MAUDE Adverse Event Report: BECTON, DICKINSON AND COMPANY, BD BIOSCIENCES BD CD34 FITC 8G12 100 TESTS CE

Catalog Number 345801

Device Problem Incorrect, Inadequate or Imprecise Result or Readings (1535)

Patient Problem No Consequences Or Impact To Patient (2199)

Event Date 05/26/2020

Event Type  malfunction  

Manufacturer Narrative

A device evaluation is anticipated, but has not yet begun.Upon completion of the investigation, a supplemental report will be filed.(b)(4).

Event Description

It was reported that there was a false positive in 2 patient samples known to be negative with a bd cd34 fitc 8g12 100 tests ce.The following information was provided by the initial reporter: they have observed unusual result using the anitbody ¿ they are observing positive expression in patient samples which they know are negative.They opened a second unit of the same lot and found the same unusual results.They tested on two lyrics using both manual prep and the duet.And observed the same result on both instruments and with both preparation methods.They are using an alternative panel for analysis as a workaround.Additionally, on 2020-06-29 the bd sales consultant provided the following additional information: if applicable, is there a confirmatory test standard procedure? yes.No.The answer is yes, in that the customer uses alternative panels/assays to test the same markers in the panel containing the reagent they are reporting.Also, did the samples have to be redrawn? no, the samples did not have to be redrawn ¿ they used the same sample when running on the alternative panel.

Event Description

It was reported that there was a false positive in 2 patient samples known to be negative with a bd cd34 fitc 8g12 100 tests ce.The following information was provided by the initial reporter: they have observed unusual result using the antibody.They are observing positive expression in patient samples which they know are negative.They opened a second unit of the same lot and found the same unusual results.They tested on two lyrics using both manual prep and the duet.And observed the same result on both instruments and with both preparation methods.They are using an alternative panel for analysis as a workaround.Additionally, on 2020-06-29 the bd sales consultant provided the following additional information: if applicable, is there a confirmatory test standard procedure? yes, no.The answer is yes, in that the customer uses alternative panels/assays to test the same markers in the panel containing the reagent they are reporting.Also, did the samples have to be redrawn? no, the samples did not have to be redrawn.They used the same sample when running on the alternative panel.Additionally, on 2020-07-22, the customer provided the following additional information: 1.What are the patient samples and target cells being analyzed? peripheral blood, bone marrow aspirate or other tissue? peripheral blood, bone marrow,csf, pleural fluid.2.How was cell viability assessed for stained samples and % viability results? viability of samples should be assessed and a cut-off value established.Our samples were within 3 days old.3.Indicate staining process steps followed ? antibody staining process followed as per sop.

