The Device Is Right

The distinction between the pharma and medical device industries is blurring. For some therapies, delivery of the drug can be crucial to ensure reliable patient outcomes. To support the current trend of more home care and patient self-administration, drug delivery devices have become more complex, often relying on software apps to support the patient and/or provide input to the health care professional.

In Europe, the medical device part of a drug device combination (DDC) was in the past assessed by the EMA as part of the Marketing Authorization Application (MAA). But with medical devices becoming increasingly complex, the European Commission added the (in)famous article 117 to the EU Medical Devices Regulation (EU) 2017/745 (EU MDR). Article 117 requires a notified body to evaluate the safety and performance of the device part of a DDC; notified bodies are organizations that have been designated by the competent authorities of the EU member states and the EU Commission to verify the safety and performance of medical devices. In short, an extra approval step is required for a DDC in Europe. 

For the device part of a DDC, unless it is a class l device, a notified body needs to evaluate the compliance of the device to the relevant sections of Annex l of the EU MDR – either as part of the CE marking of the device or by obtaining a “notified body opinion.”

Unsurprisingly, it is the “how” that makes the process more complicated, as highlighted in the guidance document from EMA.

There are three pathways that a pharma company can apply – each with pros and cons.

Pathway 1. Use a device from a third party that is already CE marked by the original manufacturer. In this instance, the MAA needs to include the evidence of CE marking (in other words, a Declaration of Conformity from the original manufacturer and where applicable a certificate from the notified body). The advantage of this approach is that the regulatory approvals of the device are not in the critical path and the documentation to be included in the MAA is minimal. However, it also means that the original manufacturer of the medical device owns the design of the device. The pharma company will be dependent on the original manufacturer to be kept up to date on any design changes to the device that may impact the MAA.

This approach can be a good strategy if the pharma company has i) multiple DDCs in their product portfolio and ii) a constructive working relationship with the medical device manufacturer.

Pathway 2. Obtain a notified body opinion. In this case, the device is not CE marked. The pharma company must provide the notified body a device dossier containing evidence that the device complies with the applicable requirements of Annex l of EU MDR. As a minimum, this should contain a risk assessment, clinical data, compliance to applicable standards, design verification and validation, and a benefit/risk statement. Notified bodies have recently agreed on a common template for submission.

The downside of obtaining the notified body opinion is that it may come into the critical path of the MAA submission; the EMA states that they prefer for the notified body opinion to already be included in the application rather than being submitted later. Notified bodies will have different timelines for providing an opinion.

The non-CE marked medical device can either be developed in-house by the pharma company or obtained from a third party. In the latter case, the evidence for the submission to the notified body for their opinion will have to be provided by that third party, who may not be willing to share their IP. It also requires the third party to have appropriate quality management system (QMS) procedures in place to ensure data are aligned with the notified body expectations.

This strategy can be effective if the pharma company has i) few DDCs in their product portfolio and ii) a constructive working relationship with a medical device manufacturer.

If the device is developed in-house by the pharma company, they also will need to have the appropriate QMS procedures in place to ensure all data needed for obtaining the notified body opinion are captured. The advantage is that the pharma company will own the IP and will also be able to evaluate the impact of device design changes to the MAA.

Pathway 3. Become a legal manufacturer of medical devices. To attain that status, the pharma company must implement a QMS compliant with the requirements of EU MDR and be inspected and certified by a notified body. The company should have all the procedures and processes to develop, CE mark, and bring to market medical devices in the EU. Implementing a medical device QMS in a pharma organization takes a significant effort and will require staffing the requisite expertise to support the QMS. The pharma company will have to comply with all aspects of EU MDR, including post-market surveillance requirements for the medical device.

On the other hand, it will allow the pharma company to develop medical devices aligned with the requirements of the drugs it is developing and CE mark those devices. For the lower risk devices, this will take the notified body out of the critical path to CE marking, as the company can self-declare and issue a declaration of conformity for the new devices that are in scope of its QMS certificate. The medium to high risk llb implantable devices and high-risk lll devices will need notified body involvement before such a declaration may be issued.

In conclusion: medical devices have a much shorter development and lifetime in the market than drugs, and will likely require more frequent changes to the device design (such as software updates, enhanced batteries, design optimizations, and so on), so there are advantages to minimizing the involvement of the notified body in the critical path to submitting MAAs or variations.

As pharma companies consider medical devices as a part of their current and future product portfolio, they must consider the regulatory pathway for the device early in the DDC development process to ensure the device approval does not come in the critical path for the MAA. In my view, when there is a high number of DDCs in the pipeline – and especially if there are also standalone medical devices like SaMD being considered – there are advantages to implementing a medical device QMS.