device that was already marketed prior to the implementation of the MDR.

According to the European Medicines Agency (EMA), the new MDR, which came into effect on May 26, 2021, significantly impacts how legacy devices are managed. The regulation stipulates that legacy devices that fall under the combination product category must comply with the new requirements, even if they were compliant before the introduction of the MDR.

In preparation for subsequent steps, stakeholders should:

• Identify whether the product qualifies as a combination product.
• Determine the classification of the device under the MDR.
• Understand the historical compliance status of the legacy device.

A comprehensive gap analysis may be beneficial to identify deviations from the new regulatory framework, clarifying which additional data and documents will be required for full compliance. This analysis will be the foundation upon which compliance strategies can be built.

Step 2: Assembling the Dossier for Regulatory Submission

The next phase involves compiling the necessary documentation for the regulatory submission. This dossier forms the core of your regulatory strategy and must align with the expectations set out by the MDR and the Notified Body involved in the review process.

The essential components of the submission dossier include:

• Technical Documentation: This must conform to Annex II of the MDR and include details such as the device description, intended use, design and manufacturing information, and risk management documentation.
• Clinical Evaluation Report (CER): For legacy devices that experience significant changes or are integrated into a combination product, a thorough clinical evaluation may be necessary.
• Post-market Surveillance Plan: Outlining how you will monitor the safety and performance of the legacy device in the post-market phase is crucial and a requirement of MDR.
• Compliance with General Safety and Performance Requirements (GSPR): A vital part of the dossier will be demonstrating how the device meets all relevant GSPR as outlined in the MDR.

Furthermore, organizations should prepare the necessary justification for how information required under Article 117 of the MDR applies to their combination product. This will involve a detailed analysis of how the drug component interacts with the device component.

It is strongly recommended to consult guidance documents provided by the Notified Body and to adopt a collaborative approach by discussing the intended strategy with them early in the process. Integrating their feedback will save time and clarify requirements.

Step 3: Engaging with Notified Bodies

Once the dossier is compiled, the next step is to engage with a Notified Body that is competent to evaluate the combination product. This interaction is critical, as the Notified Body plays an essential role in assessing conformity with the MDR.

Here are practical steps for effective engagement with Notified Bodies:

• Identify and Select a Notified Body: Verify that the Notified Body is designated for the specific type of product you are submitting. Check their scope of designation according to the official EUDAMED database.
• Pre-submission Meetings: Schedule a pre-submission meeting to discuss your dossier. This can be invaluable for obtaining insight into the Notified Body’s expectations and can help mitigate risks of non-compliance.
• Prepare the Submission Package: Compile the required documentation and submit it for review. Be prepared to respond to questions and requests for additional data promptly.

Expect the Notified Body to conduct a rigorous review process, including potential audits and on-site inspections, especially if the combination product presents novel risks or is the first of its kind within the scope of the Notified Body.

Step 4: The Review Process – What to Expect

The review process by the Notified Body is thorough and can take several months, depending on the complexity of the combination product. The aim is to ensure compliance with the requirements of the MDR and the safety and performance of the legacy device in its new role.

During the review, be prepared for the following:

• Document Requests: The Notified Body may request additional documentation or clarification of existing documents. Having an open line of communication will facilitate timely responses.
• Technical Questions: Expect inquiries regarding the clinical evaluation, risk management methodologies, and how the legacy device adheres to the latest safety standards.
• Site Audits: Be prepared for the possibility of an on-site audit of your manufacturing facility to ensure compliance with Good Manufacturing Practice (GMP) and quality management systems.

Following a comprehensive review, the Notified Body will either issue a certificate of compliance, request further information, or reject the application. It is essential to understand common pitfalls that lead to rejections, such as inadequate clinical evaluations or insufficient risk management documentation.

Step 5: Post-Approval Actions and Market Surveillance

Upon successful approval and obtaining your CE marking for the combination product, the regulatory obligations do not cease. Organizations must commit to ongoing market surveillance and compliance activities to assure continued safety and effectiveness in alignment with the MDR.

Key post-approval obligations include:

• Implementation of the Post-Market Surveillance Plan: Document and monitor the performance of the combination product, collecting data on adverse events and product performance in real-world scenarios.
• Periodic Safety Update Reports (PSUR): These must be prepared and submitted according to the risk classification of the device, as outlined in the MDR.
• Updates to Technical Documentation: Keep technical documentation and risk management files up to date with any changes in regulation, product modifications, or emerging safety data.
• Engagement with Regulatory Authorities: Establish a robust communication channel with regulatory entities and the Notified Body for any issues arising from post-market surveillance.

Moreover, the legal obligations surrounding vigilance reporting remain critical. Compliance signifies not just regulatory adherence, but also a commitment to safeguarding patient health and well-being.

Conclusion

Navigating the regulatory landscape for legacy devices in combination products can be intricate, particularly under the scrutiny of the EU MDR. By following this structured approach, regulatory affairs professionals can better manage compliance, mitigate risks, and achieve successful market entry.

To further support your compliance journey, consider leveraging the expertise provided by FDA combination product consulting services. Keeping abreast of the latest regulatory updates and guidance documents from authorities such as the EMA and Notified Bodies is equally essential for maintaining compliance in a rapidly changing environment.