Development of Chemistry, Manufacturing, and Control Standards for PGC and PGC-dANP

ABSTRACTThis application is seeking funding specifically for ChemistryManufacturingand ControlCMCof scale up production of long acting atrial natriuretic peptidedANPand its protected graft co polymerPGCexcipient for use in heart failureHFtreatmentThe extrinsic merit of this project will be the availability of cGMP grade PGC for use in prolonging the half life of various peptide drugs that are in preclinical development by other companiesOur product goal at the end of this project is cGMP grade PGC dANPAdditional funding for Toxicology and PhaseClinical Trials from a private investor will be made available at delivery of cGMP grade PGC dANPANP has a long history of efficacy in HF patients and those treated byday continuous infusion have shown smaller infarct size and lower incidence of readmission to hospital than controlsHoweversustained ANP infusion fordays in hospital setting has a very high health care cost and longer treatment is impracticalPGC dANP is a product that can be administered subcutaneously at home and can be continued for several months to further reduce future cardiac eventsimprove long term outcomesand reduce overall health care costsAt this stage we can consistently produceg batch of PGC in our laboratory and we want to scale it up tog in a cGMP facilityWe already developed the analytical requirements needed for lot release and stability testing but we need to define the widest range that will provide no significant difference in PK PD profileThis is important to reduce risk of unnecessary cost of lot rejection especially for big batches worth several $KThe Aims areto establish the widest acceptable range of values that measure QualityIntegrityPurityPotency and SterilityQIPPSas lot release indicators required by the FDA and transfer the analytical methods to the appropriate GLP facilitiesto scale up PGCs synthesis from ourg process tog and produceg cGMP grade PGCand to formulate PGC dANP in a cGMP mannerwith stability testing using QIPPS analysis in a GLP facilityPharmaIN CorpConfidential