MAUDE Adverse Event Report: TERUMO CORPORATION, FUJINOMIYA FACTORY OF TERUMO CORP IMUFLEX BLOOD BAG SYSTEM; IMUFLEX WB-RP BLOOD BAG SYSTEM WITH LR FILTER

Catalog Number 1BBWGQ506A2

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

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

Event Date 06/18/2023

Event Type  malfunction  

Event Description

The customer reported elevated white blood cell (wbc) content in a filtered whole blood unit.There was not a transfusion recipient or patient involved at the time of the unit processing, therefore no patient information is reasonably known at the time of the event.Donor unit #: (b)(6) terumo bct is awaiting return of the disposable set for evaluation.

Manufacturer Narrative

Investigation: we have not received the set returned from the customer.We therefore performed investigation based on the provided information.In regard to the production of imuflex, sealed bags are filled with solution and the line is assembled.These bags are sterilized, stacked, and placed into the blister packs.The top film of each blister pack is heat-sealed.For the leukoreduction filter, filter membranes are punched out, laminated, and integrated into soft housing.In order to ensure leukoreduction performance and to prevent filter occlusion in and hemolysis, standards have been set to control particulate removal rates and cationization levels of each filter membrane.The standards of average cationization levels of laminated filter membranes have also been set and controlled.Only the filter media that have passed the standards are incorporated into the housing.We reviewed the manufacturing record of the lot number in question and confirmed that no anomalies occurred in any process, and the products were manufactured as usual.Release testing, which includes measurements of solution concentration and volume and a visual inspection, is performed on the product concerned on a sample basis.We reviewed each testing and inspection record of the production number and confirmed that there were no anomalies in all release testing items.The product conformed to the standards.Regarding the retained sample of the lot number concerned, three sets were visually inspected.There were not any occlusions in tubing, blocking, or any abnormalities in their appearances.In addition, we measured the volume and concentration of the solution in the same manner as the release testing.We did not see any abnormalities, and the results conformed to our in-house standards.Root cause: we reviewed the manufacturing record and the testing and inspection record of the lot number concerned.We did not find any abnormalities and we were not able to identify the cause of the issue.Leukoreduction failure is commonly caused by the following factors: 1) analysis affected by blood properties of donors the following blood properties (e.G.Sickle cell trait*4 and cold agglutinin disease*5) or blood conditions on blood collection may cause wbc count failures.For the details, please refer to the excerpt from the literature.*4: transfusion.2022, 62 (9), 1727¿1730.*5: ann lab med.2018, 38 (4), 371¿374.Spurious counts and spurious results on wbc counts (spurious increase) *6 platelet aggregates large platelets nucleated red blood cells rbc resistant to lysis cryoglobulin lipids microorganisms (bacterial aggregates) *6: zandecki m, genevieve f, gerard j, godon a.Spurious counts and spurious results on haematology analyzers: a review.Part ii: white blood cells, red blood cells, hemoglobin, red cell indices and reticulocytes.International journal of laboratory hematology.2007, 29, 21¿41, table 1.2) pressure loaded on filter membranes where a physical stress on filter membranes is greater than what is expected, trapped white blood cells are pushed out of the filter membranes and may result in leukoreduction failure.For the prevention of leukoreduction failure, the instructions for use (ifu) of the product state: "[caution] do not squeeze or apply pressure on the filter while it is attached to the bag containing the filtered blood", and ¿clamp the blood filled tubing before blood enters the filter¿.

