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

ABSTRACT ZATA PharmaceuticalsIncWorcesterMAand NYBCNew YorkNYpropose to develop a closeddisposable pathogen reduction systemZ Systemfor treatment of packed Red Blood CellspRBCfor transfusionThe versatility of the proposed technology allows for several versions of the Z Systems to be createdadapted to different regulatory environmentsand for treatment of whole blood and any of its componentsHoweverin 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 USAWe have already reached several critical milestones in the development of the Z SystemsSpecificallywe havedeveloped a detailed scientific and production concept about ZATA s Anti Pathogen compoundsZAP Csand synthesizedrepresentativesZDZDand ZDdemonstrated high log reduction of various pathogensincluding Gand Gbacteriaenveloped and non enveloped virusesand protozoa in whole blood and in its components by using ZAP Cs atMSelected and used a non toxicbiocompatible quencher that neutralizes the residual ZAP Cs without changing the in vitro properties of treated RBCdeveloped extraction cartridges which enable the complete removal of ZAP C neutralization products from the treated RBC to further improve safetyandfiled patent applicationsIn this combined phase I II proposalwe 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 trialsYearExpand ZAP C familyoptimize and scale up ZAP C chemistryselect optimal ZAP C and treatment conditions enablinglog reduction of pathogens in RBCfurther develop and optimize methods of analysis and quantification of ZAP Cs and their quenching productsoptimize ZAP C deactivation and removal from treated RBCYearPrepare and qualify analytical standards of ZAP Cs and their quenching productsinitiate stability studies of ZAP Cperform full spectrum of in vitro tests to demonstrate preserved quality of treated RBCperform in vitro and in vivo ZAP C quenching products safety studiesarrange initial discussion with FDAYearProduce Z System prototypes and select the optimal systemprepare sufficient number of final Z System prototype and validate its performanceinitiate storage shelf life study of Z Systemsubmit regulatory documents and arrange GMP manufacturing for final Z system for Phase I clinical testingThe extensive Randamp D experience and capacity of NYBC in transfusion medicine and blood product manufacturingNYBC in the past developed and commercialized S D treated plasmacombined with ZATA s strong expertise in medicinal and analytical chemistry makes the development and commercialization of the proposed Z System highly feasibleAfter clinical studies leading to FDA approvalinitial market for the Z System will be blood centers in the USincluding but not limited to the NYBC family of blood centers NARRATIVE We propose the development of a simplecloseddisposable pathogen reduction system for treatment of packed red blood cellspRBCintended for transfusionThe pathogen inactivator that will be used in this system has demonstrated high log reduction of bacteriaviruses and parasites in pRBC without compromising RBCpropertiesand will be neutralized and removed after treatmentThis product will decrease the infections risks of red blood cell transfusions from known and unknown pathogens and will mitigate the need for rapid new test development for each emerging blood borne pathogen