SEARCH-CYTE TCS 0.8%

Report

Report Number: 3002806769-2025-00003
Event Type: Malfunction
Date Received: April 3, 2025
Date of Event: March 11, 2025
Report Date: April 3, 2025
Manufacturer: MEDION GRIFOLS DIAGNOSTICS AG,
Product Code: QHT
UDI-DI: 07640137340384
PMA / PMN Number: BL103898
Product Problem: Yes
Report Source: Manufacturer report
Reporter Occupation: OTHER

Narratives

Additional Manufacturer Narrative · 0

I. DOCUMENTARY INVESTIGATION. THE MANUFACTURING DOCUMENTATION OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AND DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, WAS REVIEWED AND NO DEVIATIONS WERE FOUND THAT COULD BE ASSOCIATED WITH THE REPORTED EVENT. ALL INTERNAL TESTS PERFORMED DURING THE MANUFACTURING PROCESS WERE WITHIN INTERNAL SPECIFICATIONS. AT RELEASE, THE CLAIMED CELLS, I.E. CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS CELL 4, CELL 10 AND CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, GAVE ALL STRONG 4+ REACTIONS WHEN TESTED WITH DG GEL 8 RH-PHENO, REF. 210228, LOT 23001.01, EXP. 2025-04-30. CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS CELL 4, CELL 10 AND CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, WERE PREPARED WITH DONORS (B)(6), RESPECTIVELY. THE ENTRY TYPING OF THE FOUR DONORS WAS REVIEWED AND NO DEVIATIONS WERE FOUND. THE DONORS (B)(6) WERE INDEPENDENTLY TYPED BY TWO LABORATORY TECHNICIANS WITH TWO DIFFERENT LOTS OF POLYCLONAL ANTI-E AND POSITIVE REACTIONS WERE OBTAINED. DONOR (B)(6) IS A NEW DONOR; ITS FIRST AND ONLY USE HAS BEEN IN THE MANUFACTURING OF THE CLAIMED CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS IN ANOTHER FINISHED PRODUCT FROM THE SAME MANUFACTURING CAMPAIGN. BESIDES THE CURRENT COMPLAINT, NO OTHER COMPLAINT INVOLVING THIS DONOR HAS BEEN REGISTERED TO DATE BY MEDION GRIFOLS DIAGNOSTICS AG. DONOR (B)(6) IS ALSO A NEW DONOR; ITS FIRST AND ONLY USE HAS BEEN IN THE MANUFACTURING OF THE CLAIMED CELL 4 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, AS WELL AS IN FOUR OTHER FINISHED PRODUCTS FROM THE SAME MANUFACTURING CAMPAIGN. BESIDES THE CURRENT COMPLAINT, NO OTHER COMPLAINT INVOLVING THIS DONOR HAS BEEN REGISTERED TO DATE BY MEDION GRIFOLS DIAGNOSTICS AG. TWO BLOOD UNITS OF DONOR (B)(6) HAVE BEEN USED IN THE MANUFACTURING OF SIX FINISHED PRODUCTS (INCLUDING THE CLAIMED CELL 10 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15) AMONG TWO MANUFACTURING CAMPAIGNS. BESIDES THE CURRENT COMPLAINT, NO OTHER COMPLAINT INVOLVING THIS DONOR HAS BEEN REGISTERED TO DATE BY MEDION GRIFOLS DIAGNOSTICS AG. DONOR (B)(6) IS A NEW DONOR; ITS FIRST AND ONLY USE HAS BEEN IN THE MANUFACTURING OF THE CLAIMED CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, AS WELL AS IN FOUR OTHER FINISHED PRODUCTS FROM THE SAME MANUFACTURING CAMPAIGN. BESIDES THE CURRENT COMPLAINT, NO OTHER COMPLAINT INVOLVING THIS DONOR HAS BEEN REGISTERED TO DATE BY MEDION GRIFOLS DIAGNOSTICS AG. INTERNAL STABILITY RECORDS OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AND DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, WERE REVIEWED AND THE EXPECTED RESULTS WERE OBTAINED AT ALL TIME