MAUDE Adverse Event Report: NOVO NORDISK A/S NOVOPEN 5; INSULIN DELIVERY DEVICE

Model Number N/A

Device Problems Break (1069); Defective Component (2292); Failure to Deliver (2338); Inaccurate Delivery (2339)

Patient Problems Hypoglycemia (1912); Coma (2417); Convulsion/Seizure (4406)

Event Date 08/01/2020

Event Type  Injury  

Event Description

Epileptic seizure due to the low blood glucose; severe hypoglycemia; hypoglycaemic seizure.Non-functioning novopen 5, when tried to inject, no insulin was injected; device failure.Pen plunger went back into the body of the pen instead of delivering the insulin dose; device malfunction.Penfill holder is broken; device breakage.Novopen used with a batch number from the recall 2017 ; recalled product.Blood glucose values did not lower; blood glucose abnormal.Case description: this serious spontaneous health authority case from, (b)(6) was reported by a diabetes nurse specialist.As "epileptic seizure due to the low blood glucose (severe hypoglycemia) (hypoglycemic seizure)" with an unspecified onset date, "non-functioning novopen 5, when tried to inject, no insulin was injected(device failure)," with an unspecified onset date, "pen plunger went back into the body of the pen instead of delivering the insulin dose; device component malfunction," with an unspecified onset date, "penfill holder is broken (device breakage)" with an unspecified onset date, "novopen used with a batch number from the recall 2017 (recalled product)" with an unspecified onset date, "blood glucose values did not lower (blood glucose abnormal)" with an unspecified onset date, and concerned a adult male patient who was treated with novopen 5 (insulin delivery device) from unknown start date for "diabetes mellitus type 1," novorapid penfill (insulin aspart) from unknown start date, and ongoing for "diabetes mellitus type 1" (dose and frequency 16 iu, tid).(b)(6).Weight has been rounded to a whole number due to e-submitter limitation with decimal.Current condition: diabetes mellitus type 1.(since 1973).Concomitant products included tresiba penfill(insulin degludec) solution for injection, 100 u/ml.Treatment included: glucagen.On an unknown date, in the evening, the patient had a seizure (epileptic seizure) due to the low blood glucose value (severe hypoglycemia) (values not reported) due to the non-functioning novopen 5.It was reported that, patient had blood glucose value of 5.5 mmol/l, 8 hours before the event.When the patient tried to inject himself, no insulin was injected during time because the pen plunger went back into the body of the pen instead of delivering the insulin dose.As the blood glucose values did not lower (values not reported), patient injected several times novorapid to correct hyperglycaemia.This resulted in severe hypoglycaemia complicated by seizures.The patient also bit his tongue during the seizure, causing a very severe tongue bleeding.Glucagen was administered by patient's wife, and later by the ambulance staff.On (b)(6) 2020, patient was taken to the hospital, and admitted 1 night, and received treatment during this admission (treatment unspecified) as glucagen did not respond fast enough.It was reported that the, patient was trained to use the device and after the event there were no more hypos, probably due to the use of real time sensor.The patient indicated that he has found out that, the novopen used was from the recall 2017, and discovered that the penfill holder was broken.The patient used novopen 5 till (b)(6) 2020.Action taken to novopen 5 was not reported.Action taken to novorapid penfill was reported as no change.The outcome for the event "epileptic seizure due to the low blood glucose (severe hypoglycemia)(hypoglycemic seizure)" was recovered.The outcome for the event "non-functioning novopen 5, when tried to inject, no insulin was injected(device failure)" was not reported.The outcome for the event "pen plunger went back into the body of the pen instead of delivering the insulin dose (device component malfunction)" was not reported.The outcome for the event "penfill holder is broken(device breakage)" was not reported.The outcome for the event "novopen used with a batch number from the recall 2017(recalled product)" was not reported.The outcome for the event "blood glucose values did not lower (blood glucose abnormal)" was not reported.If the sample is received, the device will be investigated to evaluate it works according to the set specifications, and intended use.This report is for a foreign device that is assessed as "similar" to us marketed novopen echo.References included: reference type: e2b company number.Reference id#: (b)(4).Reference notes: reference type: e2b report duplicate.Reference id#: (b)(4).Reference notes: igj (inspectie voor gezondheidszorg en jeugd), nl.

