BioFabUSA is advancing the manufacturing infrastructure for tissue-engineered medical products (TEMPs) in an effort to bring beneficial, advanced therapies to patients. In the FDA guidance document, “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions” regenerative medicine therapies are defined as “including [autologous and allogeneic] cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products”. In order to set novel therapies down the correct regulatory path as early in their development process as possible, regenerative medicine products, like TEMPs, should be submitted to the correct FDA Center for review. Many regenerative medicine products are combination products, and this fact can make Center jurisdiction assignment difficult because of the inherent complexity of combination products.
Combination products are therapies comprised of two or more regulated components (i.e., drug, device, or biologic), physically, chemically or otherwise combined and produced as a single entity. A combination product may also consist of two or more separate components packaged together, or multiple components packaged separately but intended for use with a specified product, where both components are required to achieve the intended therapeutic effect. The primary mode of action (PMOA) is the principal determinant of a combination product’s jurisdiction (i.e., which Center has review responsibility for the product), and in most cases, the product’s regulatory pathway. There are some secondary criteria for combination product jurisdiction assignment that are beyond the scope of this discussion.
The PMOA of a combination product is the action that is mainly responsible for how the product achieves its intended therapeutic effect (i.e., drug, device, or biologic). Thus, an understanding of the PMOA is directly linked to an understanding of the statutory definitions of a drug, device, and biologic. The statute defines a drug as a substance which affects the structure or function of the body for the diagnosis, cure, treatment, or prevention of a disease. By law, a device is a medical product which affects the structure or function of the body for the diagnosis, cure, treatment, or prevention of a condition, but does not do so principally by a chemical mode of action. Interestingly, the statutory definition of a biologic is less about how it achieves its intended therapeutic effect, but more about what it is.
Once a combination product’s jurisdiction has been determined, it is assigned to the Agency Center responsible for the product’s review. Typically, a biologic is assigned for review to the Center for Biologics Evaluation and Research (CBER), or the Center for Drug Evaluation and Research (CDER); a drug is assigned for review to CDER; and a device is assigned for review to the Center for Devices and Radiological Health (CDRH). Due to the nature of TEMPs, the Office of Tissues and Advanced Therapies (OTAT) in CBER is responsible for regulating most of these products.
As expected, the jurisdiction and regulatory pathway of your product can greatly influence the testing requirements needed to enter a clinical trial or obtain marketing authorization. Therefore, it is always best to conduct a jurisdictional and regulatory pathway analysis of your product as the foundation of your regulatory strategy. Specific BioFabUSA member questions regarding jurisdiction and regulatory pathway may be addressed in BioFabConsulting meetings with Drs. Richard McFarland and Becky Robinson-Zeigler.