Manufacturer Narrative

Investigation: we examined the set concerned, which we received.The filter of the set was rinsed with normal saline.The normal saline flowed through the filter at a flow rate of about 30 ml/min.An airtightness test (i.E.Leak test) was performed on the filter in accordance with the following procedures and we confirmed that air leaks were not observed in any locations of the filter.I) the tab sheet covering the outlet side (second side) of the filter is cut out carefully and exposed the outlet side to allow observing the frame sheet (partition) directly.Ii) air is admitted to the filter, which is submerged in water, from the outlet-tube of the filter at a gauge pressure of 39.2 kpa (0.4 kgf/cm2) for approximately 10 seconds to check whether there is any air leakage from the frame sheet (partition).We disassembled the rinsed filter to observe the appearance of filter media (membranes).We noticed creases in the filter media; however, the creases were not different from those observed in conforming products.We did not observe aggregates adhered to the filter media.After passing normal saline through the filter, we dyed the filter media with toluidine blue for observation.We noticed that the fifth and sixth filter membranes from the inlet side of the filter were dyed dark, that is, white blood cells were accumulated in these dark dyed areas.We also observed dark dyed areas in the first filter membrane from the inlet side of the filter due to minute aggregates.In regard to the production of imuflex, sealed bags are filled with solution and the line is assembled.These bags are sterilized, stacked, and placed into the blister packs.The top film of each blister pack is heat-sealed.For the leukoreduction filter, filter membranes are punched out, laminated, and integrated into soft housing.In order to ensure leukoreduction performance and to prevent filter occlusion in and hemolysis, standards have been set to control particulate removal rates and cationization levels of each filter membrane.The standards of average cationization levels of laminated filter membranes have also been set and controlled.Only the filter media that have passed the standards are incorporated into the housing.We reviewed the manufacturing record of the lot number in question and confirmed that no anomalies occurred in any process, and the products were manufactured as usual.Release testing, which includes measurements of solution concentration and volume and a visual inspection, is performed on the product concerned on a sample basis.We reviewed each testing and inspection record of the production number and confirmed that there were no anomalies in all release testing items.The product conformed to the standards.Regarding the retained sample of the lot number concerned, three sets were visually inspected.There were not any occlusions in tubing, blocking, or any abnormalities in their appearances.In addition, we measured the volume and concentration of the solution in the same manner as the release testing.We did not see any abnormalities, and the results conformed to our in-house standards.Corrected root cause: as the investigation results provided in our initial answer card, no abnormalities were observed in the manufacturing record or the testing and inspection record of the lot number concerned.We also investigated the retained samples of the lot number concerned, and the results revealed no abnormalities.In the investigation of the filter of the set returned, the fifth and sixth filter membranes from the inflow side were dyed dark with toluidine blue; therefore, occlusion may have occurred in the filter.Blood may have been filtered by the filter area which was smaller than usual, and the linear speed (flow rate per unit area) increased and consequently leukocyte leakage occurred.

Event Description

The customer reported elevated white blood cell (wbc) content in a filtered whole blood unit.There was not a transfusion recipient or patient involved at the time of the unit processing, therefore no patient information is reasonably known at the time of the event.Donor unit #: (b)(6).

• Brand Name: IMUFLEX BLOOD BAG SYSTEM
• Type of Device: IMUFLEX WB-RP BLOOD BAG SYSTEM WITH LR FILTER
• Manufacturer (Section D): TERUMO CORPORATION, FUJINOMIYA FACTORY OF TERUMO CORP; fujinomiya 418-0 004; JA 418-0004
• Manufacturer (Section G): TERUMO CORPORATION, FUJINOMIYA FACTORY OF TERUMO CORP; 818 misonodaira; fujinomiya 418-0 004; JA 418-0004
• Manufacturer Contact: makoto yoshikawa ; 818 misonodaira; fujinomiya 418-0-004 ; JA 418-0004
• MDR Report Key: 17318410
• MDR Text Key: 319231623
• Report Number: 9681839-2023-00045
• Device Sequence Number: 1
• Product Code: CAK
• Combination Product (y/n): N
• Reporter Country Code: US
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 07/13/2023

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: Health Professional
• Device Catalogue Number: 1BBWGQ506A2
• Device Lot Number: 220222AF
• Was Device Available for Evaluation?: Yes
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 06/22/2023
• Initial Date FDA Received: 07/13/2023
• Supplement Dates Manufacturer Received: 07/18/2023
• Supplement Dates FDA Received: 08/04/2023
• Was Device Evaluated by Manufacturer?: Yes
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Other