, de 16 de octubre, por el que se regulan los productos sanitarios)
(3) Royal Decree 1616/2009 on Active Implantable Medical Devices

(1) Royal Decree 1090/2015

(2) Circular 7/2004 on Clinical Investigations with MD (Circular Nº 07 / 2004, investigaciones clínicas con productos sanitarios) incorporates Royal Decree 223/2204 and other applicable regulations.

3) Registry: Ordinance SCO/3603/2003 (Orden SCO/3603/2003, de 18 de diciembre) regulates Registries of active implantable medical devices

Observational studies:
Orden SAS/3470/2009, de 16 de diciembre, covers postauthorization (observational) studies with MP for human use.

Royal decree 1085/2009, regulating X-ray devices has to be considered in addition to
• Royal Decree 1591/2009 and
• Royal Decree 1616/2009

The data protection of the participants is safeguarded by the
Law 15/1999 (Ley Orgánica 15/1999, de 13 de diciembre, de Protección de Datos de Carácter Personal)

Definition for MDs and its classification (I,IIa,IIb,III) is provided in Spanish legislation in Art 2 and Annex IX of Royal Decree 1591/2009 and Art 2 of Royal Decree 1616/2009.
Circular number 07/2007