Orphan Drugs and Combination Products: When a Home Injector Triggers MDR Article 117
For orphan therapies, the delivery architecture determines the regulatory path. Why integral, co-packaged and referenced devices must be distinguished early.
An orphan therapy often needs more than an active substance. Pre-filled pens, autoinjectors, pumps and nebulisers make treatment feasible in daily life. This makes the device component a regulatory and commercial success factor.
| Finding | Meaning for the programme | Source |
|---|---|---|
| Delivery architecture determines the regulatory framework. | Integral, co-packaged and referenced devices follow different evidence routes. | EMA Q&A Rev. 6 |
| Article 117 has no orphan-drug exemption. | An integral home injector requires the same device evidence as other medicines. | MDR, EMA Q&A |
| Notified body capacity is a critical path. | The NBOp process should run in parallel with the marketing authorisation dossier. | EMA, EFPIA |
| The orphan-device reform is not yet binding law. | COM(2025) 1023 does not automatically simplify Article 117. | European Commission |
Small populations, demanding delivery
Rare diseases cover several thousand conditions in the European Union. Therapies are often parenteral, long-term and intended for home use. The delivery format therefore shapes adherence, the care pathway and the evidence available for later value assessment and reimbursement.
The home injector is not a late packaging decision. It is a development stream with human-factors, risk-management, technical-documentation, quality and lifecycle requirements. This work should run alongside medicine development from Phase II.
Three combination types, three regulatory outcomes
Article 1(8) and 1(9) MDR distinguish combinations by market configuration and principal mode of action. The decisive question is whether medicine and device are placed on the market as one integral, exclusively combined and non-reusable product.
| Combination type | Typical configuration | Regulatory outcome |
|---|---|---|
| Integral | Pre-filled pen, autoinjector, pre-filled syringe or pre-charged inhaler as one unit | The medicinal-product framework applies. Relevant MDR GSPRs must be demonstrated for the device part. Depending on class, an EU certificate or NBOp is required. |
| Co-packaged | Medicine and a separate device in the same carton | The device remains an independent medical device and needs CE-conformity. |
| Referenced | Product information refers to a separately obtained pump or nebuliser | The device remains outside the medicinal product. CE-conformity sits with the device manufacturer. |
For integral combinations, the authorisation dossier reflects the device component. A Notified Body Opinion assesses conformity with relevant GSPRs. It is not an independent market-access certificate.
What Article 117 means for orphan programmes
Orphan designation does not change the Article 117 requirement. For class IIa, IIb, III and Is, Im or Ir, the dossier needs appropriate conformity evidence or an NBOp. A declaration of conformity may be relevant for class I. The current EMA Q&A recommends submitting this evidence with the marketing authorisation application.
The EFPIA survey describes a narrow practical pool of suitable notified bodies, pre-submission lead time and frequent additional review rounds. These figures are not regulatory deadlines. They still show why the NBOp route should be planned as a critical path. In orphan programmes, patient availability for usability and human-factors studies is limited. Joint planning prevents duplicate recruitment.
Include companion diagnostics and reimbursement early
For biomarker-selected orphan therapies, a companion diagnostic can trigger another regulatory route. Reimbursement logic also follows product architecture. An integrated administration aid can form part of the medicine. A separate device often follows its own medical-aid and care pathway.
| Timing | Priority |
|---|---|
| Preclinical to Phase I | Define the delivery target profile and deliberately classify the combination as integral, co-packaged or referenced. |
| Phase II | Determine risk class and engage suitable notified bodies early. Align device and medicine timelines. |
| Phase II to III | Build human-factors, technical-documentation and quality evidence alongside clinical development. |
| Before submission | Coordinate the NBOp dossier with Module 3 and allow sufficient review time. |
| Before launch | Define the device reimbursement route, training, operations and lifecycle changes. |
Conclusion
For orphan therapies, the delivery format shapes access, use and evidence. COM(2025) 1023 addresses orphan devices and marks an important policy development. For Article 117 today, early alignment of medicinal product, device and market-access strategy remains decisive.
Sources: [1] MDR, Regulation (EU) 2017/745, Articles 1 and 117. [2] EMA/37991/2019 Rev. 6, 1 December 2025. [3] EFPIA: Navigating EU MDR Article 117, June 2025. [4] European Commission, COM(2025) 1023 final. [5] European Commission: Rare diseases. [6] EMA EPARs for Yorvipath, Cablivi, Voxzogo, Brineura and Aspaveli.
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