Investigated

Focus on in vitro diagnostics (IVDs) From deep inside

Approximately 500,000 different medical devices currently exist in Switzerland and the European Economic Area – of which around 40,000 are in vitro diagnostic medical devices (IVDs). With the help of the scientific officers Andreas Schlegel, Evelyn Aeschlimann and Einat Schmutz, Visible gets to the bottom of this subject of medical devices, sheds light on product development, market access, surveillance and the new regulation, and highlights possible product innovations and trends.

Examples of medical devices

What do medical implants, dialysis equipment, cardiac pacemakers, dental products, plasters and dressings, visual aids, X-ray equipment, condoms, pregnancy tests, laboratory equipment and COVID-19 tests have in common? They are all medical devices monitored by Swissmedic. Before they are placed on the market, they must satisfy certain requirements and undergo what is known as a conformity assessment procedure. Up to half a million different products are available on the market.

Examples of in vitro diagnostic medical devices

In vitro diagnostic medical devices (IVDs) are a subgroup of medical devices. "An in vitro diagnostic medical device refers to any medical device for the in vitro examination of specimens, such as blood or urine, derived from the human body. They can be tests based, for example, on biological investigations, and they help monitor a person’s state of health. They include breast cancer tests, blood sugar tests or HIV tests", explains Evelyn Aeschlimann. "Manufacturers based in Switzerland are required to notify Swissmedic of their IVD products when they place them on the market in Switzerland for the first time."

Significance

The fact that the federal government has created a specific and separate legal basis for IVDs testifies to the importance of this subject. "This basis consists of two Federal Council ordinances with legal provisions. It was a major project that kept many people from various authorities busy for months", recalls Andreas Schlegel. The lead agency in this process was the Federal Office of Public Health (FOPH). "Swissmedic was consulted primarily to check the feasibility in practice."

Market access

500,000 medical devices – including around 40,000 IVDs. By way of comparison: around 5,700 human medicinal products are currently authorised in Switzerland. "Unlike the situation for medicinal products, there is no official authorisation for medical devices. It wouldn’t be workable. Instead, there’s a system of conformity assessment. This procedure is designed to prove that the applicable safety and performance requirements are satisfied and that the benefit-risk ratio is acceptable", explains Einat Schmutz. For higher-risk products, this procedure requires the involvement of a designated body. Swissmedic’s role is to designate and monitor these bodies.

Risk classes

Before it is placed on the market, every IVD is classified in one of four risk classes (A, B, C, D), where class A refers to devices that pose a low risk (see box). "In particular, the upshot of this new four-class system is that many more IVDs than before now require the involvement of a designated body in the conformity assessment", explains Schmutz. Whereas it used to be possible to place most IVDs on the market with a simple manufacturer’s self-declaration, this now applies only to class A devices, which account for about 20% of all IVDs. Devices in classes B, C and D require the involvement of a designated body. The prime concern here is the safety of the devices. "One key aspect is the clinical performance evaluation, which requires the collection of clinical data from performance studies. Patient safety is at the heart of this process", explains Einat Schmutz, and she presents an example from everyday life: "Due to the stricter requirements, gene and cancer tests have jumped from the lowest risk classes to the second highest category."

Prioritisation

Patient safety is always the priority. "Medical treatment starts with the clinical picture and the diagnosis." And, as Andreas Schlegel stresses, "a correct diagnosis increases the chances of a successful treatment. The diagnosis is based on the results delivered by IVDs. Since incorrect results can lead to serious incidents, we must always bear in mind the possible consequences for the patients. Or, in other words: we have to assess the risk involved in each case."

Swissmedic’s remit

It starts with the approval and monitoring of performance studies with IVDs. Swiss manufacturers must also notify Swissmedic when they place these IVDs on the market in Switzerland for the first time. Any serious incidents that occur in connection with medical devices must be reported to Swissmedic. As part of its market monitoring role, Swissmedic reviews compliance with the regulatory requirements on the basis of reports or spot checks. To this end, it can request documents or carry out on-site inspections. In the event of non-compliance with the requirements, Swissmedic can order measures to be taken to restore the state of legal compliance. These can include amendments to the instructions for use, bans or product recalls. Finally, in addition to its other activities, Swissmedic also monitors the maintenance of IVDs in hospitals, for example laboratory equipment.

Sources of error

Incorrect results, too high or too low measurements of analytes, manufacturing errors, calibration problems, wrong labelling, mechanical problems – the list of possible errors is long. "It’s important for the duality in the reporting system to work well. This means that both users and manufacturers must report serious incidents with IVDs. Reporting by the user is a key factor, since it reveals any non-compliance by the manufacturer and enables the manufacturer to initiate a root cause analysis", explains Evelyn Aeschlimann. To take one example: A hospital discovers that two COVID-19 tests are delivering incorrect results; here, the report must be submitted both to Swissmedic and the supplier within 2, 10 or 15 days depending on the risk in each case. On the user’s side, the report can be submitted by the professional concerned or by a suitable competent person (known as a vigilance contact person). The consequences: in order to identify the error, the manufacturer must undertake a root case analysis, for example by obtaining and examining the device concerned or by a statistical analysis. "This will enable the manufacturer to initiate any required measures", adds Einat Schmutz.

Product innovations

As in medical technology generally, IVDs too are subject to continuous development and product trends. "We can see how a lot of the operations in laboratories are now automated. The laboratory lines sometimes look like miniaturised rail systems", says Andreas Schlegel. "Robotics can help reduce errors – in addition, of course, to saving costs." Another trend is digitisation, and software is becoming increasingly important, including for the processing of huge data volumes. Gene tests are a further example: "Our knowledge of the human genome is constantly growing. This leads to ever more specific investigations in order to reach the most accurate possible diagnosis." Andreas Schlegel also expects growth in personalised medicine, including through the use of gene tests. Decentralisation is also forging ahead: "With apps downloaded to a mobile phone, medical technology is getting closer to the patient with a more direct approach."

"Our knowledge of the human genome is constantly growing. This leads to ever more specific investigations in order to reach the most accurate possible diagnosis."
Andreas Schlegel

The new regulation

"A key element is the creation of a robust legal framework designed to ensure that the safety and benefit of the devices remain at a consistently high level", says Einat Schmutz in summarising the new regulation. The Swiss rules are now in line with the European system – including the requirements relating to the traceability of devices on the market. "The allocation of roles along the supply chain is clearly regulated, with clear-cut obligations for the various operators", adds Einat Schmutz.

The legal system

Since 26 May 2022, Swissmedic has been following the new ordinances. "When a manufacturer places a new device on the market it must comply with the new requirements", says Evelyn Aeschlimann. At the same time, performance studies with IVDs are now regulated in the Ordinance on Clinical Trials with Medical Devices (ClinO-MD) and no longer in the Ordinance on Clinical Trials (ClinO). Finally, Einat Schmutz adds: "Under certain conditions, transitional provisions apply to devices that comply with old legislation – in some cases until 2028. This means that they can still be placed or made available on the market, or put into service, under the old legislation."