Examined

Combination products It all comes down to the right mixture.

Combination products are becoming increasingly important both for Swissmedic and for patients and users – but at the same time their handling is becoming ever more complex. This trend is attributable to a current harmonisation of the Swiss legal framework with the stricter European requirements for medical devices. The two specialists at Swissmedic, Bernhard Spörri and Sebastian Fuchs, discuss the various issues concerning combination products with reference to actual examples, the new regulations and the tasks of Swissmedic.

A medicinal product with a medical device component is termed a “combination product”. One classic example is a prefilled syringe. Sebastian Fuchs (Medical Devices Surveillance Inspector in the Market Surveillance division) explains what the combination involves: "While the syringe, the "application container", is a medical device, the contents of the syringe are, for example, a vaccine or medicine."

Difference between integral and non-integral

Basically, there are two types of combination products. In a non-integral combination product, the medical device component is included in the packaging or provided separately – a cough syrup is a good example: "The bottle with the cough syrup (medicinal product) and the measuring cup for the correct dosage (medical device) are provided together as a unit in the same packaging", says Bernhard Spörri (Head of the Quality Assessment unit in the Authorisation division). He continues: "In an integral combination product, the medicinal product component is manufactured together with the medical device component as a combined unit that is intended exclusively for use in this specific combination." Examples include the above-mentioned prefilled syringes and prefilled infusion pumps or a prefilled asthma inhaler. Medical devices containing a medicinal product also exist, for example a drug-coated stent.

"Sitting around the same table, we can combine our expertise in medicinal product authorisation and medical device investigation in a targeted manner."
Bernhard Spörri

The task of Swissmedic

Swissmedic has appointed an expert team to define the internal processes for assessing combination products and the associated harmonisation with the stricter regulatory requirements. "Differing legal rulings exist in some cases for medicinal products and medical devices. This is one of the reasons why the Management Board of Swissmedic has set up an interdepartmental specialist group to evaluate how these rules apply to combination products," explains Bernhard Spörri. That's why medicinal product and medical device experts sit around the same table in this specialist group. "This allows us to assess and evaluate the two aspects together. The first task of the specialist group is to prepare a strategic policy decision for the attention of the Management Board. For example, they might discuss whether Swissmedic should produce expert reports for the medicinal product part of an integral medical device (e.g. antibiotic-coated hip implants). Because highly innovative combination products may be involved, the specialist group must assess the question as to whether Swissmedic possesses sufficient specific expertise to carry out these tasks", says Bernhard Spörri. "But the overriding specialist group is also meant to act as a centre of expertise for questions on combination products", says Sebastian Fuchs. Conclusion: the specialist group is designed to serve as an interdisciplinary body for addressing questions from both sides, without becoming involved in the operational processes of authorisation and market surveillance.

Sebastian Fuchs, Medical Devices Surveillance

A sensitive issue

The positive view: The respective components are clearly regulated. The assessment of an integral combination product always involves repeated points of contact. "To give you just one example: In a prefilled syringe, the syringe, i.e. the medical device, and the medicinal product must be suitable for use together and investigated accordingly. For this investigation of compatibility, safety and functional suitability – for example dosing accuracy – the legal requirements for both medicinal products and medical devices need to be considered.
So it is helpful if we can share information about the relevant requirements for combination products across departments", explains Sebastian Fuchs.

"For combination products, interdepartmental sharing is useful."
Sebastian Fuchs

European requirements for medical devices

"Medicinal products and medical devices undergo various investigation processes before they can be placed on the market. The investigation procedure for medical devices differs fundamentally from that for the official authorisation of medicinal products", clarifies Bernhard Spörri. So-called conformity assessment bodies (the term "notified body" is used internationally) are responsible for certifying medical devices associated with higher risks. Sebastian Fuchs adds: "Since Switzerland implements the European requirements when it comes to medical devices, we must also take these into account for the combination products."

The significance of change

Many developments and changes have occurred in recent years in relation to combination products. The revision of the European requirements for medical devices four years ago also defined new requirements for the investigation of combination products. "For integral combination products, the fulfilment of the essential safety and performance requirements for the medical device component has so far been demonstrated by the manufacturers themselves. From May 2021, the manufacturers will also have to provide evidence of an independent assessment by a conformity assessment body", says Bernhard Spörri. These changes will be introduced Europe-wide, and Swissmedic intends to modify its authorisation requirements accordingly.