BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    ID CORE XT

    MDR report key: 15698703 · Received October 31, 2022

    Report

    Report Number
    3006413195-2022-00007
    Event Type
    Malfunction
    Date Received
    October 31, 2022
    Date of Event
    July 27, 2022
    Report Date
    July 29, 2024
    Manufacturer
    PROGENIKA BIOPHARMA, S.A
    Product Code
    PEP
    UDI-DI
    08437013457019
    PMA / PMN Number
    BP170154
    Removal / Correction Number
    N/A
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    FL, US
    Reporter Occupation
    OTHER HEALTH CARE PROFESSIONAL
    Health Professional
    Yes

    Narratives

    Additional Manufacturer Narrative · 0

    FOLLOWING SECTIONS HAVE BEEN UPDATED: IT IS ATTACHED, FDA REQUESTS ADDITIONAL INFORMATION LETTER AND MAIL RECEIVED IN PROGENIKA ON FEBRUARY 14, 2023, AND THE ANSWER TO THAT LETTER SENT BY PROGENIKA TO FDA BY EMAIL ON FEBRUARY 17, 2023.

    Additional Manufacturer Narrative · 0

    TO ADDRESS THIS ISSUE PROMPTLY AND PROVIDE ACCURATE RESULTS TO THE CUSTOMER, AS WELL AS TO FACILITATE FURTHER INVESTIGATION, THE GENOMIC DNA SAMPLE (B)(6) WAS SENT TO GRIFOLS LABORATORY SOLUTIONS (GLS, SAN MARCOS, TX) FOR SEQUENCING OF LU GENE (DNA SEQUENCING OF BCAM EXONS 1 TO 15). THE VARIANT LU: C.1615A>G WAS DETECTED, AND THE PREDICTED PHENOTYPE WAS LUA-, WHICH CONTRASTED WITH THE SECOND RESULT OF ID CORE XT. THE RESULT OF THE SAMPLE WAS CONFIRMED TO BE LUA-. THE FOLLOWING SOURCES OF INFORMATION HAVE BEEN REVIEWED AS PART OF THE ROOT CAUSE INVESTIGATION TO DETERMINE WHETHER THE REPORTED EVENT COULD BE ATTRIBUTED TO ID CORE XT DEVICE. A) REVIEW OF DEVICE HISTORY RECORDS OF ID CORE XT LOTS 0203000023 AND 0203000026 USED BY THE CUSTOMER IN THE REPORTED EVENT. A REVIEW OF THE DEVICE HISTORY RECORDS OF ID CORE XT LOT 0203000023 AND LOT 0203000026 WAS PERFORMED, WHICH CONFIRMED THAT NO INCIDENTS WERE REPORTED DURING THE PRODUCTION PROCESS THAT COULD BE IN RELATION THE REPORTED EVENT. LIKEWISE, QUALITY CONTROL (QC) RECORDS FOR THE LOTS RELEASED DID NOT SHOW INCIDENTS AND ALL TESTS PERFORMED MET THE ACCEPTANCE CRITERIA. SPECIFICALLY, LOT RELEASE QC RESULTS FOR PROBE SET 48 CLUSTER 3, CORRESPONDING TO LUA- PHENOTYPE FOR ID CORE XT LOTS 0203000023 AND 0203000026 WERE REVIEWED AND NO DEVIATIONS WERE DETECTED. A TOTAL OF (B)(4) REFERENCE GENOMIC SAMPLES WITH LUA- PHENOTYPE WERE INCLUDED IN THE LOT-RELEASE QC PANELS OF ID CORE XT LOTS 0203000023 AND 0203000026, RESPECTIVELY. ALL QC RESULTS WERE CORRECT, AND ALL LUA- REFERENCE SAMPLES WERE CORRECTLY DETECTED AS LUA- PHENOTYPE. B) VERIFICATION OF RETAIN SAMPLES: ON 06FEB2023, THE RETAIN SAMPLE KIT OF ID CORE XT LOT 0203000026 HAS BEEN ANALYZED ACCORDING TO PROGENIKA'S STABILITY PROGRAM REQUIREMENTS, WHICH INCLUDE THE CORRECT TYPING OF SEVERAL REPLICATES OF LUA- REFERENCE SAMPLES. THE PRODUCT IS STABLE AT THE ANALYZED TIME POINT (14 MONTHS), COMPLYING WITH ALL THE ACCEPTANCE CRITERIA. THIS FURTHER CONFIRMS THAT THE PERFORMANCE OF ID CORE XT PRODUCT REMAINS UNCOMPROMISED. C) REVIEW OF CUSTOMER'S RAW DATA: ON 07OCT2022, PROGENIKA'S PRODUCT DEVELOPMENT AND SUPPORT (PD&S) TEAM RECEIVED AND EVALUATED THE CUSTOMER´S RAW DATA. THE TWO RUNS PROCESSED ON (B)(6) 2022 AND (B)(6) 2022 BY THE CUSTOMER INCLUDED A NEGATIVE CONTROL, TWO ID CORE CONTROLS 1 & 2, AND 93 GENOMIC DNA SAMPLES, ALONG WITH THE SAMPLE (B)(6). ALL CONTROLS PASSED AS EXPECTED. ALL SAMPLES OF THE RUN WERE PROCESSED USING THE SAME REAGENT LOT (LOT 0203000026). A REAGENT LOT-SPECIFIC ISSUE WAS RULED OUT. ACCORDING TO THIS INFORMATION, THE PERFORMANCE OF ID CORE XT LOT 0203000026 IS NOT COMPROMISED, SO THE EVENT IS NOT ATTRIBUTABLE TO THE DEVICE. A REVIEW OF THE CUSTOMER RUN DATA FOR SAMPLE (B)(6) SHOWED A WEAKER THAN AVERAGE MFI (MEAN FLUORESCENCE INTENSITIES) FOR LUB PROBE (MFI OF 2364) ON RUN OF (B)(6) 2022 COMPARED TO THE MFI VALUE OF 4173 ON RUN OF 29JUL22. THE SLIGHTLY LOW SIGNAL DIFFERENCE BETWEEN LUA AND LUB PROBES OF SAMPLE (B)(6) (MFIS 1495 AND 2364 RESPECTIVELY) ON THE RUN OF THE 27JUL2022 WAS MIS-INTERPRETED BY THE ID CORE XT ANALYSIS SOFTWARE AS LUA+LUB+ INSTEAD OF LUA- AND LUB+. THE POSSIBLE CAUSES OF THIS BEHAVIOR SEEMED TO BE RELATED EITHER WITH THE SAMPLE QUALITY OR WITH SAMPLE PROCESSING (EQUIPMENT OR ANALYTICAL METHOD). THEREFORE, FURTHER INVESTIGATION STEPS WERE FOCUSED ON THESE TWO ASPECTS. FIRSTLY, RELATED WITH SAMPLE QUALITY, THE DNA SAMPLE (B)(6) QUALITY PARAMETERS (QUANTITY AND PURITY) WERE REVIEWED AND FOUND TO BE ACCEPTABLE (CONC. 29.2 NG/UL, A260/280: 1.89). THUS, A SAMPLE QUALITY ISSUE WAS RULED OUT. SECONDLY, RELATED WITH SAMPLE PROCESSING, INFORMATION FROM OTHER COMPLAINTS RECEIVED FROM THE SAME CUSTOMER, LIFESOUTH COMMUNITY BLOOD CENTER, AND RELATED WITH THIS SAME ISSUE THAT WERE REPORTED DURING THE INVESTIGATION, WAS REVIEWED. THE REVIEW OF CUSTOMER RAW DATA (LUMINEX OUTPUT FILES) SHOWED THAT ALL THE SAMPLES WITH INCORRECT LUA+ RESULT, INCLUDING SAMPLE (B)(6), WERE LOCATED IN THE OUTER ROW H OF THE 96-WELL PLATE. THE AVERAGE SIGNAL FOR LUTHERAN PROBES OF SAMPLES LOCATED IN ROW H WAS ALMOST 50% LOWER THAN THAT OF SAMPLES LOCATED IN THE MIDDLE OF THE PLATE (ROW D AS REFERENCE). THE SIGNAL OF PROBES FOR THE REST OF BLOOD GROUPS WERE ONLY SLIGHTLY AFFECTED BY THE POSITION ON THE PCR PLATE BUT PROVIDED CORRECT CALLS. SINCE LUTHERAN IS THE MOST SENSITIVE ID CORE XT BLOOD GROUP TO SUBOPTIMAL ASSAY CONDITIONS, THIS OBSERVATION SUGGESTS THAT SUBOPTIMAL PCR AMPLIFICATION CONDITIONS WERE SPECIFICALLY AFFECTING THE OUTER ROW H OF THE 96-WELL PLATE. IN THIS REGARD, THE NON-UNIFORMITY OF THE THERMAL CYCLER TEMPERATURE ACROSS THE BLOCK, DUE EITHER TO A DEFECTIVE EQUIPMENT OR TO THE USE OF DAMAGED COMPRESSION PADS TO COVER THE 96-WELL PLATE DURING THE AMPLIFICATION AND/OR THE HYBRIDIZATION, OR A PARTIAL EVAPORATION DURING THE AMPLIFICATION ARE MOST LIKELY THE ROOT CAUSES OF THE OBSERVED DISCORDANT RESULTS. COMPLAINT CODE, RUN DATE, ID CORE XT LOT, SAMPLE ID 96-WELL PLATE POSITION, LUA PREDICTED RESULT: RE22/016, 17NOV2021, 0203000023, (B)(6), H8, LUA+; 18AUG2022, 0203000026 , (B)(6), F9 , LUA-; 21AUG2022, 0203000026 , (B)(6), A2 , LUA-; RE22/021 11NOV2021, 0203000023 , (B)(6), B7 , LUA-; 27JUL2022, 0203000026 , (B)(6), H11 , LUA+; 29JUL2022, 0203000026 , (B)(6), B2 , LUA-; RE22/027 02MAR2022, 0203000024 , (B)(6), F5 , LUA-; 22OCT2022, 0203000026 , (B)(6), H1 , LUA+; RE22/028 03AUG2022, 0203000026 , (B)(6), F8 , LUA-; 26OCT2022, 0203000026 , (B)(6), H12 , LUA+; RE22/029 25MAY2022, 0203000025 , (B)(6), F11 , LUA-; 13OCT2022, 0203000026 , (B)(6), H12 , LUA+; RE23/002 03SEP2022, 0203000026 , (B)(6), H1 , LUA+; 05JAN2023, 0203000026 , (B)(6), D12 , LUA- RE23/003 14SEP2022, 0203000026 , (B)(6), H8 , LUA+; 11JAN2023, 0203000026 , (B)(6), D12 , LUA-; RE23/004 18JAN2023, 0203000026 , (B)(6), H1 , LUA+ 19JAN2023, 0203000026 , (B)(6), G4 , LUA-. D) REVIEW OF INTERNAL NONCONFORMITIES THAT COULD BE RELATED TO THIS EVENT. DURING THE REVIEW OF INTERNAL NONCONFORMITIES, ONE NONCONFORMITY (NC19/021) RELATED TO THIS MATTER WAS IDENTIFIED. THE NONCONFORMITY NC19/021 FROM 2019 CONSISTED IN A "NO CALL" RESULT IN PROBE SET 48, CORRESPONDING TO LUA PHENOTYPE IN A SAMPLE LOCATED IN THE OUTER ROW H OF THE 96-WELL PLATE DURING LOT-RELEASE QC OF ID CORE XT LOT 0203000018. A THOROUGH INVESTIGATION REVEALED THAT THE CAUSE OF THE NONCONFORMITY WAS A MALFUNCTIONING HEATER LID OF THE THERMAL CYCLER. THE ISSUE WAS RESOLVED BY REPLACING THE HEATER LID. E) ON-SITE VISIT TO THE CUSTOMER: A GRIFOLS SUPPORT SPECIALIST SCHEDULED AN ON-SITE TECHNICAL VISIT TO CHECK THE EQUIPMENT USED AND TO REVIEW THE SAMPLE PROCESSING STEPS. THE ON-SITE VISIT TOOK PLACE ON 17JAN2023. THE CONCLUSIONS TO HIGHLIGHT DERIVED FROM THE VISIT ARE: RELATED TO EQUIPMENT: ALL EQUIPMENT MET THE REQUIREMENTS FOR QUALIFICATION, CALIBRATION, AND MAINTENANCE (PIPETTES/ THERMAL CYCLER/ LUMINEX). THE CUSTOMER DOES NOT MAINTAIN TRACEABILITY OF EQUIPMENT (THERMAL CYCLERS) USED FOR SAMPLE PROCESSING, MAKING IT IMPOSSIBLE TO ESTABLISH ANY POTENTIAL CONNECTIONS WITH THE REPORTED EVENTS. RELATED TO PROCESSING, THREE DEVIATIONS WERE DETECTED: THE MICROAMP OPTICAL FILM COMPRESSION PADS HAD NOT BEEN REPLACED RECENTLY. THE ID CORE XT PACKAGE INSERT INCLUDES A WARNING (SECTION 3 WARNING AND CAUTIONS) STATING: "THE COMPRESSION PAD SHOULD MAINTAIN PERFORMANCE FOR A MINIMUM OF 20 RUNS. IT IS IMPORTANT TO EXAMINE THE PAD BEFORE EACH RUN SPECIFICALLY AFTER MORE THAN 20 USES, AS DETERIORATED COMPRESSION PADS MAY LEAD TO EVAPORATION AND FAILED REACTIONS". ONE OF THE OPERATORS USED TWO MICROAMP OPTICAL FILM COMPRESSION PADS IN AMPLIFICATION STEP INSTEAD OF ONE, CONTRARY TO THE INSTRUCTIONS SPECIFIED IN THE ID CORE XT PACKAGE INSERT. ONE OF THE OPERATORS DID NOT PERFORM THE SPIN-DOWN STEP OF THE 96-WELL PLATE REQUIRED AS STATED IN THE ID CORE XT PACKAGE INSERT. IN SUMMARY, THE ON-SITE VISIT HIGHLIGHTED THE NEED FOR FURTHER EVIDENCE COLLECTION TO DETERMINE IF ANY SPECIFIC THERMAL CYCLER IS INVOLVED IN THE REPORTED EVENT. ADDITIONALLY, DEVIATIONS FROM THE ANALYTICAL PROCESS, AS INDICATED IN THE ID CORE XT PACKAGE INSERT, WERE OBSERVED THAT MAY BE RELATED TO THE EVENT. F) REVIEW OF LIFESOUTH COMMUNITY BLOOD CENTER THERMAL CYCLERS PERFORMANCE BASED ON THE ABOVE RESULTS, OUR INVESTIGATION LED US TO INITIALLY SUSPECT THAT THE ISSUE MIGHT BE THE THERMAL CYCLER'S IMPROPER PERFORMANCE. HOWEVER, ON 26APR2023, THE CUSTOMER CONDUCTED A PERFORMANCE QUALIFICATION (PQ) OF THEIR THERMAL CYCLERS FOLLOWING PROGENIKA´S PROTOCOL (PQ). ALL RESULTS MET THE EXPECTED SPECIFICATIONS, INDICATING THAT THE THERMAL CYCLERS PERFORMANCE IS NOT THE CAUSE OF THE PROBLEM. CONCLUSION: THE CONDUCTED INVESTIGATIONS HAVE CONFIRMED THE CORRECT PERFORMANCE OF ID CORE XT PRODUCT. NO ISSUES OR DEVIATIONS HAVE BEEN IDENTIFIED CONCERNING THE QC AND MANUFACTURING PROCESSES, SAMPLE QUALITY OR THE INSTRUMENTS USED FOR PROCESSING. ALTHOUGH THE ROOT CAUSE OF THE ISSUE REMAINS UNKNOWN, IT COULD BE RELATED TO PROCESSING DEVIATION. SINCE THE TECHNICAL ON-SITE VISIT ON 17JAN2023, NO ADDITIONAL COMPLAINTS RELATED TO THIS ISSUE HAVE BEEN RECEIVED, INDICATING THAT THE PROBLEM HAS BEEN SOLVED.

