BD CD15 FITC
Report
- Report Number
- 2916837-2022-00243
- Event Type
- Malfunction
- Date Received
- September 9, 2022
- Date of Event
- August 12, 2022
- Report Date
- February 14, 2023
- Manufacturer
- BECTON, DICKINSON AND COMPANY, BD BIOSCIENCES
- Product Code
- MVU
- PMA / PMN Number
- NA
- Product Problem
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- SW
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
- Health Professional
- Yes
Narratives
ADDITIONAL INFORMATION: B.5. EVENT DESCRIPTION EDITED TO INCLUDE THE PATIENT IDENTIFIER RECEIVED. (B)(6).
H.6 INVESTIGATION SUMAMRY: ¿ SCOPE OF ISSUE AND PROBLEM STATEMENT: CUSTOMER ((B)(6) SWEDEN) REPORTED ON 12-AUG-22 THAT PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVING WEIRD SIGNAL IN V500 CHANNEL ON FACS CANTO II INSTRUMENT WHILE USING CD15 FITC. CUSTOMERS INDICATE TWO CANTO II INSTRUMENTS WERE USED, THEY HAVE TRIED WITH BOTH INSTRUMENTS, AND IT LOOKS WEIRD IN THE V500 CHANNEL. THERE¿S A NOTE ON INTAKE INTERNAL BD COMMENTS THIS COULD BE A REAGENT ISSUE OR A COMPENSATION ISSUE. THE TROUBLESHOOTING IS STILL ONGOING. NO ADDITIONAL DETAILS WERE PROVIDED RELATED TO TROUBLESHOOTING OUTCOMES OR SUPPORT PROVIDED. ¿ MANUFACTURING DEFECT TREND: ZERO (0) QUALITY NOTIFICATIONS (QN) OR NONCONFORMANCE REPORTS WERE FOUND AGAINST PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 OR SUBASSEMBLY 91-0297 BATCH 2033177, FROM EVALUATED TIMEFRAME OF 12-AUG-21 TO 12-AUG-22. ¿ BATCH HISTORY RECORD (BHR) REVIEW: PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 WAS ASSEMBLED IN BDB SAN JOSE (PLANT 1149) USING SUBASSEMBLY 91-0297 BATCH 2033177, MANUFACTURED IN BDB CAYEY PR (PLANT 1157), WHICH WAS USED TO MANUFACTURE THE FOLLOWING PRODUCTS: 1. 332778 LOT 2076505 ((B)(4) EA): ALL (B)(4) EA SOLD TO MARKET. 2. 347423 LOT 2139478 ((B)(4) EA): (B)(4) EA SOLD TO MARKET. 3. 340703 LOT 2139480 ((B)(4) EA): ALL (B)(4) EA SOLD TO MARKET . QC BHR 91-0297 BATCH 2033177 WAS REVIEWED. MATERIAL MET QC SPECIFICATIONS: FLOW CYTOMETRY STAINING OF K562 CELL LINE, TEST VS REF LOG MEAN FLUORESCENCE (LMF) LOT-TO-LOT VARIABILITY = -8 LMF CHANNELS (SPEC +/- 60 CHANNELS), AND % POSITIVE POPULATION = 95% (SPEC = 90%), PRIOR TO RELEASE. RELEASE TESTING OF SUBASSEMBLY 91-0297 (CD15 FITC) BATCH 2033177 PERFORMED ON 21-FEB-22. MATERIAL EXPIRES 31-AUG-23. 20 SUBASSEMBLY 91-0297 BATCH 2033177 WAS LATER SATISFACTORILY USED ON 20-JUN-22 AS A REFERENCE LOT DURING QC TESTING OF NEWER SUBASSEMBLY 91-0297 BATCH 2138725, MEETING % POSITIVE POPULATION (TEST BATCH 2138725 = 100% AND REF BATCH 2033177 = 100%) SPECIFICATIONS WITHOUT DISCREPANCY. ¿ COMPLAINT HISTORY REVIEW: ONE COMPLAINT REPORTED (PR# (B)(4) FROM (B)(6) SWEDEN; AGAINST PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVING WEIRD SIGNAL IN V500 CHANNEL ON FACS CANTO II INSTRUMENT WHILE USING CD15 FITC, FROM DATE RANGE OF 12-AUG-21 TO 12-AUG-22. CUSTOMER FROM (B)(6) HOSPITAL INITIALLY PROVIDED PATIENT TEST SAMPLE INFORMATION CAPTURED ON PR# (B)(4) ON 12-AUG-22, THEN SUBMITTED ADDITIONAL PATIENT TEST SAMPLE INFORMATION ON 04-NOV-22 WHICH WAS CAPTURED