BACT/ALERT I FN PLUS

Report

Report Number: 3002769706-2021-00060
Event Type: Malfunction
Date Received: November 23, 2021
Report Date: June 21, 2022
Manufacturer: BIOMÉRIEUX, INC
Product Code: MDB
PMA / PMN Number: K020815
Product Problem: Yes
Report Source: Manufacturer report
Reporter Location: EI
Reporter Occupation: OTHER HEALTH CARE PROFESSIONAL
Health Professional: Yes

Narratives

Additional Manufacturer Narrative · 0

AN INTERNAL INVESTIGATION WAS PERFORMED FOLLOWING NOTIFICATION FROM A CUSTOMER IN IRELAND THAT THEY OBTAINED FALSE POSITIVE RESULTS IN ASSOCIATION WITH BACT/ALERT I FN PLUS (REF. 412991, BATCH NUMBER 0004056863, EXPIRATION DATE 29-DEC-2021) IN A CONTEXT OF ROUTINE TESTING WITH THE EQUIPMENT BACT/ALERT 3D 0480 (SERIAL NUMBER (B)(6)).THE CUSTOMER PROVIDED A DESCRIPTION OF BOTTLE TYPE, CELL LOCATION, AND NUMBER OF POSITIVE RESULTS. NO 3D INSTRUMENT BACKUP FILES OR GRAPHS WERE PROVIDED; THE CUSTOMER HAS NONDISCLOSURE CONCERNS. INVESTIGATION: STUDY REFERENCE 1; A STUDY WAS CONDUCTED ON COMMERCIALLY AVAILABLE CHO CELL CULTURE MEDIA BY D. REINHART, L. DAMJANOVIC, C. KAISERMAYER, AND R. KUNERT: BENCHMARKING OF COMMERCIALLY AVAILABLE CHO CELL CULTURE MEDIA FOR ANTIBODY PRODUCTION: APPL MICROBIOL BIOTECHNOL (2015) 99:4645-4657 DOI 10.1007/S00253-015-6514-4. THE STUDY FOCUSED ON THE TESTING OF SEVERAL COMMERCIALLY AVAILABLE CHINESE HAMSTER OVARY (CHO) CELL MEDIA (E.G. SIGMA ALDRICH, LONZA, ETC.) TO EVALUATE THE IMPACT ON BIOPROCESS PERFORMANCE. SEVERAL POINTS PERTAINING TO THIS INVESTIGATION ARE SUMMARIZED ARE BELOW: ¿ CHO CELLS HAVE BECOME A STANDARD MAMMALIAN HOST CELL LINE FOR THE PHARMACEUTICAL INDUSTRY. ¿ ADJUSTMENTS MADE TO THE MEDIA CAN SIGNIFICANTLY IMPACT CHO CELL GROWTH WHEREAS ¿SMALL AGGREGATES MIGHT BE GOOD INDICATOR OF CELL GROWTH PERFORMANCE IN SUBSEQUENT HIGH CELL DENSITY CULTURES.¿ ¿ MATERIALS AND METHODS: ¿CULTURES WERE GROWN IN AN ISFI-X INCUBATOR SHAKER (KUHNER) AT 37°C, 140 RPM, 7% CO2 AND 90% HUMIDITY.¿ ¿ ¿UNBALANCED GLUCOSE AND AMINO ACIDS LED TO HIGH CELL-SPECIFIC LACTATE AND AMMONIUM PRODUCTION RATES.¿ STUDY REFERENCE 2: ANOTHER STUDY WAS PERFORMED FOR EVALUATING PROCESS ADJUSTMENTS INVOLVING CHO CELLS AND THE INCREASED PRODUCTIVITY OF MONOCLONAL ANTIBODIES WITHIN THE BIOTECHNOLOGY MANUFACTURING ENVIRONMENT BY L. STEPPER, F.A. FILSER, S. FISCHER, J. SCHAUB, I. GORR, AND R. VOGES: PRE-STAGE PERFUSION AND ULTRA-HIGH SEEDING CELL DENSITY IN CHO FED-BATCH CULTURE: A CASE STUDY FOR PROCESS INTENSIFICATION GUIDED BY SYSTEMS BIOTECHNOLOGY: BIOPROCESS AND BIOSYSTEMS ENGINEERING (2020) 43:1431-1443 HTTPS://DOI.ORG/10.1007/S00449-020-02337-1. SEVERAL POINTS PERTAINING TO THIS INVESTIGATION ARE SUMMARIZED ARE BELOW: ¿ ¿MONOCLONAL ANTIBODIES (MABS) AND OTHER DERIVED THERAPEUTIC PROTEINS ARE CURRENTLY ONE OF THE MOST IMPORTANT PRODUCT CLASSES IN THE PHARMACEUTICAL INDUSTRY¿TYPICAL PROCESS FORMATS COMPRISE MAMMALIAN EXPRESSION SYSTEMS SUCH AS CHINESE HAMSTER OVARY (CHO) CELLS CULTIVATED IN FED-BATCH PROCESSES WITH FINAL PRODUCTION SCALES OF SEVERAL CUBIC METERS.