    Description of Event or Problem · 0

    THE CUSTOMER REPORTED A MALFUNCTION OF ID CORE XT. SAMPLE ORIGINALLY TESTED AS LUA NEGATIVE, TESTED AS LUA POSITIVE AND THE REPETITION TESTED WITH DIFFERENT PRODUCT BATCH AS LUA NEGATIVE. NO SEROLOGICAL TESTING WAS PERFORMED.

    Description of Event or Problem · 0

    THE SAMPLES CODED AS (B)(6) WERE TESTED BY THE CUSTOMER "LIFESOUTH COMMUNITY BLOOD CENTER" WITH ID CORE XT ASSAY. BOTH SAMPLES CAME FROM THE SAME DONOR, BUT FROM TWO DIFFERENT DNA EXTRACTION EVENTS. THE RESULT OF THE FIRST TYPING PERFORMED ON 11NOV2021 WITH SAMPLE (B)(6) AND ID CORE XT LOT 0203000023 WAS NEGATIVE (LUA-), WHICH WAS IN CONTRAST TO THE RESULT OF THE SECOND TYPING PERFORMED ON 27JUL2022, USING THE ID CORE XT ASSAY LOT 0203000026 WITH SAMPLE (B)(6) WHICH PROVIDED A POSITIVE RESULT (LUA+). THE SITE REPEATED THE ASSAY WITH THE SAMPLE W070522215343Y AND LOT 0203000026 AND THE RESULT WAS CONFIRMED LUA NEGATIVE (LUA-). ALL GENOTYPE AND PHENOTYPE RESULTS WERE PROVIDED BY THE ID CORE XT ANALYSIS SOFTWARE V3.0.4.1.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    2455702 ID CORE XT ANTIGEN GENOTYPING TEST PEP PROGENIKA BIOPHARMA, S.A V3 0203000026 08437013457019

    Patients

    Seq Age Sex Outcome Treatment
    1 NA Unknown