VIDAS D-DIMER EXCLUSION II
Report
- Report Number
- 8020790-2021-00164
- Event Type
- Malfunction
- Date Received
- July 15, 2021
- Report Date
- July 15, 2021
- Manufacturer
- BIOMERIEUX SA
- Product Code
- DAP
- PMA / PMN Number
- K141133
- Product Problem
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- SZ
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
Narratives
A BIOMÉRIEUX INTERNAL INVESTIGATION HAS BEEN COMPLETED WITH THE FOLLOWING RESULTS: THE REVIEW OF THE DIFFERENT QUALITY CONTROL RECORDS VIDAS D-DIMER EXCLUSION II DID NOT HIGHLIGHT ANY ISSUE DURING MANUFACTURING, CONTROL AND PACKAGING PROCESSES A CONTROL CHART ANALYSIS WAS CARRIED OUT ON EIGHT (8) INTERNAL SAMPLES WITH TARGETS AT DIFFERENT CONCENTRATIONS BETWEEN 200 NG/ML AND 4000 NG/ML. THESE SAMPLES WERE SELECTED BECAUSE THEY HAVE TARGETS CLOSE TO THE SAMPLES RESULTS OF BIO-RAD SAMPLES. THE SAMPLES WERE TESTED ON 18 BATCHES OF VIDAS D-DIMER EXCLUSION II (ALL THE LOTS NOT EXPIRED). THERE WAS NO PARTICULAR BEHAVIOR OBSERVED WITH ANY BATCH COMPARED TO THE OTHER BATCHES. THE COMPLAINT LABORATORY TESTED BIO-RAD SAMPLES. DURING PREVIOUS INVESTIGATIONS AND ADDITIONAL TESTING, THE OUT OF RANGE TOO HIGH RESULT ON QUALITY CONTROL SAMPLES WITH THE DIFFERENT LEVELS OF THESE SAMPLES WERE REPRODUCED. THESE QUALITY CONTROL SAMPLES WERE TESTED ON SIX (6) LOTS OF VIDAS D-DIMER EXCLUSION II. IN CONCLUSION, THE CUSTOMER'S ANOMALY FOR OVERESTIMATED RESULTS WAS REPRODUCED ON SAMPLES FROM BIO-RAD. ACCORDING TO THE FIRST OUTCOMES, IT SEEMS THAT THE ISSUE IS REPRODUCED ONLY WHEN TESTING BIO-RAD SAMPLES. THE SAME PHENOMENA WAS NOT REPRODUCED ON INTERNAL SAMPLES WITH SIMILAR CONCENTRATIONS AS THOSE FROM BIO-RAD SPECIMEN. FURTHER INVESTIGATION INVOLVING INDUSTRIALIZATION AND SUPPORT LEVEL IN COLLABORATION WITH DATASCIENCE DEPARTMENT (BIOMATHS) WAS PERFORMED TO TRY TO FIND A ROOT CAUSE FOR THE HIGH RESULTS OBSERVED. THE TEAM PERFORMED TESTING ON 16 INTERNAL SAMPLES (3 NATIVE PLASMAS AND 13 SAMPLES SPIKED WITH HIGH CONCENTRATED NATURAL SAMPLES) WITH CONCENTRATIONS BETWEEN 180 AND 6300 NG/ML ON MORE THAN 50 VIDAS DEX2 BATCHES (MANUFACTURED DURING ABOUT THE LAST 3 YEARS). THE INTERNAL SAMPLES ANALYZED WERE SELECTED BECAUSE THEY HAVE A TARGET CLOSE TO THE TARGET OF THE QUALITY CONTROL SAMPLES FROM BIO-RAD. ACCORDING TO THE OUTCOMES, NO PARTICULAR SHIFT ON THE RESULTS WAS OBSERVED AND THE MAXIMUM BIAS OBSERVED WAS IN ACCORDANCE WITH VARIABILITY OF VIDAS D-DIMER EXCLUSION II ASSAY. A POSITIVE BIAS OF ABOUT ONLY 8% WAS OBSERVED FOR ONE OF THE SAMPLES ANALYZED, AND IT WAS FOR A SAMPLE WITH A TARGET AROUND 180 NG/ML WHICH IS FAR FROM THE CLINICAL THRESHOLD OF 500 NG/ML. AS A REMINDER, THE SPECIFIED CV OF INTERMEDIATE PRECISION IS < 10% FOR A SAMPLE WITH A TARGET OF 278 NG/ML. TO CONCLUDE, THE QUALITY CONTROL SAMPLES FROM BIO-RAD DO NOT HAVE THE SAME BEHAVIOR (SIGNIFICANT POSITIVE BIAS) AS THE ONE OBSERVED WITH INTERNAL SAMPLES. THE PHENOMENA REPORTED BY THE CUSTOMER ON NATURAL SAMPLES ANALYZED WERE NOT OBSERVED. FOLLOWING THE ANALYSIS CONDUCTED BY THE INDUSTRIALIZATION AND SUPPORT DEPARTMENT, A NEW SERIES OF TESTS WERE CARRIED OUT TO CONFIRM THAT THE PERFORMANCE OVER TIME OF VIDAS D-DIMER EXCLUSION II ASSAY WAS MAINTAINED AND TO CHECK IF THE SAME PHENOMENA WAS OBSERVED WITH ANY OTHER SAMPLE