MAUDE Adverse Event Report: BECTON DICKINSON CARIBE LTD. MS IGG2A ISOTYPE CONTROL APC X39 ASR

Model Number 340757

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

Patient Problems No Consequences Or Impact To Patient (2199); No Clinical Signs, Symptoms or Conditions (4582)

Event Date 12/03/2020

Event Type  malfunction  

Manufacturer Narrative

A device evaluation and/or device history review is anticipated, but is not complete.Upon completion, a supplemental report will be filed.(b)(4).

Event Description

It was reported that ms igg2a isotype control apc x39 asr gave erroneous results.The following information was provided by the initial reporter: (b)(6).Data sent by customer.(b)(6).Additional information from customer: i received this same lot on a previous order from (b)(6) 2020.We use this isotype for ldt immune panels.In the past we have noticed some patient's lymphocytes react with this lot of igg2a antibody (maybe clone specific) and be positive.We ordered it in (b)(6) and received the same lot.We have used three different cells so far with this shipment and seen positive populations past the 103 log decade.We use 5ul of the igg2a apc antibody by itself when performing qc in parallel with the current lot.We use a lysed protocol for a cell suspension and use up to one million cells in a 100ul volume for staining.It is analyzed using a bd facscanto ii flow cytometer.(b)(6).Reviewed, pending replacement product material no: 340757; batch no: 0253432.It was reported that the reagent is showing high background.(b)(6).Requested data and details on protocol.Waiting for information.(b)(6).Email from customer to clinical sale agent.We received mouse igg2a apc cat#340757 (lot#0253432) on 11/23/20 order.We qc'd it twice with two different cells and it seems to have a positive population.(b)(6).340757_0253432 is showing high background.".

Event Description

It was reported that ms igg2a isotype control apc x39 asr gave erroneous results.The following information was provided by the initial reporter: "(b)(6): (b)(6) 2020, 20:00:27 (gmt).Data sent by customer.(b)(6): (b)(6) 2020, 19:59:42 (gmt).Additional information from customer: i received this same lot on a previous order from (b)(6) 2020.We use this isotype for ldt immune panels.In the past we have noticed some patient's lymphocytes react with this lot of igg2a antibody (maybe clone specific) and be positive.We ordered it in november and received the same lot.We have used three different cells so far with this shipment and seen positive populations past the 103 log decade.We use 5ul of the igg2a apc antibody by itself when performing qc in parallel with the current lot.We use a lysed protocol for a cell suspension and use up to one million cells in a 100ul volume for staining.It is analyzed using a bd facscanto ii flow cytometer.(b)(6): (b)(6) 2020 17:10:30 (gmt) reviewed, pending replacement product.Material no: 340757; batch no: 0253432.It was reported that the reagent is showing high background.(b)(6): (b)(6) 2020 01:01:34 (gmt) requested data and details on protocol.Waiting for information.(b)(6): (b)(6) 2020 00:59:51 (gmt) email from customer to clinical sale agent we received mouse igg2a apc cat #340757 (lot #0253432) on (b)(6) 2020 order.We qc'd it twice with two different cells and it seems to have a positive population.(b)(6): (b)(6) 2020 00:57:21 (gmt) 340757_0253432 is showing high background.".

