As part of its pharmaceutical law reform, the EU legislator has proposed a modernised framework for combination products – products that combine multiple active substances within a single product or integrate medicinal products with devices, technologies, or other components. The goal: to foster innovation, reduce regulatory ambiguity, and ensure faster, safer access to cutting-edge therapies.

This article is part of our series on the ongoing reform of the European pharmaceutical legislation on medicinal products for human use (the so-called “Pharmaceutical Package”) and the latest position adopted by the EU Council. To read our first article and access the entire series, please click here.

The Current Framework: Fragmented and Ambiguous

Under the existing regime, combination products are governed by a patchwork of rules, primarily under Directive 2001/83/EC for medicinal products and the Medical Device Regulation (EU) 2017/745 (“MDR”) for device components. While the MDR already provides for certain combination options of medicinal products and medical devices, and the European Medicines Agency (“EMA”) published further guidelines, there are no corresponding statutory rules in pharmaceutical law. Ultimately, this fragmented approach has led to regulatory uncertainty, particularly for products that blur the line between drug and device, and the lack of clear definitions and pathways has often resulted in delays and inconsistencies in market access.

The Proposal: Clear Definitions and Pathways

The proposed Directive[1] introduces different combinations of active substances as eligible for marketing authorization (“MA”). These include: 

• Fixed dose combination medicinal products[2]

Fixed (dose) combination medicinal products consisting of a combination of active substances intended to be placed on the market as a single pharmaceutical form have already been recognized under the Directive 2001/83/EC. 

• Multi-medicinal product packages[3]

When the active substance cannot be included in a fixed dose combination, an MA may (in exceptional circumstances and if justified by public health reasons) be granted to a multi-medicinal product package. In this case, the MA applicant shall seek agreement concerning the submission of such an application by the competent authority concerned in advance. 

• Platform technologies[4]

Where justified for therapeutic purposes, an MA may (in exceptional circumstances) be granted for a medicinal product comprised of a fixed component and a pre-defined variable component. This allows for modular innovation in particular to target different variants of an infectious agent, or (where necessary) to tailor the medicinal product to the characteristics of an individual patient or a group of patients. Such MA application (“MAA”) also requires prior agreement with the competent authority.

Moreover, the proposal offers the first detailed statutory EU definitions of drug-medical device combinations, following the example in the US and building on MDR guidance enacted by the EMA. These include: 

• Integral combinations[5]

These are combinations of a medicinal product with a medical device where the medicinal component is principal and the device is ancillary, or where the device is intended to administer the drug and is non-reusable. This mirrors the current classification under the MDR.

In these cases, the MAA would be submitted to the competent authority to assess the safety, efficacy and benefit-risk balance of the integral combination, while the assessment of conformity of the device part follows Annex I, II of the MDR and shall be recognized by the authority.

• Co-packaged products[6]

Defined as a “medicinal product in exclusive use with a medical device” this category is established for medicinal products which are presented in a package with a medical device or to be used with a specific medical device referenced in the SmPC.

For these products, manufacturers would need to provide data on the safe and effective use of the medicinal product with the medical device but may need to provide additional benefit-risk information only upon request. Again, the assessment of the device component would fall under the MDR regime.

• Combination with other products[7]

Finally, the proposal also provides for a combination of a medicinal product with a product other than a medical device (as defined by the MDR) and where the two are intended for use in a given combination in accordance with the SmPC. This could potentially include products such as (AI) software, food or clothing. 

Similarly to the previous category, MAAs for medicinal products in combination with other products need to contain data establishing the safe and effective use of the combination while additional information for the benefit-risk balance assessment related to the non-device product may only need to be provided upon request.

For any combinations where the medicinal product is ancillary to the medical device, the existing framework of the MDR remains relevant. 

After all, while the proposed Directive provides further guidance by establishing clear definitions, there might still be uncertainties for developers with regard to borderline products where the ancillary function may not be easy to assess. Therefore, the proposed Regulation introduces the option for developers, competent authorities or a Member State to submit a request to EMA to adopt a scientific recommendation on the regulatory product status of a medicinal product.[8]

Council Position: Mostly Aligned with Minor Refinements

Following the adoption of the EU Parliament amendments in April 2024, the EU Council took its position on the proposed Directive and Regulation in June 2025. According to its mandate for negotiations (accessible under link) the EU Council appears to broadly support the proposed regulations with regard to combination products – with minor editorial amendments. Notably, it included reference not only to medical devices under the MDR but also in vitro diagnostics medical devices under Regulation (EU) 2017/746. Further, regarding combinations with non-device products, it clarified that the competent authority may request an opinion from the authority competent for the supervision of the non-device product. This could become particularly relevant for future AI systems regulated by the EU AI Act.

Looking Ahead: Innovation Meets Regulation

As healthcare innovation accelerates, the rise of complex combination products – blending medicines with cutting-edge tech – demands a modern regulatory approach. The EU’s proposed reform intends to offer just that: a clearer, more harmonised framework that supports innovation while safeguarding patient safety. By laying down clear definitions, creating dedicated pathways, and encouraging early dialogue between regulators and industry, the EU’s proposed legislation signals a more unified and innovation-friendly environment. 

[1] See Proposal for a Directive of the European Parliament and the Counsil on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC, accessible under the following link. 

[2] See Art. 15(1) Directive Proposal.

[3] See Art. 15(2) Directive Proposal.

[4] See Art. 15(3) Directive Proposal.

[5] See Art. 18 Directive Proposal.

[6] See Art. 19 Directive Proposal.

[7] See Art. 20 Directive Proposal.

[8] See Art. 61 Proposal for a Regulation of the European Parliament and the Council laying down Union procedures for the authorisation and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency, amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation 

(EC) No 1901/2006, accessible under the following link.