TYPES TESTED. THIS PARTICULAR STUDY INVOLVED THREE (3) BATCHES (TWO MANUFACTURED A COUPLE OF MONTHS AGO AND ONE BATCH WITH RECENT MANUFACTURING) AND QUALITY CONTROL SAMPLES (FROM BIO-RAD AND AUDIT MICRO CONTROL) AND NATURAL SAMPLES (INTERNAL SAMPLES AND SAMPLES FROM BIOBANK). RESULTS ON QUALITY CONTROL SAMPLES FROM BIO-RAD: THIS STUDY CONFIRMED THAT THERE IS A SHIFT (POSITIVE BIAS) OF ABOUT 20% BETWEEN THE RESULTS OBTAINED ON BIO-RAD QC SAMPLES AND THE TARGETS PROVIDED BY BIO-RAD. THIS PHENOMENON WAS SIMILAR WHATEVER THE LEVEL OF BIO-RAD QUALITY CONTROL SAMPLES AND THE LOT OF VIDAS D-DIMER EXCLUSION II TESTED. RESULTS ON NATURAL SAMPLES: THE SAME BEHAVIOR WAS NOT OBSERVED WHEN TESTING INTERNAL SAMPLES. ALL OF THEM COMPLIED WITH THEIR SPECIFICATIONS. IN ADDITION, NO EVOLUTION WAS OBSERVED OVER TIME WITH ANY OF THE THREE LOTS OF VIDAS D-DIMER EXCLUSION II COMPARED TO THEIR RELEASE. NO SIGNIFICANT DIFFERENCE OF RESULTS WERE OBSERVED FOR THE NATURAL SAMPLES FROM THE BIOBANK; THEY SHOWED TO GIVE A GOOD BETWEEN-LOT REPRODUCIBILITY. RESULTS ON QUALITY CONTROL SAMPLES FROM AUDIT MICRO CONTROL: EXCELLENT LINEARITY OUTCOMES WERE OBTAINED WITH R-SQUARE CLOSE TO 1 WHEN TESTING THE LINEARITY AND VERIFICATION KIT FROM AUDIT MICRO CONTROL AND NO SIGNIFICANT DIFFERENCE WAS OBSERVED FOR EACH POINT OF THE CURVE DEPENDING ON THE LOT TESTED. THE HYPOTHESIS TO EXPLAIN THIS BIAS IS THAT IT IS STILL LINKED TO THE QUALITY CONTROL SAMPLES FROM BIO-RAD THEMSELVES AND THE ROOT CAUSE COULD BE LINKED TO THE MANUFACTURING, A MATRIX EFFECT OR DETERMINATION OF ACCEPTABLE RANGES. A MEETING WAS CONDUCTED WITH THE BIORAD COMPANY TO SHARE THE INVESTIGATION OUTCOMES. BIOMERIEUX REQUESTED A MEETING WITH THE DEPARTMENT IN CHARGE OF VALUE ASSIGNMENT AT BIORAD; HOWEVER, THAT DEPARTMENT WAS NOT ABLE TO ACCOMMODATE A MEETING AT THIS TIME. THE OTHER ACTIONS CURRENTLY IN PROCESS WITH THE COLLABORATION OF BIO-RAD COMPANY WILL BE IMPLEMENTED IN THE CONTEXT OF CONTINUOUS IMPROVEMENT OF COMPLAINTS MONITORING AND MANAGEMENT. ACCORDING TO THE INVESTIGATION OUTCOMES, THE HYPOTHESIS TO EXPLAIN THE ISSUE OBSERVED IS LINKED TO THE QUALITY CONTROL SAMPLES FROM BIO-RAD THEMSELVES. THE POSSIBLE ROOT CAUSE COULD BE IN RELATION WITH THE MANUFACTURING, A MATRIX EFFECT OR DETERMINATION OF ACCEPTABLE RANGES. IT IS MENTIONED, IN THE PACKAGE INSERT OF QUALITY CONTROL REAGENTS FROM BIORAD AND ON BIO-RAD WEBSITE, THE FOLLOWING INFORMATION: "THE MEAN VALUES PROVIDED IN THE ASSIGNMENT OF VALUES DATA CHARTS WERE DERIVED FROM REPLICATE ANALYSES AND ARE SPECIFIC FOR EACH LOT OF PRODUCT. THE TESTS LISTED WERE PERFORMED BY THE MANUFACTURER AND/OR INDEPENDENT LABORATORIES USING MANUFACTURER SUPPORTED REAGENTS AND A REPRESENTATIVE SAMPLING OF THIS LOT OF CONTROL. INDIVIDUAL LABORATORY MEANS SHOULD FALL WITHIN THE CORRESPONDING ACCEPTABLE RANGE; HOWEVER, LABORATORY MEANS MAY VARY FROM THE LISTED VALUES DURING THE LIFE OF THIS CONTROL. VARIATIONS OVER TIME AND BETWEEN LABORATORIES MAY BE CAUSED BY DIFFERENCES IN LABORATORY TECHNIQUE, INSTRUMENTATION AND REAGENTS, OR BY MANUFACTURER TEST METHOD MODIFICATIONS. IT IS RECOMMENDED THAT EACH LABORATORY ESTABLISH ITS OWN MEANS AND ACCEPTABLE RANGES AND USE THOSE PROVIDED ONLY AS GUIDES". THE VIDAS D-DIMER EXCLUSION II TEST KITS ARE MEETING THEIR SPECIFICATIONS.
