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

Catalog Number CELLEX

Device Problems Use of Device Problem (1670); Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Anemia (1706); Cyanosis (1798); Low Blood Pressure/ Hypotension (1914); Tachycardia (2095); Vomiting (2144); Muscle Hypotonia (4531); Appropriate Clinical Signs, Symptoms, Conditions Term / Code Not Available (4581)

Event Date 05/31/2022

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 saline that was provided to the patient.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.No product was returned therefore, a device service history review was performed.The instrument has been located at the customer's site since (b)(6) 2013.As part of the review, it was determined that the instrument's last service prior to the event was on (b)(6) 2022.During this service the system checkout procedure was successfully completed indicating that the instrument had passed all tests, met all specifications, and was operational.Trends were reviewed for complaint categories,hypotension and low hematocrit.No trends were detected for these complaint categories.The cellex operator's manual section 2-3, adverse events states "hypotension may occur during any treatment involving extracorporeal circulation.Closely monitor the patient during the entire treatment for hypotension." 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: low blood pressure/hypotension and code not available: low hematocrit.(b)(4).(b)(6) 2022.

Event Description

The customer reported that an extracorporeal photopheresis (ecp) patient experienced hypotension and low hematocrit during an ecp treatment procedure.The customer stated that this was the patient's first ecp treatment procedure for graft versus host disease (gvhd).The customer reported that the patient was a low body weight patient thus an ecp blood prime treatment procedure was performed.The customer stated that during buffy coat collection the patient's blood pressure dropped from 93/63 to 77/40.The customer reported that they then administered saline iv at a rate of 10ml/kg to the patient and the patient stabilized.The customer stated that they were then able to continue with the patient's ecp treatment procedure.The customer reported that the patient's ecp treatment procedure was successfully completed with a whole blood processed volume target of 1,000mls.The customer stated that the patient's blood pressure after their ecp treatment procedure was 77/40.In addition, the customer reported that the patient's hematocrit had decreased after their ecp treatment procedure.The customer reported that the patient's hematocrit before and after their ecp treatment procedure was 25% and 21%, respectively.The customer stated that this patient usually has a low hematocrit.The customer reported that they believed that the patient's ecp treatment procedure could have caused or contributed to the patient's hypotension and low hematocrit.The customer stated that they also believed that the patient's underlying condition could have caused or contributed to the patient's hypotension and low hematocrit.The customer reported that this patient is a pediatric intensive care unit (picu) inpatient and is very sickly.The customer stated that this patient has multiple comorbidities and was already in the picu prior to starting their ecp treatments procedures.The customer reported that the patient was hemodynamically unstable at the time of their ecp treatment procedure, thus the customer believed that the patient's underlying condition could have caused or contributed to their hypotension and low hematocrit.The customer stated that the patient's following ecp treatment procedure was successfully completed; however, the patient's hematocrit continues to drop during their ecp treatment procedures.The customer reported that they have had to make some changes to their ecp treatment plan for this patient.No product was returned for investigation.

