MAUDE Adverse Event Report: GENZYME BIOSURGERY (RIDGEFIELD) SYNVISC ONE; INTRA-ARTICULAR HYALURONIC ACID

Lot Number 7RSL021 , 7RSL019

Device Problem Device Contamination With Biological Material (2908)

Patient Problems Pain (1994); Cramp(s) (2193); Ambulation Difficulties (2544)

Event Date 11/20/2017

Event Type  malfunction  

Event Description

(b)(4).This unsolicited case from united states was received on 08-dec-2017 from a nurse.This case concerns (b)(6) female patient who received treatment with synvisc one and later after 4 days of receiving injection patient was unable to walk, had pain in legs and cramping in legs.Also device malfunction was identified for the reported lot number.No past drug, medical history, concomitant medication or concurrent condition was provided.On (b)(6) 2017, the patient initiated treatment with intra-articular synvisc one injection at a dose of 1 df once (batch/lot number: 7rsl021, expiry date: unknown) for right knee arthritis in right knee.On (b)(6) 2017, after 4 days of receiving injection, patient called stating that she was unable to walk due to pain and cramping in her legs.Patient was sent for a doppler/ dvt (deep vein thrombosis) which was negative.Patient has not called back since corrective treatment: not reported for device malfunction; rest, ice and elevate and take anti-inflammatory medications for rest events.Outcome: not recovered for all events.An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation would be completed, corrective and preventive actions would be implemented.Seriousness criteria: important medical event for device malfunction.Pharmacovigilance comment: sanofi company comment for follow up dated 8-jan-2018: this case concerns a patient who has received synvisc one injection from the recalled lot and was unable to walk due to pain and cramping in legs.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

This case is cross referenced with case: (b)(4).(cluster).This unsolicited case from united states was received on (b)(6) 2017 from a nurse.This case concerns 88 year old female patient who received treatment with synvisc one and later after 4 days of receiving injection patient was unable to walk, had pain in legs/calf pain/still has swelling and pain and cramping in legs/cramping, difficulty bearing weight; 25 days later still had swelling and pain and 28 days later fluid aspirated.Also device malfunction was identified for the reported lot number.The patient had diabetes and high blood pressure.The patient had no known allergies.Concomitant medications included atorvastatin, gabapentin, hydrochlorothiazide, lisinopril and insulin glargine (lantus).No past drug was provided.On (b)(6) 2017 the patient initiated treatment with intra-articular synvisc one injection at a dose of 1 df once (batch/lot number: 7rsl021, expiry date: unknown) for right knee arthritis in right knee.The same day, patient received treatment with intra-articular synvisc one injection at a dose of 06 ml once (batch/lot number: 7rsl019, expiry date: 01-may-2020) for osteoarthritis.On (b)(6) 2017 , after 4 days of receiving injection, patient called stating that she was unable to walk due to pain and cramping in her legs.The same day, patient had difficulty bearing weight, calf pain and cramping.Venous doppler study was done.Patient was sent for a doppler/dvt (deep vein thrombosis) which was negative.Patient has not called back since.On (b)(6) 2017 25 days after first dose, patient still had swelling and pain.On (b)(6) 2017 28 days after first dose, patient visited the office and fluid was aspirated.The same day, culture sensitivity, aerobic and anaerobic culture, cell count with differentiation and gram stain all came negative.On an unknown date, patient recovered from fluid aspirated, difficulty bearing weight and still had swelling and pain.Corrective treatment: not reported for device malfunction, difficulty bearing weight, fluid aspirated, still has swelling and pain; rest, ice and elevate and take anti-inflammatory medications for rest events outcome: not recovered for unable to walk and device malfunction; recovered for rest all events a pharmaceutical technical complaint (ptc) was initiated with global ptc number 51051 with lot number: 7rsl021.An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation would be completed, corrective and preventive actions would be implemented.A pharmaceutical technical complaint (ptc) was initiated with global ptc number 51051 with lot number: 7rsl019 the production and quality control documentation for lot # 7rsl019 expiration date (05/2020) was reviewed.The investigation showed that the product met specifications.No associated non-conformances were noted.Based on the lot # batch record review & lot # frequency analysis for lot # 7rsl019 no capa is required.Sanofi global pharmacovigilance and epidemiology continuously monitors adverse event reports with or without lot numbers, and assesses possible associations with their corresponding product lot, as part of routine safety surveillance effort to detect safety signals.This review had not indicated any safety issue.As of (b)(6) 2018 there were 18 complaints on file for lot # 7rsl019: (18) adverse event reports.Sanofi would continue to monitor complaints as stated in sop rdg-sop-000440 product complaint handling to determine if a capa was required.Seriousness criteria: important medical event for device malfunction.Reporter causality: reaction with injection follow up information was received on 07-jan-2018.Global ptc number was added.Follow up information was received on 12-feb-2018.No new information was received.Additional information was received on 09-apr-2018 from the nurse.Suspect product therapy regimen added.Additional events of difficulty bearing weight, fluid aspirated and still has swelling and pain were added, event terms were updated from cramping in legs to cramping in legs/cramping and from pain in legs to pain in legs/calf pain/still has swelling and pain.Medical history, concomitant medication, labs and concurrent conditions were added.Clinical course was updated and text was amended accordingly.Follow-up information was received on 09-apr-2018.Related case id's were added.Text was amended accordingly.Additional information was received on 16-apr-2018.Ptc results were added for lot number: 7rsl019.Clinical course was updated and text was amended accordingly.Pharmacovigilance comment: sanofi company comment for follow up dated 16-apr-2018:the follow up information recived does not change the overall case assessment.This case concerns a patient who has received synvisc one injection from the recalled lot and was unable to walk due to pain and cramping in legs.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

