A CLOSED SYSTEM FOR PATHOGEN REDUCTION OF RED BLOOD CELLS FOR TRANSFUSION

摘要

ABSTRACT ZATA Pharmaceuticals, Inc. (Worcester, MA) and NYBC (New York, NY) propose to develop a closed, dispos- able pathogen reduction system (Z-System) for treatment of packed Red Blood Cells (pRBC) for transfusion. The versatility of the proposed technology allows for several versions of the Z-Systems to be created, adapted to different regulatory environments, and for treatment of whole blood and any of its components. However, in this application we focus on the development of a system for treatment of pRBC that will be integrated into the blood collection system currently used in the USA. We have already reached several critical milestones in the development of the Z-Systems. Specifically, we have: (1) developed a detailed scientific and production concept about ZATA’s Anti-Pathogen compounds (ZAP-Cs) and synthesized 3 representatives: ZD010, ZD012, and ZD014; (2) demonstrated high log reduction of various pathogens, including G+ and G- bacteria, enveloped and non-enveloped viruses, and protozoa in whole blood and in its components by using ZAP-Cs at 100-250 µM; (3) Selected and used a non-toxic, bio- compatible quencher that neutralizes the residual ZAP-Cs without changing the in vitro properties of treated RBC; (4) developed extraction cartridges which enable the complete removal of ZAP-C neutralization products from the treated RBC to further improve safety; and (5) filed patent applications. In this combined phase I/II proposal, we will pursue the following milestones with the goal for developing of a pathogen inactivation system for pRBC ready for evaluation by the FDA for use in Phase I clinical trials: Year 1: Expand ZAP-C family; optimize and scale-up ZAP-C chemistry; select optimal ZAP-C and treatment conditions enabling 6 log reduction of pathogens in RBC; further develop and optimize methods of analysis and quantification of ZAP-Cs and their quenching products; optimize ZAP-C deactivation and removal from treated RBC. Year 2: Prepare and qualify analytical standards of ZAP-Cs and their quenching products; initiate stability studies of ZAP-C; perform full spectrum of in vitro tests to demonstrate preserved quality of treated RBC; perform in vitro and in vivo ZAP-C quenching products safety studies; arrange initial discussion with FDA. Year 3: Produce Z-System prototypes and select the optimal system; prepare sufficient number of final Z-System prototype and validate its performance; initiate storage shelf-life study of Z-System; submit regulatory documents and arrange GMP manufacturing for final Z-system for Phase I clinical testing. The extensive R&D experience and capacity of NYBC in transfusion medicine and blood product manu- facturing (NYBC in the past developed and commercialized S/D-treated plasma), combined with ZATA’s strong expertise in medicinal and analytical chemistry makes the development and commercialization of the proposed Z-System highly feasible. After clinical studies leading to FDA approval, initial market for the Z-System will be blood centers in the US, including but not limited to the NYBC family of blood centers.