Regulatory Validation of Standardized Clinical Laboratory Immunohistochemistry Controls

The broadlongterm goal of this project is consistentstandardized diagnostic testing of surgicalspecimens by immunohistochemistryIHCThe methods to achieve this goal are well understood in thefield of clinical laboratory testingstandardization of reagents and protocolsautomation toreduce human errorsandthe use of standardized controls to provide test performance feedbackOver the last two decadesthe first two of these three methods were implemented for IHC testingThisgrant project focuses on the thirdstandardized IHC controlsCurrent practice teaches nonstandardized controlsEach histopathology lab typically procures test controls from leftover tissuesamples in its own paraffin block archivesThis is a strikingly different practice from clinical bloodlaboratorieswhere standardized and validated controls are produced in large quantities and soldthrough commercial vendorsWe have developed an innovative technical solutionsummarized in a series of published journalarticlesOver the lastyears and with NCI fundingour breast cancer IHControlsTM panel for HERERand PR tests recently entered clinical testing and will be submitted for regulatory clearance this yearThis DirecttoPhase II proposal addresses clinical IHC laboratory practice beyond breast cancertestingWe will expand the IHControlsTM product portfoliofromanalytesHERERand PRtoThenew IHControlsTM panels comprise the General PathologyMelanomaLung Cancerand Hematopathologytest portfoliosThis tenfold expansion is feasible with funding from a single Phase II grant becauseawe have already worked out the nuances of product designmanufacture under cGMPand testingandbthe additional analytes will mostly be class I productsThe Specific Aims of this proposal arecreation of the new IHControlsTM panelsanalytical validationincluding testing for sensitivityspecificityproduct stabilityand manufacturing reproducibilityandclinical validationincludingtesting for precisionreference intervalexpected level of stainingand limit of detectionThe applicant group comprises a broadmultidisciplinary teamincluding the MDP RandD teamstatistical support from the Tufts Clinical and Translational Science InstituteCTSIsurgical pathologistsand consultants for regulatory affairsquality systemsand IHC commercial operationsConvertingclinical laboratories from homebrew to standardized controls will be a transformative change