Event Description

This case is cross referenced with case: (b)(4).This unsolicited case from united states was received on 08-dec-2017 from a nurse.This case concerns 88 year old female patient who received treatment with synvisc one and later after 4 days of receiving injection patient was unable to walk, had pain in legs/calf pain/still has swelling and pain and cramping in legs/cramping, difficulty bearing weight; 25 days later still had swelling and pain and 28 days later fluid aspirated.Also device malfunction was identified for the reported lot number.The patient had diabetes and high blood pressure.The patient had no known allergies.Concomitant medications included atorvastatin, gabapentin, hydrochlorothiazide, lisinopril and insulin glargine (lantus).No past drug was provided.On (b)(6) 2017, the patient initiated treatment with intra-articular synvisc one injection at a dose of 1 df once (batch/lot number: 7rsl021, expiry date: unknown) for right knee arthritis in right knee.The same day, patient received treatment with intra-articular synvisc one injection at a dose of 06 ml once (batch/lot number: 7rsl019, expiry date: 01-may-2020) for osteoarthritis.On (b)(6) 2017, after 4 days of receiving injection, patient called stating that she was unable to walk due to pain and cramping in her legs.The same day, patient had difficulty bearing weight, calf pain and cramping.Venous doppler study was done.Patient was sent for a doppler/dvt (deep vein thrombosis) which was negative.Patient has not called back since.On (b)(6) 2017, 25 days after first dose, patient still had swelling and pain.On (b)(6) 2017, 28 days after first dose, patient visited the office and fluid was aspirated.The same day, culture sensitivity, aerobic and anaerobic culture, cell count with differentiation and gram stain all came negative.On an unknown date, patient recovered from fluid aspirated, difficulty bearing weight and still had swelling and pain.Corrective treatment: not reported for device malfunction, difficulty bearing weight, fluid aspirated, still has swelling and pain; rest, ice and elevate and take anti-inflammatory medications for rest events outcome: not recovered for unable to walk and device malfunction; recovered for rest all events a pharmaceutical technical complaint (ptc) was initiated with global ptc number 51051.An investigation was initiated as a result of an unexpected increase in the number of labelled adverse events received from the us market for synvisc one, lot 7rsl021.The product met all release testing at time of manufacture in june 2017.Retain samples were retested due to the unexpected increase in adverse events.Higher than expected endotoxin results were obtained.In addition, the presence of microbial contamination was also confirmed.The cause of these events was under investigation.Once this investigation would be completed, corrective and preventive actions would be implemented.Seriousness criteria: important medical event for device malfunction.Reporter causality: reaction with injection follow up information was received on 07-jan-2018.Global ptc number was added.Follow up information was received on 12-feb-2018.No new information was received.Additional information was received on 09-apr-2018 from the nurse.Suspect product therapy regimen added.Additional events of difficulty bearing weight, fluid aspirated and still has swelling and pain were added, event terms were updated from cramping in legs to cramping in legs/cramping and from pain in legs to pain in legs/calf pain/still has swelling and pain.Medical history, concomitant medication, labs and concurrent conditions were added.Clinical course was updated and text was amended accordingly.Pharmacovigilance comment: sanofi company comment for follow up dated 09-apr-2018:the follow up information recived does not change the overall case assessment.This case concerns a patient who has received synvisc one injection from the recalled lot and was unable to walk due to pain and cramping in legs.A temporal relationship can be established with the product administration.Furthermore, the concerned lot number has been identified to have malfunction by the company.Therefore, the causal relationship of the events to the products cannot be excluded.

• Brand Name: SYNVISC ONE
• Type of Device: INTRA-ARTICULAR HYALURONIC ACID
• Manufacturer (Section D): GENZYME BIOSURGERY (RIDGEFIELD); 1125 pleadantview terrace; ridgefield NJ 07657
• MDR Report Key: 7177966
• MDR Text Key: 97860975
• Report Number: 2246315-2018-00097
• Device Sequence Number: 1
• Product Code: MOZ
• Combination Product (y/n): N
• PMA/PMN Number: P940015
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: health professional
• Remedial Action: Recall
• Type of Report: Initial,Followup,Followup
• Report Date: 12/08/2017

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 01/10/2018
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Lot Number: 7RSL021 , 7RSL019
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: No
• Date Manufacturer Received: 04/16/2018
• Patient Sequence Number: 1
• Treatment: ATORVASTATIN(CON.); ATORVASTATIN(CON.); GABAPENTIN(CON.); GABAPENTIN(CON.); HYDROCHLOROTHIAZIDE(CON.); LANTUS(CON.); LISINOPRIL(CON.)
• Patient Outcome(s): Other
• Patient Age: 88 YR
• Patient Weight: 67