The purpose of this effort is to optimize the methods of application used in preclinical studies and Clinical Trials Phase I, as to conform to the needs for use in the battlefield, and to advance in the regulatory process toward a Biologic License Application by conducting Phase IIA and Phase IIB Clinical Trials of the CLOT FOAM agent. Contracting Office Address: US Army Medical Research Acquisition Activity, ATTN: MCMR-AAA, 820 Chandler Street, Frederick, MD 21702-5014 Point of Contact(s): Scott Comeau 301-619-8826
[email protected] A. The Contractor shall produce a disposable, biocompatible, low weight thermally isolated application device for use in the field by paramedics. Such a device shall be based on the principles, expertise and requirements established in the development of the investigational device used in Phase I, including: 1. Use and misuse of the device failure analysis. The objective of this risk management activity shall be to conduct a study with particular focus on the identification of potential misuse, failures or misapplications that could potentially lead to gas embolism(s) or other harms associated with the device. The analysis shall be used to characterize the safety of the existing controls, identify existing controls, and replacement components to ensure consistent performance at recommended pressure and distance settings. Two separate Failure Mode Effects Analysis (FMEAs) (Use/Misuse and Design); will be conducted in order to identify potential failures and controls for proper device function and use. It should be noted that these FMEAs shall also consider the Food and Drug Administration (FDA's) concerns regarding FDA's Medical device safety alert for embolisms. 2. Surface pressure and flow rate characterization. The purpose of the study shall be to conduct an engineering characterization on the prototype of the improved applicator device. A Class B, bench top study shall be conducted to characterize gas flow rate through the applicator tip and surface pressure on the delivery site will be studied over a range of pressure settings and distances, including alternate components, to support the safety of the device design. This includes analysis of flow rate, and surface pressure, including a fixed resistance precision orifice acting as an adjustable flow regulator, lure connectors, flexible tubing, check valve, and sterile filters. 3. Biocompatibility testing. As required for Biologics License Application (BLA) approval, a biocompatibility study of each device component must be conducted according to International Organization for Standardization (ISO) 10993-1. 4. Leachable and extractable assays. Analyze chemical compounds that migrate from any product-contact material when exposed to a solvent, typically using a variety of solvents at high temperatures. The goal of an extractable study shall be to identify as many compounds as possible that have the potential to become leachable. The process shall include identifying which components will have direct contact with biomaterial, determining if the supplier provided compendia testing, what sterilization processes will be used, and finally extracting the materials in multiple solvents. The leachables study shall be carried out in conjunction with shelf life studies at each pull point. The number of samples shall be based on the acceptable quality limit (AQL) in accordance with ISO 2859-1 or ISO 1886. B. Conduct a Phase IIA Clinical Trial as an adjunct to hemostasis in a liver surgery protocol. 1. The Phase IIA Trial shall demonstrate the safety and efficacy of the technology. Safety shall be determined by the incidence, severity and relationship of adverse events (AEs), clinical laboratory abnormalities, estimated rates of immunogenicity/viral exposure and post-surgery bleeding complications. Efficacy shall be determined by the percentage of subjects who achieve hemostatic success within the 1-minute time to hemostasis (TTH) assessment period, percentage of subjects who achieve hemostatic success within the 5-minute TTH assessment period, and the percentage of subjects who maintain hemostasis with no re-bleeding events within the 10-minute TTH period. C. Conduct a phase IIB Clinical Trial as primary treatment in a spleen laceration protocol in hemodynamically stable and noncoagulopathic patients. 1. The Phase IIB trial shall demonstrate the safety and efficacy of the technology. Safety shall be determined by the incidence, severity and relationship of adverse events (AEs), clinical laboratory abnormalities, estimated rates of immunogenicity/viral exposure and post-surgery bleeding complications. Efficacy shall be determined by the percentage of subjects who achieve hemostatic success within the 1-minute TTH assessment period, percentage of subjects who achieve hemostatic success within the 5-minute TTH assessment period, and the percentage of subjects who maintain hemostasis with no re-bleeding events within the 10-minute TTH period. D. The Contractor shall provide a detailed Product Development Plan and detailed tasks in the Performance Work Statement (PWS), Integrated Master Plan, Integrated Master Schedule and other related program documentation. These documents shall be of sufficient detail to describe the magnitude and type of work required to support U. S. Army Research and Materiel Command's mission objectives contained herein.