The EU Medical Device Regulation (MDR) Article 117 became legally binding and mandatory in May 2021, but there is no clear industry consensus regarding its application to integral drug delivery devices. The regulation is particularly unclear in the case of a device constituent part being classified as an invasive device, and whether all drug product contacting components must conform to the requirements for invasive components. There are also ambiguities regarding requirements such as notified body opinion and human factor study requirements. Unfortunately, there is no clear industry consensus regarding the application of Article 117 to integral drug delivery devices.
BioPhorum MedTech members came together in Autumn 2021 to benchmark their experiences and identify common areas of concern. Their findings are outlined in the following publication: Implementation of Article 117 of European Union Medical Device Regulation General Safety and Performance Requirements: A Position Paper.
The main issues identified by the team include:
- Applying GSPRs: there is no industry consensus on applying general safety and performance requirements (GSPRs) to integral products, leading to concerns that companies may submit different information to a notified body and receive different opinions for similar products
- Risk management: if companies continue to solely use ICH Q9: Quality risk management for process/manufacturing risks that are related to device constituents, they may not meet the prescriptive requirements of both ISO 14971: Medical devices: Application of risk management to medical devices and Chapter 1 of the GSPRs
- Labeling requirements and instructions for use: GSPR labeling requirements need to be individually evaluated to understand if the information required for the device part is necessary to support the intended use of the integral drug-device combination (DDC)
- Submission documents: it remains unclear across industry what level of documentation and data should be submitted to a notified body to demonstrate that an integral DDC conforms to the GSPRs
- Substantial change – post-approval: for manufacturers preparing for a notified body opinion (NBOp), there is no clear process to follow nor any clearly defined timelines to allow them to plan and implement product improvements and changes
- Classification: some pharmaceutical companies face challenges classifying the device part of a single integral DDC product
- Notified body engagement: obtaining an NBOp has become a vital part of the approvals process for medicinal products supported by a medical device constituent, but the changes to the regulations have not yet resulted in a set of clear instructions to industry.
In summary, inconsistencies in the interpretation of GSPR guidance create an unnecessary administrative burden for manufacturers and Notified Bodies. The paper demonstrates how Notified Body submissions could lead to divergent outputs for similar products and is supported by case studies and experiences of the team, demonstrating some of the issues experienced. The MedTech team hopes that all industry stakeholders can benefit through open collaboration to resolve these issues.
In the team’s recently published podcast supporting the position paper, Tara Cox, Head of Device Quality and Regulatory Compliance at Takeda, said that some guidance is available, but there are still many uncertainties. “Relatively few products have been through the NBOp process, so there are still a lot of unknowns. BioPhorum has been great to get together as a team and figure out what is the best knowledge of our industry, compile it in this document, and then share it.”
Commenting on the next steps for the team, Yvan Giroud, Manager, Primary Packaging & Medical Devices at CSL Behring, said “the position paper is more a starting point than the final destination. The MedTech team is currently gathering experience of the ‘Notified Bodies Opinion’ process and will use this, as well as sharing our lessons learned, to inform the development of an implementation guidance paper; to help companies streamline their own submission processes”. With an aim to publish the guidance paper in October 2022, the team also plans to publish a second podcast in May 2022 to update on this work, as well as present at several internationally attended conferences.
If you are interested in learning more about BioPhorum’s work on EU MDR article 117, or would like to join BioPhorum MedTech, please contact firstname.lastname@example.org