When does your medical device need a clinical investigation?

Under the Medical Device Regulation (EU) 2017/745 (MDR), a clinical investigation is defined as any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device of a medical device (Article 2(45)). This includes the assessment of the ability of the device to achieve its intended purpose leading to a clinical benefit. The investigation is required when existing clinical data derived from alternative sources, such as scientific literature or post-market clinical follow-up (PMCF), is insufficient to demonstrate conformity with the General Safety and Performance Requirements (GSPRs) in MDR Annex I.

Clinical studies performed with medical devices to substantiate the requirements of the MDR are called clinical investigations. However, it’s important to note that not all studies involving human participants meet the MDR definition of a clinical investigation. This definition is crucial for determining whether the specific requirements outlined in Chapter VI and Annex XV of the MDR apply to a given study.

MDR requirements for clinical investigations

Clinical investigations conducted as part of the clinical evaluation to support conformity assessment are regulated in MDR article 62(1). These investigations have requirements and need to be designed, authorised, conducted, documented and reported in accordance with the detailed provisions set out in articles 62 to 81 and Annex XV. Clinical investigations may have different goals for the device, such as establishing or verifying the performance, clinical safety and/or benefits or identifying any undesirable side effects. These investigations can involve devices that are either not yet CE marked or are CE marked but used outside their intended purpose.

The MDR also sets out basic provisions for other types of clinical investigations that may not serve this primary purpose.

According to MDR article 61, a clinical investigation is always required for implantable medical devices and class III devices, unless one of the following exemptions apply:

• the device has been designed by modifications of a device already marketed by the same manufacturer, the modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, in accordance with MDR section 3 of annex XIV and this demonstration has been endorsed by the notified body, and the clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements,
• the device was lawfully placed on the market under the previous Medical Device Directives (90/385/EEC or 93/42/EEC) (MDD), and the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific common specifications (CS) for the clinical evaluation of that kind of device, where such a CS is available, or
• if the implantable or class III device belongs to a well-established lower risk category that are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips, connectors and the clinical evaluation is based on sufficient and relevant clinical data and is in compliance with the relevant product-specific CS, where such a CS is available.

MDCG 2023-7 provides further guidance on these exemptions.

Equivalence under the MDR: when can manufacturer avoid a clinical investigation

MDR provides the possibility for manufacturers to use clinical data from a device already marketed by another manufacturer, provided that the equivalence between the devices can be clearly demonstrated. This approach may eliminate the need for a new clinical investigation, but only when strict conditions set out in the MDR are met. However, demonstrating equivalence does not remove the requirement to always conduct a clinical evaluation in accordance with the MDR and other sources of clinical data may also need to be included in the clinical evaluation.

The following technical, biological and clinical characteristics need to be considered and assessed for the demonstration of equivalence:

To rely on equivalence instead of conducting a new clinical investigation, manufacturers must justify that the compared devices are similar enough to ensure there are no clinically significant differences in safety or clinical performance. It is important to note that some of the listed characteristics must be identical, not just similar. MDCG 2020-5 includes further guidance and a table that can be used when demonstrating equivalence.

According to article 61(4) and (5) of the MDR, this is especially critical for class III and implantable devices, for which the following requirements are also mandatory:

In contrast, an agreement is not required in cases covered by Article 61(4)(1) to (3) and Article 61(6)(a) and (b), such as the established technologies mentioned above. However, sufficient levels of access to data must still be demonstrated, but this does not necessarily mean a formal agreement. Access can be based on publicly available data, shared studies, or other verifiable sources. MDCG 2023-7 provides further guidance on the sufficient levels of access to data needed to justify claims of equivalence.

Manufacturers may identify multiple equivalent devices, but each must meet all relevant criteria of technical, biological and clinical characteristics. The equivalence of each referenced device must be based on proper scientific justification and thoroughly assessed, clearly described, and convincingly demonstrated in the clinical evaluation report.