Manufacturer Narrative

Investigation summary: scope of issue and problem statement: customer reported that product: 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756 is giving false positive result, as they observe positive expression in patient samples which they know are negative.Manufacturing defect trend: product: 345801 (cd34 fitc, clone hm478g12, ce) lot: 9268840 was assembled in bdb cayey (plant 1157) using material subassembly 91-0263 batch: 9294151 manufactured in plant 1157.Material 91-0263 batch: 9294151 was used to manufacture the following materials and corresponding lots: 345801 lot: 0048756 (255 ea), 348053 lots: 0115631 (140 ea) and 9352880 (133 ea), 340668 lots: 0036142 (112 ea), 9352871 (100 ea) and 0161153 (55 ea).Refer to "batch where-used_top-down_345801-0048756" and "batch where- used_bottom-up_91-0263 batch 9294151" pdf files.Subassembly 91-0263 batch: 9294151 was manufactured according to requirements and met manufacturing and qa acceptance criteria for release.No discrepancies (oos or qn) were identified in manufacturing / testing batch history record (bhr) of subassembly 91-0263 batch: 9294151 during evaluated period of 22-jun-2019 to 22-jun-2020.Refer to bhr_91-0263-9294151 pdf file.Complaint trend: only this one (1) complaint (child (b)(6) / parent (b)(6) for product: 345801 (cd34 fitc, clone hm478g12, ce) lot: 0048756 or subassembly 91-0263 lot: 9294151 false positive result has been reported in trackwise during evaluated period of 22-jun-2019 to 22-jun-2020.From the total of (b)(4) ea vials of product: 345801, lot: 0048756, manufactured, (b)(4) ea have been sold to market, no additional claims have been reported during evaluated period of 22-jun-2019 to 22-jul-2020.It is noted no additional claims have been reported during this evaluated period against other products manufactured using same subassembly 91-0263 (cd34 fitc, clone hm478g12) batch: 9294151: 348053 lots: 0115631 (b)(4) ea) of which 88 were sold and 9352880 (b)(4) ea) of which were all sold 340668 lots: 0036142 (b)(4) ea), 9352871 (b)(4) ea) and 0161153 (b)(4 ea) of which were all sold batch history record (bhr) review: product: 345801 (cd34 fitc, clone hm478g12, ce) lot: 0048756 was assembled in plant 1157 using material subassembly 91-0263 batch: 9294151 manufactured in plant 1157, which met established acceptance criteria for product release as demonstrated by batch history record (bhr).Manufacturing was performed according to requirements and specifications without any discrepancy or nonconformance.Product: 345801, lot: 0048756 expires on 31-oct-21.Bhr for subassembly 91-0263 batch: 9294151 was reviewed and material was manufactured in accordance to specifications.The qc testing includes fluorometry against a reference lot, which met established acceptance criteria parameters for product release.Retain sample evaluation / testing: retain sample of subassembly 91-0263 batch: 9294151 was obtained from qa retain inventory in support of this investigation.Special instruction for flow cytometry (fc) testing evaluation of cd34 fitc was performed.Briefly, kg1-a cells (1x106 cells / test), which is a known cd34 positive target cell line, and normal human lysed whole blood (negative for cd34) were stained with 20 l of material 91-0263 batch: 9294151 (test) along a positive control (reference) material 91-0263 batch: 0091516 and appropriate negative controls, as described in attached special instruction protocol.Fc results show subassembly 91-0263 batch: 9294151 (test batch) detected cd34 marker on kg1-a cells positive for cd34) with comparable staining profile to reference batch 0091516.No cd34 positive signal was detected on normal lysed whole blood gated lymphocytes in both test batch: 9294151 and reference: 0091516 batch, as expected.This data confirm product; 345801 (cd34 fitc, clone hm478g12, ce) lot: 0048756 manufactured from subassembly 91-0263 batch: 9294151 performs as intended to detect cd34 antigen on a known cd34 positive target (kg1-a cells), when used as described in technical data sheet (tds) 23-5085-05 (rev.03-2018).Returned sample evaluation: samples were not requested to be returned as qa retains for subassembly 91-0263 batch: 9294151 are maintained and available for evaluation.Investigation result / analysis: customer reported that product: 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756 is giving false positive result, as they observe positive expression in patient samples which they know are negative.As customer did not provide details regarding what type of tissue sample was stained (expected to be negative), cell viability during staining or data for the fc analysis as reported on parent (b)(6) intake, a request for additional information from customer was initiated under child task (b)(6) on (b)(6) 2020.Information requested to customer in support of investigation: 1.What are the patient samples and target cells being analyzed? peripheral blood, bone marrow aspirate or other tissue? customer response: ¿peripheral blood, bone marrow, csf, and pleural fluid¿.2.How was cell viability assessed for stained samples and % viability results? viability of samples should be assessed, and a cut-off value established.Customer response: ¿our samples were within 3 days old¿.3.Indicate staining process steps followed? customer response: ¿antibody staining process followed as per sop¿.4.Please provide image (pdf or jpeg) of flow cytometry results see trying to plough through a worklist.Customer response: ¿i should have kept the printout at the start".It is noted that actual data and specific procedure steps performed while using product 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756 were unable to be obtained from customer on responses received on (b)(6) 2020 under task (b)(6).As per technical data sheet (tds) 23-5085-05 (rev.03-2018), cd34 is intended for in vitro diagnostic use in the identification of cells expressing cd34 antigen, using a bd facs brand flow cytometer.Applications: expression