ON (B)(6) 2021, A CUSTOMER IN (B)(6) NOTIFIED BIOMÉRIEUX OF AN EXTERNAL QUALITY CONTROL ISSUE (THE L1 AND L2 RESULTS WERE OUT OF EXPECTED RANGE) WHEN TESTING THE VIDAS® D-DIMER EXCLUSION II¿(DEX2) (REFERENCE #: 30455-02 , LOT #: NOT CONFIRMED, EXPIRY DATE: N/A) WITH AN EXTERNAL QUALITY CONTROL (QC) SAMPLE (LIQUICHEK D-DIMER REF: 27100, LOT: 16990). THERE IS A DISCREPANCY WITH THE LOT NUMBER INFORMATION THAT WAS PROVIDED BY THE CUSTOMER; THEREFORE, THE LOT NUMBER IS UNAVAILABLE AT THIS TIME. BIO-RAD LIQUICHEK D-DIMER CONTROL LEVELS LOW, 1,2 AND 3 REF: 27100.. LOT: 16990, RANGE FROM PACKAGE INSERT (VALUES UPDATED BY BIO RAD ON (B)(6) 2021) LEVEL 1 - 16991: 0.473 (0.374 - 0.572) MG/L, LEVEL 2 - 16992: 1.88 (1.49 - 2.28) MG/L. THE CUSTOMER PROVIDED THE FOLLOWING RESULTS (THE UNITS WERE NOT PROVIDED): L1: RESULT ON (B)(6) 2020 : 586.67 (3S*) L1: RESULT ON (B)(6) 2020: 1765.12 (3S*), GCS SUSPECTS THIS IS AN L2 VALUE L2: RESULT ON (B)(6) 2020: 1318.27 (3S*) L2: RESULT ON (B)(6) 2020: 469.52 (3S*), GCS SUSPECTS THIS IS AN L1 VALUE. *3S INDICATES THE CUSTOMER'S VALUES WERE OUT OF RANGE BY 3 STANDARD DEVIATIONS. WHILE TROUBLESHOOTING, GLOBAL CUSTOMER SERVICE (GCS) NOTICED THAT RESULTS FOR L1 AND L2 SEEM TO BE MIXED UP. THE CUSTOMER CONFIRMED THIS DISCREPANCY. NO UPDATED VALUES HAVE BEEN PROVIDED. THE RANGES OF THE BIO-RAD QC WERE UPDATED ON 20MAY2021; HOWEVER, THE CUSTOMER'S RESULTS ARE FROM 2020. THE EXPECTED RANGES CURRENT AT THE TIME OF TESTING ARE UNKNOWN. THERE IS NO PATIENT ASSOCIATED WITH THIS EXTERNAL QUALITY CONTROL SAMPLE; THEREFORE, THERE IS NO ADVERSE EVENT RELATED TO ANY PATIENT'S STATE OF HEALTH. A BIOMÉRIEUX INTERNAL INVESTIGATION WILL BE INITIATED. NOTE: PRODUCT REFERENCE 30455-02 IS NOT SOLD OR DISTRIBUTED IN THE UNITED STATES; HOWEVER, A SIMILAR PRODUCT (REFERENCE 30455-01) IS REGISTERED AND SOLD IN THE UNITED STATES.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 1069160 | VIDAS D-DIMER EXCLUSION II | VIDAS® D-DIMER EXCLUSION II | DAP | BIOMERIEUX SA |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 |