Event Description

Event verbatim [preferred term] (related symptoms if any separated by commas) seizure (epileptic seizure) due to the low bloodglucose (severe hypoglycemia) [hypoglycaemic seizure].Hypoglycemic coma [hypoglycaemic coma].Non-functioning novopen 5, when tried to inject, no insulin was injected [device failure] pen plunger went back into the body of the pen instead of delivering the insulin dose [device malfunction].Penfill holder is broken [device breakage].Amount of insulin was inadequate due to malfunctioning of novopen [incorrect dose administered by device].Novopen used with a batch number from the recall 2017 [recalled product].Blood glucose values did not lower [blood glucose abnormal].Case description: this serious spontaneous health authority case form "igj (inspectie voor gezondheidszorg en jeugd), nl" from the netherlands was reported by a diabetes nurse specialist as "seizure (epileptic seizure) due to the low bloodglucose (severe hypoglycemia)(hypoglycemic seizure)" beginning on 01-aug-2020, "hypoglycemic coma(hypoglycemic coma)" beginning on 01-aug-2020, "non-functioning novopen 5, when tried to inject, no insulin was injected(device failure)" with an unspecified onset date, "pen plunger went back into the body of the pen instead of delivering the insulin dose(device component malfunction)" with an unspecified onset date, "penfill holder is broken(device breakage)" with an unspecified onset date, "amount of insulin was inadequate due to malfunctioning of novopen(incorrect dose administered by device)" with an unspecified onset date, "novopen used with a batch number from the recall 2017(recalled product)" with an unspecified onset date, "blood glucose values did not lower(blood glucose abnormal)" with an unspecified onset date, and concerned a 58 years old male patient who was treated with novopen 5 (insulin delivery device) from unknown start date for "diabetes mellitus type 1", , novorapid penfill (insulin aspart) from 2016 and ongoing for "diabetes mellitus type 1".Patient's bmi: 27.742.Dosage regimens: novopen 5: novorapid penfill: ??-???-2016 to not reported, 24-jul-2020 to 01-aug-2020, not reported to not reported (dosage regimen ongoing); concomitant products included - lantus(insulin glargine).In the course of 2020, patient noticed he often had to inject a higher dose of insulin than he was used to which was a gradual process.The patient didn't suspect the malfunctioning of the pen as a reason for the increased dose of insulin especially since he was not informed about possible defects of this batch novopen 5.He thought that his body needed more insulin.On (b)(6) 2020, in the evening the patient had a seizure (epileptic seizure) due to the low blood glucose value (severe hypoglycemia) (values not reported) due to the non-functioning novopen 5 an hypoglycemic coma.It was reported that, patient had blood glucose value of 5.5 mmol/l, 8 hours before the event.When the patient tried to inject himself, no insulin was injected during time because the pen plunger went back into the body of the pen instead of delivering the insulin dose.As the blood glucose values did not lower (values not reported), patient injected several times novorapid to correct hyperglycaemia.This resulted in severe hypoglycaemia complicated by seizures.The patient also bit his tongue during the seizure, causing a very severe tongue bleeding.Glucagen was administered by patient's wife and later by the ambulance staff.On (b)(6) 2020, patient was taken to the hospital and admitted 1 night and received treatment during this admission (treatment unspecified) as glucagen did not respond fast enough.After experiencing the adverse events and being hospitalized the patient started to research how this could have happened and found out that the novopen used was from