THE ACCOUNT GENERATED FALSE REACTIVE PRISM HTLV-I/II RESULTS ON SEVERAL DONOR SPECIMENS THAT TESTED IMMUNOBLOT NEGATIVE. THE ACCOUNT STATED ON (B)(6) 2009, REAGENT LOT 74606M100 WAS PUT INTO USE. SINCE THEN, 123 DONOR SPECIMENS TESTED PRISM HTLV-I/II REPEATEDLY REACTIVE, BUT IMMUNOBLOT NEGATIVE. ON (B)(6) 2009, REAGENT LOT 77620M100 WAS PUT INTO USE. SINCE THEN, 104 DONOR SPECIMENS TESTED PRISM HTLV-I/II REPEATEDLY REACTIVE, BUT IMMUNOBLOT NEGATIVE. NO SPECIFIC DONOR INFORMATION OR TESTING DATA WAS PROVIDED. NO IMPACT TO PATIENT MANAGEMENT WAS REPORTED.
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Patient 1
(B)(4) - EVALUATION - INVESTIGATION IN PROCESS, NO METHOD, RESULTS OR CONCLUSION CODE CAN BE CHOSEN AT THIS TIME.THIS IS AN INITIAL REPORT. AN INVESTIGATION IS IN PROCESS. A FINAL REPORT WILL BE SUBMITTED WHEN THE INVESTIGATION IS COMPLETE.
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Patient 1
(B)(4). EVALUATION- FIELD DATA RELATED TO THE QUALITY ISSUE WITHIN THE COMPLAINT (ELEVATED REACTIVE RATES) FROM MULTIPLE CUSTOMERS AND REAGENT KITS FROM LOT 77620M100 AND 74605M100 WERE REVIEWED IN THIS INVESTIGATION. THE RESULTS OF OUR INVESTIGATION FOR LOT 74605M100 IS INCLUDED BELOW: THE INVESTIGATION FOR PRISM HTLV-I/HTLV-II REAGENT LOT 74605M100 INCLUDED A REVIEW OF FIELD DATA REPORTED TO OUR PRISM METRICS DATABASE. BOTH THE INITIAL AND THE REPEAT REACTIVE RATES OBSERVED FOR THIS LOT WERE LESS THAN THE PACKAGE INSERT UPPER 95% CONFIDENCE LIMITS FOR A COMBINED PLASMA AND SERUM POPULATION. AS SERUM IS THE SAMPLE TYPE PRIMARILY USED AT THE CUSTOMER FACILITY FOR TESTING WITH PRISM HTLV-I/HTLV-II, A REVIEW OF FIELD DATA FROM CUSTOMER SITES ALSO KNOWN TO BE USING PRIMARILY SERUM SAMPLES WAS PERFORMED. FOR LOT 74605M100, THE INITIAL REACTIVE RATE IS LESS THAN, AND THE REPEAT REACTIVE RATE EQUAL TO, THE PACKAGE INSERT UPPER 95% CONFIDENCE LIMITS FOR A SERUM POPULATION. FROM THIS INVESTIGATION, IT IS CONCLUDED THAT PRISM HTLV-I/HTLV-II REAGENT LOT 74605M100 IS MEETING PRODUCT LABEL CLAIMS. INITIAL RESULTS OF THE INVESTIGATION FOR LOT 77620M100 ARE BELOW: A REVIEW OF FIELD DATA WAS PERFORMED. REACTIVE RATES FOR LOT 77620M100 WERE COMPARED TO THE UPPER 95% CONFIDENCE LIMITS IN THE PRISM HTLV-I/HTLV-II PACKAGE INSERT (COMMODITY (B)(4)) FOR THE COMBINED SERUM/PLASMA POPULATION, AS WELL AS FOR THE SERUM POPULATION. A PRODUCT DEFICIENCY HAS BEEN IDENTIFIED IN THAT PRISM HTLV-I/HTLV-II REAGENT KIT LIST 06E50-68 LOT 77620M100 IS EXHIBITING INITIAL (SERUM) AND REPEAT REACTIVE (SERUM/PLASMA) RATES GREATER THAN THE PACKAGE INSERT UPPER 95% CONFIDENCE LIMITS. AN INVESTIGATION HAS BEEN INITIATED TO DETERMINE CAUSE.