Manufacturer Narrative

The customer's presentation provided additional information on how the patient's blood prime ecp treatment procedure was performed at the time of the event.Upon review of the customer's presentation the most likely root cause for the patient's adverse events is use error.While the customer did perform the appropriate blood prime ecp treatment procedure for this low body weight patient, the blood prime ecp treatment procedure was not performed as per the labeled blood prime instructions in the cellex operator's manual.The customer acknowledged in his presentation that the patient experienced their adverse events during the buffy coat displacement phase of the patient's blood prime ecp treatment procedure as additional red blood cells were drawn from the patient (50-100ml) in order to displace the buffy coat and no fluids were returned to the patient during this phase.In addition, the customer's presentation indicated that the patient experienced hemodilution as fluids were being returned to the patient during their blood prime ecp treatment procedure which according to the customer also contributed to the lowering of the patient's hematocrit.The customer reported that in future blood prime ecp treatment procedures for this patient they will pause the patient's blood prime ecp treatment procedure prior to the buffy coat displacement phase in order to disconnect the patient and connect the instrument to the red blood cell unit.The customer stated that the red blood cell unit will then be used to displace the buffy coat avoiding an acute hematocrit dop in the patient and any possible adverse events.The customer also reported that they would reduce the return rate of the instrument to 0ml/min to avoid hemodilution.However, if the customer had followed the detailed blood prime instructions in the cellex operator's manual section 10-15, blood prime, they would have been aware of these requirements for a blood prime ecp treatment procedure.Per the cellex operator's manual section 10-15, blood prime: " by default, the blood prime setup parameter is disabled (off).When enabled (on) the following features will be activated: 1.At the onset of buffy coat, the return flow rate will automatically be reduced to zero and the return access will be maintained with keep vein open (kvo).The operator is able to manually increase the return flow rate using the arrows on the main screen of the operator interface.2.During photoactivate, no return bag contents will be returned to the patient.3.Reinfusion of the treatment volume will begin automatically using the last user set return rate.The reinfusion rate limit is active at this point.4.Once all of the treatment volume has been reinfused, the rinseback volume will be returned to the patient automatically.5.An audible cadence will occur when rinseback is complete.The operator now has the option to: a.Repeat the rinseback using the same volume b.Enter setup and select a different rinseback volume c.Complete the treatment by pressing abort." if the customer had enabled the instrument's blood prime setup parameter, the return flow rate would have been automatically reduced to zero and no return bag contents would have been returned to the patient, thus decreasing the amount of hemodilution experienced by the patient.In addition, the cellex operator manual's blood prime instructions states, "the patient will be isovolemic during drawing/returning when double needle mode access is used and the collect and return flow rates are identical.The patient will remain isovolemic during buffy coat if the donor packed red blood cell (prbc) unit is used to displace the buffy coat and the return flow remains at the blood prime default of 0 ml/min.On average, following the instructions the patient will become approximately 170 ml fluid positive once the treated leukocytes are reinfused and rinseback is performed.Confirm that the patient is able to tolerate this positive fluid shift." if the customer had followed the cellex operator manual's blood prime instructions, they would have used the packed red blood cell unit to displace the buffy coat instead of the patient's own blood and could have possibly avoided the adverse events that were experienced by the patient.The cellex operator manual's blood prime instructions also states that the donor prbc unit should have a minimum volume of 250 ml and a minimum hematocrit of 50%.Prbcs should be as fresh as possible (less than or equal to 14 days) with the recommendation of one additional unit available as backup.In addition, the cellex operator's manual section 10-3, states the minimum hematocrit for an ecp treatment patient is 27%.The customer reported that the patient's pretreatment hematocrit was 25%.Hypotension is also a labelled side effect of the therakos® cellex® photopheresis system.Per the cellex operator manual section 2-3, adverse events, "hypotension may occur during any treatment involving extracorporeal circulation.Closely monitor the patient during the entire treatment for hypotension." trends were reviewed for complaint categories hypotension, low hematocrit, vomiting, muscle hypotonia, cyanosis, tachycardia, low hemoglobin, hypercalcemia, tachypnea.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.This investigation is now complete.Adverse event terms: low blood pressure/hypotension, code not available: low hematocrit, anemia, vomiting, muscle hypotonia, cyanosis, tachycardia, hypercalcemia, code not available: tachypnea.(b)(4).S.K.14-nov-2023.