the recall of 2017 and that the penfill holder was broken.The patient indicated that his blood glucose did not lower because the amount of insulin was inadequate due to malfunctioning of novopen 5.The suspected novopen 5 was replaced by a new one and after that the amount of insulin is at the same level as before the suspected novopen 5 showed defects.The patient said that the blood glucose was unmeasurably low for several hours , according to his sensor (freestyle libre)and measurements by finger pricks.The patient said he survived the hypoglycemic coma and the seizure because he was found just in time.The restoration of the tongue bleeding took about a week and was still recovering.However, according to the patient, the consequential physical damage was difficult to assess.Patient noticed that he had become a bit confused and sometimes experienced loss of memory.He was not allowed to drive a car for three months.In terms of emotional impact/damage he was very shocked that he probably would not have survived if his wife was late at home.The patient is now very careful about his blood glucose levels.The patient now uses a continuous glucose monitoring system (dexcom g6) to enable immediate action if needed to prevent blood glucose levels outside the normal range.Patient used the suspected novopen 5 until begin of aug (exact date was unknown).Batch numbers: novopen 5: evg0526-3, novorapid penfill: kr72n07.Action taken to novopen 5 was product discontinued due to adverse event.Action taken to novorapid penfill was reported as no change.On (b)(6) 2020 the outcome for the event "seizure (epileptic seizure) due to the low bloodglucose (severe hypoglycemia)(hypoglycemic seizure)" was recovered.On (b)(6) 2020 the outcome for the event "hypoglycemic coma(hypoglycemic coma)" was recovered.The outcome for the event "amount of insulin was inadequate due to malfunctioning of novopen(incorrect dose administered by device)" was not reported.The outcome for the event "novopen used with a batch number from the recall 2017(recalled product)" was recovering/resolving.The outcome for the event "blood glucose values did not lower(blood glucose abnormal)" was recovering/resolving.Since last submission case was updated with the following : hypoglycemic coma, inaccurate dose delivered by device added as events, tresiba penfill was removed from concomitants.References included: reference type: e2b report duplicate, reference id#: nl-novoprod-754447, reference notes: reference type: e2b report duplicate, reference id#: it 2038762, reference notes: igj (inspectie voor gezondheidszorg en jeugd), nl, reference type: mw 3500a mfr.Rpt.#, reference id#: 9681821-2020-00046, reference notes: medwatch 3500a mfr.Report number, reference type: e2b authority number, reference id#: (b)(4).On 04-nov-2020: the suspected device novopen 5 has not been returned to novo nordisk for evaluation.Patient repeated the injection many times, trying to treat hyperglycaemia, result in overdose of insulin and caused severe hypoglycaemia and seizures.Patient is a trained user.No conclusion has been reached.Long standing type 1 diabetes mellitus and concomitant use of basal insulin are significant confounding factor for blood glucose fluctuation.Reporter comment: the patient reported this the dutch health inspectorate since he was not informed about the recall by his supplier.He also reported this case to the lha (local health authority).Block c - additional dosage regimens: suspect product 2.Dose, frequency & route used 3.Therapy dates(if unknown, give duration) 6.Lot # 7.Exp.Date.#1 novorapid penfill, regimen #1 unk, subcutaneous, --/--/2016 to unk, #1 novorapid penfill 16 iu, tid, subcutaneous 07/24/2020 to 08/01/2020 kr72n07 05/--/2022 regimen # 2, #1 novorapid penfill unk, subcutaneous ongoing, regimen # 3.

