NEOBASE¿ 2 NON-DERIVATIZED MSMS KIT
Report
- Report Number
- 3002808498-2025-00001
- Event Type
- Malfunction
- Date Received
- April 29, 2025
- Date of Event
- August 17, 2023
- Report Date
- June 27, 2025
- Manufacturer
- WALLAC OY
- Product Code
- NQL
- UDI-DI
- 06438147356812
- PMA / PMN Number
- K193103
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- CA, US
- Reporter Occupation
- PHYSICIAN
- Health Professional
- Yes
Narratives
INVESTIGATION REPORT FOR THE FDA FOLLOW-UP REPORT #1 (MFR REPORT#: 3002808498-2025-00001) FALSE NEGATIVE X-ALD USING KIT 3044-0010 NEOBASE¿ 2 NON-DERIVATIZED MSMS KIT (MFG REFERENCES: COMPLAINT (B)(4)). HEALTH EFFECT INFORMATION AND ASSAY INFORMATION STILL NOT RECEIVED. THE MANUFACTURER RECEIVED INVESTIGATION DATA, INCLUDING GRAPHICAL RESULTS, FROM THE CUSTOMER ON 06-MAY-2025. THE CUSTOMER REPORTED OBSERVING A SYSTEMATIC INCREASE IN THE INTENSITY LEVEL OF THE C26:0-LPC INTERNAL STANDARD (IS) IN THEIR EXTRACTION WORKING SOLUTION (EWS) OVER A 10-DAY USAGE PERIOD. THIS TREND MAY ELEVATE THE RISK OF FALSELY LOW C26:0-LPC ANALYTE RESULTS IN DRIED BLOOD SPOT (DBS) SAMPLES, POTENTIALLY LEADING TO FALSE-NEGATIVE RESULTS IN X-ALD NEWBORN SCREENING. MANUFACTURER HAS NO INDICATION OF SIMILAR TREND BEING OBSERVED IN-HOUSE OR BY OTHER CUSTOMERS. CONSEQUENTLY, MANUFACTURER INITIATED A CONFIRMATORY IN-USE STABILITY STUDY OF THE EWS ON 13-MAY-2025 (MFG REFERENCE: (B)(4)) TO RULE OUT ANY POTENTIAL INSTABILITY ISSUE OF THE C26:0-LPC IS IN THE EWS WITHIN ITS CURRENTLY CLAIMED 2 WEEKS IN-USE PERIOD. INTERIM DATA FOR C26:0 LPC INTERNAL STANDARD (IS) SHOWS NO INCREASE IN IS INTENSITIES OBSERVED OVER THE 10-DAY PERIOD, CONSISTENT WITH MANUFACTURER'S PREVIOUS RESULTS. THE STABILITY STUDY IS ONGOING AND WILL CONTINUE FOR A TOTAL DURATION OF 17 DAYS. AN INCREASE IN IS INTENSITY COULD POTENTIALLY BE CAUSED BY INSTRUMENT OR LABWARE CONTAMINATION. INVESTIGATION AROUND THIS IS ONGOING. NOTE: SINCE AN APPROPRIATE COMPONENT CODE IS NOT AVAILABLE FOR H6 (FDA CODE 4756: APPROPRIATE TERM/CODE NOT AVAILABLE), THE MANUFACTURER RECOMMENDS ADDING THE LEVEL 2 TERM 'TEST SYSTEM' UNDER THE LEVEL 1 TERM 'BIOLOGICAL AND CHEMICAL', WITH THE DEFINITION: 'NEWBORN SCREENING TEST SYSTEM'."
HEALTH EFFECT INFORMATION AND ASSAY INFORMATION NOT RECEIVED. THE MANUFACTURING BATCH RECORDS WERE REVIEWED: NO DEVIATIONS WERE FOUND, BOTH ORIGINAL AND RETEST DEVICE LOTS PERFORMED WITHIN ACCEPTANCE RANGE. THE MDR REPORTING IS DELAYED BECAUSE THE WEBTRADER ACCOUNT NEEDED FOR ELECTRONIC SUBMISSION WAS STILL REGISTERED UNDER PERKINELMER AND WAS NOT UPDATED WHEN THE COMPANY REBRANDED TO REVVITY DURING 2023-2024.
