EU Regulation for Medical Device Combination Products: Complete Guide
Introduction
The increasing adoption of drug-device combination products has transformed modern healthcare by integrating medicinal products and medical devices into a single therapeutic solution. Products such as prefilled syringes, insulin pens, drug-eluting stents, and transdermal patches improve treatment accuracy, enhance patient compliance, and support better clinical outcomes.
However, these innovations also introduce complex regulatory requirements. Unlike standalone medicines or medical devices, combination products may fall under both pharmaceutical and medical device legislation, making regulatory planning more challenging.
Within the European Union, manufacturers must determine which legislation applies, understand how the product is classified, prepare appropriate technical documentation, and identify whether a Notified Body Opinion is required under Article 117.
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Failure to address these requirements early can lead to costly delays, additional testing, and extended approval timelines. This guide explains how medical device combination products are regulated in the European Union, the role of EU MDR, when Article 117 applies, and the key steps manufacturers should consider to achieve compliance and successful market access.
Regulatory Snapshot
Aspect | Details |
Region | European Union |
Primary Regulation | EU MDR (EU) 2017/745 |
Additional Legislation | Medicinal Product Legislation |
Key Requirement | Article 117 (where applicable) |
Regulatory Authorities | European Commission, Competent Authorities, EMA, Notified Bodies |
Applies To | Drug-device combination products marketed in the EU |
What Are Medical Device Combination Products Under EU Regulations?
A medical device combination product combines a medicinal product with a medical device to achieve a therapeutic purpose. Depending on the product’s design and intended use, the drug and device components may be integrated into a single product, supplied together in one package, or intended to be used together through labeling.
Common examples include:
- Prefilled syringes
- Insulin pens
- Drug-eluting stents
- Metered-dose inhalers
- Transdermal patches
- Auto-injectors
These products require careful regulatory assessment because both the medicinal and device components contribute to the overall safety and performance of the therapy.
Unlike standalone medical devices, combination products often require manufacturers to demonstrate compliance with both medical device regulations and medicinal product requirements, depending on the applicable regulatory pathway.
Which EU Regulations Apply to Combination Products?
The European regulatory framework for combination products is based on multiple legislative requirements rather than a single regulation.
The applicable framework depends on the product’s characteristics, intended purpose, and Primary Mode of Action (PMOA).
The key regulations include:
EU Medical Device Regulation (EU MDR) 2017/745
The EU MDR establishes requirements for medical devices marketed within the European Union. For combination products, the regulation primarily applies to the device component and its conformity assessment.
Manufacturers must demonstrate that the device component meets the applicable General Safety and Performance Requirements (GSPRs), supported by appropriate technical documentation and quality management processes.
Medicinal Product Legislation
Where the medicinal substance provides the primary therapeutic effect, the product is generally assessed under medicinal product legislation. However, the integrated device component must still satisfy relevant medical device requirements.
Article 117
Article 117 introduced additional requirements for certain integral drug-device combination products by requiring evidence that the device component complies with applicable EU MDR provisions. In many cases, this involves obtaining a Notified Body Opinion before the medicinal product can receive marketing authorization.
Together, these regulatory requirements ensure that both the medicinal product and the medical device component are appropriately evaluated for safety, quality, and performance.
How Are Combination Products Classified in the European Union?
One of the most important regulatory decisions is determining how a combination product is classified.
European regulators consider several factors, including:
- Intended purpose
- Product design
- Degree of integration
- Mechanism of action
- Primary Mode of Action (PMOA)
- Risk profile
Classification determines the applicable legislation, documentation requirements, conformity assessment process, and involvement of regulatory authorities.
For example:
Product | Primary Mode of Action | Typical Regulatory Pathway |
Prefilled Syringe | Drug | Medicinal Product + Article 117 (where applicable) |
Drug-Eluting Stent | Device | EU MDR |
Transdermal Patch | Drug | Medicinal Product |
Auto-Injector | Drug | Medicinal Product + Device Requirements |
Expert Insight
Many regulatory delays occur because manufacturers determine the applicable regulatory pathway too late in the development process. Conducting a regulatory assessment during product design helps identify documentation requirements, conformity assessment obligations, and potential regulatory risks before significant development investments are made.
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When Does Article 117 Apply?
Article 117 of the EU MDR is one of the most significant regulatory requirements affecting integral drug-device combination products in Europe.