Event Description

Case description: this serious spontaneous health authority case form "igj (inspectie voor gezondheidszorg en jeugd), nl" from the netherlands was reported by a diabetes nurse specialist as "seizure (epileptic seizure) due to the low bloodglucose (severe hypoglycemia)(hypoglycemic seizure)" beginning on (b)(6)2020, "hypoglycemic coma(hypoglycemic coma)" beginning on (b)(6)2020, "non-functioning novopen 5, when tried to inject, no insulin was injected(device failure)" with an unspecified onset date, "pen plunger went back into the body of the pen instead of delivering the insulin dose(device component malfunction)" with an unspecified onset date, "penfill holder is broken(device breakage)" with an unspecified onset date, "amount of insulin was inadequate due to malfunctioning of novopen(incorrect dose administered by device)" with an unspecified onset date, "novopen used with a batch number from the recall 2017(recalled product)" with an unspecified onset date, "blood glucose values did not lower(blood glucose abnormal)" with an unspecified onset date, and concerned a 58-year-old male patient who was treated with novopen 5 (insulin delivery device) from unknown start date for "type 1 diabetes mellitus", novorapid penfill (insulin aspart) from 2016 and ongoing for "type 1 diabetes mellitus".Current condition: type 1 diabetes mellitus (since 1973).Investigation results name: novopen 5 silver, batch number: evg0526-3.The batch documentation was reviewed.No abnormalities relating to the observed problem were found.The batch documentation has been reviewed and found to be normal.The electronic register was checked.No remarks.Confirmed both snaps are broken off the cartridge holder.The cartridge holder was damaged to a point where the pen could not be tested with a cartridge and needle attached.Due to this the function of the piston rod is affected and it may not move forward during depressing of the dose button.During development of the fault on the cartridge holder starting with a crack and to the state that the cartridge holder was in during our examination, it cannot be ruled out that the dosage accuracy was affected at a time during use.If the patient does not observe that the cartridge holder is damaged there is a risk that he/she will not receive the intended dose and experience hyperglycaemia.The snap connection on the cartridge holder is damaged.As a consequence, the cartridge holder may be difficult or impossible to mount on the pen body and the dose accuracy may be affected.The fault is caused by an error in novo nordisk a/s.Name: novorapid penfill, batch number: kr72n07, the product was not returned for examination.References included: reference type: e2b report duplicate, reference id#: (b)(4).Reference type: e2b report duplicate, reference id#: (b)(4), reference notes: igj (inspectie voor gezondheidszorg en jeugd), nl.Reference type: mw 3500a mfr.Rpt.#, reference id#: (b)(4), reference notes: medwatch 3500a mfr.Report number.Reference type: e2b authority number, reference id#: (b)(4).Final manufacturer's comment: 03-dec-2020: the suspected device novopen 5 was returned to novo nordisk for evaluation.Upon investigation of the returned pen a damaged cartridge holder was identified and the cartridge holder was damaged in a way which could cause the pen to dose inaccurate.The suspected novopen 5 batch were part of a field safety corrective action (recall (b)(4)) performed in 2017 pen for certain pen batches.The patient started using the suspected pen in 2016.In addition, the patient repeatedly injected himself several times, trying to treat hyperglycaemia, which might have resulted in overdose of insulin and caused severe hypoglycaemia and seizures.Patient is a trained user.No firm root cause conclusion has been reached.Long standing type 1 diabetes mellitus and concomitant use of basal insulin are significant confounding factor for blood glucose fluctuation.H3 continued: evaluation summary investigation results name: novopen 5 silver, batch number: evg0526-3.The batch documentation was reviewed.No abnormalities relating to the observed problem were found.The batch documentation has been reviewed and found to be normal.The electronic register was checked.No remarks.Confirmed both snaps are broken off the cartridge holder.The cartridge holder was damaged to a point where the pen could not be tested with a cartridge and needle attached.Due to this the function of the piston rod is affected and it may not move forward during depressing of the dose button.During development of the fault on the cartridge holder starting with a crack and to the state that the cartridge holder was in during our examination, it cannot be ruled out that the dosage accuracy was affected at a time during use.If the patient does not observe that the cartridge holder is damaged there is a risk that he/she will not receive the intended dose and experience hyperglycaemia.The snap connection on the cartridge holder is damaged.As a consequence, the cartridge holder may be difficult or impossible to mount on the pen body and the dose accuracy may be affected.The fault is caused by an error in novo nordisk a/s.

• Brand Name: NOVOPEN 5
• Type of Device: INSULIN DELIVERY DEVICE
• Manufacturer (Section D): NOVO NORDISK A/S; bagsvaerd, ; DA
• MDR Report Key: 10685773
• MDR Text Key: 213252156
• Report Number: 9681821-2020-00046
• Device Sequence Number: 1
• Product Code: FMF
• Combination Product (y/n): Y
• PMA/PMN Number: K123766
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,health professional
• Type of Report: Initial,Followup,Followup
• Report Date: 09/16/2020

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 10/15/2020
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Lay User/Patient
• Device Expiration Date: 09/01/2017
• Device Model Number: N/A
• Device Lot Number: EVG0526-3
• Was Device Available for Evaluation?: Device Returned to Manufacturer
• Date Returned to Manufacturer: 11/02/2020
• Date Manufacturer Received: 11/30/2020
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Treatment: LANTUS (INSULIN GLARGINE); TRESIBA PENFILL (INSULIN DEGLUDEC)
• Patient Outcome(s): Hospitalization
• Patient Age: 58 YR
• Patient Weight: 88