Many manufacturers of combination products struggle because the device component isn’t adequately documented or assessed under the EU regulation, leading to costly delays or outright rejections. With MDR article 117, these shortcomings are no longer optional: the regulation demands a Notified Body Opinion for the device part, which often reveals gaps in technical files or risk assessments. Fortunately, with structured preparation, early gap-analysis and clearly aligned technical documentation, companies can meet MDR article 117 requirements smoothly, reducing review times and improving chances of regulatory approval.

How does MDR article 117 change the approval process for combination products?

The new obligation under MDR article 117 has introduced a requirement that manufacturers of drug-device combination products must include a Notified Body Opinion (NBOp) for the device component when submitting the marketing authorisation application (MAA) for a medicinal product. One central task is preparing a robust technical file for medical devices that demonstrates conformity of the device component to the relevant General Safety and Performance Requirements (GSPRs) under Annex I of the MDR. This means that although the product is being authorised as a medicinal product, the device portion must satisfy device-specific safety, performance, clinical data, usability, risk management, biocompatibility and other relevant standards.

Our services at Billev Pharma East for medical device technical files include assistance in compiling and structuring the technical documentation, ensuring completeness according to Annex II of MDR, providing support in risk-management reports, verification/validation data, clinical evaluation where needed, usability engineering, and liaising with the chosen Notified Body. The inclusion of NBOp report becomes part of the dossier submitted to EMA or national competent authorities. Thus, compliance with MDR article 117 shifts much of the responsibility of ensuring device safety and performance earlier in the development process, and demands coordination between medicinal product and device regulatory tracks.

What evidence is required in the technical file under MDR article 117?

Under MDR article 117, the technical documentation must provide objective evidence that the device component complies with all applicable GSPRs from Annex I of the MDR. This includes, but is not limited to: design verification and validation, risk management including benefit-risk analysis, clinical evaluation (if there are device-specific clinical claims), biocompatibility studies, software verification (if applicable), sterility assurance, usability/human factors, labelling, packaging and transport. There must also be statements of applicability: for each GSPR, the manufacturer must clarify whether it applies or not, and justify any exclusions.

The documentation format is generally guided by the technical file format of Annex II of the MDR, and must be clearly structured, traceable, searchable, and include raw data or reports (not just summaries) in many cases. For example, the Notified Body Opinion (NBOp) will expect these supporting materials to assess conformity. Also essential are details of manufacturing processes, materials, accessories, instructions for use, and any interactions between medicinal and device parts.

When you engage with Billev Pharma East, our support covers assembling exactly this kind of evidence: we help figure out which GSPRs are relevant for your product, collect test reports and supplier documentation, ensure traceability, help with clinical/biocompatibility evaluations as needed, and format the technical file so that the NBOp review proceeds smoothly.

How can manufacturers demonstrate compliance with MDR article 117?

To demonstrate compliance with MDR article 117, manufacturers must show—via a structured technical file—that the device part of a drug-device combination meets the relevant General Safety and Performance Requirements (GSPRs) in Annex I and has been assessed by a notified body, resulting in a Notified Body Opinion (NBOp) for inclusion in the marketing authorisation dossier. Practical expectations and interfaces are outlined by EMA and detailed best-practice checklists are available from leading NBs.

Start with a gap analysis: map every applicable GSPR, justify any non-applicability, and identify missing evidence. Then assemble documentation per Annex II—design verification/validation, risk management (ISO 14971-aligned), labelling/IFU, manufacturing information, and device–drug interaction considerations—using a clear, searchable structure with traceability from requirements to evidence. Team-NB’s position paper gives a pragmatic view of file structure and depth expected by different NBs.

Generate objective evidence proportionate to risk: biocompatibility, sterilisation and packaging validations, usability/human-factors studies, software lifecycle evidence (where applicable), transport testing, and—when device-specific claims or safety questions arise—targeted clinical data. Leverage harmonised standards/common specifications to streamline conformity arguments. Engage the notified body early to confirm expectations, shorten Q&A cycles, and secure the NBOp in time for the MAA. TÜV SÜD and BSI both highlight timeline planning and dossier completeness as the main determinants of a smooth NB review.

Finally, maintain tight configuration control: versioning, change rationales, and a living GSPR matrix that stays aligned with design changes through lifecycle. This reduces re-work during NB queries and supports consistent assessments by regulators who rely on the NBOp for the device component.

Industry data on NBOp issuance rates

According to data from NBCG-Med (reported via MakingPharmaIndustry, April 2024), 17 out of 39 Notified Bodies that responded have already issued NBOp reports for combination products under MDR article 117. That is approximately 43.6 % of responding NBs. This number reflects early adoption but also indicates that more than half of NBs are still building or adapting their processes to fully support NBOp issuance for IDDCs (integral drug-device combinations.

What role does the notified body play in MDR article 117 assessments?

In the context of MDR article 117, a Notified Body (NB) serves as the independent authority that reviews the device component of a drug-device combination product to ensure compliance with the General Safety and Performance Requirements (GSPRs) set out in Annex I of the MDR. The NB issues a Notified Body Opinion (NBOp), which becomes a mandatory part of the marketing authorisation submission.