POINTS. II. INVESTIGATIVE TESTING TITRATION OF A SINGLE SOURCE POLYCLONAL ANTI-E, WITH SELECTED E+ RRBCS, INCLUDING THE CLAIMED CELLS (CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS CELL 4, CELL 10 AND CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15), CELLS FROM COMPETITOR WITH EXPIRATION DATE CLOSE TO THE CLAIMED PRODUCTS AS WELL AS GRIFOLS NON-EXPIRED RRBCS, WAS DONE IN MANUAL METHOD IN OUR QUALITY CONTROL LABORATORY AT MEDION GRIFOLS DIAGNOSTICS AG. THE FOUR HOMOZYGOUS E+ (ALL R2R2) RRBCS TESTED GAVE A TITER OF 1:1024, SHOWING COMPARABLE RESULTS BETWEEN THE CLAIMED CELLS (I.E. CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AND CELL 10 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15) AND THE CELL FROM COMPETITOR WITH CLOSE EXPIRATION DATE, BUT ALSO WITH A NEWER LOT OF RRBC THAT IS NON-EXPIRED. THE FOUR HETEROZYGOUS E+ RRBCS GAVE A TITER OF 1:512 EXCEPT THE CLAIMED CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, WHICH SHOWED A TITER OF 1:1024. THESE RESULTS DEMONSTRATE COMPARABLE REACTIVITY AND DOES NOT SUPPORT THE HYPOTHESIS OF AN ABNORMAL E ANTIGEN EXPRESSION OF THE CLAIMED CELL 2 OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS CELL 4, CELL 10 AND CELL 11 OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15. THUS, THE INVESTIGATIVE TESTING IS SUPPORTING THE HYPOTHESIS OF THE PRESENCE OF A LOW-TITER ANTI-E ANTIBODY IN THE PATIENT PLASMA THAT IS AT THE DETECTION LIMIT OF THE GEL SYSTEM. BASED ON ALL THE ELEMENTS, THE MOST PROBABLE ROOT CAUSE OF THE REPORTED NEGATIVE REACTIONS WITH CELL 2 (DONOR (B)(6)) OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AS WELL AS CELL 4 (DONOR (B)(6)), CELL 10 (DONOR (B)(6)) AND CELL 11 (DONOR (B)(6)) OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15, IS SAMPLE RELATED, POINTING TO A LOW-TITER ANTI-E IN THE PATIENT PLASMA WITH E SPECIFICITY THAT IS AT THE DETECTION LIMIT OF THE GRIFOLS SYSTEM. THIS LOW ANTI-E LEVEL IN THE PATIENT PLASMA SAMPLE, IN COMBINATION WITH NATURALLY OCCURRING VARIATIONS IN THE ANTIGEN DENSITY OF RED BLOOD CELLS MAY BE THE CAUSE OF THE UNEXPECTED RESULTS OBSERVED BY THE CUSTOMER. ADDITIONALLY, IT SHALL BE NOTED THAT WHILE POSITIVE RESULTS WERE OBTAINED WITH E+ CELLS RRBC FROM ALTERNATIVE REAGENTS, THE INCUBATION TIME WAS 30 MINUTES (COMPARED TO 15 MIN WHEN TESTED WITH GRIFOLS RRBC). ALSO, WITH THE UNTREATED PANEL, ONLY THE CELL 3, WHICH WAS C-E+E-K-S+S+, REACTED POSITIVE BUT THIS CELL WAS ALSO S+. THE OTHER E+ CELL (CELL 6, WHICH WAS C-E+E+K-S-) WAS NONREACTIVE WHEN UNTREATED DESPITE THE LONG INCUBATION TIME AND DID ONLY GIVE REACTIVITY AFTER ENZYME (FICIN) TREATMENT SO THAT IT CANNOT BE EXCLUDED THAT THE ANTI-E WOULD BE ONLY DETECTED IN THE ENZYMATIC TECHNIQUE WITH THE FICIN TREATED CELLS, WHICH FURTHER SUPPORTS THE PRESENCE OF A LOW TITER ANTI-E IN THE PATIENT PLASMA. NO SINGLE METHOD IS ABLE TO DETECT ALL IRREGULAR ANTIBODIES. MEDION GRIFOLS DIAGNOSTICS AG HAS NO INDICATION OF MALFUNCTION OF PRODUCTS SEARCH-CYTE TCS 0.8%, REF. 213655, LOT 644725005, EXP. 2025-03-15, AND DATA-CYTE PLUS 0.8%, REF. 213654, LOT 610025003, EXP. 2025-03-15. CONSEQUENTLY, THIS CASE IS NON-CONFIRMED.

