BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    ID CORE XT

    MDR report key: 16250532 · Received January 26, 2023

    Report

    Report Number
    3006413195-2023-00001
    Event Type
    Malfunction
    Date Received
    January 26, 2023
    Date of Event
    October 12, 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

    IT IS ATTACHED, FDA REQUESTS ADDITIONAL INFORMATION LETTER AND MAIL RECEIVED IN PROGENIKA ON MARCH,7 2023, AND THE ANSWER TO THAT LETTER SENT BY PROGENIKA TO FDA BY EMAIL ON MARCH, 16 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 LU EXONS 1 TO 15). THE VARIANTS LU: C.1615A>G LU: C.711C>T AND LU: C.1227G>T WERE 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 0203000024 AND 0203000026 USED BY THE CUSTOMER IN THE REPORTED EVENT. A REVIEW OF THE DEVICE HISTORY RECORDS OF ID CORE XT LOT 0203000024 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 0203000024 AND 0203000026 WERE REVIEWED AND NO DEVIATIONS WERE DETECTED. A TOTAL OF 26 AND 29 REFERENCE GENOMIC SAMPLES WITH LUA- PHENOTYPE WERE INCLUDED IN THE LOT-RELEASE QC PANELS OF ID CORE XT LOTS 0203000024 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 (B)(6) 2023, 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 07DEC22, PROGENIKA'S PRODUCT DEVELOPMENT AND SUPPORT (PD&S) TEAM RECEIVED AND ASSESSED THE RAW DATA PROVIDED BY THE CUSTOMER. THE RUN PROCESSED ON (B)(6) 2022 BY THE CUSTOMER INCLUDED A NEGATIVE CONTROL, TWO ID CORE CONTROLS 1 & 2, 92 GENOMIC DNA SAMPLES AND THE SAMPLE (B)(6). ALL CONTROLS PRODUCED THE EXPECTED RESULTS WITH SATISFACTORY MEDIUM FLUORESCENCE INTENSITIES (MFIS) AND RATIOS (MFI OF LUB PROBE DEVIDED BY THE SUM OF MFI OF LUB AND LUA PROBES). ALL SAMPLES OF THE RUN WERE PROCESSED USING THE SAME REAGENT VIALS. 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´S DATA FOR SAMPLE (B)(6) SHOWED A WEAKER THAN AVERAGE SIGNAL FOR LUB PROBE (1220.5). THE SIGNAL OF THE REMAINING ID CORE XT BLOOD GROUPS WAS CORRECT. THE AVERAGE SIGNAL OF LU (A-, B+) SAMPLES IN THIS RUN WAS 1671 FOR LUA PROBE (BACKGROUND) AND 5457 FOR LUB PROBE. THE SLIGHTLY LOW SIGNAL DIFFERENCE BETWEEN LUA AND LUB PROBES OF SAMPLE (B)(6) (773 AND 1220.5 RESPECTIVELY) WAS MIS-INTERPRETED BY THE ID CORE XT ANALYSIS SOFTWARE AS LUA+LUB+ INSTEAD OF LUA-LUB+. THE POTENTIAL CAUSES OF THIS BEHAVIOR SEEMED TO BE RELATED EITHER TO THE SAMPLE QUALITY OR 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. 46 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 OTHER BLOOD GROUPS WAS ONLY SLIGHTLY AFFECTED BY THE POSITION ON THE PCR PLATE BUT PRODUCED CORRECT CALLS. GIVEN THAT LUTHERAN IS THE MOST SUSCEPTIBLE ID CORE XT BLOOD GROUP TO SUBOPTIMAL ASSAY CONDITIONS, THIS OBSERVATION INDICATES 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 TO EITHER 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 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 (B)(6) 2021 0203000023 (B)(6) H8 LUA+. (B)(6) 2022 0203000026 (B)(6) F9 LUA-. (B)(6) 2022 0203000026 (B)(6) A2 LUA-. RE22/021 11NOV2021 0203000023 (B)(6) B7 LUA-. (B)(6) 2022 0203000026 (B)(6) H11 LUA+. (B)(6) 2022 0203000026 (B)(6) B2 LUA-. RE22/027 02MAR2022 0203000024 (B)(6) F5 LUA-. (B)(6) 2022 0203000026 (B)(6) H1 LUA+. RE22/028 03AUG2022 0203000026 (B)(6) F8 LUA-. (B)(6) 2022 0203000026 (B)(6) H12 LUA+. RE22/029 25MAY2022 0203000025 (B)(6) F11 LUA-. (B)(6)2022 0203000026 (B)(6) H12 LUA+. RE23/002 03SEP2022 0203000026 (B)(6) H1 LUA+. (B)(6)2023 0203000026 (B)(6) D12 LUA-. RE23/003 14SEP2022 0203000026 (B)(6) H8 LUA+. (B)(6)2023 0203000026 (B)(6) D12 LUA-. RE23/004 18JAN2023 0203000026 (B)(6) H1 LUA+. (B)(6) 2023 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 SAMPLES CODED AS (B)(6) WERE TESTED BY THE CUSTOMER "(B)(6) 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 MOLECULAR TYPING PERFORMED ON (B)(6) 2022 WITH SAMPLE (B)(6) AND ID CORE XT LOT 0203000024 WAS NEGATIVE (LUA), WHICH WAS IN CONTRAST TO THE RESULT OF MOLECULAR TYPING PERFORMED ON (B)(6) 2022, USING THE ID CORE XT ASSAY LOT 0203000026 WITH SAMPLE (B)(6) WHICH PROVIDED A POSITIVE RESULT (LUA+). ALL GENOTYPE AND PHENOTYPE RESULTS WERE PROVIDED BY THE ID CORE XT ANALYSIS SOFTWARE V3.0.4.1.

    Description of Event or Problem · 0

    THE CUSTOMER REPORTED A MALFUNCTION OF ID CORE XT. THE SAMPLE: (B)(4) ANALYZED (WORK ORDER (B)(4) ON (B)(6) 2022 USING THE ID CORE XT PROVIDED A POSITIVE RESULT (LUA+). HOWEVER, THIS RESULT WAS DIFFERENT TO OTHER SAMPLE FROM THE SAME DONOR (B)(6), ANALYSED ON (B)(6) 2022 THAT RESULTED NEGATIVE (LUA-).

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    1202601 ID CORE XT ANTIGEN GENOTYPING TEST PEP PROGENIKA BIOPHARMA, S.A V3 0203000026 08437013457019

    Patients

    Seq Age Sex Outcome Treatment
    1 NA Unknown