The field of medical devices is continually evolving, with new technologies and innovative products constantly being developed to improve patient care and enhance the practice of medicine. To ensure the safety and performance of these devices, clinical investigations must adhere to strict ethical and methodological standards. In Spain, the regulatory landscape governing clinical investigations of medical devices has recently undergone significant changes with the introduction of Real Decreto 192/2023. This decree implements EU Regulation 2017/745 on medical devices, aiming to provide a robust and harmonized framework for the conduct of clinical investigations.

The Real Decreto 192/2023 emphasizes the importance of conducting clinical investigations that adhere to high ethical standards, robust methodological approaches, and the protection of trial subjects. It does so by incorporating the principles outlined in the Real Decreto 1090/2015, which regulates clinical trials with medicinal products, as well as specific provisions from EU Regulation 2017/745. This comprehensive set of guidelines helps ensure that clinical investigations with medical devices are carried out responsibly and with the well-being of trial subjects as a top priority.

By providing a clear and detailed regulatory framework for clinical investigations, Real Decreto 192/2023 aims to streamline the authorization process, establish effective oversight mechanisms, and promote transparency and accountability in the development and assessment of medical devices. As a result, healthcare professionals, researchers, and manufacturers must familiarize themselves with the new requirements and responsibilities under this decree to ensure compliance and the successful execution of clinical investigations in Spain.

Frequently Asked Questions About Spain’s Real Decreto 192/2023 on Clinical Investigations with Medical Devices

What is the purpose of Real Decreto 192/2023?

Real Decreto 192/2023 aims to implement EU Regulation 2017/745 on medical devices in Spain. The decree provides a robust and harmonized framework for conducting clinical investigations with medical devices, emphasizing ethical standards, methodological approaches, and the protection of trial subjects.

What are the ethical principles and protections for trial subjects in clinical investigations under Real Decreto 192/2023?

The decree requires clinical investigations to adhere to ethical principles, methodological guidelines, and subject protection requirements as outlined in Real Decreto 1090/2015 and the European Union’s Regulation (UE) 2017/745.

What is the role of the Committee of Ethics in Medicines Investigation (CEIm) under the new regulation?

The CEIm provides favorable approval for clinical investigations with medical devices. The research must also have the consent of the center’s management where it will take place. The CEIm will issue opinions on clinical investigations and significant modifications of clinical investigations.

How does Real Decreto 192/2023 define the responsibilities of the Spanish Agency of Medicines and Medical Devices (AEMPS)?

The AEMPS is responsible for evaluating and authorizing clinical investigations and evaluating and resolving any significant modifications to clinical investigations. The AEMPS also informs the relevant autonomous communities of decisions made to ensure the safety of clinical investigations, fostering collaboration and coordination between different authorities.

What are the requirements for providing medical devices for clinical investigations under Real Decreto 192/2023?

The sponsor must provide medical devices intended for clinical investigations free of charge. In specific situations, other forms of supply may be authorized. All leftover products must be returned to the sponsor once the investigation is complete.

What are the documentation and record-keeping requirements under Real Decreto 192/2023?

Sponsors or their legal representatives in Spain must maintain documentation related to the clinical investigation, as specified in Annex XV of Regulation (UE) 2017/745. In the event of bankruptcy or cessation of activity, the AEMPS must be informed to establish appropriate measures for documentation conservation and/or submission.

What are the documentation and record-keeping requirements under Real Decreto 192/2023?

Sponsors or their legal representatives in Spain must maintain documentation related to the clinical investigation, as specified in Annex XV of Regulation (UE) 2017/745. In the event of bankruptcy or cessation of activity, the AEMPS must be informed to establish appropriate measures for documentation conservation and/or submission.

How does Real Decreto 192/2023 address indemnification for damages and authorization procedures?

The decree outlines the procedures for authorization of clinical investigations and indemnification of subjects for potential damages resulting from the investigation. The sponsors is responsible for ensuring that insurance or financial guarantees cover damages and liabilities incurred by the sponsors, principal investigator, collaborators, and the center where the investigation occurs.

What are the indemnification requirements for clinical investigations in Spain under Real Decreto 192/2023?

Real Decreto 192/2023 requires sponsors to provide insurance or an equivalent financial guarantee to cover potential liabilities and damages from clinical investigations. According to Article 33, the minimum guaranteed amount for liability coverage is €250,000 per person participating in the clinical investigation. This amount can be received as a lump sum indemnification or equivalent annuity. The decree also allows for a maximum insured capital or financial guarantee of €2,500,000 per clinical investigation and year. It is essential for sponsors to ensure they have adequate coverage for any potential damages arising from the clinical investigation. For more information, refer to the official Real Decreto 192/2023 document here.

How can healthcare professionals, researchers, and manufacturers ensure compliance with Real Decreto 192/2023?

It is crucial for stakeholders to familiarize themselves with the new requirements and responsibilities under Real Decreto 192/2023 to ensure compliance and the successful execution of clinical investigations. By following the guidelines set forth in the decree, stakeholders can facilitate the development of innovative and reliable medical devices, ultimately improving patient outcomes and overall healthcare quality in Spain.

What are the key differences between the previous regulations and Real Decreto 192/2023?

Real Decreto 192/2023 introduces a more comprehensive and harmonized framework for clinical investigations with medical devices, incorporating provisions from EU Regulation 2017/745. This helps streamline the authorization process, establish effective oversight mechanisms, and promote transparency and accountability in developing and assessing medical devices.

How does Real Decreto 192/2023 impact CE-marked medical devices?

Clinical investigations with CE-marked medical devices outside their intended purpose are subject to specific provisions under Real Decreto 192/2023, which includes reporting to the AEMPS and adherence to the relevant articles of the regulation. This ensures that investigations involving CE-marked products maintain high standards of safety and performance.