BY BD REPRESENTATIVE ON A NEW PR# (B)(4) , REFERRING TO SAME P NO ADDITIONAL COMPLAINTS HAVE BEEN REPORTED TO DATE FROM A TOTAL OF 527 EA UNITS SOLD TO MARKET OF ANY OF THE THREE DIFFERENT CATALOG PRODUCTS/LOTS MANUFACTURED FROM SAME SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177: (1) 332778 LOT 2076505, (2) 347423 LOT 2139478 AND (3) 340703 LOT 2139480. ¿ RETAIN SAMPLE ANALYSIS: INVESTIGATION BASED ON COMPLAINT HISTORY IN WHICH NO ADDITIONAL RELATED CLAIMS HAVE BEEN REPORTED FOR PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 TO DATE, EVALUATION OF BHR SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177 RELEASE DATA WHICH INCLUDES FLOW CYTOMETRY ANALYSIS, HISTORY OF SATISFACTORY USE OF 91-0297 BATCH 2033177 AS QC REFERENCE LOT AND WFI TASK QUESTIONS TO CUSTOMER REGARDING REPORTED PROBLEM. NO RETAIN SAMPLE TESTING DEEMED NECESSARY AT THIS TIME BASED ON SATISFACTORY PERFORMANCE EVIDENCE DURING RELEASE AND LATER USE AS QC REFERENCE LOT. ¿ RETURNED SAMPLE ANALYSIS: AS NO DATA OR DETAILS INITIALLY PROVIDED BY CUSTOMER REGARDING REPORTED PROBLEM, WFI TASK REQUESTED FOR GATHERING INFORMATION AS PART OF INVESTIGATION. REFER TO ROOT-CAUSE ANALYSIS SECTION FOR DETAILS. ¿ RISK REVIEW: RISK MANAGEMENT FILE (B)(4), REVISION 02 WAS REVIEWED. HAZARD(S) IDENTIFIED? X YES / NO; IF NO (TO ABOVE), WHAT ACTIONS WILL BE TAKEN? HAZARD ID#: 4.1. HAZARD: INFORMATION HAZARD. CAUSE: INADEQUATE INSTRUCTIONS PROVIDED BY BD. HARMFUL EFFECTS: UNABLE TO PERFORM TESTING, DELAY OF TEST RESULTS. RESIDUAL PROBABILITY: 1. RESIDUAL SEVERITY: 3. RESIDUAL RISK INDEX: 3 = ACCEPTABLE. ¿ ROOT CAUSE ANALYSIS: WFI TASK PR# (B)(4) REQUESTED INFORMATION AND CUSTOMER RESPONSE TO SUPPORT INVESTIGATION, AS DESCRIBED BELOW: 1. CUSTOMERS INDICATE PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 HAS WEIRD SIGNAL IN V500 CHANNEL. PLEASE ANSWER THE FOLLOWING: A. PROVIDE ANY SUPPORTING FLOW CYTOMETRY DATA SHOWING OBSERVED PROBLEM. B. ARE YOU USING CD15 FITC REAGENT IN COMBINATION WITH ANOTHER REAGENT FOR COUNTERSTAINING OR MULTI-TARGET STAINING OR USED ONLY FOR SINGLE COLOR STAINING? C. INDICATE IF PRIOR TROUBLESHOOTING ONGOING DURING PRIOR CALL DID RESOLVE OR IDENTIFIED THE ISSUE (I.E. COMPENSATION OR ELSE). D. PLEASE CONFIRM IF YOU HAVE RE-TESTED USING ANOTHER FRESH VIAL OF SAME LOT 2076505 OR HAVE RE-TESTED USING A DIFFERENT LOT NUMBER. IF SO, INDICATE FINDINGS AND WHICH DIFFERENT LOT USED. CUSTOMER RESPONSE: A. CUSTOMERS PROVIDED FLOW CYTOMETRY RESULTS, WHICH WAS EVALUATED AS PART OF INVESTIGATION. B. CUSTOMER IS USING PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 MIXED WITH OTHER REAGENTS (NO PRODUCT CATALOG NUMBERS/LOTS PROVIDED): CD45 V500, HLA-DR V450, CD2 APC, CD34 PERCP-CY5.5, CD117 PE-CY7, AND CD19 APC-H7. C. NO INFORMATION PROVIDED BY CUSTOMER REGARDING TROUBLESHOOTING SUPPORT RECEIVED OR RESULTS. D. CUSTOMER PERFORMED RE-TESTING USING NEW VIAL OF SAME CD15 FITC LOT 2076505, AND THEY OBSERVE SAME RESULTS. 