Medical interventions increasingly involve the use of technology and devices. New treatments may involve a medical device, combination product or in vitro diagnostic device. For sponsors this means their studies have additional regulatory requirements to meet, each on very distinct submission pathways. The assessment of the safety or performance of the device is not in scope, but the device is necessary to conduct the study. Clinical trials with human subjects where such devices are deployed must comply with applicable regulations EU CTR (Regulation (EU) 536/2014), MDR (Regulation (EU) 2017/745) and/or IVDR (Regulation (EU) 2017/746).
Identifying and managing the additional regulatory requirements for these studies can be confusing. Multiple factors must be considered, such as whether the device is CE-marked, is being used outside of its intended purpose or is custom-made. The submissions process may be further complicated by additional national regulatory and ethical requirements.
Even where there is some overlap with the study documentation, the additional device-specific regulations require extra time, effort and expertise. Missing information or a misfiled application can negatively impact a study timeline. Planning a route through the labyrinth of regulations can avoid these delays. Time dedicated to building a robust EU submission strategy in advance means time saved later on in the submissions process.
Conformity Assessment of Medical Devices and in Vitro Diagnostic Devices
In the EU, the device manufacturer is responsible for complying with and demonstrating safety standards. Medical devices do not require official authorisation from a public agency in the EU, unlike medicinal products. However, they need a conformity assessment procedure. Devices that meet EU requirements bear the CE mark upon market entry. Conformity assessment procedures vary according to the devices’ risk classes. High risk devices have greater regulatory oversight than low risk devices. The rules for risk classification of devices are listed in Annex VIII of MDR and IVDR and in the corresponding Medical Device Coordination Group (MDCG) guidance documents including MDCG 2021–24 and 2020–16.
For low-risk devices, with some exceptions, the manufacturer can conduct the conformity assessment procedure themselves and issue the EU Declaration of Conformity. Higher risk devices require an independent conformity assessment procedure by a notified body (NB). These conformity assessment procedures can consist of one or more modules, depending on the risk characteristics. The modules concern the manufacturer’s quality management system, the product’s technical documentation, the individual type-examination, production quality assurance or conformity to an EU type-examination. Typically, the process includes an audit of the manufacturer’s quality system. NBs must consult specific expert panels before granting a Certificate of Conformity for some high-risk devices. Certificates of Conformity are valid for the period indicated and shall not exceed five years. Manufacturers can request an extension of validity for further periods (less than five years). A re-assessment of conformity must be conducted as part of the extension request.
Medical devices and IVDs certified under Medical Device Directive (MDD), Active Implantable Medical Device Directive (AIMDD) or In Vitro Device Directive (IVDD) should undergo a conformity assessment procedure under the new regulations. These assessments must be carried out before the end of the transitional periods stipulated by MDR and IVDR. The large number of MDs and IVDs that must undergo new conformity assessments has exceeded the capacity of NBs. This has led to several extensions of the transitional periods.