BD CD11B (D12) APC

Additional Manufacturer Narrative

H.3. A DEVICE EVALUATION AND/OR DEVICE HISTORY REVIEW IS ANTICIPATED BUT IS NOT COMPLETE. UPON COMPLETION, A SUPPLEMENTAL REPORT WILL BE FILED.

Description of Event or Problem

IT WAS REPORTED THAT DURING USE WITH THE BD CD11B (D12) APC, ERRONEOUS RESULTS WERE OBTAINED. THIS IS THE 2ND OF 3 PATIENTS. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: MISSING FLUORESCENT SIGNAL OF ANTIBODY CD11B-APC (LOT 3114710) AFTER STAINING OF 3 PATIENT SAMPLE AND COMPARISON WITH THE LOT 3074607 PRESENTATION (WITH DOT PLOTS FROM 3 DIFFERENT PATIENTS). SO YES, THE RESULT WAS OBSERVED IN PATIENTS. IN THESE DOT PLOTS OF PATIENTS, YOU CAN SEE HOW THE ANTIBODY IS NOT FUNCTIONAL (LOT 3114710) IN COMPARISON TO ANOTHER LOT OF THE SAME ANTIBODY WHICH IS WORKING (3074607, 3038001). THIS SPADIA LAB, WHERE THIS PROBLEM HAPPENED, IS THE CLINICAL LAB WITH VERY STRICT SOPS AND STANDARDS. THEY MUST CHANGE THE TIPS AND WASH THE INSTRUMENT BETWEEN SAMPLES. IT MEANS THAT THE CARRYOVER CANNOT HAPPEN.

