MAUDE Adverse Event Report: MILTENYI BIOTEC B. V. & CO. KG BRANCH TETEROW CRYOMACS(R) FREEZING BAG 250; CONTAINER, EMPTY, FOR COLLECTION & PROCESSING OF BLOOD & BLOOD COMPONENTS

Device Problem Product Quality Problem (1506)

Patient Problem Chemical Exposure (2570)

Event Description

Our hct/p registered tissue establishment (fei 3005339821) is reporting an event as a medical device problem into medwatch per recommendation from the fda center for biologics, office of communication, outreach, and development, division of manufacturers assistance and training (matt).We received email notice on 1/5/2023 from them recommending us to report this into medwatch, and we received separate email notice from hctp_deviations@fda.Hhs.Gov that our fda cber biological product deviation report on 10/30/22 was rejected as it didn't meet the definition of an hct/p deviation per 21 crf 1271.3(dd).To summarize, our laboratory had been using miltenyi biotec cryomacs 250 bags since november 2010 to cryopreserve hpc, apheresis and mnc, apheresis products for patient cellular therapies at (b)(6) for the stem cell transplant program.These bags are primarily made from eva plastic, but there are regions of tubing that contain pvc plastic.It has recently been discovered that the manufacturer's instructions state that the injection port only should be used to transfer fluids containing dmso.Our facility had been using another port that was made of plastic that is not dmso resistant from the time of implementation in 2010 to september 26, 2022, about a week after discovery to correct the dmso transfer workflow to match manufacturer's instructions.We contacted the cryopreservation container vendor, and although they provided some documentation of studies, they acknowledged the studies were done using 100% dmso.The highest concentration of dmso we use is approximately 20% dmso.The vendor is not providing more guidance to assess impact on our unique process for our patients.According to our clinical transplant team evaluation, an initial determination based on clinical evidence over the years is that the toxicity risk to our patients is likely minimal.The following rationale supports this: 1- the dmso contact for each bag manufactured is short in duration, and 1/5th the concentration of the vendor's toxicity studies.We estimate that the total time of diluted dmso exposure in the pvc plastic region of tubing in our former process to be an approximate combined total of 30 seconds.Other than that exposure, dmso is only exposed to eva plastic regions of the container set.2- our patients are exposed only once per bag with the diluted dmso as described; therefore "neither "high doses" nor "repeated exposures" were achieved.3- there are no short- or long-term engraftment issues or any other post-transplant complications observed over this timeframe, including any adverse trends of kidney toxicity; outliers are almost always explainable clinically and are consistent with other transplant centers.4- with no pediatric program since 2009, only adults have been treated with these products during this timeframe.The fda matt division has recommended that we perform an extractables and leachables (e&l) study to collect data and perform a toxicological risk assessment (tra), with follow-up communications and documentation updates as needed once we obtain information about known and unknown risks.We are working on obtaining a vendor and contract for this e&l testing at the time of reporting.

• Brand Name: CRYOMACS(R) FREEZING BAG 250
• Type of Device: CONTAINER, EMPTY, FOR COLLECTION & PROCESSING OF BLOOD & BLOOD COMPONENTS
• Manufacturer (Section D): MILTENYI BIOTEC B. V. & CO. KG BRANCH TETEROW
• MDR Report Key: 16598204
• MDR Text Key: 312021495
• Report Number: MW5115934
• Device Sequence Number: 1
• Product Code: KSR
• Combination Product (y/n): N
• Reporter Country Code: US
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Voluntary
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial
• Report Date: 03/21/2023

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 03/22/2023
• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Was Device Available for Evaluation?: Yes
• Is the Reporter a Health Professional?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1