Submitting a medical device clinical investigation in Spain begins with determining which regulatory pathway applies under EU MDR Articles 62, 74 or 82. This classification determines whether the sponsor needs prior AEMPS authorisation, notification through NEOPS or no filing with AEMPS.
In all cases, sponsors must also consider the requirements for a favourable opinion from a Spanish Research Ethics Committee for medicinal products, or CEIm, and the conformity of each participating site’s management. The applicable national framework includes Real Decreto 192/2023 and the current AEMPS instructions for medical device clinical investigations.
How Medical Device Clinical Investigations Are Regulated in Spain
Medical device clinical investigations conducted in Spain are governed by:
- Regulation (EU) 2017/745, particularly Chapter VI and Annex XV.
- Real Decreto 192/2023, particularly Articles 30 to 34.
- Real Decreto 1090/2015 for the ethical and methodological principles applicable to CEIm review.
- The current AEMPS instructions for medical device clinical investigations.
- ISO 14155 for Good Clinical Practice in medical device investigations.
Real Decreto 192/2023 replaced most of the previous national framework established by Real Decreto 1591/2009 and Real Decreto 1616/2009. Those earlier provisions should only be mentioned where a specific transitional rule still applies.
For a legal explanation of the national requirements governing ethical review, Spanish-language documents, insurance, liability and CE-marked device investigations, see our guide to Real Decreto 192/2023 and medical device clinical investigations in Spain.
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.
Which AEMPS Submission Pathway Applies?
| Investigation | AEMPS requirement | Other requirements |
|---|---|---|
| Non-CE-marked device investigated for conformity assessment under MDR Article 62 | Prior AEMPS authorisation | Favourable CEIm opinion and site management conformity |
| CE-marked device investigated outside its intended purpose under Article 74(2) | Prior AEMPS authorisation | Same requirements and timelines as an Article 62 investigation |
| CE-marked device used within its intended purpose, with additional invasive or burdensome procedures under Article 74(1) | Notification through NEOPS at least 30 calendar days before starting | Favourable CEIm opinion and site management conformity |
| CE-marked device used within its intended purpose, without additional invasive or burdensome procedures | No AEMPS authorisation or notification | Favourable CEIm opinion and site management conformity still apply |
| Other clinical investigation under Article 82 | Consult AEMPS to determine the applicable procedure | Favourable CEIm opinion and site management conformity |
Correct classification is important because an Article 74(1) notification is not an authorisation procedure, while an Article 74(2) investigation follows the full authorisation pathway. When the purpose or regulatory classification is unclear, sponsors should consult AEMPS before submitting.
AEMPS Application Form and Submission Route
Until the relevant EUDAMED module becomes available, applications requiring AEMPS authorisation must be submitted electronically through Spain’s Registro Electrónico General and addressed to AEMPS.
The core application package includes:
- A sponsor-signed application letter addressed to the Director of AEMPS.
- Evidence of payment of the applicable AEMPS fee, currently identified in the instructions as code 8.19.
- The basic application data form included in Annex C of the AEMPS instructions.
- Sponsor, legal representative, manufacturer and monitor details.
- The CEIm opinion, or information confirming that the opinion has been requested.
- Participating site and investigator information.
- The Investigator’s Brochure.
- The Clinical Investigation Plan.
- Instructions for use and investigational-device labelling.
- The informed-consent documentation.
- The manufacturer’s declaration concerning the applicable General Safety and Performance Requirements.
- Evidence of the required insurance or financial guarantee.
Sponsors may use the European Commission’s clinical investigation application form, but must supplement it with any information required by the AEMPS Annex C that is not included in the European form. The basic data form must also be sent to the institutional AEMPS clinical investigations mailbox identified in the current instructions.
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 During the Investigation
Safety reporting must follow MDR Article 80 and MDCG 2020-10/1 Rev. 1. MDCG 2020-10/1 defines the reportable events, causality rules and deadlines, while MDCG 2020-10/2 provides the corresponding summary safety reporting form.
The submission plan should define responsibilities between the sponsor, investigators and CRO, including how events will be assessed, entered in the reporting form and communicated to AEMPS and other affected competent authorities.
Which Documents Must Be Submitted in Spanish?
Under Article 31 of Real Decreto 192/2023, the application, Investigator’s Brochure, Clinical Investigation Plan, informed consent, instructions for use and investigational-device labelling must be submitted at least in Spanish.
This statutory requirement supersedes earlier AEMPS wording suggesting that the Investigator’s Brochure and Clinical Investigation Plan could generally be accepted in English. Sponsors should plan translations before submission rather than assuming that English versions will be sufficient.
AEMPS Review Timelines
| Stage | Indicative regulatory period |
|---|---|
| Initial validation of the application | 10 calendar days, extendable by 5 |
| Sponsor response to an incomplete application | Normally up to 10 calendar days, subject to the applicable extension rules |
| AEMPS evaluation after validation | 45 calendar days |
| Additional extension for expert consultation | Up to 20 calendar days |
| Article 74(1) notification | At least 30 calendar days before the investigation begins |
| Substantial modification review | 38 calendar days, extendable by 7 |
Requests for supplementary information stop the regulatory clock. The CEIm review may proceed in parallel, but AEMPS will not issue the final authorisation without the required favourable ethical opinion. The current AEMPS instructions recommend submitting when the CEIm opinion has already been issued or is at an advanced stage.
Frequently Asked Questions
No. Article 62 and Article 74(2) investigations generally require prior AEMPS authorisation. Certain Article 74(1) PMCF investigations require notification through NEOPS, while some investigations involving CE-marked devices used within their intended purpose require neither authorisation nor notification. CEIm review and site management conformity must still be considered.
Sponsors should use the basic application data form in Annex C of the current AEMPS instructions. The European Commission application form may also be used if it is supplemented with any additional information required by Annex C.
Following validation, the standard evaluation period is 45 calendar days. The period may be extended by up to 20 calendar days for expert consultation and may be paused when AEMPS requests supplementary information.
Real Decreto 192/2023 requires the application, Investigator’s Brochure, Clinical Investigation Plan, informed consent, instructions for use and investigational-device labelling to be submitted at least in Spanish.
Yes. The CEIm provides the ethical opinion, while AEMPS conducts the competent-authority assessment. The procedures may run in parallel, but the investigation cannot begin until all applicable authorisations, opinions and site approvals are in place.
How MDx Supports Your Clinical Investigation Submission in Spain (AEMPS)
MDx CRO supports international and European sponsors with Spanish regulatory strategy, CEIm and AEMPS submissions, medical writing, site activation, monitoring, safety management and end-of-study reporting. Explore our MedTech Clinical Solutions or contact our Clinical Research team to discuss a planned investigation in Spain.
