The implementation of the European Union (EU) Medical Device Regulation (MDR) has brought significant changes to the landscape of clinical trial submissions across the EU. While the MDR aims to harmonize the regulatory framework, the reality of its implementation reveals a complex and often fragmented process. Many member states are maintaining their own local submission documents and procedures alongside the MDR requirements. This is one of the primary challenges MedTech manufacturers face in getting clinical trials approved. Despite the overarching MDR framework, local regulations and processes can differ significantly, which may lead to confusion and significant delays.
Avania has extensive MedTech expertise and puts in significant effort to keep up to date on the latest regulatory submission processes in the individual EU member states via dedicated Regulatory Taskforces. These taskforces are crucial as they routinely assess the local requirements and regulatory processes, especially as competent authorities (CAs) and ethical committees (ECs) have been streamlining and updating their processes since the MDR came into effect. Not staying up to date with regulatory processes can have significant impact on the submission process of clinical trials, as well as on adequate safety reporting.
Four Most Common Challenges
We have listed the four most common challenges manufacturers face when submitting their clinical trials in the EU:
- 1. Diverse requirements and timelines: Many member states have their own set of required documents in addition to those mandated by the MDR. These vary from standard study information forms to, for example, chamber of commerce proof of registration. The signature requirements for documents are also subject to local regulations. For instance, Polish regulations dictate the requirement for several wet-ink notarized documents, and in the Netherlands, a research declaration per site is required. Resolving these items can be time-consuming and cumbersome if the manufacturer is not aware of this during the country selection process. The variability in processes and requirements often leads to delays impacting timelines for approvals, causing frustration and potential setbacks in the initiation of clinical trials.
- 2. Different review processes: The sequence and focus of the review process varies between countries. Some countries allow for parallel submission to both the Central Ethics Committee (CEC) and the CA, while others insist on doing it in series. Countries also differ in where the CEC and CA place their specificity of the review process. For example, in the Netherlands, the CA primarily validates the study documentation, placing more emphasis on the EC’s assessment for final approval. In other countries, the CA may focus more on the technical side of the submission package, while the CEC mainly focuses on the patient-facing side of the trial.
- 3. Different response processes: Once the initial submission is in, response processes from and to the CA and CEC vary greatly between countries. Certain countries have adopted a single national portal for a consolidated submission, review, and approval process. The countries that allow for parallel submission of the trial often have their CA and CEC provide feedback separately and sometimes weeks apart, leading to the inefficient process of having to wait to finalize the documentation. The CA can pose a response timeline independent of the CEC, and the manufacturer is forced to respond while the CEC review is still pending. As both institutions require the full documentation, the CEC will then need to be provided with updated documentation during their review, if possible, and if their submission process allows for this, as submission portals may be closed during the review process. This sets the stage for a complicated back and forth between the submitter and the CEC and CA. Another way is having to submit to the CA & CEC in series, meaning manufacturers must go through a full review and approval process back-to-back. Any modifications following feedback from the latter, must be notified to the former. Once manufacturers have navigated this country-specific approval process landscape for one country, it would be beneficial when other member states would follow this decision. This is ultimately the aim of the MDR, to create a more harmonized approach across the EU. This is still far from realized and a submission to the CA in each individual country is still required, leading to study delays or even to the creation of country-specific protocols.
- 4. Other stakeholders: In certain member states, submitting a trial to the CAs and ECs may not be sufficient on its own. Often, additional regulatory authorities need to be involved as well, further complicating the process. For instance, in France, the National Commission for Information Technology and Civil Liberties (CNIL) must approve any study involving personal data. In Germany the BfS (Bundesamt für Strahlenschutz) must review the study when more than the standard of care radiation burden is placed on the subject.
Experiences From the Field
Navigating these challenges requires a strategic approach and a deep understanding of both the MDR and local regulations. Here are some of our experiences from the field and lessons learned:
- Adaptability and preparation: Successful submissions often hinge on the ability to adapt to different requirements that are continuously updated via local national regulations and prepared thoroughly; this includes understanding the specific needs of each member state and ensuring all documentation is in order and understood by manufacturers prior to starting the submission process
- Communication and collaboration: Building strong relationships with local regulatory bodies and institutions can facilitate smoother submissions. Open communication channels help in addressing any issues promptly and effectively. Avania’s in-depth knowledge and proactive approach ensures that we can effectively navigate the complexities of regulatory requirements, facilitating smoother and faster approval processes
Conclusion
The implementation of the MDR for clinical trial submissions in the EU presents a unique set of challenges. The diversity in local requirements and processes, coupled with the overarching MDR framework, necessitates a well-prepared and adaptable approach. By understanding these challenges and learning from experiences in the field, Avania can help manufacturers navigate the complexities of the submission process more effectively, ultimately contributing to faster eventual market access or post-market safety compliance.