Exceptions and special cases: When Lower-Risk Devices Cannot Skip Clinical Investigations

While a clinical investigation might not be required to demonstrate conformity with the MDR, clinical investigations are not only valuable for regulatory purposes but also provide a strategic opportunity to differentiate your medical device from similar products and to demonstrate its benefits to clinicians and users.

Additionally, exceptions and special cases exist, particularly for class I, IIa, and IIb devices. These risk class devices may still require a clinical investigation if the device:

According to MDR article 61 (11), the clinical evaluation and its documentation need to be updated throughout the life cycle of the device with clinical data obtained from the implementation of the manufacturer’s post-market clinical follow-up (PMCF) and post-market surveillance (PMS) plans. Even after a device has received a CE marking, PMCF studies may be required, especially if the device is being used outside its intended purpose. These studies are outlined in MDR article 74. The requirement for PMCF highlights the importance of continuous data collection to ensure safety and performance throughout the expected lifetime of the device and the continued acceptability of the identified risks as well as detecting new emerging previously unidentified risks. The Notified Body is responsible for verifying that the PMCF plan is suitable and includes PMCF studies where necessary to demonstrate continued conformity.

If a clinical investigation does not fall under MDR articles 62 or 74, it is governed by article 82. These types of investigations may be conducted for non-conformity assessment purposes, like for example academic interests. Article 82 sets out a minimum requirement for such investigations, but also allows Member State to apply national rules, meaning that additional country-specific regulations may apply. Therefore, it is essential to check and comply with the country-specific local regulatory requirements in the country where the investigation is conducted.

Services offered by Medfiles for clinical evaluations and clinical investigations

As described in this blog, medical device manufacturers need to carefully consider the requirements in the MDR related to clinical evaluations and investigations to ensure smooth market entry for new products or smooth transition from an MDD legacy product to an MDR compliant product. If your organisation needs any help in navigating in the complex regulatory environment, don’t hesitate to contact Medfiles’ Medical Device regulatory and clinical experts, who can help in all matters regarding clinical evaluations and investigations, from gap analysis and general consultation to planning, monitoring and documenting clinical investigations and conducting and documenting clinical evaluations.

As the MDR transition period is ongoing, and the final deadlines for the transition from an MDD legacy product to an MDR compliant product are quickly approaching (31 December 2027, for MDD NB certified class III devices, and class IIb implantable devices except the established technologies mentioned in this blog post and 31 December 2028, for other MDD NB certified devices, and upclassified devices which did not require MDD NB certification), the time to act for planning MDR compliant clinical evaluation updates and clinical investigations is now.

Author: Emma Talvitie 
Regulatory Affairs Expert, Medical Devices and IVDs  

Emma Talvitie is a medical device and in vitro diagnostic (IVD) regulatory affairs professional with a Master of Science (Tech.) degree in biotechnology, who has over 4 years of professional experience in MD and IVD regulatory affairs. Emma has a strong background in IVD regulatory affairs and assay development. During her studies she focused on assay development, especially in molecular diagnostics and immunoassays. She started her career by updating the IVDD compliant technical documentation of an IVD analyser to be compliant with the IVDR. She has also been responsible for planning, executing, data analysis and reporting of IVD assay verification and validation studies and contributed to writing and reviewing IVDR and FDA 510(k) documentation for IVD assays.

Since April 2023, as a Regulatory Affairs Expert at Medfiles, Emma has worked in varying projects helping clients with regulatory issues and compiling technical documentation for multiple medical devices and IVDs. Emma is exited about contributing to the development of innovative, high-quality devices that meet both regulatory requirements and user needs.  

See also:

• ISO 14155:2026 – What’s new for medical device clinical investigations
• What to know about medical device and IVD class changes and transition periods
• EU IVDR: Compliance with technical documentation, notified body processes and transition periods
• What importers and distributors need to know about EU MD and IVD regulations – regulatory compliance, labelling and marketing materials
• Guide: How to meet MDR Good Clinical Practice requirements in practice