Description of Event or Problem · 0

A CUSTOMER REPORTED UNEXPECTED NEGATIVE ANTIBODY SCREENING/IDENTIFICATION RESULTS FOR ONE PATIENT SAMPLE, OBTAINED WITH CELL 2 (E+E-, DONOR: (B)(6) OF SEARCH-CYTE TCS 0.8%, REF. 213655, LOT: 644725005, EXP. 2025-03-15, AS WELL AS WITH CELL 4 (E+E+, DONOR: (B)(6), CELL 10 (E+E-, DONOR: (B)(6) AND CELL 11 (E+E+, DONOR: (B)(6) OF DATA-CYTE PLUS 0.8%, REF. 213654, LOT: 610025003, EXP. 2025-03-15. THE SAMPLE "(B)(6)" (COLLECTION DATE NOT PROVIDED) ORIGINATES FROM A 86-YEAR-OLD FEMALE PATIENT DIAGNOSED WITH ACUTE GASTROINTESTINAL (GI) BLEED. THERE WAS NO AVAILABLE INFORMATION REGARDING HISTORY OF ANTIGEN TYPING, ANTIBODY, NOR TRANSFUSION. BASED ON THE DOCUMENTATION PROVIDED: ON (B)(6) 2025, SAMPLE "(B)(6)" WAS TESTED ON ERYTRA 1082 (SN: (B)(6), SOFTWARE VERSION 4.3.3, REAGENT PACK VERSION 2.2) AT 22H01 WITH SEARCH-CYTE TCS 0.8%, REF. 213655, LOT: 644725005, EXP. 2025-03-15, ON DG GEL 8 ANTI-IGG CARD, LOT: 24033.01, EXP. 2025-07-31. WHILE BOTH CELL 1 (C+C-; E-; K+K+; S+S+) AND CELL 3 (C-; E-; K-; S+S-) GAVE 2+ REACTIONS, THE CELL 2 (C-; E+E-; K-; S-) WAS INTERPRETED AS NEGATIVE. ANTIBODY IDENTIFICATION WAS PERFORMED AT 22H37 ON THE SAME INSTRUMENT AND WITH THE SAME CARD LOT, USING DATA-CYTE PLUS 0.8%, REF. 213654, LOT: 610025003, EXP. 2025-03-15: CELL 1 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 2 (C-; E-; K+K+; S+S+) WAS INTERPRETED AS 2+. CELL 3 (C+C+; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 4 (C-; E+E+; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 5 (C-; E-; K-; S+S-) WAS INTERPRETED AS 2+. CELL 6 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 7 (C+C-; E-; K-; S+S-) WAS INTERPRETED AS 2+. CELL 8 (C+C-; E-; K+K+; S-) WAS INTERPRETED AS 2+. CELL 9 (C+C-; E-; K-; S+S+) WAS INTERPRETED AS 1+. CELL 10 (C-; E+E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 11 (C-; E+E+; K-; S-) WAS INTERPRETED AS NEGATIVE. AUTOCONTROL WAS NEGATIVE. BASED ON TO THE REACTIVITY PATTERNS, THE PRESENCE OF ANTI-C WITH DOSAGE, ANTI-S AND ANTI-K WAS SUSPECTED. THE CURRENT ANTIGEN TYPING PERFORMED TESTED THE PATIENT AS POSITIVE FOR C AND S ANTIGENS, AND NEGATIVE FOR C, E, K AND S ANTIGENS. ACCORDINGLY, ADDITIONAL TESTING WAS REQUIRED AND CONDUCTED: IN ORDER TO EXCLUDE THE PRESENCE OF AN ANTI-C, CELL 1 (C+C-, E-; K-; S-) OF AN ALTERNATIVE IDENTIFICATION PANEL REAGENT WAS TESTED IN TUBE METHOD (AHG) AND REACTED NEGATIVE. ADDITIONAL ANTIBODY IDENTIFICATION TESTING WAS ALSO PERFORMED USING ANOTHER ALTERNATIVE IDENTIFICATION PANEL REAGENT, WITH A 30 MIN INCUBATION AT 37°C IN MANUAL GEL METHOD. TESTING WAS DONE ON UNTREATED CELLS AS WELL AS WITH FICIN TREATMENT: UNTREATED CELLS. CELL 1 (C+C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 2 (C+C-; E-; K+K+; S-) WAS INTERPRETED AS 2+. CELL 3 (C-; E+E-; K-; S+S+) WAS INTERPRETED AS 3+. CELL 4 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 5 (C+C+; E-; K-; S+S+) WAS INTERPRETED AS 2+. CELL 6 (C-; E+E+; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 7 (C-; E-; K+K+; S-) WAS INTERPRETED AS 1+. CELL 8 (C-; E-; K-; S+S-) WAS INTERPRETED AS 2+. CELL 9 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 10 (C-; E-; K-; S+S+) WAS INTERPRETED AS 3+. CELL 11 (C+C-; E-; K-; S+S-) WAS INTERPRETED AS 3+. AUTOCONTROL WAS NEGATIVE. FICIN TREATED CELLS. CELL 1 (C+C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 2 (C+C-; E-; K+K+; S-) WAS INTERPRETED AS 2+. CELL 3 (C-; E+E-; K-; S+S+) WAS INTERPRETED AS 4+. CELL 4 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 5 (C+C+; E-; K-; S+S+) WAS INTERPRETED AS NEGATIVE. CELL 6 (C-; E+E+; K-; S-) WAS INTERPRETED AS 4+. CELL 7 (C-; E-; K+K+; S-) WAS INTERPRETED AS 2+. CELL 8 (C-; E-; K-; S+S-) WAS INTERPRETED AS NEGATIVE. CELL 9 (C-; E-; K-; S-) WAS INTERPRETED AS NEGATIVE. CELL 10 (C-; E-; K-; S+S+) WAS INTERPRETED AS NEGATIVE. CELL 11 (C+C-; E-; K-; S+S-) WAS INTERPRETED AS NEGATIVE. BASED ON THE RESULTS, THE ANTI-C HAS BEEN RULED OUT. THE CELL TESTED IN TUBE METHOD WHICH WAS C+C-E-K-S-, REACTED NEGATIVE. ALSO, WITH THE TESTED ALTERNATIVE IDENTIFICATION PANEL IN MANUAL GEL TECHNIQUE, CELL 1 WAS C+C-E-K-S- AND GAVE A NEGATIVE REACTION WHEN UNTREATED (WITH 30 MIN INCUBATION) BUT ALSO WHEN TREATED WITH FICIN, WHICH IS KNOWN TO ENHANCE REACTIVITY OF ANTIBODY AGAINST RHESUS ANTIGENS. ADDITIONALLY, THE CELL 11, WHICH WAS C+C-E-K-S+S-, EVEN THOUGH IT GAVE A 3+ REACTION WHEN UNTREATED, WAS FOUND NEGATIVE AFTER FICIN TREATMENT AND 30 MIN INCUBATION (WHICH ON THE OTHER HAND MATCHES WITH THE PRESENCE OF ANTI-S FOLLOWING DESTRUCTION OF S ANTIGEN SITES). THE RESULTS OF UNTREATED AND FICIN TREATED CELLS (WITH AN INCUBATION OF 30 MINUTES) FROM THE ALTERNATIVE IDENTIFICATION PANEL IN MANUAL GEL METHOD ENABLES TO IDENTIFY ANTI-E WITH DOSAGE, ANTI-K AND ANTI-S. HOWEVER, WITH THE UNTREATED PANEL, ONLY THE CELL 3, WHICH WAS C-E+E-K-S+S+, REACTED POSITIVE BUT THIS CELL WAS ALSO S+. THE OTHER E+ CELL (CELL 6, WHICH WAS C-E+E+K-S-) WAS NEGATIVE SO IT CANNOT BE EXCLUDED THAT THE ANTI-E WOULD BE ONLY DETECTED IN THE ENZYMATIC TECHNIQUE WITH THE FICIN TREATED CELLS. THE E+ CELLS SHOWED AN INCREASED REACTIVITY AFTER ENZYME (FICIN) TREATMENT. THE HETEROZYGOUS CELL 6 (E+E+K-S-) REACTED NEGATIVE WHEN UNTREATED (WITH 30 MIN INCUBATION) BUT WAS ENHANCED AFTER FICIN TREATMENT (WITH 30 MIN INCUBATION) AND GIVING A 4+ REACTION, WHICH SUPPORTS THE PRESENCE OF A LOW TITER ANTI-E. CUSTOMER CONFIRMED THAT NO TITER HAS BEEN PERFORMED, AND THAT THE SAMPLE WAS OUT OF THE TESTING RANGE TO PERFORM A TITER. ACCORDING TO L2 INVESTIGATION, REVIEW OF RAW IMAGES SHOWED NO EVIDENCE OF COMPROMISED GEL CARD INTEGRITY. RESULT IMAGE FILES ARE VISUALLY CONSISTENT WITH THE INSTRUMENT ALGORITHM REACTION GRADE ASSIGNMENTS, AND ALL NEGATIVE CELL BUTTONS APPEAR CLEANLY NEGATIVE, WITH NO IRREGULAR CELL BUTTON SHAPES OR VOLUMES NOTED. INSTRUMENT LOG REVIEW SHOWED NO ERRORS DURING THE TIME OF TESTING THAT COULD AFFECT THE REPORTED SAMPLE RESULTS. DAILY QUALITY CONTROL PASSED AS EXPECTED FOR 11 MARCH 2025. THERE IS CURRENTLY NO EVIDENCE TO SUGGEST AN ISSUE WITH THE INSTRUMENT OF SOFTWARE.

Devices

Seq	Brand	Generic	Product Code	Manufacturer	Model	Lot	UDI-DI
573892	SEARCH-CYTE TCS 0.8%	REAGENT RED BLOOD CELLS FOR ANTIBODY DETECTION	QHT	MEDION GRIFOLS DIAGNOSTICS AG,	N/A	644725005	07640137340384

Patients

Seq	Age	Sex	Outcome	Treatment
1	86 YR	Female