Understanding how to complete a clinical investigation submission in Spain with the AEMPS is essential for manufacturers and sponsors working under the EU MDR. Although the MDR brought greater harmonization across Europe, Spain maintains several national provisions that every sponsor must follow. Below is a clear, SEO‑optimized overview to help you navigate the updated process introduced on January 30, 2023.
How Clinical Investigations Are Regulated in Spain
Clinical investigations in Spain are governed by long‑standing national laws:
- Royal Decree 1591/2009 on medical devices
- Royal Decree 1616/2009 on active implantable devices
- Circular Nº 07/2004, which sets out ethical and methodological requirements similar to those used for medicinal product studies
Together, these regulations define how to obtain administrative approval and what documents sponsors must provide.
Key Stakeholders in a Clinical Investigation Submission in Spain (AEMPS)
Three main stakeholders are involved in every submission:
1. AEMPS (Spanish Competent Authority)
Reviews and authorizes the clinical investigation submission in Spain.
2. CEIMs (Ethics Committees)
Issue a favorable or negative ethical opinion for studies involving human subjects.
3. Clinical Sites (“Centros de investigación”)
Conduct the Clinical Investigation Plan (CIP) according to MDR and ISO 14155.
Updated AEMPS Submission Process Under the EU MDR
Since May 26, 2021, the MDR imposed stricter rules for clinical investigations. These requirements are mainly defined in:
- Article 70 (submission obligations for experimental devices)
- Annex XV, Chapter II (application content and documentation)
Previously, Spain used Circular Nº 07/2004, including templates such as:
- Annex B – application form
- Annex 1 – manufacturer’s essential requirements declaration
- Annex 2 – sponsor’s declaration
As of January 30, 2023, the AEMPS updated all annexes to match MDR requirements.
New AEMPS Annexes for Clinical Investigation Submissions
Annex A – MDR Submission Requirements
This annex explains all documentation needed for an MDR‑compliant clinical investigation submission in Spain AEMPS.
Annex B – Substantial Modification Requirements
Covers modifications following MDCG 2021‑28.
Annex C – Updated Application Form
Aligned with Annex XV Chapter 2.1 and includes new fields such as:
- Clinical Evaluation Plan reference
- Details on medicinal substances, human/animal tissues
- Identification of the Notified Body (if applicable)
- Confirmation of AEMPS–CEIM communication
- Manufacturer’s declaration on GSPRs (excluding aspects under investigation)
- Use of the term “Supervisor” instead of “Monitor”
Annex D – Updated Manufacturer GSPR Declaration
Now aligned with Annex XV Chapter 4.1.
Important Requirements for AEMPS Clinical Investigation Submissions
The updated process highlights several national expectations:
Site Director Agreement Required
In addition to AEMPS approval and CEIM opinion, the site director must sign a contract authorizing the clinical investigation.
Accepted Languages
- English accepted: Investigator’s Brochure (IB) and Clinical Investigation Plan (CIP).
- Spanish required: CIP summary, Patient Information Sheet, Informed Consent, Instructions for Use, labeling, and all authorization request forms.
Safety Reporting
Must follow MDCG 2020‑10/2 Rev 1 safety reporting procedures.
Submission Pathways for Clinical Investigations in Spain
Spain offers different submission pathways depending on the study type:
1. Full AEMPS Submission
Required for:
- Premarket clinical investigations with non‑CE‑marked devices
- CE‑marked devices used outside their intended purpose (MDR Article 74.2)
2. Notification via NEOPS
Used for PMCF studies with CE‑marked devices used within intended purpose but deviating from standard practice.
3. No Authorization or Notification
For observational PMCF studies fully aligned with CE‑marked intended use.
4. Consultation With AEMPS
For studies under MDR Article 82 involving non‑CE‑marked or off‑label CE‑marked devices, but not intended to support CE marking.
How MDx Supports Your Clinical Investigation Submission in Spain (AEMPS)
MDx CRO provides end‑to‑end support for sponsors navigating the updated Spanish submission pathway. Our services include:
- Clinical & regulatory strategy
- Medical writing
- GSPR checklist creation
- Notified Body application support
- Design of IB and CIP aligned with MDR & ISO 14155
- Ethics Committee submissions
- AEMPS clinical investigation submissions
- Site qualification, activation, monitoring & management
- PMCF and Article 82 studies
Our experts guide you through every stage (from planning to submission to study execution) ensuring full compliance with MDR and Spanish national requirements.