of cd34 in the characterization of hematologic neoplasia.Composition: cd34 (anti-hpca-2) clone 8g12, is derived from hybridization of mouse sp2/0-ag14 myeloma cells with spleen cells of balb / c mice immunized with the human cell line kg-1a.Cd34 is composed of mouse igg1 heavy chains and kappa light chains.Cd34 is a human progenitor cell antigen.Each reagent is supplied in pbs containing gelatin and 0.1% sodium azide.Bottling concentration for cd34 fitc clone 8g12 is 25 g/ml or 0.025 g/l.Recommended reagent volume = 20 l per test, or 20 l (0.025 g / l) = 0.5 g per test.Storage and handling: the antibody reagent is stable until the expiration date shown on the label when stored at 2-8 °c.Do not use after the expiration date.Do not freeze reagent or expose it to direct light during storage or incubation with cells.Keep the outside of the reagent vial dry.Do not use the reagent if you observe any change in appearance.Precipitation or discoloration indicates instability or deterioration.Specimen: regent can be used for immunophenotyping by flow cytometry with a variety of specimen types, including peripheral blood, bone marrow aspirates or biopsies, and other body fluids or tissues.Each type of specimen can have different storage conditions and limitations that should be considered prior to collection and analysis.Samples with large numbers of nonviable cells can give erroneous results due to selective loss of populations and to increased nonspecific binding of antibodies to non-viable cells.Viability of samples should be assessed, and a cut-off value established.A cut-off value of at least 80% viable cells has been suggested.Performance characteristics: specificity: the cd34 antigen is a single-chain transmembrane glycoprotein with a molecular weight ranging from 105 to 120 kda.It is expressed on immature hematopoietic precursor cells and all hematopoietic colony-forming cells in bone marrow and blood.Cd34 antigen is also found on capillary endothelial cells and approximately 1% of human thymocytes.Normal peripheral blood lymphocytes, monocytes, granulocytes, and platelets do not express the cd34 antigen.Approximately 60% of b-cell acute lymphoid leukemias express the cd34 antigen.The antigen is not expressed on chronic lymphoid leukemias or lymphomas.Limitations: conjugates with brighter fluorochromes (pe, apc) will give greater separation than those with other dyes (fitc, percp).When populations overlap, calculation of the percentage of cells positive for the marker can be affected by the choice of fluorochrome.Use of monoclonal antibodies in patient treatment can interfere with recognition of target antigens by this reagent.This should be considered when analyzing samples from patients treated in this fashion.Bd biosciences has not characterized the effect of the presence of therapeutic antibodies on the performance of this reagent.Single reagents can provide only limited information in the analysis of leukemias and lymphomas.Using combinations of reagents can provide more information than using the reagents individually.Multicolor analysis using relevant combinations of reagents is highly recommended.As reagents can be used in different combinations, laboratories need to become familiar with the properties of each antibody in conjunction with other markers in normal and abnormal samples.Bd product release criteria for cd34 fitc clone 8g12.Qc testing release data for 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756 under subassembly 91-0263 batch: 9294151 indicated that fluorometry test met established acceptance criteria parameters for product release.Zero (0) manufacturing process non-conformances or deviations were identified in the evaluated bhr.Risk analysis: risk analysis applicable for product: 345801 (cd34 fitc, clone 8g12, ce) is available under failure mode effect analysis (fmea) document cd348g12fmea rev.04.Hazard(s) identified? x , yes, no.Reviewed item: 1.Conjugated antibody - final product.Function: to detect a specific cell surface marker.Potential function failure: not perform to the spec / claim.Potential effects of failures: end user: wrong result-no matching profile-customer.Inconvenience-additional testing, cost, and time.Potential cause of failure: 18.Improper use of material by the user.Occurrence: 3, severity: 7, detection: 2, risk priority number (rpn): 42, risk acceptability: rpn < 90 will be acceptable, risk current controls: 1.Labeling, and 2.Customer education, new hazard: none, mitigation(s) enough x, yes, no.Root cause analysis: root cause is not determined.Evidence demonstrates manufacturing process was performed according to requirements and met specifications without discrepancy.Special instruction functional flow cytometry test performed in support of investigation, show subassembly 91-0263 batch: 9294151 detected cd34 marker on kg1-a cells (which are positive for cd34) with comparable staining profile to reference batch: 0091516.No cd34 positive signal was detected on normal lysed whole blood lymphocytes (which are cd34 negative), as expected.This data confirm product: 345801 (cd34 fitc, clone hm478g12, ce) lot: 0048756 manufactured from subassembly 91-0263 batch: 9294151 performs as intended to detect cd34 antigen on a known cd34 positive target (kg1-a cells).Based on the investigation performed, the claim is not confirmed, and no further actions are deemed necessary at this time.Conclusion: product: 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756 manufactured from subassembly 91-0263 batch: 9294151 was manufactured according to specifications.The review of the manufacturing batch history record (bhr) or release records and functional flow cytometry test performed indicates that the issue was unlikely to have been caused during manufacturing.Based on investigation performed it is determined the claim is not confirmed.Bd will continue to monitor for related claims associated to performance issue using product: 345801 (cd34 fitc, clone 8g12, ce) lot: 0048756.