2. DESCRIBE STEP-BY-STEP PROCESS FOLLOW FOR STAINING, FLOW CYTOMETRY ACQUISITION AND ANALYSIS. CUSTOMERS RESPONSE: CUSTOMERS INDICATE THEY USED 10 UL OF REAGENT FROM A 1:8 DILUTION MIXTURE. NO DETAILED STEP-BY-STEP PROCESS DESCRIBED OF HOW PRODUCT WAS USED FOR STAINING ALONG OTHER REAGENTS IN MIXTURE PREPARED OR HOW COMPENSATION PERFORMED. PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LABEL AND INSTRUCTION FOR USE (IFU) 23-6925-03 INDICATES TO USE APPROPRIATE VOLUME OF MONOCLONAL ANTIBODY TO 100 UL OF WHOLE BLOOD AS INDICATED IN VIAL LABEL. VIAL LABEL FOR THIS PRODUCT INDICATES TO USE 20 UL OF REAGENT FOR STAINING SAMPLES, BUT CUSTOMER USED 10 UL OF A 1:8 DILUTION INSTEAD, WHICH IS SUBOPTIMAL VOLUME FOR STAINING SAMPLES USING CD15 FITC REAGENT. CUSTOMER INDICATES PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVE WEIRD SIGNAL IN V500 CHANNEL WHILE USING CD15 FITC REAGENT ALONG A MIXTURE OF OTHER REAGENTS COMBINED BY CUSTOMER. IT IS NOTED THERE IS NO V500 PRODUCT OR RELATED CONJUGATE FORMAT MANUFACTURED AT BDB CAYEY PR (PLANT 1157) WHERE PRODUCT 332778 LOT 2076505 WAS MANUFACTURED FROM PURIFICATION TO FITC CONJUGATION AND FINAL FORMULATION STAGE TO POTENTIALLY CAUSE EXPOSURE WITH A V500 FLUOROCHROME SUBSTANCE. PER IFU 23-6925-03, PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) RECOGNIZES A MARKER PRESENT ON GREATER THAN 95% OF MATURE PERIPHERAL BLOOD GRANULOCYTES AND PRESENT AT LOW DENSITY ON CIRCULATING MONOCYTES. CD15 IS ABSENT FROM IMMATURE AND MATURE RESTING PERIPHERAL BLOOD AND LYMPHOID TISSUE B AND T CELLS, AND NK CELLS. CD15 IS EXPRESSED ON VIRTUALLY ALL PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA AND BY 80% OR MORE OF LEUKEMIC BLASTS IN A GIVEN ACUTE MYELOID LEUKEMIA (AML). CUSTOMER PROVIDED FLOW CYTOMETRY DATA SHOW THEY USED PRODUCT 332778 LOT 2076505 ALONG A MIXTURE OF OTHER REAGENTS, USING SUBOPTIMAL CONCENTRATION (10 UL OF A 1:8 DILUTION), GATED ON LYMPHOCYTES, INCLUDING A CD45 V500 WHICH DETECTS A HIGHLY EXPRESSED LEUCOCYTE MARKER (CD45) WHERE THEY REPORTED A WEIRD SIGNAL EVENT PROFILE ON THE V500 CHANNEL. IT IS NOTED THAT CAREFUL REAGENT SELECTION AND INSTRUMENT SETUP IS NECESSARY WHENEVER USING MULTICOLOR FLOW CYTOMETRY PANELS (REFER TO DOCUMENT 23-13501-00, BD BIOSCIENCES MULTICOLOR FLOW CYTOMETRY SETUP AND DESIGN GUIDANCE). PER CITED GUIDANCE, IT IS RECOMMENDED TO USE BRIGHTER FLUOROCHROMES FOR DIMLY EXPRESSED MARKERS AND DIMMER FLUOROCHROMES FOR HIGHLY EXPRESSED MARKERS. FLUORESCENCE SPILLOVER IS CONSIDERED THE MOST IMPORTANT FACTOR AFFECTING RESOLUTION SENSITIVITY IN MULTICOLOR FLOW CYTOMETRY EXPERIMENTS AND SHOULD BE ADJUSTED TO MINIMIZE AMOUNT OF SPILLOVER BACKGROUND FROM OTHER FLUOROCHROMES THRU PROPER COMPENSATION AND CONTROLS. IT CANNOT BE RULED OUT THAT SUBOPTIMAL INSTRUMENT COMPENSATION SETTINGS OR STAINED CONTROL SAMPLES COULD BE A CAUSE FOR OBSERVED ATYPICAL SIGNAL IN V500 CHANNEL, AS REPORTED. EVALUATION OF BATCH HISTORY RECORDS (BHR) OF PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 UNDER ITS SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177, SHOW IT MET ESTABLISHED BD PERFORMANCE SPECIFICATIONS WITHOUT DISCREPANCIES, AS EVIDENCED BY ROUTINE FLOW CYTOMETRY ANALYSIS DATA AND LATER USE