Additional Manufacturer Narrative

SCOPE OF ISSUE: THE SCOPE OF ISSUE IS LIMITED TO PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710. PROBLEM STATEMENT: CUSTOMER (LABORATORY OF CLINICAL IMMUNOLOGY AND SEROLOGY, OSTRAVA, CZECH REPUBLIC) REPORTED ON (B)(6) 2023 THAT PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 HAS MISSING FLUORESCENCE SIGNAL AFTER STAINING PATIENT SAMPLES AND COMPARING WITH A PRIOR REFERENCE LOT 3074607. CUSTOMER MEASURED MORE PATIENTS BY THIS ANTIBODY THAT DAY. CUSTOMER FIGURED IT OUT BEFORE ANY RESULTS WERE SENT TO THE CLINICIANS, REPEATED THE PATIENTS RIGHT AWAY THAT DAY WITH ANOTHER BATCH AND IT WAS FINE THERE. INVESTIGATION SUMMARY: MANUFACTURING DEFECT TREND: THERE ARE ZERO (0) QUALITY NOTIFICATIONS (QN) OR NONCONFORMANCE REPORTS AGAINST PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 OR SUBASSEMBLY 91-0415 (CD11B APC) BATCH 3095009, FROM EVALUATED DATE RANGE FROM 03-AUG-22 TO 03-AUG-23. BATCH HISTORY RECORD (BHR) REVIEW: PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 WAS ASSEMBLED IN BDB CAYEY (PLANT 1157) USING SUBASSEMBLY 91-0415 (CD11B APC) BATCH 3095009, WHICH WAS USED TO MANUFACTURE THE FOLLOWING PRODUCTS: 1. 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 (334 EA): A. (B)(4) EA UNITS SOLD TO MARKET B. (B)(4) EA UNITS BLOCKED PER GLOBAL HOLD H23-07 2. 340936 (CD11B APC, CLONE D12, ASR) LOT 3114730 (255 EA): A. (B)(4) EA SOLD TO MARKET B. (B)(4) EA BLOCKED PER GLOBAL HOLD H23-07 3. 340937 (CD11B APC, CLONE D12, RUO) LOT 3114725 (206 EA): A. (B)(4) EA SOLD TO MARKET B. (B)(4) EA BLOCKED PER GLOBAL HOLD H23-07 QC BHR 91-0415 (CD11B APC) BATCH 3095009 WAS REVIEWED. MATERIAL MET SPECIFICATIONS PRIOR RELEASE: FLUOROMETRY TEST VS REFERENCE (SPECIFICATION -40% TO +80% OF REFERENCE) RESULT OF -22%, AND AGFC PERCENT FREE FLUOROPHORE (SPECIFICATION =20% OF FREE APC CONJUGATE DYE) RESULT OF 8.8%, PRIOR TO RELEASE. MATERIAL EXPIRES 28-FEB-25. NO DISCREPANCY IDENTIFIED ON EVALUATED QC RECORDS AND DATA. FORMULATION MANUFACTURING BHR OF MATERIAL 91-0415 (CD11B APC) BATCH 3095009 AND CONJUGATION BULK MATERIAL 50-00236 (CD11B APC) BATCH 3080848 BHR WERE EVALUATED. NO DISCREPANCY OR DEVIATION IDENTIFIED ON EVALUATED FORMULATION BHR FOR0004-PR (REV. 20), WHICH DEMONSTRATE MATERIAL 91-0415 (CD11B APC) BATCH 3095009 WAS FORMULATED AT APPLICABLE BOTTLING CONCENTRATION (0.05 MG/ML) AND FOLLOWING MANUFACTURING SPECIFICATION INSTRUCTIONS 91-0415MS-PR (REV.2). NO DISCREPANCY OR DEVIATION IDENTIFIED ON EVALUATED CONJUGATION BHR OF BULK MATERIAL 50-00236 (CD11B APC) BATCH 3080848. O ASSESSMENT OF BHR IN-PROCESS DATA OF BULK CD11B APC FRACTIONS POOLED SHOW CHARACTERISTICS OF HIGHER FREE (PURE) CD11B IGG AB CONTENT THAN CD11B APC CONJUGATE ON BATCH 3080848, NOT ALIGNED WITH APC TO ANTIBODY CONCENTRATION AND APC SIZING REQUIREMENTS, WHICH EXPLAINS THE LOW (NEARLY NEGATIVE) SIGNAL ON AFFECTED CD11B APC PRODUCTS MANUFACTURED USING SUBASSEMBLY MATERIAL 91-0415 (CD11B APC) BATCH 3095009. COMPLAINT HISTORY REVIEW: TWENTY-ONE (21) COMPLAINT REPORTS AGAINST PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 FROM 03-AUG-22 TO 03-AUG-23 RELATED TO POOR/DIM SIGNAL PERFORMANCE. AFFECTED PRODUCTS WERE MANUFACTURED USING SAME SUBASSEMBLY MATERIAL 91-0415 (CD11B APC) BATCH 3095009. REFER TO ATTACHED CAPA PR#8466530_CD11B APC_AFFECTED MATERIALS & TREND ANALYSIS_15-AUG-23¿ EXCEL FILE FOR CD11B APC COMPLAINT HISTORY DETAILS. 8577952 (THIS COMPLAINT), 7960438, 8029494, 8039274, 8070833, 8102139, 8112256, 8118732, 8281419, 8281453, 8291143, 8337057, 8337201, 8403713, 8414054, 8437653, 8445758, 8454512, 8472729, 8522283 AND 8577889 RETAIN SAMPLE ANALYSIS: FLOW CYTOMETRY TESTING WAS PERFORMED ON RETAIN SAMPLES OF 91-0415 (CD11B APC) BATCH 3095009 AND BULK MATERIAL 50-00236 (CD11B APC) BATCH 3080848, WHICH CONFIRM POOR SIGNAL CLAIMS IS ATTRIBUTED TO AFFECTED BULK MATERIAL BATCH 3080848 AS THE PROBLEM SOURCE. REFER TO ¿91-0415-3095009 TEST VS 3 REF LOTS RETAIN FC TEST DATA_SSC VS FL4¿ AND ¿50-00236-3080848 BULK TEST VS 3 REF LOTS RETAIN FC TEST DATA¿ FILES FOR RETAIN TEST RESULTS. INVESTIGATION, ROOT-CAUSE ANALYSIS AND CORRECTIVE/PREVENTIVE ACTIONSESCALATED TO CAPA PR# 8466530. RETURNED SAMPLE ANALYSIS: THE CUSTOMERS SAMPLE/DATA WAS NOT REQUESTED BECAUSE RETAIN SAMPLE WAS TESTED AND REPORTED PERFORMANCE PROBLEM WAS CONFIRMED. RISK REVIEW: RISK MANAGEMENT FILE 100310RA ¿ANTIBODIES AND ANTIBODY CONJUGATES CE-IVD¿, REV. 02 WAS REVIEWED. HAZARD(S) / END USER RISK (RUO PRODUCTS ONLY) IDENTIFIED? _X_ YES / _ _NO IF NO (TO ABOVE), WHAT ACTIONS WILL BE TAKEN? N/A HAZARD ID#: _3.1.3_ HAZARD: _FUNCTIONAL HAZARD_ CAUSE: _ PRODUCT DEGRADE BEFORE ASSIGN EXPIRATION DATE _ HARMFUL EFFECTS: _WRONG RESULT-NO MATCHING PROFILE_ RESIDUAL SEVERITY: _3_ RESIDUAL PROBABILITY: _1_ RESIDUAL RISK INDEX: _3 = ACCEPTABLE_ POTENTIAL CAUSES: BASED ON THE INVESTIGATION RESULTS, THE CAUSE IS ATTRIBUTED TO INCORRECT CD11B APC ANTIBODY FRACTION POOLING DURING CONJUGATION OF BULK MATERIAL 50-00236 (CD11B APC) BATCH 3080848 USED TO FORMULATE SUBASSEMBLY 91-0415 (CD11B APC) BATCH 3095009 USED FOR PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710. REFER TO CAPA FOR INVESTIGATION DETAILS. INVESTIGATION RESULT / ANALYSIS: THE INVESTIGATION WAS PERFORMED AND BASED ON THE REVIEW OF COMPLAINT TREND, DEFECT TREND, BHR REVIEW, RISK ANALYSIS, CUSTOMER PROVIDED DATA AND RETAIN SAMPLE ANALYSIS, THE COMPLAINT OF PERFORMANCE PROBLEM REPORTED AGAINST PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710 WAS CONFIRMED. INVESTIGATION, ROOT-CAUSE ANALYSIS AND CORRECTIVE/PREVENTIVE ACTION WAS ESCALATED TO CAPA AND SITUATION ANALYSIS. CONCLUSION: BASED ON INVESTIGATION FINDINGS AND RESULTS FOR PRODUCT 333143 (CD11B APC, CLONE D12, CE-IVD) LOT 3114710, COMPLAINT IS CONFIRMED.

