MAUDE Adverse Event Report: TERUMO BCT SPECTRA OPTIA; SPECTRA OPTIA IDL SET

Catalog Number	4123201
Medical Device Problem Codes	Adverse Event Without Identified Device or Use Problem (2993); Insufficient Device Problem Information (3190)
Health Effect - Clinical Code	Appropriate Clinical Signs, Symptoms and Conditions Term/Code Not Available (4581)
Date of Event	04/02/2020
Type of Reportable Event	Serious Injury
Additional Manufacturer Narrative
Investigation is in process, a follow-up report will be provided.Dayama, a., bhargava, r., kurmi, s., jain, s., & dua, v.(2020).Autologous stem cell transplant in adult multiple sclerosis patients: a study from north india.Neurology india, 68(2), 454.Https://doi.Org/10.4103/0028-3886.284385.
Event or Problem Description
Per journal article "autologous stem cell transplant in adult multiple sclerosis patients: a study from north india" by aniruddha dayama, rahul bhargava, santosh r kurmi, sachin jain, vikas dua abstract: introduction: autologous stem cell transplant (asct) provides long periods of progression-free-survival in multiple sclerosis (ms).This is an observational study to demonstrate the safety of asct in ms patients at a transplant center in north india using a lymphoablative regimen.Materials and methods: ms patients > 18 years referred by a neurologist or who came of their own volition were evaluated.Kurtzke expanded disability status scale (edss) score was calculated and those with a score of >7 were excluded.Informed written consent was taken.Mobilization was done with g-csf with prednisolone to prevent disease flare-up.A minimum of 2 × 106 cd34 cells/kg was collected.Conditioning regimen consisted of rabbit atg and cyclophosphamide.Rituximab 375 mg/m2 was given to prevent ebv reactivation and disease relapse.Antibiotic prophylaxis was given with levofloxacin, fluconazole, and valacyclovir.Any persistent change in edss scores =0.5 was considered significant.Results: twenty patients were included.Seven patients had positive urine cultures prior to transplant and were treated before starting any chemotherapy.Majority patients were women (13/20).All patients developed febrile neutropenia, which was managed as per department policy.There was no mortality.Subjective symptoms improved in all patients.Edss score improved in 6/19 patients (5/6 with rrms) with no disease progression in any patient at a median follow-up duration of 242 days.Conclusion: asct can be done safely for patients with relatively high edss scores with additional precautions for screening for infections.Rrms patients with the active disease show most improvement.Spms patients may not show significant improvement in the short term.Specific details, such as patient information and outcome, were not included in the article for these events, therefore this report is being provided as a summary of the events.It is unknown at this time if medical intervention was required for these events the collection set is not available for return because it was discarded by the customer.
Additional Manufacturer Narrative
This report is being filed to provide additional information in h.6 and h.11.Investigation: an investigation was conducted for a journal article that references terumo bct product.Journal article, titled ¿¿¿autologous stem cell transplant in adult multiple sclerosis patients: a study from north india.¿¿¿ by dayama et al was reviewed with primary purpose of screening for allegations of terumo bct device causing or contributing to death/injury or device malfunctions.Product evaluation: part evaluation is not feasible for this journal article investigation because there are many months between collection of data, to peer review, to final publication.Investigational details: the purpose of the journal article study is noted in the article abstract: abstract: introduction: autologous stem cell transplant (asct) provides long periods of progression¿¿¿free¿¿¿survival in multiple sclerosis (ms).This is an observational study to demonstrate the safety of asct in ms patients at a transplant center in north india using a lymphoablative regimen.Materials and methods: ms patients ¿¿¿ 18 years referred by a neurologist or who came of their own volition were evaluated.Kurtzke expanded disability status scale (edss) score was calculated and those with a score of ¿¿¿7 were excluded.Informed written consent was taken.Mobilization was done with g¿¿¿csf with prednisolone to prevent disease flare¿¿¿up.A minimum of 2 ¿¿ 106 cd34 cells/kg was collected.Conditioning regimen consisted of rabbit atg and cyclophosphamide.Rituximab 375 mg/m2 was given to prevent ebv reactivation and disease relapse.Antibiotic prophylaxis was given with levofloxacin, fluconazole, and valacyclovir.Any persistent change in edss scores ¿¿¿0.5 was considered significant.Results: twenty patients were included.Seven patients had positive urine cultures prior to transplant and were treated before starting any chemotherapy.Majority patients were women (13/20).All patients developed febrile neutropenia, which was managed as per department policy.There was no mortality.Subjective symptoms improved in all patients.Edss score improved in 6/19 patients (5/6 with rrms) with no disease progression in any patient at a median follow¿¿¿up duration of 242 days.Conclusion: asct can be done safely for patients with relatively high edss scores with additional precautions for screening for infections.Rrms patients with the active disease show most improvement.Spms patients may not show significant improvement in the short term.Summary of terumo bct product in relation to the journal article: materials and methods mobilization and stem cell collection patients were mobilized with g¿¿¿csf (biosimilar) 10 ¿¿g/day for 5 days with prednisolone 1 mg/day to prevent disease flare¿¿¿up.Patients underwent femoral vein catheterization for stem cell harvest and were harvested on spectra optia apheresis machine (terumobct, colorado, usa).Pre¿¿¿harvest and post¿¿¿harvest cd34 counts