AS QC REFERENCE LOT FOR TESTING NEWLY MANUFACTURED 91-0297 (CD15 FITC, CLONE MMA) BATCH 2138725. ADDITIONALLY, COMPLAINT HISTORY REVEALS NO ADDITIONAL RELATED COMPLAINTS AGAINST PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 OR ANY OF THE THREE PRODUCTS (332778 LOT 2076505, 347423 LOT 2139478 AND 340703 LOT 2139480) MANUFACTURED USING SAME SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177, OF WHICH 527 EA HAVE BEEN SOLD TO MARKET TO CURRENT DATE OF INVESTIGATION. ROOT-CAUSE FOR REPORTED INCIDENT WHILE USING PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 CANNOT BE DETERMINED. PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 TESTED UNDER SUBASSEMBLY 91-0297 BATCH 2033177, MET ESTABLISHED BD RELEASE ACCEPTANCE CRITERIA, USING SINGLE REAGENT STAINING AND NOT IN COMBINATION WITH OTHER REAGENTS, WHICH REQUIRES OPTIMIZATION, PROPER CONTROLS, AND COMPENSATION, AS PREVIOUSLY INDICATED. INVESTIGATION FOUND PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 PERFORMS AS INTENDED, CUSTOMER USED SUBOPTIMAL PER TEST VOLUME CONCENTRATION FOR TESTING (OFF-LABEL USE), THERE IS NO HISTORY OF ADDITIONAL COMPLAINTS, NO DISCREPANCY OR DEVICE PROBLEM DETECTED ON EVALUATED RECORDS AND TEST HISTORY INCLUDING SUCCESSFUL USE AS REFERENCE LOT UNDER SUBASSEMBLY 91-0297 BATCH 2033177, HENCE COMPLAINT IS UNCONFIRMED, AND NO FURTHER ACTIONS DEEMED NECESSARY AT THIS TIME. ¿ CONCLUSION: BASED ON THIS INVESTIGATION FOR PRODUCT 332778 (CD15 FITC, CE) LOT 2076505, THIS COMPLAINT IS UNCONFIRMED, AND NO FURTHER ACTIONS DEEMED NECESSARY AT THIS TIME.
H.6. INVESTIGATION SUMMARY: PATIENT #2 REFER TO INVESTIGATION SUMMARY DESCRIBED UNDER PR# (B)(4) FOR INVESTIGATION DETAILS AND CONCLUSIONS FOR THIS COMPLAINT. ¿ SCOPE OF ISSUE AND PROBLEM STATEMENT: CUSTOMER ((B)(6) HOSPITAL, OREBRO, SWEDEN) REPORTED ON 12-AUG-22 THAT PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVING WEIRD SIGNAL IN V500 CHANNEL ON FACS CANTO II INSTRUMENT WHILE USING CD15 FITC. CUSTOMERS INDICATE TWO CANTO II INSTRUMENTS WERE USED, THEY HAVE TRIED WITH BOTH INSTRUMENTS, AND IT LOOKS WEIRD IN THE V500 CHANNEL. THERE¿S A NOTE ON INTAKE INTERNAL BD COMMENTS THIS COULD BE A REAGENT ISSUE OR A COMPENSATION ISSUE. THE TROUBLESHOOTING IS STILL ONGOING. NO ADDITIONAL DETAILS WERE PROVIDED RELATED TO TROUBLESHOOTING OUTCOMES OR SUPPORT PROVIDED. ¿ MANUFACTURING DEFECT TREND: ZERO (0) QUALITY NOTIFICATIONS (QN) OR NONCONFORMANCE REPORTS WERE FOUND AGAINST PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 OR SUBASSEMBLY 91-0297 BATCH 2033177, FROM EVALUATED TIMEFRAME OF (B)(6) 2021 TO (B)(6) 2022. ¿ BATCH HISTORY RECORD (BHR) REVIEW: PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 WAS ASSEMBLED IN BDB SAN JOSE (PLANT 1149) USING SUBASSEMBLY 91-0297 BATCH 2033177, MANUFACTURED IN BDB CAYEY PR (PLANT 1157), WHICH WAS USED TO MANUFACTURE THE FOLLOWING PRODUCTS: 1. 332778 LOT 2076505 (400 EA): ALL 400 EA SOLD TO MARKET 2. 347423 LOT 2139478 (82 EA): 64 EA SOLD TO MARKET 3. 