What is the timeline for obtaining approval for a clinical investigation under Real Decreto 192/2023?

The timeline for obtaining approval for a clinical investigation depends on the investigation’s complexity and the involved parties’ responsiveness. The CEIm’s favorable approval, the consent of the center’s management where the investigation will take place, and the AEMPS’s evaluation and authorization are required before commencing the investigation.

How can investigators and sponsors stay informed about regulatory changes and updates related to Real Decreto 192/2023?

Investigators and sponsors should regularly consult official sources, such as the AEMPS’s website and the Spanish Official Gazette (BOE), to stay informed about regulatory changes and updates. Additionally, networking with industry professionals, attending relevant conferences, and participating in training programs can help stakeholders stay up-to-date with the latest information.

What penalties or consequences can result from non-compliance with Real Decreto 192/2023?

Non-compliance with Real Decreto 192/2023 can result in penalties or sanctions, including fines, suspension or withdrawal of authorization for the clinical investigation, and potential legal action. The severity of the consequences depends on the nature and extent of the non-compliance, as well as any potential risks posed to trial subjects or the public.

How does Real Decreto 192/2023 impact international clinical investigations conducted in Spain?

International clinical investigations conducted in Spain are subject to the same requirements and responsibilities outlined in Real Decreto 192/2023. Ensuring compliance with the regulation is crucial for the successful execution of international clinical investigations and developing of safe and performance medical devices for the global market.

Impact on Clinical Studies with medical devices in Spain

Spain’s Real Decreto 192/2023 aims to improve the regulatory framework surrounding clinical studies in Spain with medical devices by introducing new provisions that safeguard the safety and performance of these products. By focusing on ethical principles, subject protection, and a streamlined authorization process, the decree helps to promote responsible clinical investigations in Spain.

Healthcare professionals, researchers, and manufacturers must familiarize themselves with the new requirements and responsibilities under Real Decreto 192/2023 to ensure compliance and the successful execution of clinical investigations. This will ultimately contribute to the development of safe and performance medical devices for the benefit of patients and the healthcare system.

As clinical investigations play a crucial role in the development and approval of new medical devices, it is essential that stakeholders work together to adhere to the regulations set forth in Real Decreto 192/2023. By following these guidelines, they can help facilitate the development of innovative and reliable medical devices, improving patient outcomes and overall healthcare quality in Spain.

A new position paper from the Mirror-MDCG Clinical Working Group, composed of representatives from 11 Notified Bodies and approved by Team-NB, clarifies how data from off-label medical device use should be viewed and handled under the EU Medical Device Regulation (MDR) 2017/745. Distributed through the CIRCABC platform, the paper aims to harmonize understanding across Notified Bodies and manufacturers when such data emerge during clinical evaluation or post-market surveillance.

Understanding “Off-Label” Use Under MDR

The term off-label use is not explicitly defined in the MDR. However, Annex XIV, Part B—which outlines requirements for Post-Market Clinical Follow-Up (PMCF)—expects manufacturers to identify misuse or off-label use of their devices proactively as part of their ongoing data collection and analysis.
This is because off-label use, intentional or unintentional, can influence a device’s safety, performance, and benefit–risk profile.

Unlike the pharmaceutical sector—where “off-label use” is well established and tied to product labeling and authorized indications—the concept for medical devices remains less formally defined. In practice, off-label use refers broadly to a device being used outside its intended purpose as described in the manufacturer’s instructions for use (IFU) or technical documentation.

Why It Matters: Data Relevance and Clinical Evidence

The Team-NB position paper emphasizes that data generated from off-label use can sometimes offer valuable safety and performance insights—but such data cannot be directly used to support the intended purpose of a device unless carefully analyzed and justified.
Manufacturers should therefore:

• Identify and record instances of off-label use through PMCF and Post-Market Surveillance (PMS) systems.
• Assess relevance and scientific validity of such data when considering it in the clinical evaluation or trend reporting.
• Differentiate between misuse due to human factors and genuine clinical necessity or innovation.

Any insights drawn from off-label data must be clearly documented, and the rationale for inclusion or exclusion in the device’s clinical evaluation report (CER) should be justified according to MDR Annex XIV, Part A.

Implications for Manufacturers and Notified Bodies

For manufacturers, this position paper serves as a reminder that off-label use is both a risk management consideration and a potential data source. It requires active monitoring, not passive recording.
Notified Bodies, for their part, are expected to evaluate how manufacturers:

• Capture and categorize off-label usage events.
• Integrate off-label findings into PMCF and PMS activities.
• Apply conclusions from such data to risk–benefit assessments and updates to labeling or IFUs.

When recurring off-label use indicates a systematic clinical need not covered by the original intended purpose, manufacturers may need to initiate a design or labeling review and consider regulatory reassessment.

Moving Toward Harmonized Practice

By formalizing its view, Team-NB and the participating Mirror-MDCG Clinical Working Group aim to improve consistency and transparency across Notified Bodies when reviewing PMCF and CER documentation that includes off-label data.
This harmonization will help reduce uncertainty for manufacturers and contribute to more robust post-market evidence across the EU.

How MDx CRO Supports Manufacturers

MDx CRO assists manufacturers in integrating off-label monitoring into PMCF and PMS plans, ensuring that data handling and reporting align with MDR expectations.
Our team supports clinical evaluation, PMCF study design, and Notified Body submission strategy, helping you interpret real-world data responsibly—whether it originates from intended or off-label use.

Learn more about our Regulatory Affairs Services and Clinical Research Solutions, or contact us to discuss compliance strategies for MDR Annex XIV requirements.