CONFIRM ANTI-ESTROGEN RECEPTOR (ER) (SP1) RABBIT MONOCLONAL PRIMARY ANTIBODY

Description of Event or Problem

THERE WAS AN ALLEGATION OF DISCREPANT NEGATIVE RESULTS WITH THE CONFIRM ANTI-ESTROGEN RECEPTOR (ER) (SP1) RABBIT MONOCLONAL PRIMARY ANTIBODY ASSAY FOR 2 PATIENT SAMPLES TESTED ON A BENCHMARK ULTRA SYSTEM. FOR PATIENT 1, THE TUMOR TISSUE FROM THE BIOPSY WAS NEGATIVE. THE SAME TISSUE BLOCK WAS SENT TO AN EXTERNAL LABORATORY, WHERE THE TUMOR WAS IDENTIFIED AS POSITIVE (50%, POSITIVITY SCORE) ON A BOND SYSTEM. ON (B)(6) 2025, THE SAME TISSUE BLOCK WAS SENT TO ANOTHER LABORATORY, WHERE THE TUMOR WAS EVALUATED AS POSITIVE. ON 17-NOV-2025: FOR PATIENT 2, THE TUMOR WAS EVALUATED AS NEGATIVE. EXTERNAL VERIFICATION ON A BOND SYSTEM USING THE SAME TISSUE BLOCK REVEALED POSITIVE STAINING (40% POSITIVITY SCORE). ON (B)(6) 2025 THE SAME TISSUE BLOCK WAS SENT TO ANOTHER LABORATORY, WHERE THE TUMOR WAS EVALUATED AS POSITIVE.

Additional Manufacturer Narrative

THE BENCHMARK ULTRA SYSTEM SERIAL NUMBER WAS (B)(6). IT WAS NOTED THAT THE LABORATORY HAD EXPERIENCED SIGNIFICANT CONTAMINATION IN THE EZ PREP LINE. ON 09-DEC-2025, THE FIELD SERVICE ENGINEER (FSE) REMOVED AND CLEANED THE EZ PREP RESERVOIR. THE INVESTIGATION IS ONGOING.

Additional Manufacturer Narrative

THE PROVIDED IMAGES FROM THE BOND SYSTEM SHOW STRONGER NUCLEAR EXPRESSION IN MORE TUMOR CELLS THAN THOSE PROVIDED STAINED WITH THE CONFIRM ER ANTIBODY. THERE IS DISCORDANCE OF MORPHOLOGIES AMONG THE IMAGES PROVIDED, SO IT IS NOT ENTIRELY CLEAR WHETHER THE APPROPRIATE CASES, AND/OR FIELDS OF VIEW, ARE ADEQUATELY REPRESENTED. ADDITIONALLY, NO BREAST CARCINOMA POSITIVE CONTROL TISSUE IMAGE IS AVAILABLE TO EVALUATE FOR APPROPRIATE STAINING. THE CUSTOMER'S PROTOCOL REPORTS SHOW A MODIFIED STAINING PROTOCOL. PRODUCT LABELING STATES: "A POSITIVE TISSUE CONTROL MUST BE INCLUDED WITH EACH STAINING RUN." AND "A CONFIRM ANTI-ER (SP1) ANTIBODY NEGATIVE RESULT DOES NOT EXCLUDE THE PRESENCE OF ER. NEGATIVE REACTIONS IN BREAST CARCINOMAS MAY BE DUE TO LOSS OR MARKED DECREASE OF EXPRESSION OF ANTIGEN. THEREFORE, IT IS RECOMMENDED THAT THIS ANTIBODY BE USED IN A PANEL OF ANTIBODIES INCLUDING PROGESTERONE RECEPTOR." PRODUCT LABELING FURTHER STATES: "THE CLINICAL INTERPRETATION OF ANY POSITIVE STAINING, OR ITS ABSENCE, MUST BE EVALUATED WITHIN THE CONTEXT OF CLINICAL HISTORY, MORPHOLOGY AND OTHER HISTOPATHOLOGICAL CRITERIA...IT IS THE RESPONSIBILITY OF A QUALIFIED PATHOLOGIST TO BE FAMILIAR WITH THE ANTIBODIES, REAGENTS AND METHODS USED TO PRODUCE THE STAINED PREPARATION." THE CUSTOMER'S EZ PREP RESERVOIR WAS REPORTEDLY CONTAMINATED FOR AN UNKNOWN PERIOD, WHICH MAY HAVE CONTRIBUTED TO AN UNSATISFACTORY STAINING ENVIRONMENT. PRODUCT LABELING STATES: "ANY DEVIATION FROM RECOMMENDED TEST PROCEDURES MAY INVALIDATE EXPECTED RESULTS. APPROPRIATE CONTROLS MUST BE EMPLOYED AND DOCUMENTED. USERS WHO DEVIATE FROM RECOMMENDED TEST PROCEDURES MUST ACCEPT RESPONSIBILITY FOR INTERPRETATION OF PATIENT RESULTS." THE INVESTIGATION DID NOT IDENTIFY A PRODUCT PROBLEM.