Prefilled syringes, pens, autoinjectors and inhalers are medicines to their manufacturers and patients — but the device that delivers the dose has its own regulatory life. Article 117 of the EU Medical Device Regulation quietly reshaped how these drug-device combinations reach the market, adding a device-conformity step into the medicinal marketing-authorisation dossier. For any company developing an integral combination product, it is a requirement that can determine the submission timeline.
What Article 117 actually changed
Article 117 of Regulation (EU) 2017/745 (the MDR) amended Annex I of Directive 2001/83/EC, the core medicines directive. For a single integral drug-device combination — where the medicine and the delivery device form one non-reusable product with a pharmacological principal mode of action — the marketing-authorisation dossier must now include evidence that the device part meets the relevant requirements of the MDR. Where the device already carries a CE mark, its EU Declaration of Conformity or certificate can be used. Where it does not, the dossier must instead contain a Notified Body Opinion (NBOp) confirming that the device part conforms to the applicable General Safety and Performance Requirements (GSPRs) in Annex I of the MDR. The MDR has applied since 26 May 2021, and this requirement applies to affected marketing-authorisation applications accordingly.
Integral, co-packaged or referenced — the distinction matters
Not every product that pairs a drug with a device follows the same route:
- Single integral products (a prefilled syringe, a prefilled pen, an autoinjector, a metered-dose or dry-powder inhaler, certain patches) are regulated as medicines. It is here that the Article 117 NBOp route applies when the device is not separately CE-marked.
- Co-packaged devices (for example, a vial supplied with a separate reconstitution syringe) and separately obtained/referenced devices must be fully CE-marked and MDR-compliant in their own right — they do not use the NBOp route.
Getting this classification right at the outset determines the entire regulatory strategy, because it dictates whether you need a device CE certificate, a Notified Body Opinion, or reliance on an existing marked device.
The guidance that shapes the dossier
Two EMA documents do most of the practical work. The guideline on quality documentation for medicinal products when used with a medical device (EMA/CHMP/QWP/BWP/259165/2019), effective from January 2022, sets out the quality expectations for integral, co-packaged and referenced devices. The EMA’s questions-and-answers on implementation of the MDR and IVDR, updated most recently in December 2025, addresses the Article 117 process and the NBOp itself. On the borderline questions — is this a device, a medicine, or a combination? — MDCG 2022-5 (revised in October 2024) provides the European Commission’s principles-based framework.
The Notified Body Opinion process — and its bottleneck
Under the NBOp route, a notified body designated for the relevant device type examines the device technical documentation against all applicable MDR GSPRs: design, manufacturing, risk management, biocompatibility, usability, packaging and shelf-life among them. It then issues an opinion — not a CE certificate — that the applicant includes in the medicinal dossier. Notified bodies typically indicate the opinion itself takes in the region of two to six months, though there is no statutory deadline and total lead time depends heavily on the quality of the submission and on scheduling.
That scheduling point is the real risk. Article 117 created demand for NBOp services from a notified-body network already stretched by the wider MDR certification workload. Capacity has been building, but for many sponsors the binding constraint is simply securing a slot with a designated body in time — which is why NBOp planning belongs at the start of a combination-product programme, not the end.
A shifting wider framework
The combination-product rules sit inside a device framework still in transition. Regulation (EU) 2023/607 staggered the MDR transition deadlines — broadly, higher-risk devices to 2027 and others to 2028 — to ease the certification backlog. In December 2025 the Commission went further, proposing a targeted revision of the MDR and IVDR to reduce burden and address bottlenecks, with consultation running into 2026. That proposal is early in the legislative process and its detailed effect on the combination-product regime is not yet settled, so Article 117 remains firmly in force and should be planned for as it stands today.
How PQRA helps
PQRA supports developers of drug-device combination products across the pharma-device boundary: classifying the product correctly, assembling the device conformity or Notified Body Opinion evidence, aligning the quality dossier with EMA expectations, engaging notified bodies early to protect the timeline, and coordinating the regulatory and quality workstreams so the medicinal submission is not held hostage to the device. Our combined regulatory, quality and medical-device expertise is built for exactly this overlap.
To plan the regulatory route for your drug-device combination product, get in touch with the PQRA team.
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