were done on bd facs canto iitm (bd biosciences, san jose, ca, usa) in all patients to get a minimum yield of 2 ¿¿ 106 cells/kg.Conditioning regimen the conditioning regimen was a lymphoablative regime with rabbit anti¿¿¿thymocyte globulin (atg) [sanofi] 0.5 mg/kg on day¿¿¿6 and then 1 mg/kg on day¿¿¿5 to day¿¿¿2.Cyclophosphamide was given at a dose of 50 mg/kg on day¿¿¿5 to day¿¿¿2 with mesna.Antiemetics were used as per department protocol.Rituximab (biosimilar) was given on day¿¿¿7 and day +30 at a dose of 375 mg/m2 to prevent epstein barr virus reactivation secondary to atg use.Prophylaxis for infections all patients received levofloxacin, fluconazole, co¿¿¿trimoxazole, and valacyclovir as part of prophylaxis during and post¿¿¿transplant period till day +30.Co¿¿¿trimoxazole and valacyclovir were continued till day +90.Febrile neutropenia was managed as per departmental policy for transplant patients.Follow¿¿¿up patients continued their routine follow¿¿¿up with a neurologist to assess any persistent change in edss scores ¿¿¿0.5 points, which was considered significant.Mri scan was planned in case of any acute change and at 1¿¿¿year post¿¿¿transplant to assess disease activity.Results a total of 20 patients were included in this study.One patient out of twenty was from the united kingdom and has been lost to follow¿¿¿up with no response to repeated communication attempts.Most of the patients were from north india with one each from east, west, and southern part of india.The patient demographics and details of their transplant are recorded in table 1.The majority of the patients were female (13/20, m:f: 1.8:1).The median age of the study population was 31.5 years (range 22¿¿¿65 years).More than half of the patients had spms (11/20) with no active lesion on their mri.Only six out of 9 (66%) of rrms patients had active disease on mri contrast scans.All except one rrms patient were refractory to ¿¿¿2 lines of therapy.Pretransplant urine culture was positive in 7 patients (sr.No.3, 4, 6, 7, 9, 11, 18) which was treated prior to mobilization.The median cd34 count was 6.07 ¿¿ 106 cd 34 cells/kg (range 2.69¿¿¿13.19 ¿¿ 106/kg).Nineteen (95%) patients developed febrile neutropenia with only two (10%) positive blood cultures.There was no immediate and day +100 mortality.The median follow¿¿¿up duration was 242.5 days (110¿¿¿380).The median edss score was 5.5 (range 1¿¿¿7).Progression¿¿¿free survival (pfs) was measurable in 19/20 patients as one patient was lost to follow¿¿¿up after 110 days.Seven out of nineteen patients (36.8%) have shown improvement in edss score during the short¿¿¿term follow¿¿¿up of the study and these include six patients of rrms (66.6%) and one patient of spms (10%).However, none of the patients have shown any disease progression clinically.The short¿¿¿term pfs was 100% at one year.However, this may not hold true in long term.All of the patients had a subjective improvement such as fatigue or stiffness.However, this was not measured on any scoring scale.Conclusion the study shows that asct can be done safely for patients with relatively high edss scores with additional precautions for screening for infections.Rrms patients with the active disease on mri show the most improvement.Spms patients may not show significant improvement in the short term.None of our patients has progressed in short¿¿¿term follow¿¿¿up and ahct has not impacted any patient adversely.The study has its limitations with its small patient size and short¿¿¿term follow¿¿¿up.A long¿¿¿term follow¿¿¿up is required to assess the eventual impact of ahct in this subgroup.Better selection of patients may lead to further improvement in outcomes.Per an internal technical report, the phenomenon of bacterial contamination in blood products, especially platelets, is known to occur.With current technologies, given the nature of microorganisms on human skin and the mechanical act of piercing the skin coupled with the fact that platelets must be incubated at room temperature it is not possible to eliminate this phenomenon from occurring.The devices terumo bct manufactures in lakewood / littleton, co, vietnam, costa rica and harmac to collect, separate and store blood products are terminally sterilized to an sal of ¿¿¿ 1.0 x 10-6.Additionally, a sterility assurance system has been designed and employed to ensure this sal will be achieved for every product manufactured.Therefore, it may be concluded bacterial contamination observed in collected blood products from terumo bct devices is most likely due to the inherit hazard of collecting blood as it relates to bacterial contamination.(see attachment in the content tab).Disposables lot history: since this was a journal publication to demonstrate the safety of asct in ms patients at a transplant center in north india using a lymphoablative regimen performed between january 2017 and january 2018, the lot numbers were not requested; therefore, a disposable lot history search could not be conducted.Since this was a journal publication to demonstrate the safety of asct in ms patients at a transplant center in north india using a lymphoablative regimen performed between january 2017 and january 2018, the lot numbers were not requested; therefore, a dhr search could not be conducted for this specific incident.All lots must meet acceptance criteria for release.Root cause: a root cause assessment was performed for the nineteen patients who developed febrile neutropenia with two positive blood cultures.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: * patients' underlying disease diagnosis or comorbidities * complications associated with prolonged use of central venous access.* neutropenia caused by cytotoxic anticancer chemotherapy resulting in patient vulnerability to invasive infections.Dayama, a., bhargava, r., kurmi, s., jain, s., & dua, v.(2020).Autologous stem cell transplant in adult multiple sclerosis patients: a study from north india.Neurology india, 68(2), 454.Https://doi.Org/10.4103/0028-3886.284385.