340703 LOT 2139480 (63 EA): ALL 63 EA SOLD TO MARKET QC BHR 91-0297 BATCH 2033177 WAS REVIEWED. MATERIAL MET QC SPECIFICATIONS: FLOW CYTOMETRY STAINING OF K562 CELL LINE, TEST VS REF LOG MEAN FLUORESCENCE (LMF) LOT-TO-LOT VARIABILITY = -8 LMF CHANNELS (SPEC +/- 60 CHANNELS), AND % POSITIVE POPULATION = 95% (SPEC = 90%), PRIOR TO RELEASE. RELEASE TESTING OF SUBASSEMBLY 91-0297 BATCH 2033177 PERFORMED ON 21-FEB-22. MATERIAL EXPIRES 31-AUG-23. SUBASSEMBLY 91-0297 BATCH 2033177 WAS LATER SATISFACTORILY USED ON (B)(6) 2022 AS A REFERENCE LOT DURING QC TESTING OF NEWER SUBASSEMBLY 91-0297 BATCH 2138725, MEETING % POSITIVE POPULATION (TEST BATCH 2138725 = 100% AND REF BATCH 2033177 = 100%) SPECIFICATIONS WITHOUT DISCREPANCY. ¿ COMPLAINT HISTORY REVIEW: ONE COMPLAINT REPORTED (PR# (B)(4) FROM (B)(6) HOSPITAL, OREBRO, SWEDEN; AGAINST PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVING WEIRD SIGNAL IN V500 CHANNEL ON FACS CANTO II INSTRUMENT WHILE USING CD15 FITC, FROM DATE RANGE OF (B)(6) 2021 TO (B)(6) 2022. CUSTOMER FROM (B)(6) HOSPITAL INITIALLY PROVIDED PATIENT TEST SAMPLE INFORMATION CAPTURED ON PR# (B)(4) ON (B)(6) 2022, THEN SUBMITTED ADDITIONAL PATIENT TEST SAMPLE INFORMATION ON (B)(6) 2022 WHICH WAS CAPTURED BY BD REPRESENTATIVE ON A NEW PR# (B)(4) WHICH IS PART OF INITIAL PR# (B)(4) CASE. NO ADDITIONAL COMPLAINTS HAVE BEEN REPORTED TO DATE FROM A TOTAL OF 527 EA UNITS SOLD TO MARKET OF ANY OF THE THREE DIFFERENT CATALOG PRODUCTS/LOTS MANUFACTURED FROM SAME SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177: (1) 332778 LOT 2076505, (2) 347423 LOT 2139478 AND (3) 340703 LOT 2139480. ¿ RETAIN SAMPLE ANALYSIS: INVESTIGATION BASED ON COMPLAINT HISTORY IN WHICH NO ADDITIONAL RELATED CLAIMS HAVE BEEN REPORTED FOR PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 TO DATE, EVALUATION OF BHR SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177 RELEASE DATA WHICH INCLUDES FLOW CYTOMETRY ANALYSIS, HISTORY OF SATISFACTORY USE OF 91-0297 BATCH 2033177 AS QC REFERENCE LOT AND WFI TASK PR# 6132110 QUESTIONS TO CUSTOMER REGARDING REPORTED PROBLEM. NO RETAIN SAMPLE TESTING DEEMED NECESSARY AT THIS TIME BASED ON SATISFACTORY PERFORMANCE EVIDENCE DURING RELEASE AND LATER USE AS QC REFERENCE LOT. ¿ RETURNED SAMPLE ANALYSIS: AS NO DATA OR DETAILS INITIALLY PROVIDED BY CUSTOMER REGARDING REPORTED PROBLEM, WFI TASK PR# (B)(4) REQUESTED FOR GATHERING INFORMATION AS PART OF INVESTIGATION. REFER TO ROOT-CAUSE ANALYSIS SECTION FOR DETAILS. ¿ RISK REVIEW: RISK MANAGEMENT FILE (B)(4), REVISION 02 WAS REVIEWED. HAZARD(S) IDENTIFIED? X YES / NO ___ IF NO (TO ABOVE), WHAT ACTIONS WILL BE TAKEN? HAZARD ID#: __4.1_ HAZARD: _INFORMATION HAZARD___ CAUSE: __ INADEQUATE INSTRUCTIONS PROVIDED BY BD___ HARMFUL EFFECTS: __ UNABLE TO PERFORM TESTING, DELAY OF TEST RESULTS___ RESIDUAL PROBABILITY: __1___ RESIDUAL SEVERITY: ___3___ RESIDUAL RISK INDEX: ___3 = ACCEPTABLE___ IMPLEMENTATION: __ TECHNICAL DATA SHEET ___ NEW HAZARD: __NONE___ MITIGATION(S) SUFFICIENT X YES / NO IF NO (TO ABOVE), WHAT ACTIONS WILL BE TAKEN? ¿ ROOT CAUSE ANALYSIS: WFI TASK PR# (B)(4) REQUESTED INFORMATION AND CUSTOMER RESPONSE TO SUPPORT INVESTIGATION, AS DESCRIBED