MAUDE Adverse Event Report: BECTON DICKINSON CARIBE LTD. BD CD103 FITC CE

Catalog Number 333155

Device Problems Incorrect, Inadequate or Imprecise Result or Readings (1535); Device Ingredient or Reagent Problem (2910)

Patient Problem No Clinical Signs, Symptoms or Conditions (4582)

Event Date 12/02/2021

Event Type  malfunction  

Event Description

It was reported during use with bd cd103 fitc ce erroneous results were obtained and there was low reagent signal.There was no report of patient impact.The following information was provided by the initial reporter: surprising negativity when assessing cd103 when other marker expression / clinical details were considered.Internal qc for cocktail was met for analysis, positive cd103 cases experienced either side of negative case.Sample sent to two other labs for confirmation (uhbw bristol and cardiff & vale uhb).Uhbw found same negative expression, cardiff found weakly positive although also uses dako ab as well as ber-act8.Customer still reviewing biological reasoning for this negativity.Uncertain about performance of antibody, however still reviewing this.Were patient samples involved? yes.Do they always perform a confirmatory test? there is no single confirmatory test but cd103 is not used in isolation in a flow cytometry panel.In a non-standard/typical phenotype other test modalities would and have been used if hcl is in the differential diagnosis.Were incorrect results reported to the clinician? i¿m not even sure there were ¿incorrect¿ results but yes the results achieved have been reported for cd103 (and other panel markers).Were patients treated based on erroneous results? patient diagnosis has not yet been concluded as some investigations are still underway so no treatment has been given.If yes, was there any negative impact to the patient? n/a.

Manufacturer Narrative

Date of event: unknown.The date received by manufacturer has been used for this field.A device evaluation is anticipated, but has not yet begun.Upon completion of the investigation, a supplemental report will be filed.

Event Description

It was reported during use with bd cd103 fitc ce erroneous results were obtained and there was low reagent signal.There was no report of patient impact.The following information was provided by the initial reporter: surprising negativity when assessing cd103 when other marker expression / clinical details were considered.Internal qc for cocktail was met for analysis, positive cd103 cases experienced either side of negative case.Sample sent to two other labs for confirmation (uhbw bristol and cardiff & vale uhb).Uhbw found same negative expression, cardiff found weakly positive although also uses dako ab as well as ber-act8.Customer still reviewing biological reasoning for this negativity.Uncertain about performance of antibody, however still reviewing this.Were patient samples involved? yes.Do they always perform a confirmatory test? there is no single confirmatory test but cd103 is not used in isolation in a flow cytometry panel.In a non-standard/typical phenotype other test modalities would and have been used if hcl is in the differential diagnosis.Were incorrect results reported to the clinician? i'm not even sure there were 'incorrect' results but yes the results achieved have been reported for cd103 (and other panel markers).Were patients treated based on erroneous results? patient diagnosis has not yet been concluded as some investigations are still underway so no treatment has been given.If yes, was there any negative impact to the patient? n/a.