Event Description

The customer presented this case during the 2023 association for the advancement of blood & biotherapies at (b)(6) on (b)(6) 2023.The customer's presentation provided additional information on how the patient's blood prime ecp treatment procedure was performed at the time of the event.On (b)(6) 2023, the customer reported in their presentation that the patient had the following pre-procedure vitals: temp 37c, blood pressure (bp) 93/83, heart rate (hr) 159 beats/min, respiration rate (rr) 22 breaths/minute and an oxygen saturation (spo2) of 99%.The patient's pre-procedure labs were hemoglobin (hb) 8.4 gm/dl, hematocrit (hct) 25%, and ionized calcium (ical) 5.1 mg/dl.The customer stated that one hour into the patient's blood prime ecp treatment procedure, during buffy coat collection, the patient experienced acute hypotension, vomiting, muscle weakness ("floppy") and turned blue.The customer reported that the patient's vitals at the time of event were temp 37c, bp 77/40, hr 183/min, rr 30/min, and spo2 97%.The customer stated that the patient's labs at the time of the event were hb 6.3 gm/dl, hct 19%, and ical 6.4 mg/dl.The customer reported that the patient's blood prime ecp treatment procedure was paused, and normal saline 10ml/kg was administered to the patient and the patient stabilized.The customer stated that they were then able to continue with the patient's blood prime ecp treatment procedure.The customer reported that they were able to complete the patient's blood prime ecp treatment procedure with the contents of both the return and treatment bags as well as the leftovers of the packed red blood cell unit reinfused to the patient.The customer stated that the patient's color returned to normal, and their vitals normalized upon the completion of their blood prime ecp treatment procedure.The customer reported that the patient's vitals post treatment were temp 37.2c, bp 122/79, hr 138/min, rr 19/min, and spo2 97%.The customer stated that the patient's post labs were hb 7.9 gm/dl, hct 23%, and ical 6 mg/dl.The customer reported that an acute drop in the patient's hematocrit and blood volume depletion were responsible for the patient's adverse events.The customer stated that during the buffy coat displacement phase of the patient's blood prime ecp treatment procedure additional red blood cells were drawn from the patient (50-100ml) to displace the buffy coat with no fluid returned to the patient.The customer reported that there was also hemodilution from the fluids that were returned to the patient during their blood prime ecp treatment procedure which also contributed to the patient's lowering hematocrit.The customer stated that a positive fluid balance could not be avoided.The customer reported that there was no evidence of hemolysis and the patient's workup was negative.The customer stated that their new pre procedure blood prime ecp treatment plan for this patient would include the following: provide the patient with a blood transfusion if their hematocrit is less than 36% before their blood prime ecp treatment procedure in order to counter hemodilution, the red blood cell unit for the patient's blood prime ecp treatment procedure should be at least 280ml with a hematocrit of 65-75% in order for there to be enough for the buffy coat displacement, and to monitor the patient's hematocrit, hemoglobin, and ionized calcium pretreatment, during buffy coat displacement and posttreatment in order to identify an acute drop in these values.The customer reported that they will also pause the instrument before the buffy coat is displaced in order to disconnect the patient and reconnect the instrument to the red blood cell unit.The customer stated that they will then use the red blood cell unit to displace the buffy coat instead of the patient's own blood thus avoiding the patient's hematocrit drop.The customer reported that the return rate for the instrument will also be changed to zero so no fluids would go back to the patient in order to avoid hemodilution.

• Brand Name: CELLEX PHOTOPHERESIS SYSTEM
• Type of Device: CELLEX PHOTOPHERESIS SYSTEM
• Manufacturer (Section D): MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; blanchardstown, dublin ; EI
• Manufacturer (Section G): MACK MOLDING COMPANY; 608 warm brook rd; cruiserath road; arlington VT 05250
• Manufacturer Contact: mark wendelken ; 440 route 22 east; suite 302; bridgewater, NJ 08807
• MDR Report Key: 14877462
• MDR Text Key: 295069009
• Report Number: 3013428851-2022-00053
• Device Sequence Number: 1
• Product Code: LNR
• Combination Product (y/n): Y
• Reporter Country Code: US
• PMA/PMN Number: P860003
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional
• Reporter Occupation: Physician
• Type of Report: Initial,Followup
• Report Date: 11/14/2023

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: 06/01/2022
• Initial Date FDA Received: 06/30/2022
• Supplement Dates Manufacturer Received: 10/15/2023
• Supplement Dates FDA Received: 11/14/2023
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 01/31/2013
• 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
• Patient Age: 13 MO
• Patient Sex: Female
• Patient Weight: 11 KG