Description of Event or Problem

IT WAS REPORTED THAT DURING USE WITH THE BD CD11B (D12) APC, ERRONEOUS RESULTS WERE OBTAINED. THIS IS THE 2ND OF 3 PATIENTS. THE FOLLOWING INFORMATION WAS PROVIDED BY THE INITIAL REPORTER: MISSING FLUORESCENT SIGNAL OF ANTIBODY CD11B-APC (LOT 3114710) AFTER STAINING OF 3 PATIENT SAMPLE AND COMPARISON WITH THE LOT 3074607. PRESENTATION (WITH DOT PLOTS FROM 3 DIFFERENT PATIENTS). SO YES, THE RESULT WAS OBSERVED IN PATIENTS. IN THESE DOT PLOTS OF PATIENTS, YOU CAN SEE HOW THE ANTIBODY IS NOT FUNCTIONAL (LOT 3114710) IN COMPARISON TO ANOTHER LOT OF THE SAME ANTIBODY WHICH IS WORKING (3074607, 3038001). THIS SPADIA LAB, WHERE THIS PROBLEM HAPPENED, IS THE CLINICAL LAB WITH VERY STRICT SOPS AND STANDARDS. THEY MUST CHANGE THE TIPS AND WASH THE INSTRUMENT BETWEEN SAMPLES. IT MEANS THAT THE CARRYOVER CANNOT HAPPEN.