If you are a manufacturer of a drug-led combination product, you may need to include a Notified Body Opinion (NBO) in your Marketing Authorization Application (MAA). In the following paragraphs, you will find a step-by-step overview to find out whether this is applicable to you and, if so, how to achieve this important milestone in your product’s pathway to market. 

 

 

1. Assess whether Article 117 of the MDR is applicable to your combination product.  

 

Article 117 of the Medical Device Regulation (EU) 2017/745 (MDR) amends Annex I of Directive 2001/83/EC, point 12 of section 3.2, requiring to provide evidence of compliance with the General Safety and Performance Requirements (GSPRs) of the MDR for the device part of your Drug-Device Combination (DDC), when submitting your Marketing Authorization Application (MAA). 

 

Article 117 of the MDR applies to Drug-Device Combinations (DDCs) that meet the following definitions, as defined in Article 1 (§8 and §9, respectively): 

• DDCs incorporating, as an integral part, a medicinal product whose action is principal to that of the device; for example, a drug-eluting implant that slowly and locally releases the drug. 

• DDCs intended to administer a medicinal product, which are placed on the market in such a way that the device and the medicinal product form a single integral product intended exclusively for use in the given combination and which is not reusable; for example, pre-filled syringes or transdermal patches 

 

Therefore, if your product falls under either of these definitions, then refer to the steps below to find out how to comply with MDR requirements for the device part. 

 

 

2. Classify the device part of your combination product 

 

The MDR classifies medical devices into class I, Ir (“r” stands for “reusable”), Is (“s” stands for “sterile”), Im (“m” stands for “measuring function”), IIa, IIb and III, based on their intended purpose and related risks. In particular, Annex VIII of the MDR lists 22 rules, that should be assessed for applicability to the device part of your Drug-Device Combination: if multiple rules apply, the strictest rule resulting in the highest classification determines the class of the device part.

 

For example, according to Rule 20 of Annex VIII, inhalers are classified as class IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product or they are intended to treat life-threatening conditions, in which case they are classified as class IIb.

 

Of note, Annex VIII of the MDR should be read in combination with the MDCG guidance 2021-24 – “Guidance on classification of medical devices” to ensure the appropriate interpretation of the rules.

 

3. Check whether the device part is already CE marked.

 

There are three cases to be considered here:

 

a) If the device part is a class I (non-sterile, non-measuring and non-reusable surgical instrument) and is CE marked under MDR, include the Declaration of Conformity in the MAA, and ensure that the device is used within its intended use. No further steps are required.

 

b) If the device part is of any other class than I and is CE marked, include the EU certificate issued by the Notified Body in the MAA. No further steps are required.

 

c) If the device part is of any other class than I and is not CE marked, refer to the steps below.

 

4. Contact a Notified Body and obtain a quotation for a Notified Body Opinion (NBO).

 

You should select a Notified Body that is designated under the MDR and whose scope of technical competence covers devices as per Article 117. To find the Notified Bodies currently designated, please consult the NANDO (New Approach Notified and Designated Organisations) website.

 

 

5. Collect all the available Technical Documentation (TD) of the device part and perform a gap analysis against the requirements defined in Annex II of the MDR.

 

This includes, but is not limited to, design and manufacturing details, the risk management file and performed verification and validation activities (including their traceability). If the device is active, the electromagnetic compatibility and software development details should also be included.

 

6. Address any gap identified, by integrating the TD, coordinating with suppliers to obtain any additional necessary information, or running any potential additional test/s.

 

Medidee has a long track record of supporting medical device manufacturers with their Technical Documentation. We provide gap analysis services for multiple companies and help them succeed in addressing such gaps. Do not hesitate to contact us, should you feel that you would also benefit from our support.

 

7. Sign the quote with the chosen Notified Body.

 

8. Compile the Technical Documentation as per Annex II of the MDR, and submit it to the Notified Body for review.

 

9. Be ready for multiple assessment cycles, as needed.

 

Medidee has successfully supported clients in compiling the Technical Documentation, submitting it, and interacting with Notified Bodies. As questions are raised during the review process by the Notified Body, we help you address them in a timely and comprehensive manner.

 

10. Once all questions with the Notified Body are closed, the Notified Body will finalize and send you the Notified Body Opinion Report, for you to include in your MAA.

 

EMA and National Competent Authorities (NCAs) recommend submitting evidence of compliance with the GSPRs of the MDR for the device part of your combination product already in the initial MAA for the medicinal product to avoid additional clock stops.

 

As an example of timeframes to be considered for obtaining a NBO, TÜV SÜD has published on its website the required Application Form for Notified Body Opinion per Article 117, laying out the timelines of their examination process. According to their process, getting a non-binding quotation after submission of the Technical Documentation could take up to 2 months, and the review process may take 3 more months, depending on the questions raised.

 

Hence, at least 6 months should be accounted for obtaining the Notified Body Opinion once the Technical Documentation is ready. Early contact with a Notified Body and performing a gap analysis of the Technical Documentation of the device part against MDR requirements are critical steps necessary for you to draw the project timelines.

 

If this is something you are currently working on, do not hesitate to check our full offering of Combination Products Services, or to reach out directly for expert support. 

 

This article was written by Bruno Strappa (MSc) and Rima Padovani (PhD, RAC).