MAUDE Adverse Event Report: MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED CELLEX PHOTOPHERESIS SYSTEM

Catalog Number CELLEX

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

Patient Problems Anemia (1706); Fatigue (1849); Pallor (2468)

Event Type  Injury  

Manufacturer Narrative

The system was used for treatment.This case is reportable as a mdr due to the medical intervention of the iv iron infusion and blood transfusion that were provided to the patients.Since this event is associated with the treatment, this mdr will be against the instrument.From the instrument perspective, there was no known instrument malfunction and no instrument issue was alleged by the customer.No service was requested by the customer for this adverse event.A device service history review could not be performed as an instrument serial number was not provided.Anemia is a labelled adverse event within the cellex operator's manual.In section 2-2 adverse events of the cellex operator's manual it states "treatment frequency exceeding labeling recommendations may result in anemia." trends were reviewed for complaint categories anemia, fatigue, and pallor.No trends were detected for these complaint categories.The assessment is based on information available at the time of the investigation.Complaints are monitored through tracking and trending.If a trend is detected, further investigation will be conducted.Adverse event terms: anemia, fatigue, and pallor comp (b)(4).

Event Description

In the journal article entitled development of iron deficiency anemia in patients undergoing extracorporeal photopheresis: comparison of the uvar and cellex instruments by m.Moosavi, et al,, j clin apher.2020;1-7; the authors retrospectively analyzed thirty four patients (fifteen males and nineteen females; average age 53 years (22-77 years)) who were treated with extracorporeal photopheresis (ecp) from 2015 to 2019 for iron deficiency anemia (ida).The patients were being treated with ecp for graft versus host disease (gvhd), cutaneous t-cell lymphoma (ctcl), bronchiolitis obliterans syndrome (bos) and other.Ida was defined by a decrease in hemoglobin following treatment with concomitant decrease in mean cell volume, mean corpuscular hemoglobin concentration, increased red blood cell (rbc) distribution width, and/or iron studies compatible with ida.During the four-year study period, thirteen patients (38%) underwent treatment with the previous uvar device while twenty one patients (62%) received treatment on the newer cellex instrument.Twenty-seven of the patients developed anemia as defined as hemoglobin below the adult (>18 years) reference ranges (<12.9 g/dl for male and <11.4 g/dl for female).Nineteen of these patients (56%) developed both clinical and laboratory evidence of ida with an average decrease of hemoglobin of 3.2 g/dl.A statistically significant drop in hemoglobin was noted in the cellex treated patients (p <.01) but not within the uvar treated patients, perhaps secondary to a lack of a manual return, which was present in the earlier uvar procedure.The cellex treated patients who developed ida experienced a significantly greater drop in hemoglobin (2.6 g/dl (0-6.1) p =.04) than those treated on the uvar (1.3 g/dl (0.2-3.6).The patients receiving ecp were all hemodynamically stable outpatients.However, four patients who received ecp with the cellex instrument developed ida requiring supplemental iron.Two of these patients were treated with iv iron infusion, one was treated with oral iron supplementation, and one patient received transfusion with two units of packed red blood cells as she was overtly symptomatic with increased fatigue and generalized pallor.The patients who received iron supplementation improved through normalization of both hematological parameters and subsequent iron studies.While no significant differences based on ecp indication (ie, diagnosis) were found between the groups, patients with gvhd appeared more likely to experience ida.When grouping the patients with gvhd and bos together and comparing them to the ctcl group, there was a significant difference in the drop in hemoglobin, at least in the cellex group (p =.03).Patients with gvhd and bos tend to start on ecp regimens of twice weekly for a period of approximately eight weeks while patients with ctcl are typically treated twice every other week.Regardless of the instrument used, anemic patients treated twice weekly experienced a statistically larger drop in hemoglobin compared to those treated less frequently (2.6 vs 1.2 g/dl, p =.004); this drop in hemoglobin was more pronounced in patients with ida getting treated twice weekly (3.4 vs 1.4 g/dl; p =.003).The authors concluded that ida is a risk of chronic ecp therapy and is likely secondary to retained blood components in the instrument.The temporal relationship between anemia and ecp treatment has a direct correlation with the treatment schedule.Patients undergoing ecp treatment should be closely monitored for the development.The uvar device is no longer marketed as it has been retired/sunset.The uvar product manufacturing was discontinued in 2018.

• Brand Name: CELLEX PHOTOPHERESIS SYSTEM
• Type of Device: CELLEX PHOTOPHERESIS SYSTEM
• Manufacturer (Section D): MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; blanchardstown, dublin D15 T X2V; EI D15 TX2V
• Manufacturer (Section G): MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; college business & tech park; cruiserath road; blanchardstown, dublin D15 T X2V; EI D15 TX2V
• Manufacturer Contact: megan vernak ; shelbourne building; 53 frontage rd suite 300; hampton, NJ 08827
• MDR Report Key: 11281036
• MDR Text Key: 230458592
• Report Number: 2523595-2021-00014
• Device Sequence Number: 1
• Product Code: LNR
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: P860003
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: literature
• Reporter Occupation: Physician
• Type of Report: Initial
• Report Date: 02/04/2021

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Catalogue Number: CELLEX
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 01/05/2021
• Initial Date FDA Received: 02/04/2021
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is the Device Single Use?: No
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Reuse
• Patient Sequence Number: 1
• Patient Outcome(s): Required Intervention