MAUDE Adverse Event Report: MILTENYI BIOTEC B.V. & CO. KG CLINIMACS CD34 REAGENT

Model Number	70103
Medical Device Problem Code	Appropriate Device Problem Term/Code Not Available (3191)
Health Effect - Clinical Code	No Clinical Signs, Symptoms or Conditions (4582)
Date of Event	11/12/2021
Type of Reportable Event	Malfunction
Event or Problem Description
Customer performed cd34+ enrichment on the clinimacs plus device s/n (b)(4) using clinimacs ls tubing set l/n 7201200191, expiry date 2023-05-01 and cd34 reagent l/n 6210900028, expiry date 2022-02-01.The process resulted in 16% of cd34 positive cell recovery according to customer quality assessment.Average yield reported by this customer lies between 50 and 85%.The customer used program cd34 selection 2.The capacity of this enrichment program in combination with the corresponding ts (ts ls) is 120x109 total nucleated cells (white blood cells) and 1200x106 (1,2 x109) labeled cells.According to the data provided by the customer, the labeled sample contained 73.37x109 cells and 0.3% labelled cells, therefore it was within the specifications of the process.According to the data, provided by the customer, the labeling incubation time was 30' at rt on an orbital shaker at 25 rpm, and for the wash steps the cell sample was centrifuged for 15minutes at 200g+25rpm with no brake, at rt.Except for the non-substantially increased centrifugation force, this corresponds to the protocol recommended by miltenyi and should therefore have no negative influence on the labeling of the cd34 positive cells.The viability before as well as after separation was over 98%.The process code was (b)(4).The process code analysis revealed that no technical errors occurred during the process.Instrument setup, priming and separation were performed successfully, no stop or backstep key was pressed during the process and no pump door opening occurred.The sample loading time was between 510 and 539 seconds, which does not exceed expected sample loading time.Analysis of the investigation questionnaire also revealed that the apheresis product was stored overnight at the concentration 249x106/ml.This concentration is too high and might negatively affect the labeling efficiency.If the overnight storage needs to take place it is recommended to dilute the sample to achieve a concentration not higher than 2x108 (200x106)/ml.It is also recommend storing the sample at room temperature, which in our experience leads to the best separation results.2-8°c are not recommended.No flow cytometry data from the negative fraction bag (nfb) and buffer waste bag (bwb) are available.This data would be crucial to understand the location of the cells, that ware not recovered in the target cell bag.This is important to determine the root cause.The complaint database was checked for similar complaints for the involved reagent and tubing set lot.For neither another performance related complaint was reported.Root cause: a clear root cause could not be found.There is no indication for a product failure, neither for the reagent, the tubing set or the instrument used in the process.A common cause for a low recovery is insufficient labeling of the target cells with cd34 reagent.In this case, the following factors can have caused or contributed to an insufficient labeling: suboptimal overnight sample storage conditions (temperature, cell concentration, lack of dilution with autologous plasma) insufficient blocking of unspecific binding.In cases where autologous plasma is removed, blocking with igg is recommended.Further factors could not be excluded based on the information available: high amounts of platelets and/or granulocytes in the sample causing cell aggregation and unspecific binding.Donor specific factors leading to a low labeling efficiency cannot be excluded.Following preventive actions are recommended to the customer: always analyze the original fraction for platelet and granulocyte content reduce thrombocyte and granulocyte count.By unspecific binding they can consume reagent.Filtrate the product in case of a suboptimal quality, for example high granulocyte/platelet count.Analyze the content of the nfb and bwb to allow a comprehensive investigation in case of performance issues.If a substantial amount of target cells is found in the nfb and bwb, filter these cells and repeat the process on these pooled non target cell fractions if necessary, to increase overall recovery.Use igg to block unspecific binding if autologous plasma is removed and/or granulocyte/platelet count is high.

• Brand Name: CLINIMACS CD34 REAGENT
• Common Device Name: CLINIMACS CD34 REAGENT
• Manufacturer (Section D): MILTENYI BIOTEC B.V. & CO. KG; friedrich-ebert-str. 68; bergisch gladbach, 51429 ; GM 51429
• Manufacturer (Section G): MILTENYI BIOTEC B.V. & CO. KG; friedrich-ebert-str. 68; bergisch gladbach, 51429 ; GM 51429
• Manufacturer Contact: bettina-judith hö]hlich ; friedrich-ebert-str. 68; bergisch gladbach, 51429 ; GM 51429
• MDR Report Key: 13002272
• Report Number: 3005290010-2021-00015
• Device Sequence Number: 4796472
• Product Code: OVG
• UDI-Device Identifier: 04049934004827
• UDI-Public: 04049934004827
• Combination Product (Y/N): N
• Initial Reporter Country: US
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Serviced by Third Party (Y/N): Unknown
• Reporter Type: Manufacturer
• Report Source: Health Professional,User Facility
• Initial Reporter Occupation: Other Health Care Professional
• Type of Report: Initial
• Report Date (Section B): 12/14/2021

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
• Operator of Device: Health Professional
• Device Model Number: 70103
• Device Catalogue Number: 200-070-103
• Device Lot Number: 6210900028
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Type of Report(Section G): Thirty-Day
• Initial Date Received by Manufacturer: 11/29/2021
• Initial Report FDA Received Date: 12/14/2021
• Was Device Evaluated by Manufacturer? (Y/N): Device Not Returned to Manufacturer
• Is the Device Labeled for Single Use? (Y/N): Yes
• Is This a Single-Use Device that was Reprocessed and Reused on a Patient? (Y/N): No
• Usage of Device: Initial
• Patient Sequence Number: 1
• Patient Sex: Unknown