| Model Number INT2204B |
| Device Problem
Insufficient Information (3190)
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| Patient Problem
Insufficient Information (4580)
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| Event Date 07/19/2021 |
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Event Type
Injury
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Manufacturer Narrative
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References: schmidt, m., et al.(2011).Efficiency of pathogen inactivation system intercept under experimental conditions.Vox sanguinis 101(suppl 1):226[abstract p367].Stormer, m., et al.(2008).Spore-forming organisms in platelet concentrates: a challenge in transfusion bacterial safety.Transfus med 18(6): 371-376.
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Event Description
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Transfusion-transmitted bacterial infection [pt: transfusion of an infectious agent via product].Date cerus received: 23-jul-2021, 28-jul-2021, 29-jul-2021, 30-jul-2021, 31-jul-2021, 02-aug-2021 (in)the patient involved in this report is (b)(6) ab positive male with aplasia.Product complaint #: (b)(4).Set lot#: ce21a20l71.Product code #: int2204.Batch #: 13166.Illuminator serial #: (b)(4).Din #: not reported.On 23-jul-2021, cerus became aware of a suspected transfusion-transmitted bacterial infection (ttbi) [pt: transmission of an infectious agent via product].This event was formally reported to cerus on 28-jul-2021 as a spontaneous serious adverse event (sae) report ((b)(4) ) by dr.(b)(6), associate director of hemovigilance and transfusion safety coordinator at (b)(6).This report of a suspected ttbi involved an intercept treated platelet concentrate (pc) transfused at (b)(6) hospital on (b)(6) 2021.Further information on the initial report was received on 28-jul-2021, 29-jul-2021, 30-jul-2021, 31-jul-2021, 02-aug-2021 from the reporter dr.(b)(6).Platelet collection: on (b)(6) 2021 17:22h, an apheresis platelet and plasma were collected on trima.Apheresis platelet was stored in pas solution and apheresis plasma was sent for fractionation.On (b)(6) 2021, the implicated pc was treated with an intercept blood system large volume processing set (processing set product code / set lot number: int2204b/ce 21a20l71) and illuminated with the intercept blood system for platelets from 09:13h - 9:19h, approximately 16 hours after collection.The treatment report showed successful illumination with no indication of illuminator malfunction or irregularities.The implicated intercept pc (expiration date: 22-jul-2021) was donated by a (b)(6) male.It was reported that a donor sample was taken pre-donation and archived.After the adverse event report this sample was cultured for the purpose of pathogen detection and the final result of this test was reported as negative after 10 days.Additional donor investigations by efs are in progress.Patient's clinical course: this report involved a (b)(6) ab positive male with a history of aplasia requiring outpatient blood transfusion support.This patient has received intercept pc in the past and the only reported transfusion reaction was erythema in (b)(6) 2021.His concurrent medical conditions and concomitant medications were not reported.On (b)(6) 2021 this patient experienced a sae of suspected ttbi [pt: transmission of an infectious agent via product] due to bacillus cereus (b.Cereus) after receiving an intercept pc.This sae occurred while the patient was receiving the transfusion in an outpatient hematology department of the hospital.On (b)(6) 2021, the patient received the one unit of intercept pc and two units of red blood cells (rbc) for treatment of aplasia.Patient tolerated the transfusions well, there were no reports of signs or symptoms concerning for transfusion reaction.On (b)(6) 2021, the patient received the one unit of intercept pc for aplasia from 11:30h-12:25h.At 12:30h, after receiving the entire unit of intercept pc, he developed hypotension, chills, fever (39.5°c), tachycardia, severe pain the arms, nausea and vomiting.He was transferred to intensive care unit for higher level of care and antibiotic therapy.Per report, this patient had a negative pre-transfusion bacterial detection test on (b)(6) 2021.Post-transfusion bacterial detection patient blood culture performed on (b)(6) 2021 was positive for b.Cereus bacteria.At the time of this narrative ((b)(6) 2021), the patient's clinical status was reported as stable.On 09-aug-2021, review of the product release records for int2204b lot ce21a20l71 was performed by cerus.The released product met all functional and quality requirements.A review of the batch history indicated that there were no other product complaints reported for this lot.There was no report of device malfunction associated with this case.Intercept apheresis platelet investigation: per electronic communication from dr.