many products, particularly those used as companion diagnostics, can fall within both definitions. When evaluating whether a product is a drug or a medical device, consider the following:

• The intended purpose of the product
• The mode of action—does it produce its primary effect through pharmacological, immunological, or metabolic means?
• The means by which it achieves its intended purpose

When dealing with products functioning as both drugs and devices, the manufacturer must be cautious in interpreting the intended use, which may lead to significant implications for compliance, regulatory pathway selection, and documentation requirements.

Step 2: The Role of Article 117 in Drug-Device Classification

Article 117 of the EU MDR specifically addresses instances where a drug may be classified as a medical device. According to this article, if a medicinal product falls under the definition of a medical device due to a specific function of the medicinal component, it is treated as a combination product. Article 117 establishes the framework for assessing these combination products and their necessary regulatory processes.

The key considerations include:

• Does the medicinal product contain an active substance intended to have a medical effect, making it a drug?
• Is the primary intended action that of a medical device?
• What are the risks associated with the dual-use product?

To comply with Article 117, manufacturers must ensure that they submit appropriate documentation to their notified body, including a detailed description of the combination product, intended use, and any associated risks. As part of this process, manufacturers should prepare evidence of previous evaluations performed on either the current or past formulations, clinical data supporting the medical claims, and post-market surveillance plans. This ensures the combination product meets the General Safety and Performance Requirements (GSPR) outlined in Annex II of the EU MDR.

Step 3: Engaging with a Notified Body for Evaluation

Following the identification of the product’s regulatory classification per Article 117, the next step involves engaging with a Notified Body. It is crucial to understand that not all products classified through Article 117 will require the same level of scrutiny. Notified Bodies play a pivotal role in assessing conformity with the EU MDR, making their early involvement critical for successful regulatory outcomes.

The process typically involves:

• Choosing an appropriate Notified Body based on experience with combination products.
• Preparing a Technical Documentation file that meets the requirements detailed in Annex II of the EU MDR.
• Submitting a request for conformity assessment, including supporting clinical and non-clinical data.

During this stage, attention to detail is paramount. Include comprehensive documentation regarding the product’s safety and efficacy profile, which is critical for the Notified Body’s evaluation. Ensure that all referenced studies or clinical trials adhere to Good Clinical Practice (GCP) standards to facilitate smoother assessment and eventual approval.

Step 4: Complying with General Safety and Performance Requirements (GSPR)

The General Safety and Performance Requirements outlined in Annex I of the EU MDR map the expectations for both drugs classified as medical devices and traditional medical devices. For a successful evaluation by a Notified Body, adherence to these requirements is non-negotiable.

Key GSPR considerations include:

• Ensuring product design is safety-focused and performs as intended.
• Incorporating a complete risk management process in compliance with ISO 14971.
• Conducting clinical evaluations, which may be combined with prior clinical data from drug assessments, to support the safety and efficacy of the product.

Manufacturers should comprehensively document the results from clinical evaluations, safety reports, and expected performance outcomes to substantiate compliance with GSPR. This documentation is pivotal, as it directly influences the notified body’s assessment and will further inform the Product Information compiled for end-users and healthcare providers.

Step 5: Navigating EUDAMED Registration and Post-Market Surveillance

Once the regulatory pathways have been established and approvals secured, manufacturers must take steps to document and communicate the regulatory status through EUDAMED. The European Database on Medical Devices (EUDAMED) is a crucial component of EU regulatory oversight, requiring all manufacturers to register their products and ensure transparency.

Essential activities for EUDAMED compliance include:

• Registering the Notified Body as well as details of the product’s classification.
• Maintaining up-to-date records of product safety and performance through ongoing post-market surveillance (PMS) programs.
• Reporting incidents or adverse events associated with the product to ensure rapid response and risk mitigation.

Establishing a feedback mechanism for healthcare professionals utilizing the product allows manufacturers to continuously collect safety and performance data, which is vital for ongoing compliance with regulatory expectations. This PMS process further supports the necessity for periodic review of safety data, enhancing the overall lifecycle management of the combination product.

Conclusion: Preparing for Future Regulatory Challenges

As the landscape of drug-device products continues to evolve in the EU, staying abreast of changes in regulations, guidance documents, and emerging industry standards is paramount for manufacturers. The effective management of regulatory pathways, including Article 117, GSPR, and post-market commitments, serves as a foundation for successful compliance and market access. By leveraging this guide and engaging diligently with notified bodies, regulatory consultants, and clinical data sources, companies can navigate the complexities of the EU’s drug-device regulations efficiently.

For further information, manufacturers should consult the official resources such as the European Commission Medical Devices Overview and ensure that they are informed on latest developments in EUDAMED.