DURING THE INVESTIGATION, THE MANUFACTURER DID NOT RECEIVE ANY INFORMATION REGARDING THE HEALTH EFFECTS OF THE ADVERSE EVENT ASSOCIATED WITH THE MEDICAL DEVICE. SPECIFICALLY, NO DETAILS WERE PROVIDED CONCERNING THE CLINICAL SIGNS, SYMPTOMS, OR MEDICAL CONDITIONS EXPERIENCED BY THE AFFECTED PATIENT AS A RESULT OF THE EVENT. MANUFACTURER DID NOT RECEIVE THE CONCERNED ARCHIVED X-ALD PATIENT SAMPLE FOR SEQUENCING TO CLARIFY PATIENT'S ABCD1 GENE. MANUFACTURER CONFIRMATORY IN-USE STABILITY STUDY WAS PERFORMED DURING 13-MAY-2025 TO 30-MAY-2025 (MFG REFERENCE (B)(4)) TO RULE OUT THE SUSPECTED INSTABILITY ISSUE OF THE C26:0-LPC INTERNAL STANDARD (IS) IN THE EXTRACTION WORKING SOLUTION (EWS) WITHIN ITS CLAIMED 2 WEEKS IN-USE PERIOD. THE STABILITY TESTING WAS CONDUCTED IN ACCORDANCE WITH GUIDELINE EN ISO 23640 IN VITRO DIAGNOSTIC MEDICAL DEVICES - EVALUATION OF STABILITY OF IN VITRO DIAGNOSTIC REAGENTS AND CLSI EP25-ED2 EVALUATION OF STABILITY OF IN VITRO MEDICAL LABORATORY TEST REAGENTS, 2ND EDITION. IN THE COMPLETED STABILITY STUDY WITH THREE DIFFERENT NEOBASE 2 IS COMPONENT LOTS (AFTER THEIR REAL-TIME STORAGE OF 10, 12 AND 14 MONTHS AT +2-8°C), THE CURRENTLY ESTABLISHED 2 WEEKS (14 DAYS) EWS IN-USE STABILITY PERIOD WAS CONFIRMED AS THE PREPARED EWS REMAINED STABLE UNTIL 17 DAYS PERIOD IF HANDLED AND STORED ACCORDING TO THE NEOBASE 2 PRODUCT IFU. BECAUSE THIS CONFIRMATORY EWS IN-USE STABILITY STUDY WAS INITIALLY TRIGGERED DUE TO SUSPECTED C26:0-LPC IS INSTABILITY CONCERNS OVER THE EWS USE, MORE DETAILED STABILITY TRENDS GRAPHS FOR THIS SPECIFIC ANALYTE ARE ATTACHED AS AN APPENDIX TO THIS REPORT. AS CLEARLY SEEN IN THESE TREND GRAPHS WITH ALL THREE TESTED NEOBASE 2 IS LOTS, THE SUSPECTED INCREASE IN THE C26:0-LPC IS SIGNAL LEVELS CANNOT BE SEEN IN THIS INTERNALLY CONDUCTED EWS IN-USE STABILITY STUDY, AND MORE IMPORTANTLY ALSO THE MEASURED NEOBASE 2 FROZEN CONTROL LOW AND HIGH RESULTS REMAIN FIRMLY STABLE OVER THE ENTIRE EWS IN-USE STABILITY STUDY PERIOD 0-17 DAYS. BASED ON THE ADDITIONAL CONFIRMATORY 17 DAYS IN-USE STABILITY STUDY OF THE NEOBASE 2 EWS PREPARED FROM 10, 12 AND 14 MONTHS OLD NEOBASE 2 IS COMPONENT LOTS, THE FOLLOWING CURRENTLY ESTABLISHED IN-USE TIMES WERE CONFIRMED: ONCE OPENED AND RECONSTITUTED, USE THE RECONSTITUTED NEOBASE 2 INTERNAL STANDARDS VIAL IMMEDIATELY FOR THE PREPARATION OF ONLY A SINGLE EWS. AFTER THE EWS PREPARATION, IT CAN BE USED FOR 2 WEEKS WHEN STORED AT +2-+8 °C PROTECTED FROM LIGHT. WHEN NOT IN USE, STORE THE EWS PROTECTED FROM LIGHT IN A GLASS LABORATORY BOTTLE WITH FIRMLY SEALED SCREW CAP CLOSURE AT +2-+8 °C. IN ADDITION TO INTERNAL STABILITY STUDY, AT THE REQUEST OF THE CUSTOMER, THE MANUFACTURER PERFORMED ANOTHER STABILITY STUDY AT THE CUSTOMER'S FACILITY (CALIFORNIA DEPARTMENT OF PUBLIC HEALTH, RICHMOND, CA). THE RESULTS OF THIS EXTERNAL STUDY WERE CONSISTENT WITH THOSE OBTAINED IN THE MANUFACTURER'S CONFIRMATORY STUDY. IT WAS ORIGINALLY ANTICIPATED THAT AN INCREASE IN IS INTENSITY COULD POTENTIALLY BE CAUSED BY INSTRUMENT OR LABWARE CONTAMINATION. HOWEVER, DURING THE VISIT TO THE CUSTOMER SITE, NO ISSUES WITH THE WORKFLOW WERE IDENTIFIED THAT WOULD HAVE CAUSED CONTAMINATION AND NO C26:0-LPC SPECIFIC INSTRUMENT CONTAMINATION WAS OBSERVED. AS A CONCLUSION, NO MALFUNCTION OF DEFICIENCY OF PRODUCT COULD BE IDENTIFIED. ROOT CAUSE FOR THE FALSE NEGATIVE RESULT COULD NOT BE CONCLUDED.
