What is a Combination Product Under EU Regulation?

In the EU, a 'combination product' is referred to as a 'medicinal product/device combination' or an 'integral product'. EU MDR Article 1(9) and EU Regulation 536/2014 (Clinical Trials Regulation) address scenarios where a device incorporates a medicinal product as an integral part. The primary regulatory pathway — and which competent authority leads the review — depends on which element (the device or the drug) is the principal mode of action. This determination is made by the EMA (European Medicines Agency) or national competent authorities and is not always straightforward.

Regulatory Pathway Determination: Device-Led vs Drug-Led

If the product's principal mode of action is achieved by the device component, and the medicinal product is ancillary, the product is regulated as a medical device under EU MDR — but with an obligation to consult the EMA or a national medicines authority on the medicinal component. If the product's principal mode of action is achieved by the medicinal component, it is regulated as a medicinal product under EU pharmaceutical law (Directive 2001/83/EC or EU Regulation 2019/6) — with the device component assessed as part of the marketing authorisation. Most drug-delivery devices (prefilled syringes, autoinjectors, inhaler devices without drug) are regulated purely as devices.

Drug-Eluting Devices: The Most Complex Category

Drug-eluting devices — such as drug-eluting stents, antibacterial-coated orthopaedic implants, and antibiotic-releasing wound dressings — are typically classified as medical devices under EU MDR but require EMA consultation. MDR Annex I Section 12 establishes the safety and performance requirements for devices incorporating medicinal substances. The Notified Body must consult the EMA (or a national medicines authority) on the quality, safety, and usefulness of the medicinal substance and must take the resulting scientific opinion into account. This consultation adds significant time to the certification process.

Prefilled Syringes and Delivery Systems

Prefilled syringes, autoinjectors, and pen injectors are typically classified as Class IIa or Class IIb medical devices under MDR when assessed as standalone devices (without the drug). When the syringe is filled with a specific drug and co-packaged, the regulatory pathway depends on how the product is presented and whether the device and drug are integral. Manufacturers of delivery system devices must ensure their technical files address compatibility with the drug formulation, extractables/leachables testing under ISO 11040-4, and dose accuracy evidence.

Key Technical Requirements for Device-Led Combinations

For device-led combination products regulated under EU MDR, the Technical File must include, in addition to standard device requirements: documentation of the medicinal substance's quality, safety, and performance as a component of the device, a risk-benefit analysis that includes risks arising from the medicinal component, EMA or national medicines authority consultation request and resulting scientific opinion, biocompatibility data covering the medicinal substance's interaction with the device, and where applicable, clinical evidence for the combined product from clinical investigations.

Practical Pathway for Turkish Combination Product Manufacturers

Turkish manufacturers of combination products should take the following steps: (1) Determine the principal mode of action and confirm whether device-led or drug-led classification applies — engage a regulatory affairs specialist with combination product experience, (2) Select an EU Notified Body with explicit combination product experience — not all Notified Bodies are experienced in this area, (3) Initiate early dialogue with the EMA or national medicines authority regarding the medicinal component consultation requirement, (4) Ensure your clinical evidence plan encompasses the combination product as a whole, not just the device component, (5) Budget for extended certification timelines — combination product pathways typically take 12–36 months depending on novelty and clinical evidence requirements.

Conclusion

Combination products represent a challenging but commercially significant product category — drug-device combinations often command premium pricing and strong clinical adoption. Turkish manufacturers with the technical capability and regulatory commitment to navigate the combination product pathway can access markets and margin profiles that purely device-only products cannot reach.