MAUDE Adverse Event Report: MILTENYI BIOTEC B. V. & CO. KG CRYOMACS FREEZING BAG 50; CONTAINER, EMPTY, FOR COLLECTION & PROCESSING OF BLOOD & BLOOD COMPONENTS

Model Number	74400
Health Effect - Clinical Code	Insufficient Information (4580)
Date of Event	08/17/2021
Type of Reportable Event	Malfunction
Event or Problem Description
Product quality issue- particulates observed in cell product clinical lots frozen in cryomacs50 freezing bag (initially lot 7200400270, also observed in lot 7200300724).When thawing and preparing subject cct6005-012's autologous gd2-car t cells for infusion, visual inspection showed blue particulates.Subsequent microscopic inspection of multiple bags from the same clinical manufacturing run for subject cct6005-012 also detected particulates of unknown origin.Infusion was canceled; patient did not receive this product.Gram stain, mycoplasma, and 14-day sterility results of the cell product are all negative.A larger root cause analysis has detected microscopic particulates in cryopreserved doses from three separate clinical manufacturing lots all frozen in cryomacs 50 freezing bags from lot 7200400270.At (b)(6) suggestion we have filed an official customer complaint and are working with their contracted analytical lab to characterize the visible and microscopic particulates.During our root cause analysis, we have also found microscopic particulates in cryomacs50, lot # 7200300724.We reported the product quality issue for autologous t-cells transduced with retroviral vector (14g2a-cd8.Bb.Z.Icasp9) expressing gd2 chimeric antigen receptor (gd2cart) to fda and voluntarily paused all infusions while we finalize root cause investigation and implement a risk mitigation plan.Detected both visible and subvisible particles of unknown origin in multiple bags from the same clinical lot, across multiple clinical lots.Fda safety report id# (b)(4).

• Brand Name: CRYOMACS FREEZING BAG 50
• Common Device Name: CONTAINER, EMPTY, FOR COLLECTION & PROCESSING OF BLOOD & BLOOD COMPONENTS
• Manufacturer (Section D): MILTENYI BIOTEC B. V. & CO. KG
• MDR Report Key: 12583281
• Report Number: MW5104409
• Device Sequence Number: 1205306
• Product Code: KSR
• UDI-Device Identifier: 04049934000270
• UDI-Public: (01)04049934000270
• Initial Reporter State: CA
• Initial Reporter Country: US
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Serviced by Third Party (Y/N): N
• Reporter Type: Voluntary
• Initial Reporter Occupation: Physician
• Type of Report: Initial
• Report Date (Section B): 10/01/2021
• 4 Devices were Involved in the Event: 1 2 3 4

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: 03/15/2023
• Device Model Number: 74400
• Device Catalogue Number: 200-074-400
• Device Lot Number: 7200400270
• Was Device Available for Evaluation?: Yes
• Initial Date Received by Manufacturer: Not provided
• Initial Report FDA Received Date: 10/05/2021
• 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
• Patient Age: 13 YR
• Patient Weight: 33