Manufacturer Narrative

H6: investigation summary.Manufacturing defect trend: product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 was assembled in bdb cayey (plant (b)(4)) using material subassembly 91-0419pr batch 0349658 manufactured in bdb cayey (plant (b)(4)).Material 91-0419pr batch 0349658 was used to manufacture the following materials and corresponding lots: ¿ 333155 lot 1015695 ((b)(4) ea), and ¿ 340944 lot 1015692 ((b)(4) ea).Refer to "where-used_top-down_333155-1015695" and "where-used_bottom-up_91-0419pr-0349658" pdf files.Subassembly 91-0419pr batch 0349658 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 91-0419pr batch 0349658 during evaluated period of 03-dec-20 to 03-dec-21.Refer to qc bhr 91-0419pr-0349658 pdf file.O root cause analysis: root cause cannot be determined.Customer indicates product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 antibody is showing negative expression.Data provided by customer was evaluated, product-stained lymphocyte population as expected, and no performance problem observed.Evidence demonstrates manufacturing process was performed according to requirements; product met release specifications without discrepancy and later used satisfactorily as reference lot under 91-0419pr batch 0349658 for qc release test of newer subassembly 91-0419pr batch 1019531.¿ complaint history review: only one (1) complaint pr# (b)(4) for product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 or subassembly 91-0419pr batch 0349658 related to antibody is showing negative expression have been reported in trackwise during evaluated period of 03-dec-20 to 03-dec-21.It is noted there is no additional complaints reported against product 333155 lot 1015695 from a total of (b)(4) ea sold to market or other product manufactured (refer to manufacturing defect trend section) using subassembly 91-0419pr batch 0349658: ¿ 340944 lot 1015692 ((b)(4) ea).¿ risk review: risk analysis applicable for product 333155 (cd103 fitc, clone ber-act8, ce-ivd) is available under risk analysis document cd103fmea (rev.02).Evaluation was based on information hazards, which might trigger a problem to customer to properly perform testing while using reagent.Hazard(s) identified? x yes no.Reviewed item: 1.Conjugated antibody - final product.To detect specific cell surface marker.Potential function failure: 2.Not to perform to the spec/claim.Potential effect of failure: 3.Wrong result - no matching profile.Customer inconveniences, additional testing, cost and time.Potential cause of failure: 14.Incorrect volume used @ customer site.18.Improper use of material by the user.Severity: 7.Occurrence: 3.Detection: 2.Rpn: 42 = acceptable.Current controls: 1.Customer education, and 2.Labeling -detailed procedures.Implementation verification: instruction for use or insert = ifu.New hazard: none mitigation(s) enough x yes no.¿ batch history record (bhr) review: product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 was assembled in plant (b)(4) using material subassembly 91-0419pr batch 0349658 manufactured in plant (b)(4), which met established acceptance criteria for product release thru fluorometry testing, as demonstrated by evaluated batch history record (bhr) following quality control (qc) document sj91-0419prqc-pr-06 (rev.1).Manufacturing was performed according to requirements and met specifications without any discrepancy or nonconformance.Product 333155 lot 1015695 expires on 31-mar-2022.¿ returned sample analysis: samples were not requested to be returned, since qa retains are kept for subassembly 91-0419pr batch 0349658, if needed for evaluation.Additional information was requested to customer under wfi task pr#, aiming to clarify questions and obtain information in support to this investigation.Refer to investigation summary section for details.¿ retain sample analysis: no retain sample testing deemed necessary at this time.Refer to investigation summary section for details.¿ investigation summary: customer reported product antibody is showing negative expression.Customers indicate internal qc for cocktail was met for analysis, but when they sent to two other labs for confirmation, one lab was negative while another was weak positive.No details of customer cocktail or data was provided.Additional information was requested under wfi tasks pr# (b)(4) and pr# (b)(4), aiming to clarify questions and obtain information in support to this investigation.Response obtained confirm customer is not having a performance problem while using product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695, but a situation they were investigating internally which was later confirmed by customer to be an anomaly related to individual patient disease and not the product which ¿is working ok¿.Questions and customers response under wfi tasks pr# (b)(4) and pr# (b)(4): 1.Customer indicate using product 333155 (cd103 fitc, ce-ivd) lot 1015695 in a flow cytometry panel, which previously met internal qc.A.Please indicate what does this panel contains, including details of which other antibody(ies) used and quantity dispensed (ul) of each for staining each tube samples.B.Was product 333155 (cd103 fitc, ce-ivd) lot 1015695 used during internal qc panel meeting your internal spec? what is your spec vs actual result? response: a.Panel contain 8 color reagents: cd103 fitc (cat.333155 lot 1015695), cd22 pe (cat.337899), cd19 percp-cy5.5 (cat.332780), cd123 apc (cat.658171), cd11c pe-cy7 (cat.561356), cd25 bv421 (564033) and cd45 v500c (cat.655873).I.Customer indicate using 3 ul/test for staining each sample tested.It is noted the optimal volume indicated on this cd103 fitc product (label 23-7018-02) is 20 ul/test while customer used much lower volume than indicated for optimal results.B.Customer did not indicate any internal performance specification for using product 333155 (cd103 fitc, ce-ivd).2.Describe step-by-step process follow for staining, flow cytometry acquisition and analysis.A.Indicate reagent volume (ul) used for staining sample(s).B.Indicate which type of target sample cells (human peripheral blood, cell line, lymphoid tissue, etc.) used for staining.C.Where samples fresh (same day), previously stored, previously freeze, or fixed prior to staining/processing? please specify details.I.Was viability of samples assessed/evaluated? please specify details and results.Response: a.Customer used 3 ul/per test for staining, instead of bd recommended 20 ul/test.B.Customer stained edta collected human bone marrow cells.C.Customer indicate having collected fresh samples, stored at rt during transport and used within 1 day of collection.I.Viability of samples was not assessed.3.Indicate if a reference batch used for comparing results.If so, provide product mat.