Regulatory guidelines in biomedical research

This video provides an in-depth exploration of the regulatory and operational complexities involved in developing and preparing a novel medical device for clinical trials, using the "Posture Project" for scoliosis treatment as a detailed case study. The speaker, Karlien Boon-Ceelen, shares her experience transitioning into a regulatory and product safety role while managing the development of a sophisticated spinal correction system. The primary goal of the project is to design an optimal treatment method that provides effective spinal correction while allowing for natural growth in young children, thus minimizing the need for multiple, psychologically and physically taxing surgeries common with traditional metal rod and screw systems.

The core innovation of the Posture Project is the use of a Dyneema material cable system, developed by DSM Biomedical, designed to slide along existing rods. This mechanism allows the spine to grow while maintaining correction, offering a significant improvement over fixed metal constructs or those requiring repeated operations. The project also addresses degenerative scoliosis in the elderly, where the cable system helps prevent screw breakout in osteoporotic vertebrae. The progression of the project highlighted the critical need for defining regulatory roles, as it was the first time for DSM Biomedical to act as the legal manufacturer of a medical device in the Netherlands, and the first time for MUMC+ to serve as the sponsor of a medical device clinical trial.

A major challenge detailed in the transcript was managing the system integration and regulatory documentation across multiple legal entities. The final treatment system comprised three components: the main cable (manufactured by DSM Biomedical BV), a leader accessory (manufactured by DSM Biomedical Inc.), and a tensioner accessory (manufactured in-house by MUMC+). All three devices, developed by different legal entities, had to be documented and approved as a single, cohesive system working in conjunction with existing rods and screws before entering the clinical trial phase. This complexity necessitated intense, cross-functional collaboration facilitated by InSciTe, involving clinicians, engineers, regulatory specialists, quality personnel, and the clinical trial center.

Beyond the immediate clinical trial preparation, the project also included parallel workstreams focused on future concept improvements, such as working with Syllog on a crosslink device and collaborating with Indova University of Technology to develop a software system. This software is intended to assist surgeons in determining the most optimal construct—specifically, where to place the cables and screws—underscoring the integration of advanced technology (like software as a medical device) within the regulatory framework of complex implant systems. The speaker’s personal journey, culminating in a part-time assignment as a regulatory and product safety specialist, emphasizes the paramount importance of regulatory expertise in translating scientific innovation into safe, compliant, and patient-focused medical solutions.

Key Takeaways: • Regulatory Roles Define Deliverables: The project underscored the critical distinction and responsibilities associated with the "legal manufacturer" role (DSM Biomedical) and the "sponsor of a clinical trial" role (MUMC+). Defining these roles early is essential for determining the specific documentation and deliverables required for regulatory approval to conduct the clinical trial. • Compliance is a Collaborative System: Successful medical device development, especially for regulated products, requires intricate cooperation across diverse functions, including clinicians, engineers, quality assurance, and regulatory specialists. Organizations must invest in platforms or facilitators (like InSciTe in this case) to manage these complex interactions. • Multi-Entity Manufacturing Requires Unified Documentation: When a medical device system is composed of components manufactured by different legal entities (e.g., DSM BV, DSM Inc., and MUMC+), all components must be documented and regulated as a single, integrated system to ensure safety and efficacy during the clinical trial phase. • Innovation Must Address Regulatory Constraints: The Dyneema cable system was designed not only for clinical efficacy (allowing growth, preventing screw breakout) but also to simplify the patient journey by aiming for a single operation instead of multiple procedures, demonstrating how regulatory-compliant innovation can directly improve patient quality of life. • The Importance of Regulatory Specialization: The speaker’s shift from a senior scientist to a regulatory and product safety specialist highlights the growing need for technical experts who also possess deep knowledge of compliance frameworks to bridge the gap between R&D and market readiness. • Software as a Medical Device (SaMD) Integration: The parallel development of a software system (with Indova University) to assist surgeons in optimizing the placement of cables and screws demonstrates the trend of integrating sophisticated AI/software tools directly into surgical planning and execution, which introduces additional regulatory and validation requirements. • Clinical Trial Readiness Requires Complete Traceability: A core lesson learned was precisely "what did we actually have to document and deliver in the end" to satisfy the clinical trial requirements, emphasizing the need for robust data engineering and audit trails from the earliest stages of design and development. • Addressing Unmet Needs in Vulnerable Populations: The project specifically targeted young children (allowing growth) and the elderly (preventing screw breakout in osteoporotic bone), illustrating the need for device innovation that caters to specific physiological and pathological challenges within the life sciences sector. • Proactive Concept Improvement: Conducting parallel workstreams focused on future improvements (e.g., crosslink device with Syllog) while preparing for the initial clinical trial is a best practice for maintaining a competitive edge and ensuring continuous product lifecycle management under regulatory oversight.