Combination studies

Devices containing a medicinal substance   

Trials that are clinical investigations within the meaning of Article 2(45) of the MD Regulation and investigate a device that incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product (including a medicinal product derived from human blood or human plasma), and that has an action ancillary to that of the device (Article 1(8) of the MD Regulation), must be notified to Fimea as clinical investigations of medical device. In addition, it must be determined whether the trial must be notified to Fimea as a clinical trial.    

If the action of the medicinal product is primary, the combination is governed by medicines legislation (Article 1(9) of the MD Regulation) and the trial need not be notified as a clinical investigation of medical device. However, the general safety and performance requirements according to Annex I to the MD Regulation must be met.    

Devices intended to administer a medicinal product   

According to Article 1(9) of the MD Regulation, devices intended to administer a medicinal product are governed by the MD Regulation, so therefore clinical trials conducted with such devices must be notified to Fimea. However, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable (Article 1(9) of the MD Regulation), the product is governed by the medicines regulation and the trial need not be notified to Fimea. However, the general safety and performance requirements according to Annex I to the MD Regulation must be met.   

More detailed instructions on the application procedure for clinical investigations governed by the MD Regulation are available in the section entitled:   

Clinical investigations of devices  

Further information   

EMA/321925/2021 Rev.2 (pdf). Questions & Answers for applicants, marketing authorisation holders of medicinal products and notified bodies with respect to the implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/746)   

In vitro diagnostic device in a clinical drug trial   

If an IVD device has a medicinal intended purpose in a clinical trial and the device is not CE-marked for the intended purpose concerned, the device must be either:  

• an IVD device for performance study (Article 2(45) of the IVD Regulation); OR  

• ‘custom-made’ (Article 5(5) of the IVD Regulation).   

If the IVD device is not ‘custom-made’, an application or notification regarding performance studies must be submitted to Fimea in accordance with Article 58 or 70 of the IVD Regulation.   

Companion diagnostic performance studies   

Performance studies that involve companion diagnostics (CDx; Article 2(7) of the IVD Regulation) are subject to the same requirements as the performance studies listed in Article 58(2) of the IVD Regulation, i.e., an application concerning the study must be submitted to Fimea. If left-over samples are used in the study, it must be notified to Fimea.    

More detailed information about the notification and application procedure for performance studies is available in the section entitled:   

Performance studies of IVD devices  

Further information  

MDCG 2022-10 (pdf) Q&A on the interface between Regulation (EU) 536/2014 on clinical trials for medicinal products for human use (CTR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) 

To open a larger image: right-click on the image and select to open the image in a new tab. References can be found at the end of the page. 

The chart presents the processing routes for different trial applications on a general level. In various exceptional situations, the processing routes may differ from those presented, and they are always processed on a case-by-case basis.  

Accessible version of the chart: Application process for combined studies (pdf)

Chart references :

(1) Classification, Definition of medical device  

(2) Combined studies,  Supervision of clinical drug trials , Studies using devices  

(3) Also includes devices combining pharmacotherapy and diagnostics (CDx), 2017/746 Article 2(7). If the medicine and the medical device are studied simultaneously, the processing may also take place simultaneously on the basis of an authority’s assessment (Act 2021/719, section 18, third subsection).  

(4) Further information: MDCG 2022-5. Fimea’s Clinical Drug Trials Department and Fimea’s Clinical Device Trials Department will communicate internally as necessary.  

(5) Medicine and device subject to pharmaceutical legislation: device information is provided via the CTIS as part of the IMPD documentation. If the medicine and device are included in the same trial, separate device documentation is delivered either directly to Tukija or via the CTIS. Further information and electronic form: Combined drug and device trials (www.tukija.fi).  

(6) Fimea’s secure mail address is secmail.fimea.fi and the recipient is [email protected].  

Fimea offers informal advice to those conducting combination studies. The advice focuses on combination studies planned to be conducted in Finland and the related regulatory requirements.

Advice related to combination studies can be sought through Fimea's Innovation Office.