Manufacturer Narrative

H6 investigation summary: customers reported three (3) complaints against product 340757 (mouse igg2a apc, clone x39, asr) lot 0253432 where high background or positive signal using this isotype negative control.Mouse igg2a antibody reacts specifically with keyhole limpet hemocyanin (klh), an antigen not expressed on human cells or human cell lines.No positive signal is expected when used on stained human blood for flow cytometry analysis.As described on retain sample analysis section, a series of functional flow cytometry and elisa tests were performed in plant 1157 and 1149 in support to investigation.Briefly, flow cytometry testing¿s confirm positive signal on subassembly 91-0339pr (igg2a apc) batch 0216925 when challenged on stained peripheral blood mononuclear cells (pbmcs) and later pre-washed lysed whole blood (lwb) cells, but not always detected when tested on human lwb without prior washing.Elisa specificity test confirmed retain sample of 91-0339pr (igg2a apc) batch 0216925 and comparative reference batch were mouse igg2a isotype and kappa light chain.This finding helped discard presence of any other potential antibody contaminant of a different isotype and light chain specificity other than mouse igg2a kappa.Later experiments found that positive signal problem was also detected on bulk conjugate material 50-00154 batch 0148333 but not on parent purified bulk 45-9050 batch 9182336.Investigation reveals the contaminant material present in subassembly 91-0339pr batch 0216925 and material component 50-00154 batch 0148333 was effectively blocked using cd62l (45-7440) purified antibody, which is a mouse igg2a kappa antibody, hence confirms cd62l is the contaminant present on affected materials.During investigation, remaining bd stock (23 vials) of product 340757 (igg2a apc, clone x39 asr) lot 0253432 on inventory at bdb san jose (plant 1149), were blocked in sap system.Bulk conjugate 50-00154 batch 0148333 was used on (b)(6) 2020 to produce 3 vials of custom product 621631 lot 0168459 by customs technology team (ctt).This material was blocked in plant 1149.Investigation revealed retained parent bulk 45-9050 (igg2a pure) batch 9182336 is not contaminated with cd62l.Tracking of material movements for aliquots performed in inventory control (ic) at plant 1157 show that cd62l (45-7440) was present in ic work area while handling purified bulk igg2a (45-9050).50-00154 batch 0148333 apc conjugation bhr was evaluated, and no evidence of concomitant process occurred with other potential contaminant antibodies while working with affected igg2a (not shared columns, working area, labware, technician or periods).The pures (45-stages) inventory control handling and aliquot dispatch was evaluated, and based on the material flow reveals pure cd62l (45-7440 batch 9288524) and mouse igg2a (45-9050 batch 9182336) were handled concurrently on (b)(6) 2020 during an aliquoting process at inventory control area in plant 1157.No evidence was found of cross-contamination of pure cd62l (45-7440 batch 9288524) with igg2a (45-9050 batch 9182336) as cd62l product was functionally tested and show expected positive signal.¿ most probable cause of the positive signal on 91-0339pr (igg2a apc) batch 0216925 and bulk 50-00154 batch 0148333 is that a contamination with cd62l pure was inadvertently introduced during the aliquoting process of cd62l (45-7440 batch 9288524) pure and igg2a (45-9050 batch 9182336) pure handled on (b)(6) 2020 at inventory control (ic) in plant 1157).No other material aliquots were impacted as described on the investigation.Contaminated igg2a pure aliquot was dispatched for use in conjugation area for manufacturing bulk conjugate component 50-00154 (igg2a apc) batch 0148333, hence affecting subassembly 91-0339pr (igg2a apc) batch 0216925 used to manufacture product 340757 (mouse igg2a apc, clone x39, asr) lot 0253432 in plant 1157 and product 621631 (igg2b fitc / igg2b pe / igg1 percp-cy tm 5.5 / igg2a apc) lot 0168459 manufactured by customs technology team (ctt) using affected bulk component.Corrective actions taken and recommended: an awareness discussion of the event was completed on (b)(6) 2021 with ic personnel and extended to all manufacturing areas in in plant 1157.As part of the immediate corrective actions, requirements, and opportunities for line clearance documentation during ic aliquot process was discussed.Cid 2977935 was initiated on (b)(6) 2021 to determine if capa will be initiated and sa bdb-21-4173 was initiated on (b)(6) 2021.Conclusion: product 340757 (mouse igg2a apc, clone x39, asr) lot 0253432 manufactured from subassembly 91-0339pr batch 0216925 was confirmed to have a positive signal not expected for a negative control and determined to be a contamination with cd62l.Based on investigation performed, the claimed is confirmed.H3 other text : see h10.

• Brand Name: MS IGG2A ISOTYPE CONTROL APC X39 ASR
• Type of Device: ISOTYPE CONTROL
• Manufacturer (Section D): BECTON DICKINSON CARIBE LTD.; vicks drive; lot no. 6; cayey PR
• MDR Report Key: 11103438
• MDR Text Key: 251541906
• Report Number: 3008352382-2020-00004
• Device Sequence Number: 1
• Product Code: MVU
• UDI-Device Identifier: 00382903407576
• UDI-Public: 00382903407576
• Combination Product (y/n): N
• PMA/PMN Number: NA
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: other,user facility
• Type of Report: Initial,Followup
• Report Date: 06/16/2021

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: 08/31/2022
• Device Model Number: 340757
• Device Catalogue Number: 340757
• Device Lot Number: 0253432
• Was Device Available for Evaluation?: No
• Initial Date Manufacturer Received: 12/04/2020
• Initial Date FDA Received: 12/31/2020
• Supplement Dates Manufacturer Received: 06/16/2021
• Supplement Dates FDA Received: 06/29/2021
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1