BELOW: 1. CUSTOMERS INDICATE PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 HAS WEIRD SIGNAL IN V500 CHANNEL. PLEASE ANSWER THE FOLLOWING: A. PROVIDE ANY SUPPORTING FLOW CYTOMETRY DATA SHOWING OBSERVED PROBLEM. B. ARE YOU USING CD15 FITC REAGENT IN COMBINATION WITH ANOTHER REAGENT FOR COUNTERSTAINING OR MULTI-TARGET STAINING OR USED ONLY FOR SINGLE COLOR STAINING? C. INDICATE IF PRIOR TROUBLESHOOTING ONGOING DURING PRIOR CALL DID RESOLVE OR IDENTIFIED THE ISSUE (I.E. COMPENSATION OR ELSE). D. PLEASE CONFIRM IF YOU HAVE RE-TESTED USING ANOTHER FRESH VIAL OF SAME LOT 2076505 OR HAVE RE-TESTED USING A DIFFERENT LOT NUMBER. IF SO, INDICATE FINDINGS AND WHICH DIFFERENT LOT USED. CUSTOMER RESPONSE: A. CUSTOMERS PROVIDED FLOW CYTOMETRY RESULTS, WHICH WAS EVALUATED AS PART OF INVESTIGATION. B. CUSTOMER IS USING PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 MIXED WITH OTHER REAGENTS (NO PRODUCT CATALOG NUMBERS/LOTS PROVIDED): CD45 V500, HLA-DR V450, CD2 APC, CD34 PERCP-CY5.5, CD117 PE-CY7, AND CD19 APC-H7. C. NO INFORMATION PROVIDED BY CUSTOMER REGARDING TROUBLESHOOTING SUPPORT RECEIVED OR RESULTS. D. CUSTOMER PERFORMED RE-TESTING USING NEW VIAL OF SAME CD15 FITC LOT 2076505, AND THEY OBSERVE SAME RESULTS. 2. DESCRIBE STEP-BY-STEP PROCESS FOLLOW FOR STAINING, FLOW CYTOMETRY ACQUISITION AND ANALYSIS. CUSTOMERS RESPONSE: CUSTOMERS INDICATE THEY USED 10 UL OF REAGENT FROM A 1:8 DILUTION MIXTURE. NO DETAILED STEP-BY-STEP PROCESS DESCRIBED OF HOW PRODUCT WAS USED FOR STAINING ALONG OTHER REAGENTS IN MIXTURE PREPARED OR HOW COMPENSATION PERFORMED. PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LABEL AND INSTRUCTION FOR USE (IFU) 23-6925-03 INDICATES TO USE APPROPRIATE VOLUME OF MONOCLONAL ANTIBODY TO 100 UL OF WHOLE BLOOD AS INDICATED IN VIAL LABEL. VIAL LABEL FOR THIS PRODUCT INDICATES TO USE 20 UL OF REAGENT FOR STAINING SAMPLES, BUT CUSTOMER USED 10 UL OF A 1:8 DILUTION INSTEAD, WHICH IS SUBOPTIMAL VOLUME FOR STAINING SAMPLES USING CD15 FITC REAGENT. CUSTOMER INDICATES PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 HAVE WEIRD SIGNAL IN V500 CHANNEL WHILE USING CD15 FITC REAGENT ALONG A MIXTURE OF OTHER REAGENTS COMBINED BY CUSTOMER. IT IS NOTED THERE IS NO V500 PRODUCT OR RELATED CONJUGATE FORMAT MANUFACTURED AT BDB CAYEY PR (PLANT 1157) WHERE PRODUCT 332778 LOT 2076505 WAS MANUFACTURED FROM PURIFICATION TO FITC CONJUGATION AND FINAL FORMULATION STAGE TO POTENTIALLY CAUSE EXPOSURE WITH A V500 FLUOROCHROME SUBSTANCE. PER IFU 23-6925-03, PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) RECOGNIZES A MARKER PRESENT ON GREATER THAN 95% OF MATURE PERIPHERAL BLOOD GRANULOCYTES AND PRESENT AT LOW DENSITY ON CIRCULATING MONOCYTES. CD15 IS ABSENT FROM IMMATURE AND MATURE RESTING PERIPHERAL BLOOD AND LYMPHOID TISSUE B AND T CELLS, AND NK CELLS. CD15 IS EXPRESSED ON VIRTUALLY ALL PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA AND BY 80% OR MORE OF LEUKEMIC BLASTS IN A GIVEN ACUTE MYELOID LEUKEMIA (AML). CUSTOMER PROVIDED FLOW CYTOMETRY DATA SHOW THEY USED PRODUCT 332778 LOT 2076505 ALONG A MIXTURE OF OTHER