Key legislative revisions in EU for Combination Products: Is your Re-registration of your Device or Drug on Track?

The combination product market is growing and will continue to do so with advances in medical technology paving the way towards safer and more efficient patient care. Drug-device combinations like prefilled syringes, refillable implantable reservoirs, regenerative patches, and automatic dose delivering units help reduce user errors and improve treatment options. Products that combine medicinal products for human use and medical device are bridging the divide between the pharmaceutical and medical device industries.

As the medical device industry is dealing with the medical device regulation and changes it brings along, the combination products are facing an additional uncertainty. The healthcare industry which traditionally approaches medical devices and medicinal product as two separate areas of expertise, is presented with new challenges, requiring regulatory strategies to effectively address new requirements while facilitating market access. Industry participation is needed to shape the framework at European level and guidance’s addressing, for example in the upcoming broad stakeholders' workshop organized by RAPS and TOPRA. The new EU-MDR provides a lot of new and additional reviews for continued market access of both devices with ancillary drugs and drugs with supportive medical devices. 

An increasing number of products in development are not able to fit neatly into a specific definition or classification.  The science behind the development addresses the healthcare need. However, the question if this translates into the effective regulatory timelines or feedback is not that simple. Companies often require an additional stage of discussion with the notified body and/or the competent authority during the regulatory process. This could also prove to be a hurdle for small companies with advanced therapies or truly novel innovative products as the regulatory pathway to market is undefined, has implications on the development related costs and can cause a certain ambiguous feeling surrounding the discussions. In all fairness, a robust regulatory strategy and advice prior to outlining a testing plan, design verification and validation would be a better approach. The changes in clinical scenarios/ preferred practice keep the market demand closer to the newer developments, whilst the differences in clinical practical across the globe are important consideration for worldwide effective regulatory strategy.

The medicinal products are often developed with considerations of patent applications and data protection concerns, making the life cycle typically longer than that of a medical device. As part of life cycle management drug delivery systems are developed in collaboration with device manufacturers using different delivery mechanisms to overcome the complexity of the current delivery system, in order to overcome the constraints observed during the clinical practice. The technological developments and advances in manufacturers understanding of the clinical application post market, needs of different populations and subpopulations often create possibilities of use of a different medical technology than that was studied. Apart from the innovative products, such technologies are increasingly expanding the application of existing medicines even for new applications and new indications.  

The considerations for testing a combination of drug-device together as a system, quality, stability, nonclinical testing and clinical perspective depends on the type of combination product. Regulatory requirements of content of dossier in the form of CTD for the medicinal part and technical file for the medical device are the widely known aspects for combination product submissions, however, the content to provide the evidence of quality and safety differs product wise. Post-market evaluations also need to differentiate between quality aspects associated with the individual component and to the combined use. 

The landscape is significantly changing for medical device manufacturers. The extent of change is at the moment a matter of awareness and obtaining clear guidance. We at Qserve can help you shape the regulatory strategy and submissions with a clear way forward to the market.

For any specific questions, you may have regarding your device’s compliance to the new regulations, feel free to reach out below at: +31 (0)20 78 82 630 or send a mail to 


Ashwini Kulkarni
Post date: August 31, 2018
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