(b)(6) on (b)(6) 2021, the implicated unit of intercept pc was transfused on day 4 of shelf life.Efs received the implicated intercept pc two hours after the patient's sae onset and stored for less than 24 hours at 4°c prior to being sent to the bacteriology lab.Gram stain demonstrated gram positive rods and culture grew b.Cereus bacteria.The bacteria isolated from the implicated intercept pc and patient showed similar antibiogram phenotype with overlapping minimum inhibitory concentrations (mic) for each of the tested antibiotics.Retrograde bacterial contamination was ruled out by the reporter due to high bacterial load represented by the positive gram stain.B.Cereus strain comparison analysis will be performed by the french national reference center.The remaining tubing of the intercept pc is under bacterial analysis.Platelet container leakage test is in progress at the efs quality control lab.Co-component (i.E., recovered plasma for fractionation) will be retrieved and cultured for bacteria, results are pending.Intercept pc was not from a split unit and was not associated with red cell concentrate (rcc).Plasma was being returned from the clinical site "lfb" to efs (the centre pays de loire region-nantes area).Reporter assessment: the reporter assessed the event of a ttbi [pt: transmission of an infectious agent via product] as severe in severity and serious due to hospitalization and medically significant.The reporter considered the causality for the event to be probable in relation to the intercept blood system for platelets device because the preliminary microbiology assessment done post-transfusion indicated b.Cereus contamination and probable in relation to intercept pc as the incident occurred immediately following transfusion of the implicated unit.Cerus medical reviewer assessment: cerus medical reviewer agrees with the reporter's assessment that the event of ttbi [pt: transmission of an infectious agent via product] is severe in severity and, agrees that this event is serious due to hospitalization and being medically significant (as per the reporter).The cerus medical reviewer considers the causality for the event of ttbi [pt: transmission of an infectious agent via product] to be possible in relation to intercept-treated pc, pending further investigation, but not related to a failure of the intercept blood system for platelets device to perform as designed.The cerus medical reviewer considered the expectedness for the event of septic transfusion reaction to be expected based on applicable cerus safety reference information as bacterial contamination is expected to occur with any transfused platelet product including intercept- treated pc.The culture of the same bacterial strains from the patient and pc and the gram stain reactivity of the pc are in keeping with a septic transfusion reaction.This case represents the first septic transfusion reaction related to bacillus sp.Contamination reported with platelets treated with the intercept blood system, with over 6 million platelet concentrates transfused worldwide.Intercept is indicated for the inactivation of a broad spectrum of pathogens including b.Cereus.The effectiveness against b.Cereus in the vegetative state is >= 6.0 log10 in pas; in the spore forming state is 3.6 log10 in pas.Laboratory studies have shown that b.Cereus spores enter the vegetative state when exposed to the platelet storage bag environment (stormer et al., 2008).In this case, pathogen inactivation was performed 16 hours after collection, sufficient time for many spores to enter the vegetative state.Other research has shown full inactivation of b.Cereus bacilli spiked into apheresis platelet units similar in type and age to the unit in this case (schmidt et al., 2011), nevertheless, bacillus spores are known to be relatively resistant to pathogen inactivation.It is feasible that bacterial spores were present at the time of intercept treatment that escaped inactivation and germinated during the 4 days of platelet storage to cause a septic transfusion reaction.At the time of this report, further results from the implicated platelet donor, residual platelet container/bag, medical device and co-component testing are pending.Further information from the reporter are requested, including investigations of possible bag leaks and details of the transfusion reaction and its investigation.Pathogen reduction studies using the implicated bacillus strain are indicated to assess susceptibility.
