MAUDE Adverse Event Report: BECTON DICKINSON CARIBE LTD. BD CD3 APC-H7 SK7 ASR

Model Number	641406
Medical Device Problem Code	Incorrect, Inadequate or Imprecise Result or Readings (1535)
Health Effect - Clinical Code	No Consequences Or Impact To Patient (2199)
Date of Event	06/24/2020
Type of Reportable Event	Malfunction
Additional 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 or Problem Description
It was reported that during use and prior to expiration the antibodies are degrading with a bd cd3 apc-h7 sk7 asr.The following information was provided by the initial reporter: antibodies degrade.The customer found (b)(4) dye degradation after using a period before expiry date.Additionally, on 2020-07-13 the customer provided the following additional information: was the reagent being used in a lab developed test for clinical use? yes.If so was there any impact to the patient? may misinterpret the diagnosis.Did samples need to be redrawn? no.Was there any delay in treatment? no.
Additional Manufacturer Narrative
H.6.Investigation: manufacturing defect trend: product cd3 apc-h7 sk7 asr material 641406, lot 0059882 was assembled in bdb san jose (plant 1149) using material subassembly 91-0730, lot 0035129 manufactured in bdb cayey (plant 1157).Material 91-0730 lot 0035129 was used to manufacture the following materials and corresponding lots: ¿ 641415, lot 0059881.¿ 641406, lot 0059882.Refer to batch where used bottom-up analysis_91-0730 lot 0035129 pdf file.Product 641406 ,lot 0059882, expires on 11/30/2020.Out-of-specification (oos) or qn investigations were not identified in the device history record (dhr).Subassembly 91-0730 batch 0035129 was manufactured according to requirements and met manufacturing and qa acceptance criteria for release.The subassembly 91-0730 batch 0035129 was manufactured using conjugate manufactured at plant 1149: mat.No.50-00421 cd3 apc-h7 lot 9276686.No discrepancies (oos/qn) were identified in manufacturing/testing process history of subassembly 91-0730 during evaluated period from 24/jun/20 to 24/jun/19.¿ complaint trend: no additional complaints related to same defect/symptom of product 641406 lot 0059882 or subassembly 91-0730 lot 0035129 as checked in trackwise system from date 06/24/20 to 26/jun/19.All 430 ea of the batch, manufactured of product cd3 apc-h7 sk7 asr material 641406 lot 0059882 (subassembly 91-0730 lot 0035129), were sold to market with no additional claims reported during evaluated period of 24/jun/20 to 24/jun/19.¿ batch history record (bhr) review: product 641406 (cd3 apc-h7 sk7 asr) lot 0059882 was assembled in bdb cayey (plant 1157) using material subassembly 91-0730 batch 0035129 manufactured in bdb cayey (plant 1157), which met established acceptance criteria for product release as demonstrated by device history record (dhr).Manufacturing was performed according to requirements and specifications without any discrepancy or nonconformance.Dhr for subassembly 91-0730 batch 0035129 was reviewed and material was manufactured in accordance with specifications.The qc testing includes fluorometry and a measurement for ratio of spillover against a reference lot met established acceptance criteria parameters for product release.¿ retain sample evaluation / testing: two retain samples from the subassembly 91-0730 batch 0035129 were requested and delivery to qc laboratory at bbd cayey plant 1157 to perform the qc testing for fluorometry and a measurement for ratio of spillover (ros) against the reference 91-0730 lot 0051010 (exp 11/30/2020) following the established procedures.The second retain sample was sent to bdb san jose to perform the functional test corresponding to the conjugate bulk using reference 91-0730 lot 0051010 (exp 11/30/2020).¿ returned sample evaluation: the samples were not requested to be returned, since there is qa retain samples available for the subassembly 91-0730 batch 0035129.One sample was requested for bdb cayey plant 1157 to be evaluated according the material qc specifications and established procedures.The second retain sample was sent to bdb san jose plant 1149 for functional test.The second material retain sample was sent with one retention sample of reference 91-0730 lot 0051010 (exp 11/30/2020).¿ investigation result / analysis: the cd3 antibody, clone sk7,8,9 is derived from the hybridization of ns-1 mouse myeloma cells with spleen cells isolated from balb/c mice immunized with human thymocytes.The following are supplied in buffer containing a stabilizer and a preservative: apc-h7 reagent volume per test = 5 l.Concentration of reagent = 100 g/ml.Stabilizer = bsa.Preservative = proclin®300.Recommended reagent volume = 5 l per test, or 5 l (100 g/1000 l) = 0.5 g per test.Based on product 641406 technical data sheet (tds for cd3 (sk7)) 23-3599-11 (ver.2/2015), product 641406 is an analyte specific reagent (asr) and its performance characteristics are not established for use in diagnostic or therapeutic procedures.Customer claimed that product 641406 (cd3 apc-h7 sk7 asr) lot 0059882 is showing tandem dye degradation after using the product before expiry date and this was causing the loss of the apc channel resolution.Customer did not included data of affected lot 641406 (cd3 apc-h7 sk7 asr) lot 0059882.The investigation for this claim was reported as an antibody or tandem dye degradation.However, event description pointed out to a spillover from apc-h7 to apc channel.The qc testing release data for 641406 (cd3 apc-h7 sk7 asr) lot 0059882 subassembly 91-0730 batch 0035129 indicated that fluorometry and ratio of spillover against a reference lot met established acceptance criteria parameters for product release.The manufacturing process non-conformances nor additional similar claims for this product or the other two bd catalogs have not been reported.Evidence supported that issue was unlikely to have been caused during manufacturing process.Further the subassembly 91-0730 lot 0059882 (exp 08/31/2020) was evaluated through functional test and the bdb qc test for fluorometry and ros (ratio of spillover) using reference lot 0051010 (exp 11/30/20020).On the functional test both lots of cd3 apc-h7 that were used to stain normal blood specimens, recognized the t cells subset of the lymphocyte population.The reagent functioned as intended.Batch 0035129 is brighter that batch 0051010.The fluorometry and ros test met established acceptance criteria parameters for product as previously happened during its release.According to product 641406 technical data sheet (tds for cd3 (sk7)) 23-3599-11 (ver.2/2015)), apc-h7 conjugates, show changes in their emission spectra with prolonged exposure to paraformaldehyde or light.It is also recommended to avoid paraformaldehyde for overnight storage of stained cells.There is no evidence to rule out one of the causes as the root cause of the event reported by the customer.Based on investigation performed it is determined the claim is not confirmed.¿ risk analysis: risk analysis applicable for product 641406 (cd3 apc-h7 sk7 asr) is available under failure mode effect analysis (fmea) document fmea cd3 sk7 ce cd3sk7fmea rev.07 and sop6078-03 rev 07-antibodies and antibody conjugates asr / ruo products (100311ra) (fmea) document cd452d1fmea rev.06.Hazard(s) identified? x yes no.Reviewed item: (2) conjugates.Function: to provide correct detectable signal when detect the cell surface marker potential function failure: wrong signal - dim and/or bright emission.Potential effects of failures: end user: wrong result ¿ no matching profile -customer inconveniences ¿ additional testing, cost, and time.Potential cause of failure: poor conjugation - over / under conjugation.Occurrence: 4.Severity: 7.Detection:2.Risk priority number (rpn): 56.Risk acceptability: rpn < 90 will be acceptable.Implementation: 1.Mfg spec.Modification range.2.R&d conjugation process.3.Stability testing.4.In-process checks new hazard: none.Mitigation(s) enough x yes ¿ no.Sop6078-03 rev 07-antibodies and antibody conjugates asr / ruo products (100311ra).#1.Hazard(s) identified? x yes ¿ no.Hazard #:3.1.1- functional hazard.Cause: -improper storage onsite, as well as at customer site, temperature, and light exposure.Severity: 3.Probability: 1.Risk index:3.Risk evaluation: acceptable.Implementation: technical data sheet, vial label.Risk control: 1) technical service support, 2) labeling/tds.New hazard: none.Mitigation(s) sufficient x yes ¿ no.#2.Hazard(s) identified? x yes ¿ no.Hazard #:3.1.4- functional hazard.Cause: -prolonged exposure of cells to paraformaldehyde can lead to autofluorescence in violet channel.Severity: 3.Probability: 1.Risk index:3.Risk evaluation: acceptable.Implementation: technical data sheet.Risk control: 1) caution in tds: ¿for overnight storage of stained cells, wash and resuspend in buffer without paraformaldehyde after 1 hour of fixation¿.New hazard: none.Mitigation(s) sufficient x yes ¿ no.¿ root cause analysis: root cause is not determined.Evidence demonstrates manufacturing process was performed according to requirements and specifications without discrepancy.Based on the investigation performed, the manufacture batch record review, the established bdb qc testing performed and the functional test to a retention sample of the subassembly 91-0730 lot 0059882 it is considered a customer related issue and not a manufacturing process issue.Therefore, claim is unconfirmed, and no further actions are deemed necessary at this time.¿ conclusion: product 641406 (cd3 apc-h7 sk7 asr) lot 0059882, manufactured from subassembly 91-0730 batch 0035129, was manufactured according to specifications.The investigation performed, the manufacture batch record review, the established bdb qc testing performed, and the functional test indicate that the issue was unlikely to be originated 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 641406 (cd3 apc-h7 sk7 asr) lot 0059882.H3 other text : see h.10.
Event or Problem Description
It was reported that during use and prior to expiration the antibodies are degrading with a bd cd3 apc-h7 sk7 asr.The following information was provided by the initial reporter: antibodies degrade the customer found tandem dye degradation after using a period before expiry date.Additionally, on 2020-07-13, the customer provided the following additional information: was the reagent being used in a lab developed test for clinical use? yes.If so was there any impact to the patient? may misinterpret the diagnosis.Did samples need to be redrawn? no.Was there any delay in treatment? no.

