Continued Clinical Development of a Novel Pleural and Tracheal Sealant - Project Abstract A range of lung diseases and critical illnesses, including complications of mechanical ventilation, as well as trauma can result in air leak from the lung (pneumothorax). These leaks often require immediate life-saving measures to stabilize for subsequent reparative interventions. Continued care can further be complicated by chronic air leaks (bronchopleural fistula, BPF) requiring need for prolonged chest tube drainage and/or invasive surgery and can be difficult to manage. These all result in significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. However, at present there are only limited options for directly repairing pleural leaks, particularly chronic leaks, and new therapeutic interventions are critically needed. We have developed a novel sealant patch consisting of methacrylated dopamine-conjugated methacrylated seaweed-derived alginate (ALG-MA-DA). The patch has desired materials properties, including tailorable stiffness, elasticity, and adhesive strength, and is easily transported and applied to the lung surface. We have further designed, tested, and documented safety and efficacy in initial pre-clinical studies utilizing ex vivo and in vivo small and large (rat/pig) models of lung injuries. With current Catalyze support and close collaboration, we have worked on optimizing patch manufacturing, including production, sterilization, storage, and development of initial critical quality attributes, as well as application in pre-clinical (rat/pig) models of pleural and tracheal injury with concurrent Department of Defense funding. We have also initiated documentation including a quality management plan (QMP), FDA audit readiness, and a pre-IDE template. We are now ready to develop an FDA-driven IDE enabling package and planning for initial clinical investigations. This will be done with Accelerator and GMP manufacturing partner, the Mayo Clinic. The developed system will fall under the FDA category as a class III medical device given both its invasive application and its use in supporting or sustaining human life. As such, the proposed Specific Aims remain consonant with the goals of the NIH Catalyze Program HL-26-020, “Product Definition – Medical Device Prototype Optimization”. Specific Aims 1. Regulatory alignment of GMP manufacturing processes and codification of final critical quality attributes for optimal sterilization, preservation, and storage conditions of GMP-grade patches 2. Development of the FDA-driven IDE-enabling package