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Patient 1
(B)(4): REACTIVITY ORIGINATING FROM THE HTLV-I VIRAL LYSATE. THIRTY OF 79 PRISM HTLV-I / HTLV-II REAGENT LOTS, LIST NUMBER 06E50-68, HAVE EXHIBITED INITIAL REACTIVE RATES (IRR) AND/OR REPEAT REACTIVE RATES (RRR) THAT EXCEED THE PACKAGE INSERT 95% CONFIDENCE INTERVAL UPPER LIMIT. MULTIPLE CUSTOMER COMPLAINTS RELATED TO REACTIVE RATES FROM SEVERAL SITES REPRESENTING VARIOUS GEOGRAPHIC AREAS FOR THESE LOTS HAVE BEEN RECEIVED SINCE (B)(6) 2008. FOUR RISK EVALUATIONS WERE PERFORMED DURING THE COURSE OF THE INVESTIGATION. THERE WAS NO IMPACT TO PRODUCT FUNCTIONALITY OR PRODUCT PERFORMANCE. THE PACKAGE INSERT ONLY CONTAINS THE COMBINED REACTIVE RATE PERFORMANCE DATA FOR THE DESIGN VALIDATION LOTS, AND DID NOT REFLECT THE PERFORMANCE OF THE 3 INDIVIDUAL DESIGN VALIDATION LOTS. ALTHOUGH THERE WAS A CORRELATION FOR REPEAT REACTIVE RATE WITH S/CO OF THE DONOR POPULATION AND POSITIVE CALIBRATOR COUNTS; ADJUSTING THE ASSAY CUTOFF VALUE BY SELECTION OF THE POSITIVE CALIBRATOR DILUTION FACTOR (DF) DID NOT SIGNIFICANTLY INFLUENCE THE REACTIVE RATE. THE HTLV-I COMPONENTS OF THE ASSAY, WHICH INCLUDES THE HTLV-I MICROPARTICLE CONCENTRATE, HTLV-I PROBE CONCENTRATE, AND GLYCOPROBE CONCENTRATE, WERE ASSOCIATED WITH THE NONSPECIFIC REACTIVITY FOR NON-CONFIRMING REACTIVE SAMPLES OBTAINED FROM CUSTOMERS. HOWEVER, NO CORRELATION BETWEEN REACTIVE RATES AND FINAL CONCENTRATION OF THESE COMPONENTS IN THE REAGENT KIT WAS IDENTIFIED. THE COMMON REAGENT OF THE HTLV-I COMPONENTS IS THE HTLV-I LYSATE. A CHANGE POINT RELATED TO A BEST PRACTICES IMPROVEMENT TO THE HTLV-I LYSATE MANUFACTURING CORRELATED WITH REACTIVE RATE. HOWEVER, NON-CONFIRMING REACTIVE SAMPLES EXHIBITED AN INTERACTION WITH HTLV-I ASSAY COMPONENTS REGARDLESS OF REAGENT LOT. SOME NON-CONFIRMING REACTIVE SAMPLE REACTIVITY WAS REDUCED BY PRETREATMENT WITH HETEROPHILE BLOCKING REAGENTS AND CYSTEINE REDUCTANT, SUGGESTING THAT THE REACTIVITY WAS A RESULT OF A SAMPLE-SPECIFIC ANTIBODY INTERACTION WITH COMPONENTS OF THE ASSAY REAGENTS. THE PROBABLE CAUSE OF SOME REAGENT LOTS EXHIBITING IRR AND/OR RRR THAT EXCEED THE PACKAGE INSERT 95% CONFIDENCE INTERVAL UPPER LIMIT IS THAT THESE CLINICAL RESULTS WERE OBTAINED FROM THE 3 CLINICAL LOTS COMBINED AND DOES NOT ACCURATELY REPRESENT THE INDIVIDUAL CLINICAL LOT IRR AND RRR PERFORMANCE. A CONTRIBUTING FACTOR FOR THE HIGHER THAN EXPECTED REPEAT REACTIVE RATES OBSERVED AT MULTIPLE CUSTOMER SITES FOR THE PRISM HTLV-I/HTLV-II ASSAY IS A SAMPLE-SPECIFIC ANTIBODY INTERACTION WITH THE MICROPARTICLE AND PROBE COMPONENTS OF THE ASSAY REAGENTS. THE TARGET OF THIS REACTIVITY ORIGINATES FROM THE HTLV-I VIRAL LYSATE.