• Brand Name: BD CD3 APC-H7 SK7 ASR
• Common Device Name: NA
• Manufacturer (Section D): BECTON DICKINSON CARIBE LTD.; vicks drive; lot no. 6; cayey PR
• MDR Report Key: 10275884
• Report Number: 2647876-2020-00001
• Device Sequence Number: 10951142
• Product Code: MVU
• UDI-Device Identifier: 00382906414069
• UDI-Public: 00382906414069
• Combination Product (Y/N): N
• Initial Reporter Country: TW
• PMA/510(K) Number: NA
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Reporter Type: Manufacturer
• Report Source: foreign,other,user facility
• Initial Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date (Section B): 09/01/2020

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
• Operator of Device: Other
• Device Expiration Date: 11/30/2020
• Device Model Number: 641406
• Device Catalogue Number: 641406
• Device Lot Number: 0059882
• Was Device Available for Evaluation?: No
• Initial Date Received by Manufacturer: 06/24/2020
• Supplement Date Received by Manufacturer: 06/24/2020
• Initial Report FDA Received Date: 07/15/2020
• Supplement Report FDA Received Date: 09/01/2020
• Is This a Single-Use Device that was Reprocessed and Reused on a Patient? (Y/N): No
• Patient Sequence Number: 1
• Outcome Attributed to Adverse Event: Other