¿ ¿ ¿¿STUDIES HAVE CONFIRMED THE APPLICATION OF INCREASED BIOMASS FROM PRE-STAGE CULTIVATION FOR HIGH SEEDING CELL DENSITY IN PRODUCTION SCALE TO IMPROVE MONOCLONAL ANTIBODY YIELDS AND DECREASE PROCESS TIMES IN INTENSIFIED PROCESSES.¿ ¿ ¿FOR SEED CULTIVATION, CELLS WERE THAWED AND PASSAGED IN SHAKE FLASKS (CORNING, USA) EVERY 3 DAYS WITH INCUBATOR SETTINGS OF 120 RPM (50 MM ORBITAL THROW), 36.5°C AND 5% CO2. ¿ FED-BATCH PROCESSES: ¿A METABOLIC SHIFT FROM LACTATE PRODUCTION TO LACTATE CONSUMPTION LEADS TO AN IMPROVED PROCESS PERFORMANCE WITH RESPECT TO PRODUCTIVITY AND CELL GROWTH.¿ ALTHOUGH THE CUSTOMER DID NOT PROVIDE ANY SPECIFIC INFORMATION ON THE PREPARATION OF CHO CELLS FOR INOCULATION INTO THE BACT/ALERT CULTURE BOTTLES, THE TWO STUDIES PERTAINING TO THE USE OF CHO CELLS IN INDUSTRY PROCESSES AND THE TWO EXAMPLES OF COMMERCIAL VENDORS FOR CHO CELLS DEMONSTRATE THE REQUIREMENT OF A PERCENTAGE OF CO2 (E.G. 7%, 5%) IN THE PREPARATION OF THESE CELLS IN ORDER TO OBTAIN A VIABLE CULTURE OF CELLS FOR USE. THE BACT/ALERT DETECTION SYSTEM (REAGENT AND INSTRUMENT) UTILIZES THE COLORIMETRIC SENSOR AND REFLECTED LIGHT TO MONITOR THE PRESENCE OF AN INCREASE OF CARBON DIOXIDE (CO2) THAT OCCURS DURING THE GROWTH OF AN ORGANISM IN THE BACT/ALERT BOTTLE. THE PROCESS OF USING CO2 IN THE PREPARATION OF CHO CELLS AND THE INOCULATION OF A CHO SAMPLE INTO A BACT/ALERT CULTURE BOTTLE, COULD RESULT IN THE RESIDUAL CO2 PRESENT PRIOR TO ANY ¿TRUE¿ ORGANISM GROWTH AND POTENTIALLY CAUSE A FALSE POSITIVE RESULT. IN ADDITION, CULTIVATION OF CHO CELLS RESULTS IN A HIGH CELL DENSITY SAMPLE, AS SHOWN BY THE TWO STUDIES. INOCULATION OF A HIGH CELL DENSITY SAMPLE INTO A BACT/ALERT CULTURE BOTTLE COULD INTERFERE (NOISE) WITH THE REFLECTANCE READINGS AND NOT DETECT ANY ACTUAL GROWTH OF AN ORGANISM, POTENTIALLY RESULTING AS A FALSE POSITIVE BOTTLE. BOTH ARTICLES ALSO INVOLVED AN EVALUATION OF LACTATE IN RELATION TO CHO CELLS AND THE ASPECTS OF BIOPROCESSING. THE SAMPLE COMPOSITION WITH LEVELS OF LACTATE AND LOW PH COULD POTENTIALLY AFFECT THE HEADSPACE OF CO2 IN THE CULTURE BOTTLE, IN TURN, POTENTIALLY AFFECTING THE BOTTLE SENSOR TO TRIGGER AN UNWANTED RESPONSE (E.G. FALSE POSITIVE RESULT). DEVICE HISTORY RECORD AND COMPLAINT ANALYSIS: REVIEW OF MANUFACTURING DATA AND THE COMPLAINTS DATABASE DID NOT REVEAL ANY SYSTEMIC QUALITY ISSUE FOR EITHER PRODUCT. DOCUMENTATION REVIEW: THE INVESTIGATOR REVIEWED THE INSTRUCTIONS FOR USE [IFU] AND BACT/ALERT 3D USER MANUAL WHICH PROVIDES ADEQUATE DIRECTIONS TO REDUCE THE CHANCES OF OBTAINING FALSE POSITIVE RESULTS WITH BACT/ALERT BOTTLES. INFORMATION IN THE BACT/ALERT 3D USER MANUAL, SPECIFICALLY APPENDIX C (POSITIVES BEST PRACTICES FOR PREVENTING FALSE POSITIVES) IS PROVIDED TO THE USER PERTAINING TO SAMPLE VOLUME, LOADING AND UNLOADING CULTURE BOTTLES, AND MAINTAINING AN ENVIRONMENTAL TEMPERATURE FLUCTUATION AT A MINIMUM TO REDUCE THE CHANCES OF OBTAINING FALSE POSITIVE RESULTS WITH BACT/ALERT CULTURE BOTTLES: ¿ DO NOT FILL THE BACT/ALERT CULTURE BOTTLES OVER THE RECOMMENDED VOLUME IN THE INSTRUCTIONS FOR USE FOR BOTTLE TYPE. ¿ FAILURE TO ACHIEVE ADEQUATE LEUKOCYTE REDUCTION MAY RESULT IN FALSE POSITIVE READINGS ¿ ENSURE THE TEMPERATURE WHERE THE INSTRUMENT IS LOCATED FLUCTUATES AT A MINIMUM (E.G. INSTRUMENT IS AWAY FROM DIRECT VENTS, WINDOW DRAFTS). ¿ WHEN INSERTING THE CULTURE BOTTLE INTO THE 3D INSTRUMENT, ENSURE THE BOTTLE IS FULLY SEATED INTO THE CELL. ¿ LIMIT THE LOADING TIME TO 2 MINUTES IN ONE AREA AND CLOSE THE DRAWER TO ALLOW THE EQUILIBRATION OF TEMPERATURE BEFORE LOADING IN THE SAME AREA AGAIN. CLOSE THE DRAWER SECURELY AFTER WORK IS DONE. ¿ LIMIT THE UNLOADING TIME TO 15 MINUTES IN ONE AREA AND CLOSE THE DRAWER TO ALLOW THE EQUILIBRATION OF TEMPERATURE BEFORE LOADING IN THE SAME AREA AGAIN. CLOSE THE DRAWER SECURELY AFTER WORK IS DONE. ¿ DO NOT LOAD TOO MANY BOTTLES INTO ONE DRAWER AT THE SAME TIME WHERE OTHER BOTTLES ARE LOCATED THAT HAVE ALREADY REACHED INCUBATION TEMPERATURE. ¿ SPACE OUT THE LOADING OF BOTTLES BY LOADING INTO DIFFERENT INSTRUMENT DRAWERS. ¿ CAUTION: IF A LARGE NUMBER OF BOTTLES ARE LOADED INTO THE INCUBATION MODULE AT THE SAME TIME AND IN THE SAME AREAS, A LARGE HEAT MASS LOSS WITHIN THE RACKS MAY OCCUR. THIS HEAT LOSS MAY TRIGGER THE ACCELERATION OR RATE ALGORITHMS TO ERRONEOUSLY FLAG POSITIVE. ¿ KEEP TRACK OF HOW MANY TIMES A PARTICULAR CELL, RACK, OR INSTRUMENT HAS A HIGH NUMBER OF CULTURE BOTTLES WITH FALSE POSITIVE RESULTS (E.G. CELL MIGHT NEED TO BE CALIBRATED) ¿ CELLULAR SAMPLES MAY CAUSE FALSE POSITIVES DUE TO CELL RESPIRATION AND PRODUCTION OF CO2 THAT IS DETECTED BY THE BOTTLE¿S SENSOR AND THE INSTRUMENT¿S ALGORITHM. THE SAMPLE VOLUME AND/OR CELLULAR DENSITY MAY NEED TO BE ADJUSTED TO PREVENT INSTRUMENT FALSE POSITIVES. THE CUSTOMER IS RESPONSIBLE FOR VALIDATION OF THEIR USE OF THE SYSTEM. CONCLUSION: BASED ON THE INFORMATION ABOVE, THERE IS NO EVIDENCE OF ANY BOTTLE MALFUNCTION WITH THE BACT/ALERT IFA PLUS, IFN PLUS, INST CULTURE BOTTLE LOTS. MONITORING AND DETECTION METHODS FOR BOTTLE DEFECTS ASSOCIATED WITH POTENTIAL FALSE POSITIVE RESULTS ARE PART OF THE MANUFACTURING AND QUALITY CONTROL PROCESSES FOR BACT/ALERT CULTURE BOTTLES.