Introduced as part of EU MDR (EU) 2017/745, Article 117 strengthens the regulatory assessment of the medical device component within certain medicinal products. Its purpose is to ensure that the integrated device complies with the applicable General Safety and Performance Requirements (GSPRs) of the EU MDR before the medicinal product receives marketing authorization.
Article 117 generally applies when:
- The medicinal product incorporates a medical device as an integral part of the product.
- The device component is not already CE marked for the intended purpose.
- Compliance with the relevant EU MDR requirements must be demonstrated during the medicinal product authorization process.
In these situations, manufacturers are typically required to obtain a Notified Body Opinion confirming that the device component meets the applicable EU MDR requirements.
Role of Notified Bodies in Combination Product Compliance
Notified Bodies play a critical role in the regulatory assessment of certain drug-device combination products within the European Union. Their primary responsibility is to evaluate whether the medical device component complies with the applicable requirements of EU MDR (EU) 2017/745, particularly when Article 117 applies.
Rather than assessing the medicinal product itself, the Notified Body focuses on the safety, performance, and conformity of the integrated device component. Following its assessment, the Notified Body issues an opinion that forms part of the medicinal product’s marketing authorization dossier.
Technical Documentation Requirements for EU Combination Products
Robust technical documentation is essential to demonstrate that the medical device component of a combination product complies with applicable EU MDR requirements. Well-prepared documentation also helps streamline regulatory reviews and supports faster market access.
Manufacturers should maintain documentation that includes:
- Product description and intended use
- Device design specifications
- General Safety and Performance Requirements (GSPR) checklist
- Risk management documentation
- Verification and validation reports
- Usability engineering evidence (where applicable)
- Clinical evaluation or performance data
- Labeling and Instructions for Use (IFU)
- Manufacturing and quality records
The scope of documentation depends on the product type, classification, and regulatory pathway. Preparing these documents during product development reduces the likelihood of major gaps during regulatory review.
Best Practices for EU MDR Compliance
A proactive regulatory strategy helps manufacturers navigate the European approval process more efficiently. The following best practices can support successful compliance:
Start Regulatory Planning Early
Identify the applicable regulatory pathway during the product concept phase rather than after design completion.
Determine PMOA Correctly
Accurate determination of the Primary Mode of Action ensures the appropriate regulatory framework is applied from the beginning.
Develop Documentation Throughout the Product Lifecycle
Technical documentation, risk management, and clinical evidence should evolve alongside product development rather than being compiled immediately before submission.
Implement an Effective Quality Management System
A well-established Quality Management System supports design controls, supplier management, manufacturing consistency, and post-market compliance.
Engage Regulatory Experts
Early collaboration with regulatory specialists can help manufacturers avoid costly redesigns and improve submission readiness.
Expert Insight
Regulatory compliance should not be viewed as the final stage of product development. Integrating regulatory planning, quality management, and risk management from the earliest phases creates a smoother path to market while reducing overall development costs.
How Operon Strategist Supports EU Combination Product Compliance
Successfully navigating the European regulatory framework requires expertise in both medicinal product legislation and medical device regulations. Operon Strategist helps manufacturers develop practical regulatory strategies that align with product design, intended use, and target markets.
Our support includes:
- Regulatory pathway assessment
- Primary Mode of Action (PMOA) evaluation
- Article 117 compliance strategy
- Technical documentation preparation and review
- CE Marking support for applicable device components
- Quality Management System implementation
- Risk management documentation
- Global regulatory planning for international market access
Planning to Launch a Drug-Device Combination Product in Europe?
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FAQ's
What is the EU regulation for medical device combination products?
Drug-device combination products in the European Union are regulated under EU MDR (EU) 2017/745 alongside medicinal product legislation. The applicable pathway depends on the product’s classification, intended purpose, and Primary Mode of Action (PMOA).
What is Article 117 under the EU MDR?
Article 117 requires certain integral drug-device combination products to demonstrate that the medical device component complies with applicable EU MDR requirements. This often involves obtaining a Notified Body Opinion before marketing authorization.
When is a Notified Body Opinion required?
A Notified Body Opinion is generally required when an integral drug-device combination product contains a device component that is not already CE marked for its intended purpose and falls within the scope of Article 117.
Is CE Marking required for all combination products?
No. The need for CE Marking depends on the product’s regulatory pathway, the role of the device component, and whether the device is marketed separately or forms an integral part of the medicinal product.
How is the Primary Mode of Action (PMOA) determined?
PMOA is determined by identifying which component—drug, device, or biologic—provides the principal therapeutic effect. This assessment is fundamental to selecting the correct regulatory pathway.