Event or Problem Description
Per journal article "autologous stem cell transplant in adult multiple sclerosis patients: a study from north india" by aniruddha dayama, rahul bhargava, santosh r kurmi, sachin jain, vikas dua abstract: introduction: autologous stem cell transplant (asct) provides long periods of progression¿¿¿free¿¿¿survival in multiple sclerosis (ms).This is an observational study to demonstrate the safety of asct in ms patients at a transplant center in north india using a lymphoablative regimen.Materials and methods: ms patients ¿¿¿ 18 years referred by a neurologist or who came of their own volition were evaluated.Kurtzke expanded disability status scale (edss) score was calculated and those with a score of ¿¿¿7 were excluded.Informed written consent was taken.Mobilization was done with g¿¿¿csf with prednisolone to prevent disease flare¿¿¿up.A minimum of 2 ¿¿ 106 cd34 cells/kg was collected.Conditioning regimen consisted of rabbit atg and cyclophosphamide.Rituximab 375 mg/m2 was given to prevent ebv reactivation and disease relapse.Antibiotic prophylaxis was given with levofloxacin, fluconazole, and valacyclovir.Any persistent change in edss scores ¿¿¿0.5 was considered significant.Results: twenty patients were included.Seven patients had positive urine cultures prior to transplant and were treated before starting any chemotherapy.Majority patients were women (13/20).All patients developed febrile neutropenia, which was managed as per department policy.There was no mortality.Subjective symptoms improved in all patients.Edss score improved in 6/19 patients (5/6 with rrms) with no disease progression in any patient at a median follow¿¿¿up duration of 242 days.Conclusion: asct can be done safely for patients with relatively high edss scores with additional precautions for screening for infections.Rrms patients with the active disease show most improvement.Spms patients may not show significant improvement in the short term.Specific details, such as patient information and outcome, were not included in the article for these events, therefore this report is being provided as a summary of the events.It is unknown at this time if medical intervention was required for these events the collection set is not available for return because it was discarded by the customer.

• Brand Name: SPECTRA OPTIA
• Common Device Name: SPECTRA OPTIA IDL SET
• Manufacturer (Section D): TERUMO BCT; lakewood CO 80215
• Manufacturer (Section G): TERUMO BCT; 10810 w. collins ave; lakewood CO 80215
• Manufacturer Contact: scot hilden ; 10810 w. collins ave; lakewood, CO 80215
• MDR Report Key: 19920391
• Report Number: 1722028-2024-00326
• Device Sequence Number: 8094671
• Product Code: LKN
• UDI-Device Identifier: 05020583123205
• UDI-Public: 05020583123205
• Combination Product (Y/N): N
• Initial Reporter Country: IN
• PMA/510(K) Number: K183081
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Serviced by Third Party (Y/N): Unknown
• Reporter Type: Manufacturer
• Report Source: Foreign,Literature,Health Professional
• Initial Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date (Section B): 08/06/2024

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
• Operator of Device: Health Professional
• Device Catalogue Number: 4123201
• 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: 07/12/2024
• Supplement Date Received by Manufacturer: 10/10/2024
• Initial Report FDA Received Date: 08/06/2024
• Supplement Report FDA Received Date: 10/11/2024
• Was Device Evaluated by Manufacturer? (Y/N): No
• 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
• Outcome Attributed to Adverse Event: Other
• Patient Sex: Unknown