MAUDE Adverse Event Report: VECTURA GROUP LIMITED BREELIB INHALATION SYSTEM

Model Number BREELIB STARTER PACK EU1

Device Problem Failure to Deliver (2338)

Patient Problem Dyspnea (1816)

Event Date 09/06/2021

Event Type  malfunction  

Manufacturer Narrative

This report was identified as a missed report to fda, during inspection readiness review of safety data and is subsequently being submitted as late.This report mirrors the initial submission to eu competent authorities.A fu report is also being submitted, which downgrades the case to non-reportable.This report is being submitted to the fda as the suspect breelib is a similar device to the 510(k) cleared fox mobile device.

Event Description

The incident was reported to the manufacturer (vectura) from bayer, with ref no.(b)(4)on 10 sep 2021 concerning breelib inhalation system.This case report from germany, concerns a 43-year old female patient with pulmonary arterial hypertension (pah) who experienced dyspnoea and was hospitalised after not being able to inhale using the device.Bayer and vectura have a co-partner relationship where the breelib medical device is supplied to patients to use with ventavis (iloprost) therapy for pah in eu and latin american markets.The patient, who is enrolled in a patient support program, started receiving ventavis (iloprost) therapy (dose and frequency unknown) with the breelib inhalation system for the treatment of her pah on an unknown date.On (b)(6) 2021 it was reported that the breelib did not work and the patient could not inhale as usual.She became short of breath, was scared and drove to the hospital.The dates of hospitalization were provided as (b)(6) 2021 to ongoing.It was reported by the bayer's patient support program via the complaints process, that the "breelib lights up red and green briefly and switches off immediately." the breelib device was subsequently exchanged and the patient continued to inhale using the device as usual.Details of the treatment at the hospital were not provided.Details of medical history and concomitant medication was not provided.Follow-up information has been requested from the distributor on reason for hospitalization, resolution date and concomitant medication.The device has been requested by vectura for investigation to determine if the reported fault can be reproduced and the root cause of any confirmed fault.The risk analysis will be reviewed for appropriateness should a device fault be confirmed.Dyspnoea is a common adverse event for iloprost, the medicinal product nebulized using the breelib inhalation system, according to the ventavis smpc.The patient was unable to inhale their medication and experienced shortness of breath.In the event of missed dosing of ventavis®, adverse events related to the patient's pulmonary hypertension may be experienced such as shortness of breath (dyspnoea), feeling tired, chest pain, light-headedness and syncope.Vectura considers the event of dyspnoea, as an unexpected event according to the breelib instructions for use (ifu) and potentially related to missed dose(s) of ventavis, due to the breelib device not working (pending device investigation).

Manufacturer Narrative

Case was determined as a non-reportable incident as the misuse (incorrect cleaning technique), resulted in liquid ingress into the device and the device malfunction.This report was identified as a missed report to fda, during a retrospective inspection readiness review versus 21 cfr part 803 (mdr).Consequently, this report is being submitted to the fda as the suspect breelib is a similar device to the 510(k) cleared fox device.

Event Description

The incident was reported to the manufacturer (vectura) from bayer, with ref no.(b)(4) on 10 sep 21 concerning breelib inhalation system.This case report from germany, concerns a 43-years old female patient with pulmonary arterial hypertension (pah) who experienced dyspnoea and was hospitalized after not being able to inhale using the device.Bayer and vectura have a co-partner relationship where the breelib medical device is supplied to patients to use with ventavis (iloprost) therapy for pah in eu and latin american markets.The patient, who is enrolled in a patient support program, started receiving ventavis (iloprost) therapy (dose and frequency unknown) with the breelib inhalation system for the treatment of her pah on an unknown date.On 06 sep 2021 it was reported that the breelib did not work and the patient could not inhale as usual.She became short of breath, was scared and drove to the hospital.The dates of hospitalization were provided as 06 sep 2021 to 08 sep 21.The patient was hospitalized at the university hospital wuppertal, heusnerstrasse 40, 42283 wuppertal, germany.It was reported by the bayer's patient support program via the complaints process, that the "breelib lights up red and green briefly and switches off immediately." the breelib device was subsequently exchanged on (b)(6) 2021 and the patient continued to inhale using the device as usual.Adverse event information: details of medical history and concomitant medication was not provided.It was understood that the patient was treated with oxygen therapy at the hospital.Patient denied consent for sharing her hospital summary details.No further patient information was provided.In section e of this medwatch form, the hospital's address is added as was requested by bfarm, but [?]no' is selected for hcp as we did not have direct contact with the physician.Dyspnoea is a common adverse event for iloprost, the medicinal product nebulised using the breelib inhalation system, according to the ventavis smpc.The patient was unable to inhale their medication and experienced shortness of breath.In the event of missed dosing of ventavis®, adverse events related to the patient's pulmonary hypertension may be experienced such as shortness of breath (dyspnoea), feeling tired, chest pain, light-headedness, and syncope.Vectura considers the event of dyspnoea, as an unexpected event according to the breelib instructions for use (ifu) and potentially related to missed dose(s) of ventavis, due to the breelib device not working.The case was downgraded to [?]not related' based on the quality investigation.Quality investigation: the device was requested for investigation and was received by vectura on (b)(6) 2021.The reported fault was confirmed during the quality investigation.The device base unit casings were opened and the unit was disassembled.Evidence of liquid damage was found on the internal components of the printed circuit board (pcb) and in the rear of the air control unit (acu).The root cause of the fault was determined as 'damaged unit' due to liquid ingress.This is considered a misuse event by the patient, due to not following the correct cleaning technique and thus the complaint was assessed as not attributable to the device.The breelib instructions for use (ifu) instruct the user to clean the base unit by wiping the housing with a damp cloth or a disinfecting tissue, after each use.The ifu includes the following caution in section 8.2.1:"be careful not to get the base unit wet.Water inside the base unit can seriously affect its performance.".