Event Description

It was reported that there was a false positive in 2 patient samples known to be negative with a bd cd34 fitc 8g12 100 tests ce.The following information was provided by the initial reporter: they have observed unusual result using the anitbody ¿ they are observing positive expression in patient samples which they know are negative.They opened a second unit of the same lot and found the same unusual results.They tested on two lyrics using both manual prep and the duet.And observed the same result on both instruments and with both preparation methods.They are using an alternative panel for analysis as a workaround.Additionally, on 2020-06-29 the bd sales consultant provided the following additional information: if applicable, is there a confirmatory test standard procedure? yes no the answer is yes, in that the customer uses alternative panels/assays to test the same markers in the panel containing the reagent they are reporting.Also, did the samples have to be redrawn? no, the samples did not have to be redrawn ¿ they used the same sample when running on the alternative panel.Additionally, on 2020-07-22 the customer provided the following additional information: 1.What are the patient samples and target cells being analyzed? peripheral blood, bone marrow aspirate or other tissue? peripheral blood, bone marrow,csf, pleural fluid 2.How was cell viability assessed for stained samples and % viability results? viability of samples should be assessed and a cut-off value established.Our samples were within 3 days old.3.Indicate staining process steps followed ? antibody staining process followed as per sop.

Manufacturer Narrative

The following field was updated with additional information: b.5.Describe event or problem.

• Brand Name: BD CD34 FITC 8G12 100 TESTS CE
• Type of Device: NA
• Manufacturer (Section D): BECTON, DICKINSON AND COMPANY, BD BIOSCIENCES; 2350 qume drive; san jose CA 95131
• MDR Report Key: 10258305
• MDR Text Key: 225598676
• Report Number: 2916837-2020-00045
• Device Sequence Number: 1
• Product Code: MVU
• Combination Product (y/n): N
• PMA/PMN Number: NA
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,other,user facility
• Type of Report: Initial,Followup,Followup
• Report Date: 09/16/2020

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Device Operator: Other
• Device Expiration Date: 10/31/2021
• Device Catalogue Number: 345801
• Device Lot Number: 0048756
• Was Device Available for Evaluation?: No
• Initial Date Manufacturer Received: 06/19/2020
• Initial Date FDA Received: 07/10/2020
• Supplement Dates Manufacturer Received: 06/19/2020; 06/19/2020
• Supplement Dates FDA Received: 08/04/2020; 09/16/2020
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Patient Outcome(s): Other