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Event Description
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Cerus received additional follow-up information on this event on: 06-aug-2021, 18-aug-2021, 03-sep-2021, 10-sep-2021 from the reporter, dr.(b)(6).And fenwal below is an update to the initial report submitted 27-aug-2021.Update to the patient clinical course: (new information) on (b)(6) 2021, the patient had a staph aureus infection and was treated with unspecified antibiotics.(new information) on an unspecified date, the patient had been transfused via a peripherally inserted central catheter (picc), which was shown to be infected with s.Aureus and removed.(revised information) on (b)(6) 2021, the patient had a pre-transfusion blood culture performed and the result was negative.It was reported this culture was completed as a follow up to ensure a negative result prior to transfusion on (b)(6) 2021, following the recent s.Aureus infection.On the same day, the patient received the one non-implicated unit of intercept pc and two units of red blood cells (rbc) for treatment of aplasia.Patient tolerated the transfusions well, there were no reports of signs or symptoms of a transfusion reaction.It was noted that a standard peripheral transfusion set was used for this transfusion.A central line was not used.(revised information) on (b)(6) 2021, the patient received the implicated unit of intercept pc for aplasia from 11:30h-12:25h via transfusion set.At 12:30h, after receiving the entire unit of intercept pc, he developed hypotension, chills, fever (39.5 c), tachycardia, severe pain in the arms, nausea and vomiting.He was transferred to intensive care unit for higher level of care and antibiotic therapy.Per report, the post-transfusion blood culture performed was positive for b.Cereus.The patient's clinical status was reported as stable.The patient was treated with amikacin/tazocillin and vancomycin/levofloxacin upon the blood culture being positive for b.Cereus.(new information) on (b)(6) 2021 at 11:15h, a gram-stain was performed and was "positive" at 14:00h.The platelet concentrate line was clamped with a roller clamp that is part of the infusion set when sent from the hospital to efs.Efs sent it to their microbiology lab.On this day, the patient was transfused with another pc via a transfusion set.Further details on this transfusion were not reported.Update to the intercept apheresis platelet investigation: efs investigation (new information): isolates from the plt bag were requested by cerus for pi studies.No additional isolates from the platelet bag were available; however, the bacterial strain isolated from the platelet concentrate could be obtained.A transfer of the sample to cerus was pending confirmation that a carrier could be sent for the transfer.B.Cereus strain comparison analysis (genotyping) will be performed by the french national reference center (cnr) at (b)(6) (hospital).The reporter will follow up with dr.(b)(6).At the time of this report, the analysis had not been finalized by the cnr and no deadline was available.A segment of a line that was contiguous with the bag was cultured, and was considered same product as what was in the bag, and was found to be contaminated by b.Cereus.Platelet container leakage test (underwater pressure test) at the efs cpdl facility quality control lab confirmed no leak.The container was subsequently sent to fenwal (fk) in la chatre for further testing.There was no leak identified there, either (see below report).Co-component (i.E., recovered plasma for fractionation) was sent back from the fractionator, "lfb".The central tube was broken at its' base.On either (b)(6) the residual plasma was cultured for bacteria and results were negative as of (b)(6) 2021.Fenwal investigation (new information): on an unspecified date, the implicated storage container was sent to fenwal, france sas (fenwal) for investigation.On 12-aug-2021, the implicated storage container was received by fenwal.They received an emptied platelet storage bag with the presence of transfusion needle inserted into the middle outlet fitting.On 18-aug-2021, fenwal completed their investigation.In summary, an inspection of the container was performed.Physical characteristics were assessed, as well as connection and weld integrity.A pressure test at 0.6 bar under water was performed, and no leaks were identified.All physical characteristics were within specification.No defects and no compromise to container integrity were identified.Fenwal review of the batch manufacturing records did not reveal any non-conformities during production.The review of the batch file also had not revealed any non-conformities recorded during production.Update to the medical reviewer assessment (revised statement): cerus medical reviewer agrees with the reporter's assessment that the event of a suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] is severe in severity and, agrees that this event is serious due to hospitalization and being medically significant (as per the reporter).The cerus medical reviewer considers the causality for the event of a suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] to be possible in relation to intercept-treated pc, pending further investigation, but not related to a failure of the intercept blood system for platelets device to perform as designed.The cerus medical reviewer considered the expectedness for the event of septic transfusion reaction to be expected based on applicable cerus safety reference information as bacterial contamination is expected to occur with any transfused platelet product including intercept- treated pc contaminated post-treatment.The cerus reviewer notes that the gram stain on the platelet bag was performed on the day after the transfusion reaction, and growth may have occurred during the interim period.The presence of bacteria in the bag and their concentration at the time of the transfusion reaction is unknown.
