New regulation since May 2021 Clinical trials with medical devices 2.0

Medical devices, for example knee replacements, artificial heart valves, catheters for internal procedures or software for MRI scanners, must be clinically tested before they can be placed on the market. New regulations on the corresponding requirements were introduced on 26 May 2021 and harmonised across Europe. Swissmedic's Isabel Scuntaro and Simone Frank are monitoring the new procedure. Using an example, they explain how the clinical trials are conducted.

Simone Frank
Simone Frank
Isabel Scuntaro
Isabel Scuntaro
The European Regulation…

…regulates the detailed requirements for clinical trials with medical devices. This harmonisation enables the European countries to specify a uniform pro­cedure, at least for part of the trials.

The consequences for Switzerland…

…are wide-ranging, as evidenced by the numerous major changes. As of May 2021, Switzerland now has its own Ordinance on Clinical Trials with Medical Devices. What has mostly changed is the collaboration between Swissmedic and the ethics committees – which has now become closer. Whereas they used to work independently of each other, ­according to the new legislation Swissmedic can now approve clinical trials only if they have first been approved by an ethics committee. Approval procedures are conducted in parallel in Switzerland. This means that the sponsor – i.e. the organisation or indivi­dual responsible for arranging a clinical trial – submits its application and subsequent submissions to both agencies at the same time. Conducting these processes in parallel also minimises the associated workload.

"The consequences for Switzerland are wide-ranging."

Isabel Scuntaro
The consequences of the new regulations…

…for the Medical Devices Clinical Investigation ­division (MDCI) primarily involve close consultation beforehand with the ethics committees, and particularly with swissethics, the Swiss Association of Research Ethics Committees. To ensure the smoothest possible process and the rapid notification of a decision, the detailed procedure for submissions had to be agreed and the synchronisation steps specified for the mutual sharing of information during the procedures. Even the granting of the "legal hearing" (all those affected by a decision are entitled to express their views on the matter) had to be coordinated. Working together, they revised various publications for the submissions and arranged training courses for the ethics committees. In Eur­ope, the MDCI division has been working in various working groups and participating in discussions with authorities, and has also edited publications on the implementation of the new regulation.

In order to adapt the process, the MDCI division had to revise all the relevant forms, letters and resources for medical device trials. In all, over 90 documents had to be newly produced or thoroughly updated. Practical information and forms for the new approval procedures were published on 1 April 2021 and widely distributed. Since 1 May 2021, all submissions to the MDCI division have been processed according to the new legislation.

Swissmedic remains on the ball. In particular, it will evaluate the experience acquired and further optimise the new procedures.

Medicines differ from medical devices…

…in that the former are always eliminated from the body, whereas the use of medical devices is not reversible. Any problems that arise must be rectified, for example by surgery. Whereas a doctor or hospital is highly unlikely to develop an innovative medicine, new medical devices are often designed by doctors, small or medium-sized businesses, start-ups or young spin-off companies. A well-equipped workshop is often the only requirement. For medical devices, the approach to – and precautions for – clinical trials are difficult to standardise, and corrections repeatedly have to be made by Swissmedic.

The procedure at Swissmedic…

…concerns devices that have not yet undergone a conformity assessment and therefore cannot be placed on the market since they are not CE-marked, as well as devices that are used other than as intended (off-label use) or devices that are prohibited in Switzerland. It is often the case with prohibited devices that insufficient clinical data on performance and safety are available, or that the device has been revised as a result of clinical incidents, leading to supplementary clinical trials.

The example of the vertebral implant shows just how…

…complex the development of a new device can be. First of all, the manufacturer has to develop the device from the technical point of view. Given the possible risks, comprehensive documentation must be prepared, including a summary of the technical development (specifically, the manufacturer explains how standards and requirements are satisfied), the preclinical tests in the laboratory – possibly with animals – and, if available, experience of its use in humans. Only then can an application be submitted requesting the approval of a clinical trial. When Swissmedic has received the complete documentation, its content is checked and reviewed for compliance with the legal requirements. For example, a vertebral implant must be durable and its sterility demonstrated, and the materials used must be compatible with the human body. While the clinical development of medicinal products is often subdivided into three phases, this number can vary with medical devices. Medical devices often combine various aspects and components. Not infrequently they involve a mix of proven and innovative aspects, for example novel materials or a new design, resulting in assessments on a case-­by-case basis with little standardisation. For a vertebral implant, Swissmedic will check whether the technical introduction and monitoring of the implanting surgeons, precautions, interim analyses and the criteria for stopping the trial are appropriate for the degree of innovation.