The regulation and market approval of Drug Device Combination Products (DDCPs) in Europe is a specialized and intricate process due to the combined nature of medicinal and device components. Manufacturers are required to seek a Notified Body Opinion (NBOp), which is a component of the conformity assessment for the EU Medical Device Regulation (MDR)2017/745, when these goods combine a drug product with a device component that is essential to safety or performance. This article guides you through the essential steps to successfully obtain the Notified Body Opinion report — a critical requirement for marketing integral drug-device combination products in the European market.
What Are Drug Device Combination Products (DDCPs)?
Combination Products incorporate a device and a drug in a single administration to provide either diagnostic or therapeutic advantages. Examples are pen injectors, auto injectors, prefilled syringes, inhalers, Ophthalmic, nasal sprays, drug-eluting stents etc. These products have dual characteristics, which place them under the regulatory jurisdiction of both pharmaceutical and medical device frameworks and this requires that they be thoroughly compliant.
Regulatory Foundation: Article 117 of the MDR
The EU MDR, Article 117, introduces special consideration to Integral drug device combination products that are mainly intended to be regulated as medicinal products. Manufacturers seeking marketing authorization for these products must present a Notified Body Opinion that confirms the conformity of the device constituent part to the General Safety and Performance Requirements (GSPRs) established by the MDR. Obtaining this NBOp is mandatory: without it, the European Medicines Agency (EMA) will not approve the combination product for the EU market.
When Do You Need a Notified Body Opinion?
A Notified Body Opinion is required when your medicinal product contains an integral device component (a “drug device combination product”) and:
● The device part is not CE marked for the intended use within the combination, and
● The manufacturer’s EU Declaration of Conformity or a relevant EU Certificate from a Notified Body is not available for that particular device use.
This usually occurs when the device and medication are produced as one cohesive unit and sold as a medication (e.g., a drug releasing implant, auto-injector, pen injector or pre-filled syringe).
In these cases, the Notified Body must review the device component’s conformity to the General Safety and Performance Requirements (GSPRs) of Annex I of the MDR, providing a third-party opinion that becomes part of the Marketing Authorization Application (MAA) to EMA or national authorities. CE-marked devices intended for a use that falls outside their original certification (new delivery route, new drug, etc.) may also require a new NB opinion. Non-integral products (co-packaged or referenced separately) generally do not need a separate Notified Body Opinion.
Importance of the Notified Body Opinion Report
The Notified Body Opinion is a third-party verification that the embedded device component in the Drug Device Combination complies with relevant MDR Safety and Performance requirements. It:
● Demonstrates compliance of the device appliance constituent part,
● Is required by EMA for marketing authorization,
● Facilitates coordinated regulation across by authorities,
● Helps identify and mitigate risks arising from device-device interactions.
How to Obtain the Notified Body Opinion Report
To prove that the device component of your DDCPs satisfies MDR safety and performance standards, you must obtain the Notified Body Opinion. These steps ensure your product meets regulatory expectations and clears a key hurdle for market authorization by EU authorities.
1. Establish Applicability of Article 117 MDR
Determine if your product qualifies as an integral Drug Device Combination Product under Article 117, where the drug product has the primary mode of action, but the device part significantly affects safety or performance.
2. Select an Appropriate Notified Body
Select a Notified Body which is authorized to determine appliance conformity under the scope of the MDR applicable to your combination product
3. Prepare Device Technical Documentation
Assemble robust technical documentation focused on the appliance component, covering:
● Design and manufacturing processes
● Risk management and performance testing
● Product Verification and Validation
● General Safety and Performance Requirements.
While not requiring a full, standalone medical device technical file, the documentation must still be comprehensive.
4. Submit Documentation and Request NB Opinion
Send your documentation to the Notified Body and formally request a conformity opinion.
Early and open feedback between the NB and the respected individual can help streamline the evaluation process.
5. Address NB Queries Promptly
Respond effectively in case of clarification or additional information requests in order to prevent delays in assessments.
6. Receive and Incorporate NB Opinion
After the review is complete, the NB verifies that the device complies with its opinion. This report must be included as part of the Marketing Authorization Application (MAA) to EMA.
Challenges and Best Practices
● Prepare detailed documentation addressing the complexity of drug-device
interactions.
● Ensure that regulatory personnel in the pharmaceutical and device manufacturers have strong interdisciplinary teamwork.
● Early on in the development process, involve the Notified Body.
● Keep current with MDR updates and harmonized standards.
● Focus risk management on device functions which are critical to overall product safety.
How 3iconcept Facilitate Your Success ?
Navigating the regulatory landscape of drug device combination products requires specialized knowledge. At 3iconcept, our integrated regulatory and technical expertise supports you by:
● Assessing qualification under Article 117 MDR,
● Preparing targeted technical documentation,
● Guiding Notified Body selection and communication,
● Assisting with NB query resolution and opinion integration,
● Structuring submissions aligned with EMA expectations.
Your path to market is accelerated when you work with 3iconcept, which also guarantees strong compliance and product safety.
Conclusion
The acquisition of a Notified Body Opinion Report plays a critical role in the path of whole drug/appliance combination products in Europe. This view confirms that the safety and performance of the device component are compliant with the basis of MDR requirements, which will facilitate marketing authorization with EMA.Documentations, strategic NB engagement, and appreciable preparation are the biggest keys to success. Through the cooperation of industry leaders with expert partners such as
3iconcept Medical Solution, manufacturers are free to safely and conveniently move their life-saving combination therapy through this complicated road, making the therapeutic option widely available to patients throughout Europe and beyond.