# and lot#.A.Indicate if you have any lot-to-lot variability specifications and what is your specification.Response: a.No information provided by customer.4.Provide flow cytometry data showing observed problem.Response: data provided by customer was evaluated.As previously indicated, it was confirmed reported situation is not a performance issue while using product 333155 (cd103 fitc, ce-ivd) lot 1015695.As per product instruction for use (ifu) 23-5646-02, product 333155 (cd103, clone ber-act8, ce-ivd) is intended for in vitro diagnostic use in the identification of cells expressing cd103 antigen, using a bd facs brand flow cytometer.Applications expression of cd103 antigen in the characterization of hematologic neoplasia.Composition cd103, clone ber-act8 is composed of mouse igg1 heavy chains and kappa light chains.Storage and handling the antibody is stable until the expiration date shown on the label when stored at 2-8 °c.Do not use after expiration date.Do not freeze reagent or expose it to direct light during storage or incubation with cells.Keep outside of reagent vial dry.Do not use reagent if you observe any change in appearance.Precipitation or discoloration indicates instability or deterioration.Specimens: reagents 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 number of nonviable cells can give erroneous results due to selective loss of populations and to increased nonspecific binding of antibodies to nonviable 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.Procedure: add appropriate volume of cd103 fluorochrome-conjugated monoclonal antibody to 100 ul of whole blood in a 12 x 75-mm tube.Refer to appropriate vial label for volume.Analytical results: abnormal numbers of cells expressing this antigen or aberrant expression levels of the antigen can be expected in some disease states.It is important to understand the normal expression pattern for this antigen and its relationship to expression of other relevant antigens in order to perform appropriate analysis.Figure 1 on ifu 23-5646-02 shows representative data analyzed with a bd facs brand flow cytometer.Performance characteristics.Specificity cd103 recognizes the e subunit of integrin e7, an integrin also known as the human mucosal lymphocyte (hml) antigen.Integrin e7 is preferentially expressed on human intestinal intraepithelial lymphocytes (iel).Cd103 also reacts with most t cells present in the oral and bronchial mucosa.Most cases of hairy cell leukemia were found to be cd103 positive.List of common problems, possible causes and solutions are provided in ifu 23-5646-02 page 5.Herein, "staining dim or fading" includes 'insufficient reagent" as one of the causes, in which solution is "repeat staining with increased amount of antibody".It was observed from customer provided flow cytometry data, product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 performs as intended.Response obtained from customer confirm customer is not having a performance problem while using product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695, but a situation they were investigating internally which was later confirmed by customer to be an anomaly related to individual patient disease and not the product which ¿is working ok¿.This data confirms product performs as intended.Based on investigation findings including evaluation of customer provided data, no additional claims reported against product 333155 lot 1015695 or subassembly 91-0419pr batch 0349658, and evidence of no discrepancies found on evaluated bhr, this claim is not confirmed, and no further actions are deemed necessary at this time.¿ conclusion: product 333155 (cd103 fitc, clone ber-act8, ce-ivd) lot 1015695 manufactured from subassembly 91-0419pr batch 0349658, was manufactured, and complies with bd specifications.Based on investigation performed it is determined claim is not confirmed and no further actions are necessary at this time.

• Brand Name: BD CD103 FITC CE
• Type of Device: NA
• Manufacturer (Section D): BECTON DICKINSON CARIBE LTD.; vicks drive; lot no. 6; cayey PR
• Manufacturer (Section G): BECTON DICKINSON CARIBE LTD.; vicks drive; lot no. 6; cayey PR
• Manufacturer Contact: phillip emmert ; 9450 south state street; sandy, UT 84070 ; 8015296192
• MDR Report Key: 13097392
• MDR Text Key: 286058546
• Report Number: 2647876-2021-00379
• Device Sequence Number: 1
• Product Code: MVU
• Combination Product (y/n): N
• Reporter Country Code: UK
• PMA/PMN Number: NA
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Other,Foreign,User Facility
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 03/11/2022

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: 03/31/2022
• Device Catalogue Number: 333155
• Device Lot Number: 1015695
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 12/02/2021
• Initial Date FDA Received: 12/28/2021
• Supplement Dates Manufacturer Received: 03/11/2022
• Supplement Dates FDA Received: 03/21/2022
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 01/15/2021
• Is the Device Single Use?: No
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1