MDR 2017/745 for Drug-Device Combinations: What Every RA Professional Must Know

Three weeks before the submission deadline, his technical reviewer flags an issue: "The device component section references MDD. Shouldn't this be MDR now?"

He checks the timeline. The MAA was drafted when MDD certificates were still valid.
Now the transitional period has shifted, and half his GSPR references are pointing to the wrong regulation.

The gap that costs months: understanding exactly how MDR 2017/745 applies to your combination product—not just knowing it exists, but knowing which provisions trigger which requirements.

Breaking it down: the complete framework for MDR compliance in drug-device combinations.

MDR Scope: Where Drug-Device Combinations Fit

Why this matters: Misunderstanding MDR scope leads to either over-engineering your submission or missing critical requirements entirely.

The Medical Device Regulation (EU) 2017/745 replaced the Medical Device Directive (93/42/EEC) as the primary legislation governing medical devices in the European Union. But its impact extends well beyond standalone devices.

For drug-device combinations, MDR creates a dual framework:

The key insight: even when your combination product is regulated primarily as a medicinal product, MDR doesn't disappear. It establishes the safety and performance baseline your device component must meet.

The Two Pathways: Device-Led vs Medicine-Led

Why this matters: The principal mode of action (PMOA) determines your entire regulatory strategy. Getting this wrong means rebuilding your dossier from scratch.

MDR distinguishes between two types of integral drug-device combinations based on which action is principal:

Medicine-Led DDCs: Article 1(8) and 1(9)

When the medicinal substance has the principal action, MDR Article 1(8) and 1(9) define how the device component is handled:

Device-Led DDCs: Ancillary Medicinal Substance

When the device's mode of action is principal, the product is regulated fully under MDR. The medicinal substance is considered "ancillary"—supporting the device's primary function.

Before the Notified Body can issue a CE certificate, they must obtain a scientific opinion from either:

• A National Competent Authority (NCA) for medicinal products, OR
• The European Medicines Agency (EMA)

This opinion addresses the quality and safety of the substance, including the benefit/risk of incorporating it into the device.

General Safety and Performance Requirements (GSPRs)

Why this matters: GSPRs are the backbone of MDR compliance. For combination products, you need to demonstrate compliance even when regulated primarily as a medicinal product.

MDR Annex I contains the General Safety and Performance Requirements—the essential standards every medical device must meet. For combination products, the relevant GSPRs depend on the device component's function and risk profile.

Section 12: The Critical GSPR for DDCs

Annex I, Section 12 specifically addresses devices incorporating substances that, if used separately, would be considered medicinal products. Key requirements include:

Classification Rules for Combination Products

Why this matters: Classification determines your conformity assessment route, documentation requirements, and whether you need Notified Body involvement.

MDR Annex VIII establishes classification rules for medical devices. For combination products, classification applies to the device component and directly impacts the regulatory pathway.

Automatic Uplift for Ancillary Substances

Rule 14 of MDR Annex VIII states that devices incorporating a substance that, if used separately, would be considered a medicinal product are automatically classified as:

Classification for Medicine-Led DDCs

For integral DDCs where the medicinal product has the principal action, the device classification matters for determining the conformity pathway under Article 117:

Conformity Assessment Requirements

Why this matters: The conformity assessment pathway determines what documentation you need in your MAA dossier and how long the device component approval will take.

MDR provides multiple conformity assessment routes depending on device classification. For combination products, Article 117 (which amended Directive 2001/83/EC) specifies what evidence is acceptable.

What a Notified Body Opinion Must Confirm

The NB Opinion must confirm full compliance with the relevant GSPRs set out in MDR Annex I. Key points:

• Full compliance required: Partial compliance is not acceptable. CHMP and NCAs don't assess GSPR compliance themselves.
• GSPRs must be listed: The opinion should specify which GSPRs were assessed.
• Applicant can choose any NB: The NB must be designated for the specific type of medical device under MDR.

The Notified Body Role in DDCs

Why this matters: Notified Body capacity is limited, and engagement timelines can extend 12-18 months. Understanding when you need them—and when you don't—is critical for planning.

Notified Bodies play different roles depending on whether your DDC is device-led or medicine-led:

Selecting a Notified Body for DDCs

For combination products, NB selection should consider:

• NANDO designation: NB must be designated for your device type under MDR (not MDD)
• DDC experience: Combination products have unique requirements; experienced NBs reduce review cycles
• Capacity and timeline: Current NB backlogs can extend timelines significantly
• Geographic considerations: EU location requirements for certain activities

For detailed NB selection guidance, see our Notified Body Selection Guide.

Labeling Requirements Under MDR

Why this matters: Labeling errors can delay approvals and require costly re-packaging. Understanding what's required—and what's prohibited—prevents surprises.

MDR Annex I, Chapter III specifies labeling requirements for medical devices. For combination products, the approach depends on whether the device has its own CE mark:

Post-Market Surveillance Obligations

Why this matters: PMS obligations apply immediately—even during transitional periods. Missing these requirements can result in enforcement action.

MDR significantly strengthened post-market surveillance requirements compared to MDD. For combination products, certain MDR PMS obligations apply regardless of which legislation governs the product:

MAH Responsibilities for Device Changes

For all drug-device combinations, the Marketing Authorization Holder must determine whether changes to the device component impact:

• Delivery of the medicinal product
• Quality of the medicinal product
• Safety of the medicinal product
• Efficacy of the medicinal product

If changes lead to a new or updated EU certificate or NB Opinion, this must be submitted as part of an appropriate post-authorization variation procedure. See our EMA Variations Framework 2026 guide for current requirements.

Transitional Provisions and Deadlines

Why this matters: Transitional provisions are complex and have shifted multiple times. Understanding current deadlines prevents costly missteps.

MDR Article 120 provides transitional provisions for devices certified under MDD that don't yet have MDR certification. For combination products, key dates include:

Article 120(3c) Conditions

For devices that didn't require NB assessment under MDD but now do under MDR, the transitional period until 31 December 2028 applies only if:

• No significant changes to design or intended purpose
• Continued compliance with MDD requirements
• Appropriate QMS in place
• MDR requirements for PMS, vigilance, and economic operator registration are met

A Practical Framework for DDC Manufacturers

Why this matters: This framework translates MDR requirements into actionable steps for your regulatory strategy.