FOLLOW-UP REPORT. ON 07-MAY-2025 MANUFACTURER RECEIVED INFORMATION THAT THE CUTOFF FOR C26:0-LPC HAS BEEN CHANGED FROM GREATER THAN EQUAL TO 0.49 MOL/L TO GREATER THAN EQUAL TO 0.47 MOL/L ON (B)(6) 2024. THEREFORE, IN THE FIRST RETEST THE MEASURED C26:0-LPC CONCENTRATION 0.47 MOL/L WAS AT CUTOFF, NOT BELOW AS STATED IN THE INITIAL REPORT.
ON 28-MAR-2025, REVVITY RECEIVED INFORMATION CONCERNING THE 3044-001U NEOBASE¿ 2 NON-DERIVATIZED MSMS KIT FROM (B)(6) HEALTH REGARDING A FALSE NEGATIVE SCREENING RESULT FROM A NEWBORN WHO LATER CONFIRMED FOR X-LINKED ADRENOLEUKODYSTROPHY (X-ALD). THE SPECIFIC PRIMARY MARKER FOR X-ALD IS C26:0-LPC. NO INFORMATION ON NEWBORN DATE OF BIRTH HAS BEEN RECEIVED, THE NEWBORN SCREENING (NBS) SPECIMEN WAS TESTED ON (B)(6) 2023 USING 3044-001U LOT#: 745872. THE REPORTED RESULT INDICATED LOW RISK TO X-ALD (RESULT: 0.33 MOL/L, BELOW LABORATORY ESTABLISHED TIER-1 CUTOFF OF 0.49 MOL/L). INITIAL SCREENING PERFORMED AT (B)(6). ON (B)(6) 2025, AFTER ABOUT 15 MONTHS FROM THE INITIAL TESTING, (B)(6) HEALTH BECAME AWARE THAT THE PATIENT IS DIAGNOSED HAVING X-ALD. LABORATORY RETESTED THE RETAINED, ORIGINAL NBS SPECIMEN TWICE ON 11-FEB-2025 USING 3044-001U, LOT#: 753026. IN THE FIRST RETEST THE MEASURED C26:0-LPC CONCENTRATION 0.47 MOL/L WAS STILL BELOW LABORATORY ESTABLISHED CUTOFF. THE SECOND RETEST WITH FRESH REAGENTS (I.E. NEWLY PREPARED EXTRACTION WORKING SOLUTION (EWS) GAVE THE RESULT OF 0.62 MOL/L, WHICH WAS ABOVE THE ESTABLISHED CUTOFF. CUSTOMER INDICATED CONCERN THAT THE REAGENTS ARE NOT STABLE FOR THE PERIOD OF TIME INDICATED IN THE IFU. THE REAGENT SUSPECTED WAS C26:0LPC INTERNAL STANDARD. A COMPLAINT WAS FILED TO REVVITY/WALLAC OY 03-APR-2025.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 1428079 | NEOBASE¿ 2 NON-DERIVATIZED MSMS KIT | NO MATCH | NQL | WALLAC OY | 3044-001U | ORIGINAL TESTING 745872 | 06438147356812 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | NA | Unknown |