Relevant information about the clinical investigations in Spain
Since the implementation of the new EU MDR, there has been significant standardization in the processing of clinical investigation submissions throughout Europe. Each country, however, may have its own national provisions.
This article is intended for clinical research experts who need to undertake a clinical investigation submission in Spain for medical devices using the new update process (January 30, 2023). this article offers a general overview of the process’s requirements.
In Spain, the conduct of clinical investigations with medical devices has been governed by
- The Royal Decree on Medical Devices (Royal Decree 1591/2009) and
- The Royal Decree on active implantable medical devices (Royal Decree 1616/2009)
- and the Circular Nº 07/2004
outlining the ethical and methodological rules that need to be followed (these are similar to the rules for clinical research with medicine products), the steps that need to be taken to get administrative approval, and the paperwork that the sponsors of this research need to provide.
In the Spanish Clinical Investigation, there will be three key stakeholders.
- The Spanish Competent Authority, AEMPS, reviews and approves the submission of clinical investigations in Spain.
- The Ethics Committees, CEIMs, that issue a negative or favourable opinion in the clinical investigation in human subjects.
- The Clinical Site, “centros de investigación”, that will perform the Clinical Investigator Plan with human subjects.
How to submit a submission for approval of a clinical investigation to the AEMPS.
After May 26th, the EU MDR 207/745 indicates the new requirements for the submission of clinical investigations. Those requirements are mainly specified in
- Article 70 defines that the sponsor must prepare and submit a request for experimental devices covered by Article 62.
- Annex XV, Chapter II, of the MDR.
Officially, the submission process had required using the Circular Nº 07/2004, that provided the additional local requirements and templates such as
- Annex B. Application form for authorization of clinical investigations with medical devices.
- Annex 1. Template for the manufacturer’s declaration of compliance with the essential requirements
- Annex 2. Template for the sponsor’s declaration for devices intended for clinical investigations.
On January 30th, the AEMPS has updated the process and the Annexes to include explicitly the MDR requirements.
- The Annex A is the Submission Requirements for Clinical Investigations following the EU MDR Annex XV.
- The Annex B is the Substantial Modification requirements for clinical investigations under Medical Device Regulation (no previous annex to be updated) according to MDCG 2021-28.
- The Annex C is the Application Form (updating the prior Annex B). The application form has been updated according to the Annex XV chapter 2.1. with the following fields:
- Details and/or reference to the investigational device clinical evaluation plan;
- Information as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;
- Using the term of “Supervisor”, that covers the full implementation of the GCPs in the clinical investigation, instead of “Monitor”.
- Details to identify the notified body, if already involved at the stage of application for a clinical investigation;
- Confirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and
- The statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.
- The Annex D is the manufacturer’s declaration of compliance with the General Safety and Performance Requirements (update to the prior Annex 1).This Annex has been updated according to Annex XV chapter 4.1
In the updated submission process, it is highlighted that
- In addition to the AEMPS authorization and the ethics committee’s favorable opinion, the site director’s consent is required, which is a contract between the sponsor and each site where the clinical investigation will take place.
- The Investigator’s Brochure and the Clinical Investigation Plan (the study protocol) may be accepted in English.
- The Clinical Investigation Plan summary, the Patient Information and Informed Consent form, the Request for Authorization or Notification of Authorization, as well as the Instructions for Use and Labeling of the Investigational Medical Device, must always be presented in Spanish.
- Safety notifications for investigational medical devices can be done with the form from the MDCG 2020-10/2 Rev 1 “Guidance Safety report Form”
Clinical Investigations in Spain: Other National Provisions
There are many circumstances in clinical investigations using medical devices that must be properly distinguished in order to understand the national provisions that each of them must meet.
The ethics committee’s approval and the site director’s consent are required for all clinical investigations.However, communication with the AEMPS may vary in the following scenarios:
- Full AEMPS Submission Process: Clinical Investigations with medical devices without CE Marking (Pre-market) or Clinical Investigations under article 74.2 such as clinical investigations to assess a device outside of its intended.
- Notification to the AEMPS by NEOPS: Post Market Clinical Follow Up Clinical Investigations for approved indications with variation from usual clinical practice (standard of care)
- No authorization or notification is required. Post Market Clinical Follow Up Clinical Investigations that are observational (following the normal clinical practice/standard of care) and the medical device is used for approved indications (following the Instructions for Use)
- Consultation with the AEMPS about the process. Clinical investigations under article 82 such as clinical investigations that are not pursuant a regulatory purpose without the CE Marking or with CE Marking but to assess a device outside of its intended purpose.
How can MDT help?
With the introduction of the MDR, the requirements for clinical investigations have grown significantly. Whether you are a medical device manufacturer or bioengineering research centre, our team can assist you in developing a compliance strategy and will be with you every step of the way.
Our Clinical Research Services for Clinical Investigations for MDR CE Mark have been tailored for the needs of the manufacturers and sponsors of medical devices and include:
- Clinical and Regulatory strategy
- Medical writing
- Creation and completion of GSPR checklists
- Support with notified body applications
- Design the Investigator Brochure and the Clinical Investigation Plan according to the MDR and ISO 14155:2020
- Ethics Committee Submission
- AEMPS Clinical Investigation Submissions
- Site Qualification and Activation
- Site Monitoring and Management
- Submission and implementation of Clinical Studies under article 82
- Submission and implementation of PMCF studies