An application for authorisation of an integral combination product (a medicinal product with an integral medical device component) in the EU must prove that the medical device component meets the general safety and performance requirements (GSPRs) according to Annex I of the EU-MDR.
According to Article 117 EU-MDR, in the absence of an EC certificate a Notified Body Opinion (NBOp) on the conformity of the integral medical device component must be included where the integrated medical device is a product of the following classes:
- class Is
- class Im
- class IIa
- class IIb
- class III
These requirements are also applied in Switzerland.
What are the Swissmedic requirements for an NBOp?
The NBOp is an essential element of the authorisation documentation for the assessment of an integral combination product.
- The NBOp should therefore be evidence of a robust, complete and unambiguous assessment of the conformity of the medical device component(s) with the applicable GSPRs.
- Swissmedic bases its assessment of integral combination products in the context of the authorisation procedure on the statements included in the NBOps.
Why did Swissmedic subject a sample of ten NBOps to a detailed review?
To verify whether the information currently included in the NBOps is sufficient and appropriate for this purpose, Swissmedic medicinal product authorisation experts together with Swissmedic medical devices surveillance inspectors subjected a sample of ten NBOps to a detailed review.
- Only the content of and statements in the NBOps were reviewed.
- There was no review of the technical documentation on the medical device components as these fall within the area of responsibility of the Notified Bodies.
What was the outcome of review of the NBOps?
In general, the NBOps showed considerable variation in terms of extent and format.
- In addition, recurrent content-related deficiencies and critical points were identified.
- The ten NBOps in the sample did not completely address the questions on the medical device component(s) that are relevant for the authority.
- It is not clear from the NBOps evaluated whether all applicable GSPRs are met for the complete and final medical device component of the integral combination product throughout the entire life cycle.
- Whilst the competence of the Notified Bodies is not in question, the content of the NBOps reviewed shows shortcomings in terms of completeness and plausibility.
- They are therefore of limited use in terms of completing and supplementing the review by the authorities.
What were the frequent critical shortcomings identified in the NBOps reviewed?
1. Unclear/incomplete scope of the NBOp with regard to the medical device components assessed
Example:
- Unclear which medical device components of the combination product are covered by the NBOp, for example whether the NBOp for an autoinjector also covers the prefilled syringe and the needle.
2. Codes and classification missing/incorrect
Examples:
- Active devices such as spring-loaded autoinjectors are classified as non-active devices.
- MDS code for sterile products missing.
3. Applicable GSPRs not correctly identified and met
Examples:
- GSPR 14.1 missing (device intended for use in combination with other devices). This is particularly important if not the complete medical device component is part of the NBOp.
- Missing or implausible justifications for the non-applicability of GSPRs.
- Applicable GSPRs inconsistent.
- Conformity confirmed despite obvious data gaps.
4. Superseded standards applied
Examples:
- Application of superseded standards in the areas of risk management, usability, biocompatibility.
5. Insufficient verification and validation data
Examples:
- Missing or incomplete data on biocompatibility, usability, transport validation and aging.
- Data not transferrable to the version of the medical device component that is part of the combination product submitted for authorisation.
6. Gaps in the available data on the medical device component are passed on to the authority for review, even when this is not within the area of responsibility of the authority.
What are Swissmedic’s expectations regarding NBOps?
Based on this review, experience to date with submitted NBOps and in accordance with Article 117 EU-MDR, Swissmedic has issued the following list of conditions to be met on the key content and expected quality of NBOps for the authorisation assessment.
- Those medical device components which are covered and not covered must be clearly identified and the relation to the combination product must be described.
- Product description and intended use should be described.
- Specified classification and codes should be correct.
- Full conformity with applicable GSPRs based on data should be confirmed.
- Applicable GSPRs should be correctly identified.
- Plausible justification for non-applicable GSPRs.
- Applied standards, incl. version, should be listed.
- A summary of the reviewed data (a.o., biocompatibility, transport, aging, usability) should be available. The data are applicable for the version of the medical device component that is part of the combination product to be authorised.
- Data gaps should be identified; recommendations concerning these are limited to the area of responsibility of the authority.
- There is a clear conclusion/statement on conformity of the components assessed with the applicable GSPRs.
- Type, version, date and revisions of and persons responsible for the NBOp should be clearly indicated.
Whose responsibility is it to ensure that an NBOp plausibly proves the conformity of the medical device components by meeting the general safety and performance requirements (GSPRs) according to Annex I of the EU-MDR
It is the responsibility of the applicant for the combination product to ensure that the NBOps plausibly prove the conformity of the medical device components.
- Applicants submitting the corresponding authorisation applications must critically assess the NBOps before submission.
- Unclear and incomplete NBOps may result in delays in authorisation, whereas conclusive NBOps support the authorisation process for combination products, including adherence to timelines.
Source: Swissmedic