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Event Description
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Cerus received additional follow-up information on this event on: 23-sep-2021, 14-oct-2021, and 22-oct-2021.Updates to the platelet collection: (revised information) on (b)(6) 2021 17:22h, an apheresis platelet and plasma were collected on trima apheresis machine.Apheresis platelets were stored in pas solution and apheresis plasma was sent for fractionation.On (b)(6) 2021, the implicated pc was treated with an intercept blood system large volume processing set (processing set product code / set lot number: int2204b/ce 21a20l71; expiration date (b)(6) 2021) and illuminated with intercept illuminator serial number (b)(6) from 09:13h - 09:19h, approximately 16 hours after collection.The treatment report showed successful illumination with no indication of illuminator malfunction or irregularities.Updates to the patient's clinical course: (revised information) this report involved a 64-year-old ab positive male with a history of aplasia and thrombocytopenia requiring medical blood transfusion support.This patient has received intercept pc in the past and had no history of transfusion reaction.His concomitant medications were not reported.On (b)(6) 2021 this patient experienced a sae of suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] due to bacillus cereus (b.Cereus) after receiving an intercept pc.This sae occurred while the patient was receiving the transfusion in a medical hematology department of the hospital.(new information) on (b)(6) 2021, the patient recovered from aplasia.(revised information) on (b)(6) 2021, the patient received the implicated unit of intercept pc for aplasia from 11:30h-12:25h via transfusion set.At 12:30h, after receiving the entire unit of intercept pc (361ml / 5.21x10^11 platelets /plasma+ssp+), he developed hypotension, chills/rigors, fever (39.5c), tachycardia, severe pain in the arms, nausea, and vomiting.He was transferred to intensive care unit for higher level of care and antibiotic therapy.Per report, the post-transfusion bacterial culture performed from the patient and aerobic and anaerobic tests performed from the platelet bag were positive for b.Cereus.The patient's clinical outcome within 24 hours of the reaction was reported as improved.The patient was treated with amikacin/tazocillin and vancomycin/levofloxacin upon the bacterial culture being positive for b.Cereus.The platelet concentrate line was clamped with a roller clamp that was part of the infusion set when sent from the hospital to efs.Efs sent it to their microbiology lab.A gram stain was performed shortly after 24 hours.On the same day, effet indésirable receveur "eir" also took place.(new information) on (b)(6) 2021, between 11:15h and 14:00h, a sampling occurred with a "positive" gram-stain result at 14:00h.The sample was then cultured for 10 days confirming the positive result.On this day, the patient was transfused with another intercept pc via a transfusion set.Further details on this transfusion were not reported.(new information) on (b)(6) 2021, the patient's clinical status was reported as stable.Update to the efs investigation: (new information) b.Cereus strain comparison analysis (genotyping) was performed at the french national reference center (cnr) at henri mondor (hospital).Sequence analysis of the platelet concentrate and patient blood samples was performed using the illumina mi seq platform with high coverage.Sequences were compared to a reference strain of b.Cereus.The conclusion from the genotypic comparison was that the strains were similar and had a common origin with just one allelic variation.The patient blood culture strain was not directly compared with the platelet concentrate residuum strain.However, both were compared with cnr reference strain, and found to be of the same type.No further information was expected as this was reported as the final report from efs.The final report received was attached to the "efit" declaration form and was confirmed to have been sent to ansm.Updated medical reviewer assessment: (revised information) cerus medical reviewer agrees with the reporter's assessment that the event of a suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] is severe in severity and, agrees that this event is serious due to hospitalization and being medically significant (as per the reporter).The cerus medical reviewer considers the causality for the event of a suspected transfusion-transmitted bacterial infection [pt: transmission of an infectious agent via product] to be possible in relation to intercept-treated pc, but not related to a failure of the intercept blood system for platelets device to perform as designed.The intercept blood system inactivates a broad spectrum of viruses and bacteria.There is no pathogen inactivation process that has been shown to eliminate all pathogens.Bacterial contamination post-intercept treatment of the product cannot be ruled out due to improper product handling.(revised information) this event represents the first septic transfusion reaction related to bacillus sp.Contamination reported with platelets treated with the intercept blood system.The effectiveness against b.Cereus in the vegetative state is high at >=6.0 log10 in pas; however, in the spore forming state is 3.6 log10 in pas.Laboratory studies have shown that b.Cereus spores enter the vegetative state when exposed to the platelet storage bag environment (stormer, m., et al.2008.Transfus med 18(6): 371-376).In this event, pathogen inactivation was performed 16 hours after collection, sufficient time for many spores to enter the vegetative state.Other research has shown full inactivation of b.Cereus bacilli spiked into apheresis platelet units similar in type and age to the unit in this event (schmidt, m., et al.2015.Transfusion 55(9): 2104-2112), nevertheless bacillus spores if present in the pc before intercept treatment, are known to be relatively resistant to pathogen inactivation.
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