EU MDR Article 117 for Drug-Device Combinations: what it is, when it applies, and how to plan for the Notified Body opinion

EU MDR Article 117 for Drug-Device Combinations: what it is, when it applies, and how to plan for the Notified Body opinion

If you make a drug–device combination where the medicinal substance is primary and the device is an integral part of the finished product (think pre-filled syringes, pens, on-body injectors, drug-eluting implants), EU MDR Article 117 is the instrument that bridges medicines and devices. It amends Directive 2001/83/EC to require evidence that the device constituent meets MDR Annex I General Safety and Performance Requirements (GSPR)—usually via a Notified Body Opinion (NBOp) that you include in the market authorisation application (MAA).

When Article 117 applies (and when it doesn’t)

Article 117 applies if all of the below are true:

• The product is a single, non-reusable, integral combination of a medicine with a device.
• The principal mode of action is pharmacological, immunological or metabolic (so the product is regulated as a medicinal product).
• The device part is not already CE-marked for that intended purpose (or it is, but there’s a significant change/different use that needs reassessment).

In those cases, you must provide either a declaration/certificate or an Notified Body opinion showing GSPR conformity of the device part in your MAA. EMA’s Q&A and scientific guideline lay out the triggers, examples, and dossier expectations (including for lifecycle changes post-authorisation).

Not in scope:

• Co-packaged devices (separate items sold together) are handled differently—typically you reference the device’s own CE evidence; no NBOp for Article 117 is required.
• Stand-alone devices (no medicinal component) follow MDR device routes, not Article 117

What goes into the Notified Body Opinion dossier

The Notified Body reviews the device constituent against MDR Annex I General Safety and Performance Requirments. Expect to submit (right-size to your risk and novelty):

• Intended purpose & classification rationale (even though the product is authorised as a medicine, the device part is “classified” to scope the GSPRs/risks).
• Design/manufacture information (key drawings/specs, critical processes, supplier controls).
• Materials & biocompatibility / chemical characterisation (per ISO 10993 suite, risk-based).
• Usability/human factors (esp. if lay users or dose-accuracy claims).
• Sterilisation/aseptic interface (what’s in Notified Body scope vs. in the pharmaceutical aseptic remit).
• Risk management (ISO 14971 aligned), verification/validation evidence, and (if applicable) a clinical evaluation for claims/risks attributable to the device constituent.

Top causes of delays include: incomplete submissions and poorly structured technical files. Their template-like contents map is a good benchmark for planning.

Logistics & timelines: where programs slip (and how to avoid it)

Operationally, the NBOp must be ready in time for your MAA—and certain procedures (e.g., Mutual Recognition Procedure/Repeat Use Procedure) expect the opinion before you start the procedure. That means device evidence development has to run in parallel with pivotal pharmaceutics/CMC and clinical.

What to plan for:

• Engage a Notified Body early to confirm scope & codes, dossier expectations, and slots. Many sponsors plan ~3–6 months for a first NBOp on a straightforward, non-novel injector, longer if there’s novel tech, complex biocompatibility, or human-factors iterations. (Exact lead-times vary by Notified Body capacity and dossier quality.) Industry case collections from EFPIA highlight that iteration cycles and Q&A rounds are the main schedule drivers—more than the formal “review clock.”
• Changes after approval: EMA’s Q&A clarifies when device changes trigger a new/revised NBOp and how to route them as variations. Team-NB’s paper proposes a risk-based test for “substantial” changes to the device part (i.e., changes that could impact GSPRs). Build a change-assessment SOP aligned to that logic.
• Common pitfalls: missing/fragmented evidence (e.g., material specs and supplier data), unclear lines between pharma aseptic controls and device sterilisation validation, and absent usability rationales for lay-use claims. These are repeatedly cited as causes of stop-clocks and resubmissions.

Which Notified Bodies can issue an Article 117 opinion?

Any Notified Body designated under MDR (EU) 2017/745 with the right designation codes and scope for your device constituent can issue the opinion. The European Commission’s NANDO database lists all MDR-designated Notified Bodys; you should filter by Regulation (EU) 2017/745 and the applicable codes to identify a Notified Body to partner with.

What do authorities and industry Feedback on Article 117?

Recent EFPIA work (2025) highlights sponsor experiences with NBOp submissions—emphasising the need for clearer expectations, early Notified Body engagement, and risk-based lifecycle change handling aligned with the medicines variations framework.

Team-NB advocates that a  risk-based criteria for when device changes in an integral product are “substantial” enough to require a new NBOp, aiming to harmonise decisions across Notified Bodys. They also outline documentation expectations for Article 117 submissions.

Key Points

• Article 117 is now a standard gate for integral DDCs: plan Notified Body engagement and GSPR evidence early.
• The right Notified Body is the one designated under MDR with the correct codes—verify in NANDO and confirm capacity.
• Expect timeline risk from dossier gaps and Q&A cycles; use published Notified Body checklists/best practices to de-risk.
• For changes after approval, align with EMA Q&A and Team-NB to decide when a new NBOp and a variation are required.