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.

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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.

In light of the forthcoming Medical Device Regulation (MDR) and the delay in the complete functionality of the electronic system referenced in Article 73 (EUDAMED), the MDCG 2020-10 Rev 1 provides essential guidance. With Eudamed not being ready on the MDR’s effective date, the guidelines under MDCG 2020-10 Rev 1 become instrumental in outlining the processes for safety reporting in clinical research.

Key Points from MDCG 2020-10 Rev 1:

• Safety Reporting Modalities: The document thoroughly describes the reporting modalities for Serious Adverse Events (SAEs) and offers a summary tabulation reporting format.
• Adherence to Regulations: It emphasizes that medical device safety reporting during clinical studies must be consistent with the guidelines in Article 80 of Regulation (EU) 2017/745, also known as the Medical Device Regulation (MDR).

For a clinical investigation involving medical technology, utilizing the electronic system as stipulated in MDR Article 73 means the sponsor must promptly share the following with every Member State involved:

• Any SAE that can be directly or potentially linked to the investigational device, comparator, or the procedure.
• Any device defect that could have escalated to a serious adverse event under different circumstances.
• Further details on any aforementioned event.

The timeframe set for reporting these adverse events varies based on the severity of the incident. While the clinical trial sponsor might initially provide an incomplete report, it’s crucial to follow up with a detailed one to maintain timely reporting.

The guidance not only covers the basic safety reporting protocols but also delves deeper into the post-market clinical follow-up (PMCF) investigations for CE-marked MedTech products. Here, the guidelines laid out in MDR Articles 87 to 90 play a pivotal role.

Safety Reporting in PMCF Clinical Investigations

It’s noteworthy that while the vigilance measures outlined in the aforementioned articles are applicable to PMCF clinical studies, the MDCG 2020-10 Revision 1 remains relevant. This is primarily because the reporting of significant adverse events linked to previous investigational devices should align with the reporting prerequisites mentioned in EU MDR 2017/745 Article 80.

The guidance document provides an essential roadmap for Safety reporting SOPs, Safety reporting plans, and Clinical Investigation plans. This is invaluable for MedTech Manufacturers, sponsors, and CROs involved in clinical research activities with medical devices.

FAQs about MDCG 2020-10 Rev 1

• What events need reporting? Report all SAEs and suspected unexpected serious adverse device effects (SUSADEs).
• What’s the reporting timeframe? Report SAEs within 15 days and SUSADEs within 7 days post the sponsor’s awareness.
• What should a safety report include? Details about the sponsor, investigator, device, event date, event description, outcome, and other pertinent data.

For more comprehensive insights on safety reporting for medical devices, delve into the MDCG 2020-10 Rev 1 guidance document.

Expert panels on medical devices and in vitro diagnostic devices (Expamed)

What this post covers
This article explains and contextualizes a Clinical Evaluation Consultation Procedure (CECP) opinion issued by the EU Expert Panels (Expamed) on October 2022. We’re not republishing the scientific opinion; instead, we summarize what the panel concluded, why CECP matters for Class III and other high-risk devices, and what practical actions manufacturers and notified bodies (NBs) should consider. Our case study is the publicly available CECP opinion concerning a Class III implant used for reinforcement of abdominal soft tissue in ventral and hiatal hernia repair. We highlight how panels judge the sufficiency of clinical evidence, how benefit–risk is weighed, and how PMCF commitments—including registry follow-up—are used to address residual uncertainty. For the official documents, see the Commission’s expert-panel portal, the master list of CECP opinions, and the PDF of the specific opinion discussed here. 

CECP in a nutshell

Under MDR Article 54 and Annex IX, Section 5.1, certain high-risk devices undergo an additional, independent check of the Clinical Evaluation Assessment Report (CEAR) performed by the NB. The expert panel issues a scientific opinion that the NB must consider—especially if the panel finds the level of clinical evidence insufficient or raises concerns about benefit–risk, alignment of evidence with intended purpose and indications, or adequacy of the post-market clinical follow-up (PMCF) plan. If the NB does not adopt the panel’s advice, Annex IX, 5.1(g) requires the NB to justify that decision in its conformity-assessment report. 

Scope of the October 2022 opinion

The consultation related to a fully resorbable mesh with a resorbable hydrogel coating, indicated for reinforcement of abdominal soft tissue in ventral and hiatal hernia repair, assessed within the competence area of General and plastic surgery and dentistry (BSI NB 2797; file CECP-2022-000227). These administrative and device-scope details are recorded in the published opinion and its Commission news entry. 

What the expert panel decided

The panel concurred with the NB on the appropriateness and sufficiency of the manufacturer’s clinical data and agreed with the NB’s benefit–risk assessment. The opinion notes publication of a new multicentre study adding 84 patients with 24-month follow-up to the dataset and reports no indication of higher recurrence or complication rates compared with established routine techniques. At the same time, the panel emphasized that sample sizes across trials and registries were relatively small and follow-up relatively short, supporting the need for longer-term data. 

PMCF expectations and real-world data

The PMCF Plan was considered acceptable. It calls for further clinical-data collection to identify long-term adverse effects, including those related to device–tissue interaction, and for tracking in two quality registries—HerniaMed and ACHQC—to expand the evidence base over the device’s expected lifetime. The panel’s stance illustrates how CECP leverages real-world registries to complement trials and literature when total exposure and follow-up duration are still maturing. 

What manufacturers should take from this

• Think “totality of evidence.” CECP panels look at the sum of literature, clinical investigations, registries, and the PMCF plan. Smaller cohorts and shorter follow-up aren’t automatic blockers if a credible plan exists to close gaps post-certification, but the plan must be specific about endpoints, timelines, and data sources. For reference, the Commission’s “List of opinions provided under the CECP” shows multiple cases in which panels flagged evidence sufficiency, intended-purpose alignment, or PMCF robustness. 
• Align intended purpose, indications, and SSCP. Panels will check whether the intended purpose/indications match the evidence presented and whether claims are mirrored in the SSCP and labeling. Divergences often lead to scope restrictions, targeted PMCF, or time-limited certificates. The Commission’s Expert Panels hub outlines the panels’ remit and how their opinions integrate into NB assessments.
• Prepare for “justify if you diverge.” If your NB does not fully adopt the panel’s advice, it must justify why in its report (Annex IX, 5.1(g)). Anticipate this by designing evidence and PMCF strategies that are straightforward to adopt—e.g., leveraging recognized registries and clearly defining success metrics and risk signals. 

Why this opinion matters beyond hernia repair

Although device-specific, the October 24, 2022 case neatly shows how CECP functions as a calibrated check on high-risk devices: validate benefit–risk for the intended purpose, acknowledge dataset limits, and enforce structured PMCF to address residual uncertainty. For sponsors approaching CECP, this is a model of how to present fit-for-purpose clinical evaluation, align claims with evidence, and build PMCF that uses registries and longer-term outcomes to demonstrate continued performance and safety.

See the official CECP opinion (PDF) and the Commission’s news entry for the canonical record.