REAGENTS, USING SUBOPTIMAL CONCENTRATION (10 UL OF A 1:8 DILUTION), GATED ON LYMPHOCYTES, INCLUDING A CD45 V500 WHICH DETECTS A HIGHLY EXPRESSED LEUCOCYTE MARKER (CD45) WHERE THEY REPORTED A WEIRD SIGNAL EVENT PROFILE ON THE V500 CHANNEL. IT IS NOTED THAT CAREFUL REAGENT SELECTION AND INSTRUMENT SETUP IS NECESSARY WHENEVER USING MULTICOLOR FLOW CYTOMETRY PANELS (REFER TO DOCUMENT (B)(4), BD BIOSCIENCES MULTICOLOR FLOW CYTOMETRY SETUP AND DESIGN GUIDANCE). PER CITED GUIDANCE, IT IS RECOMMENDED TO USE BRIGHTER FLUOROCHROMES FOR DIMLY EXPRESSED MARKERS AND DIMMER FLUOROCHROMES FOR HIGHLY EXPRESSED MARKERS. FLUORESCENCE SPILLOVER IS CONSIDERED THE MOST IMPORTANT FACTOR AFFECTING RESOLUTION SENSITIVITY IN MULTICOLOR FLOW CYTOMETRY EXPERIMENTS AND SHOULD BE ADJUSTED TO MINIMIZE AMOUNT OF SPILLOVER BACKGROUND FROM OTHER FLUOROCHROMES THRU PROPER COMPENSATION AND CONTROLS. IT CANNOT BE RULED OUT THAT SUBOPTIMAL INSTRUMENT COMPENSATION SETTINGS OR STAINED CONTROL SAMPLES COULD BE A CAUSE FOR OBSERVED ATYPICAL SIGNAL IN V500 CHANNEL, AS REPORTED. EVALUATION OF BATCH HISTORY RECORDS (BHR) OF PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 UNDER ITS SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177, SHOW IT MET ESTABLISHED BD PERFORMANCE SPECIFICATIONS WITHOUT DISCREPANCIES, AS EVIDENCED BY ROUTINE FLOW CYTOMETRY ANALYSIS DATA AND LATER USE AS QC REFERENCE LOT FOR TESTING NEWLY MANUFACTURED 91-0297 (CD15 FITC, CLONE MMA) BATCH 2138725. ADDITIONALLY, COMPLAINT HISTORY REVEALS NO ADDITIONAL RELATED COMPLAINTS AGAINST PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 OR ANY OF THE THREE PRODUCTS (332778 LOT 2076505, 347423 LOT 2139478 AND 340703 LOT 2139480) MANUFACTURED USING SAME SUBASSEMBLY 91-0297 (CD15 FITC, CLONE MMA) BATCH 2033177, OF WHICH 527 EA HAVE BEEN SOLD TO MARKET TO CURRENT DATE OF INVESTIGATION. ROOT-CAUSE FOR REPORTED INCIDENT WHILE USING PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 CANNOT BE DETERMINED. PRODUCT 332778 (CD15 FITC, CLONE MMA, CE-IVD) LOT 2076505 TESTED UNDER SUBASSEMBLY 91-0297 BATCH 2033177 MET ESTABLISHED BD RELEASE ACCEPTANCE CRITERIA, USING SINGLE REAGENT STAINING AND NOT IN COMBINATION WITH OTHER REAGENTS, WHICH REQUIRES OPTIMIZATION, PROPER CONTROLS, AND COMPENSATION, AS PREVIOUSLY INDICATED. INVESTIGATION FOUND PRODUCT 332778 (CD15 FITC, CE) LOT 2076505 PERFORMS AS INTENDED, CUSTOMER USED SUBOPTIMAL PER TEST VOLUME CONCENTRATION FOR TESTING (OFF-LABEL USE), THERE IS NO HISTORY OF ADDITIONAL COMPLAINTS, NO DISCREPANCY OR DEVICE PROBLEM DETECTED ON EVALUATED RECORDS AND TEST HISTORY INCLUDING SUCCESSFUL USE AS REFERENCE LOT UNDER SUBASSEMBLY 91-0297 BATCH 2033177, HENCE COMPLAINT IS UNCONFIRMED, AND NO FURTHER ACTIONS DEEMED NECESSARY AT THIS TIME. ¿ CONCLUSION: BASED ON THIS INVESTIGATION FOR PRODUCT 332778 (CD15 FITC, CE) LOT 2076505, THIS COMPLAINT IS UNCONFIRMED, AND NO FURTHER ACTIONS DEEMED NECESSARY AT THIS TIME. H3 OTHER TEXT : SEE H. 10.
A DEVICE EVALUATION IS ANTICIPATED, BUT HAS NOT YET BEGUN. UPON COMPLETION OF THE INVESTIGATION, A SUPPLEMENTAL REPORT WILL BE FILED.
