CFI Pathogen Inactivation of Human Plasma Units

PROJECT SUMMARY
The rapid spread of the Zika viruswhich can have a significant impact on neurological disorders in unborn
fetuses and potentially adultsthe recent outbreak of the extremely virulent Ebola virusperiodic emergence of
SARSrecurrent outbreaks of potentially pandemic strains of influenza such as H Nthe continuing epidemic
of MERS and the worldwide AIDS epidemic have highlighted a persistent concern in the health care
communitythe need for effective pathogen inactivation and removal techniques for human blood plasma and
plasma derived productsThere is no commercially availableFDA approved technology for the inactivation of
non enveloped viruses in pooled human plasma and biologicsand only one approved method for units of
plasmawhich can inactivate somebut not all known non enveloped virusesThis dearth of FDA approved
pathogen inactivation technologies could pose a significant future threat for known and new viruses in human
plasma and biologicsWe propose to develop a physical pathogen inactivation technologyCFIfor the
inactivation of both non enveloped and enveloped viruses as well as pathogenic bacteria and parasites in
human plasmaplasma protein products and biologicsCFItechnology is applicable to both pooled human
plasma and units of plasmathe more globally significant focus of the current applicationCFIcritical fluid inactivationutilizes supercritical and near critical fluidsSuperFluidsor SFSSuperFluidsare normally gases whichwhen compressedexhibit enhanced thermodynamic properties of
solvationpenetrationselection and expansionThese gases are used to permeate and saturate virus and
pathogen particlesThe SFS saturated particles then undergo decompression andas a result of rapid phase
conversionvirus inflation and rupture at their weakest pointsWe have demonstrated that the CFIcritical
fluid inactivationprocess inactivates both enveloped viruses such as MuLVVSVSindbisHIVall completely
inactivatedTGEand BDVDand the non enveloped viruses PolioAdenoEMCcomplete inactivationReoand Parvo viruseswhile preserving biological activity of the CFI treated productIn research collaboration
with the National Institute of Biological Standards and ControlNIBSCLondonEnglandour CFI inactivated
more thanlogs of human Parvovirus Bone of the smallest and toughest virusesin human plasma in a
two stage CFIunit in less thansecondsWe have also demonstrated that SFS can disrupt and inactivate
microorganisms such as Ecolithick walled prokaryotes such as Bacillus subtilis and tough eukaryotes such
as Saccharomyces cerevisiae at viral inactivation SFS conditionsCFI can be used with viral reduction
methods such as nanofiltration as an orthogonal method of pathogen clearanceand is versatile for refinement
to treat cellular bloodThe present data have been generated using prototypes of our pilot scale CFI unitOur Phase I Specific Aims are toDesign and construct a portable and comparably versatile bench top CFI
unit for parallel treatment of single units of human plasmaandCFI treat human plasma in the designed
bench top device using a customized blood bagand rigorously characterize the CFI treated units of human
plasma for protein and enzyme activitiesOur Phase II Specific Aims are toComplete characterization of
CFI treated units of human plasma using customized blood bag in the bench top CFI prototypeConduct
toxicological and neoantigenic studies of CFI treated human plasma in small animal modelsand select best
CFI design in terms of performanceoperations and costandDraft INDestablish and conduct pre IND
meeting with FDAprepare and file a Drug Master FileDMFfor the manufacturing of CFI treated human
plasma unitsIn Phase IIIwe will construct bench top CFI units for blood banksand through licensing
agreementsprovide equipment and technology transfer as well as prevention and maintenance support to
blood banks PROJECT NARRATIVE
There are a number of emerging viruses such as ZikaWest NileEbolaSARSpotential pandemic strains of
influenzaH Nthe Mexican swine flubacteriaparasites and a number of potential bioterrorism pathogens
such as smallpox that are of concern to the safety of the human plasma supplyCurrent approaches for
pathogen inactivation in biologics are not always effective against a wide spectrum of human and animal
virusesare sometimes encumbered by process specific deficienciesand often result in denaturation of the
biologicals that they are designed to protectCFI pathogen inactivation technology gives pathogens thebendsinactivating them without damaging proteins and enzymes in medically important transfusion fluids
such as human plasmaThis purely physical technique does not involve the use of heatchemicals and or
irradiationeach of which has significant drawbacks in the viral inactivation of human plasmaAs suchwhile
CFI is capable of inactivating wide classes of virusesbacteria and parasitesit has negligible negative impact
on biological integrity and potency of the treated fluidsWe have developedtested and validated this process
using continuous flow laminar flow devicesand now plan to scale this technology down for units of human
plasma using a novelportable bench top CFI device using blood bagsThe potential impact of a generallyapplicable physical technology for inactivating viruses and emerging pathogens with high retention of biological
activity will be very significantCFI technology will also be impactful in developing countries and hot zones for
the clearance of viruses from human plasma