Review by the NB includes evaluation of risk management, design verification/validation, usability, biocompatibility, and all functions of the device that could impact patient safety or performance. The NB also looks at the interaction between the medicinal component and the device, particularly where the device part depends on the drug or could affect its efficacy or safety.

Furthermore, the quality and completeness of the technical documentation submitted to the NB substantially impacts the speed and outcome of the NBOp. Missing data or unclear statements of applicability for certain GSPRs often lead to questions, delays, or required corrective actions.

Finally, the NB’s opinion is not a stand-alone certification of the medicinal product—it specifically addresses the device section and its conformity. Regulatory authorities (EMA or national ones) use that opinion alongside medicinal evidence to make the final decision on market authorisation. This collaboration forms the backbone of how MDR article 117 is implemented in practice.

How does MDR article 117 affect collaboration between regulators and notified bodies?

MDR article 117 fosters a more integrated interaction between regulatory authorities (like the EMA or national competent authorities) and Notified Bodies when dealing with combination products. Because the device component must receive an NBOp before or during the medicinal product review, regulators rely on the NB’s assessment to inform their evaluation of the overall product.

This requirement means timelines must be coordinated. If the NBOp report isn’t ready by the time the Marketing Authorisation Application (MAA) is submitted, it can cause delays. Early engagement between the applicant, the NB, and regulatory authority helps clarify expectations, reduce surprises, and align documentation.

Also, both regulators and NBs may issue guidance, questions & answers (Q&A) documents or position papers to harmonize interpretations. For example, Team-NB, EFPIA, and others have highlighted inconsistencies among different NBs in how they interpret some GSPRs or what evidence is acceptable. Such collaborative guidance helps industry predict what will be required.

In short, under MDR article 117, the device-side review by NB and medicinal product review by competent authorities must be tightly intertwined. Effective collaboration reduces regulatory risk, accelerates approval, and ensures safety.

Survey results on delays due to NBOp timing

A survey of 14 EFPIA member companies (2025) showed that 64% of companies require at least two rounds to address queries from the NBs due in part to incomplete device-side technical documentation or waiting for the NBOp. These findings illustrate that for most firms, MDR article 117 is not just a regulatory formality—it is a real factor contributing to delays when collaboration and communication are not optimised.

What practical challenges do companies face when implementing MDR article 117?

Several real-world obstacles arise when companies try to comply with MDR article 117:

• limited notified body capacity: Not all NBs have the expertise or resources to conduct NBOp assessments for combination products. This leads to bottlenecks or long waiting times.
• Variability of interpretation: differences among NBs (and sometimes among Member States) in how specific GSPRs are interpreted or what level of evidence is expected can cause confusion. What one NB considers sufficient may be inadequate for another.
• Documentation complexity and completeness: Assembling the required evidence (clinical, usability, biocompatibility, risk management etc.) in sufficient detail takes time and often reveals gaps that require additional work.
• Timeline misalignments: ensuring the NBOp is ready in time for the MAA submission is difficult. Delays in device-part assessment can derail overall approval schedules.
• Cost and resource burdens: the need for additional testing, external consultants, possibly redesigns, and repeated rounds of questions from NB can increase both project timelines and budgets. Smaller companies are especially affected.

Understanding these challenges early is crucial. Companies can mitigate risk by planning ahead, engaging early with NBs, mapping GSPRs, and conducting gap analyses to avoid surprises.

How can early planning help streamline technical file preparation under MDR article 117

Early planning can make all the difference in technical file preparation under MDR article 117, especially by allowing manufacturers to foresee and address potential gaps long before the submission. By conducting a gap analysis early, you understand which of the General Safety and Performance Requirements (GSPRs) apply and where evidence is still missing, which reduces risk of surprises later. Engaging with a Notified Body early also helps: you can clarify expectations, obtain feedback on draft documents, and align timelines so that the Notified Body Opinion (NBOp) is ready in time for the marketing authorisation process. Ensuring that all device-drug interaction aspects, usability, labelling and packaging, risk management, and material traceability are well documented from the start streamlines review cycles. According to EFPIA, companies that invested time in proactive planning saw fewer NB queries and faster reviews. Best practice guidance from BSI emphasises completeness and structure of the technical documentation as key to avoiding delays. Early planning helps integrate medicinal product and device-side requirements smoothly, which is central to meeting MDR article 117 without costly rework or last-minute adjustments.

Read also:

• Why is MDR Annex II crucial for medical device technical file approval?
• Why must lifecycle management be part of medical device technical file preparation?
• Is your medical device technical file aligned with ISO 14971 risk management requirements?

Sources: 1 – MakingPharmaIndustry. (2024, April). Integral Drug-Device Combinations (IDDCs) and MDR Article 117: Data from NBCG-Med shows that 17 out of 39 Notified Bodies have issued NBOp to date, 2 – EFPIA. (2025, June). Navigating EU MDR Article 117: EFPIA Industry Experience.