IT WAS REPORTED THAT DURING USE WITH BD CD15 FITC ERRONEOUS RESULTS WERE OBTAINED ON ON 2 PATIENT SAMPLES. NO PATIENT IDENTIFICATION WERE INITIALLY PROVIDED WHEN WE REPORTED MFR. # (B)(4) . WE NOW HAVE PATIENT SAMPLE ID #S. THIS RECORD IS TO CAPTURE PATIENT (B)(6). THERE WAS NO REPORT OF PATIENT IMPACT. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: WE ARE EXPERIENCING PROBLEM WITH CD15 FITC (REF (B)(4), LOT 2076505) ON OUR TWO CANTO IIS. WE HAVE TRIED WITH BOTH INSTRUMENTS AND IT LOOKS REALLY WEIRD IN THE V500 CHANNEL. WHEN WE DO COMPENSATION SETUP ON THE INSTRUMENT WE USE THE STRONGEST FLOUROCHROME FOR EACH CHANNEL. SINCE WE USE V500 FOR CD45 (AND ONLY CD45) IT IS VERY IMPORTANT FOR US TO HAVE A NORMAL APPEARANCE IN THAT CHANNEL. THE ANTIBODY IN QUESTION IS RECENTLY OPENED AND IS FRESH.
IT WAS REPORTED THAT DURING USE WITH BD CD15 FITC ERRONEOUS RESULTS WERE OBTAINED ON 2 PATIENT SAMPLES. NO PATIENT IDENTIFICATION WERE PROVIDED. THERE WAS NO REPORT OF PATIENT IMPACT. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: WE ARE EXPERIENCING PROBLEM WITH CD15 FITC (REF (B)(4), LOT 2076505) ON OUR TWO CANTO IIS. WE HAVE TRIED WITH BOTH INSTRUMENTS AND IT LOOKS REALLY WEIRD IN THE V500 CHANNEL. WHEN WE DO COMPENSATION SETUP ON THE INSTRUMENT WE USE THE STRONGEST FLOUROCHROME FOR EACH CHANNEL. SINCE WE USE V500 FOR CD45 (AND ONLY CD45) IT IS VERY IMPORTANT FOR US TO HAVE A NORMAL APPEARANCE IN THAT CHANNEL. THE ANTIBODY IN QUESTION IS RECENTLY OPENED AND IS FRESH.
IT WAS REPORTED THAT DURING USE WITH BD CD15 FITC ERRONEOUS RESULTS WERE OBTAINED ON ON 2 PATIENT SAMPLES. NO PATIENT IDENTIFICATION WERE INITIALLY PROVIDED WHEN WE REPORTED MFR. # 2916837-2022-00243 . WE NOW HAVE PATIENT SAMPLE ID #S. THIS RECORD IS TO CAPTURE PATIENT (B)(6). THERE WAS NO REPORT OF PATIENT IMPACT. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: WE ARE EXPERIENCING PROBLEM WITH CD15 FITC (REF (B)(4), LOT 2076505) ON OUR TWO CANTO IIS. WE HAVE TRIED WITH BOTH INSTRUMENTS AND IT LOOKS REALLY WEIRD IN THE V500 CHANNEL. WHEN WE DO COMPENSATION SETUP ON THE INSTRUMENT WE USE THE STRONGEST FLOUROCHROME FOR EACH CHANNEL. SINCE WE USE V500 FOR CD45 (AND ONLY CD45) IT IS VERY IMPORTANT FOR US TO HAVE A NORMAL APPEARANCE IN THAT CHANNEL. THE ANTIBODY IN QUESTION IS RECENTLY OPENED AND IS FRESH.
IT WAS REPORTED THAT DURING USE WITH BD CD15 FITC ERRONEOUS RESULTS WERE OBTAINED ON ON 2 PATIENT SAMPLES. NO PATIENT IDENTIFICATION WERE PROVIDED. THERE WAS NO REPORT OF PATIENT IMPACT. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: WE ARE EXPERIENCING PROBLEM WITH CD15 FITC (REF (B)(4), LOT 2076505) ON OUR TWO CANTO IIS. WE HAVE TRIED WITH BOTH INSTRUMENTS AND IT LOOKS REALLY WEIRD IN THE V500 CHANNEL. WHEN WE DO COMPENSATION SETUP ON THE INSTRUMENT WE USE THE STRONGEST FLOUROCHROME FOR EACH CHANNEL. SINCE WE USE V500 FOR CD45 (AND ONLY CD45), IT IS VERY IMPORTANT FOR US TO HAVE A NORMAL APPEARANCE IN THAT CHANNEL. THE ANTIBODY IN QUESTION IS RECENTLY OPENED AND IS FRESH.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 2215854 | BD CD15 FITC | NA | MVU | BECTON, DICKINSON AND COMPANY, BD BIOSCIENCES | 2076505 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | Unknown |