Description of Event or Problem · 0

A CUSTOMER IN (B)(6) NOTIFIED BIOMÉRIEUX OF FALSE POSITIVE RESULTS IN ASSOCIATION WITH BACT/ALERT IFN PLUS (REF. 412991, BATCH NUMBER 0004056863, EXPIRATION DATE 29-DEC-2021) IN A CONTEXT OF ROUTINE TESTING WITH THE EQUIPMENT BACT/ALERT 3D 0480 (SERIAL NUMBER (B)(4)). IT WAS REPORTED THAT THE ISSUE IMPACTED 8 BOTTLES OF THE FOLLOWING LOTS: BACT/ALERT IFA+, LOT 0004100062 (RELATED COMPLAINT (B)(4)) , BACT/ALERT IFN+, LOT 0004056863 , AND BACT/ALERT INST, LOT 0001056868 (RELATED COMPLAINT (B)(4)). SAMPLE TYPES WERE A MIX OF AEROBIC AND ANAEROBIC, AND ALSO A MIX OF SAMPLES THAT CONTAINED CELLS (PRODUCT) AND DID NOT CONTAIN CELLS (MEDIA). IT WAS REPORTED THAT THE FALSE POSITIVE RESULTS WERE CONFIRMED BY SUBCULTURE. A BIOMÉRIEUX FIELD SERVICE ENGINEER (FSE) VISITED THE CUSTOMER SITE AND PERFORMED ANNUAL MAINTENANCE; NO EQUIPMENT FAULTS OR TECHNICAL ISSUES WITH THE BACT/ALERT 3D WERE IDENTIFIED. THERE IS NO INDICATION OR REPORT FROM THE CUSTOMER THAT THE FALSE POSITIVE RESULTS LED TO ANY ADVERSE EVENT RELATED TO ANY PERSON'S STATE OF HEALTH. THE IMPACTED PRODUCT REFERENCE (BACT/ALERT® IFN PLUS ¿ REF. 412991) IS NOT AN IVD PRODUCT; HOWEVER THE BACT/ALERT® FN PLUS ¿ REF. 410852 IS THE SAME FORMULATION AND IS AN IVD.

Devices

Seq	Brand	Generic	Product Code	Manufacturer	Model	Lot	UDI-DI
1757917	BACT/ALERT I FN PLUS	BACT/ALERT I FN PLUS	MDB	BIOMÉRIEUX, INC		0004056863

Patients

Seq	Age	Sex	Outcome	Treatment
1		Unknown