Manufacturer Narrative

A retrospective review of the case was carried out since the first follow-up report was submitted and it resulted in the conclusion that the clinical outcome experienced by the patient as described in the complaint report did not meet the definition of serious injury as defined by 21cfr 803.3 in addition to misuse being identified as the root cause of device malfunction.

Event Description

The incident was reported to the manufacturer (vectura) from bayer, with ref no.(b)(4) on 10 sep 21 concerning breelib inhalation system.This case report from germany, concerns a 43-year old female patient with pulmonary arterial hypertension (pah) who experienced dyspnoea and was hospitalized after not being able to inhale using the device.Bayer and vectura have a co-partner relationship where the breelib medical device is supplied to patients to use with ventavis (iloprost) therapy for pah in eu and latin american markets by bayer.The patient, who is enrolled in a patient support program, started receiving ventavis (iloprost) therapy (dose and frequency unknown) with the breelib inhalation system for the treatment of her pah on an unknown date.On 06 sep 2021 it was reported that the breelib did not work and the patient could not inhale as usual.She became short of breath, was scared and drove to the hospital.The dates of hospitalization were provided as (b)(6) 2021 to (b)(6) 21.The patient was hospitalized at the (b)(6) hospital (b)(6), (b)(6), germany.It was reported by bayer's patient support program via the complaints process, that the "breelib lights up red and green briefly and switches off immediately." the breelib device was subsequently exchanged on (b)(6) 2021 and the patient continued to inhale using the device as usual.Adverse event information: details of medical history and concomitant medication was not provided.It was understood that the patient was treated with oxygen therapy at the hospital.As the patient had complained that the device did not work, it is assumed that they missed treatments on the day that the device malfunctioned (acute drug underdose).Per the breelib risk management plan (drm-00099), accounting for the clinical severity of the patient cohort that the ventavis drug is indicated for (moderate risk pah patients, who-fc-iii), acute drug underdose from missed treatment is considered to only result in negligible harm with an associated severity score of 1, on a scale of 1 to 6 with 1 being negligible harm (inconvenience/discomfort) and 6 being catastrophic harm (death).Per drm-00099, had the patient in question missed treatments for more than 24 hours i.E., chronic underdose, the associated severity score would have been a score of 3 on the same scale, with 3 having the potential to result in injury or impairment requiring professional medical or surgical intervention but not requiring hospital admission.Pah is a chronic disease with progressive decline in cardiopulmonary function.Deteriorating cardiopulmonary function primarily manifests as progressive shortness of breath (dyspnoea).A meta-analysis by tremblay e.Et al 2022 shows that pah therapies reduce clinical worsening including symptomatic progression and pah related hospitalisation.However, analysis by zelt et al 2022 of prospective and retrospective data indicates that pah therapies do not correlate with survival.Therefore, pah is a progressive disease and therapies are supportive delaying the natural progression of the disease and are non-curative.Studies show that acute treatment interruption does not affect the clinical situation.Data from preston in 2018 showed that acute interruption in oral prostaglandin does not result in acute deterioration and data from mereles 2007 showed that off treatment cardiopulmonary parameters assessed during the night were not different to daytime parameters.Inhaled iloprost is a stable analogue of prostacyclin, acts for 30-120 min but varies from patient to patient.A syndrome described as rebound has been noted to occur upon abrupt cessation of continuous systemic prostacyclin infusion leading to acute dyspnoea, pallor, weakness, dizziness, and in some cases death.The pulmonary selectivity of inhaled iloprost helps overcome many of the drawbacks of injectable prostanoids, notably systemic and administration-related side-effects.Rebound effects after overnight rest or following temporary interruption of dosing with inhaled iloprost have not been observed.Alveolar deposition provides higher local concentrations of drug and will result in pharmacodynamic effects persisting beyond the disappearance of iloprost from the systemic circulation (nice, 2007).Given that the patient in question panicked and drove to the hospital and did not exhibit any other clinical symptoms apart from dyspnoea that may indicate a potential to result in life threatening injury or deterioration in status of health necessitating immediate medical or surgical intervention to prevent irreversible impairment or damage to a body function, the clinical sequalae described in this case is considered to be consistent with a situation that resulted in or had the potential to only cause trivial impairment or damage, per 21 cfr 803.3.Following a physician review of this case, it is vectura's view that the clinical sequalae could not have caused or contributed to an event of death or serious injury or necessitate medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.The fact that the patient was able to drive to hospital indicates that the dyspnoea was temporary and not life threatening at the time of occurrence.Consequently, the event is being considered as not meeting the definition of 'serious injury' and is deemed non-reportable.Note that the breelib inhalation system is not 510(k) cleared but this report is being submitted because the breelib device is considered to be a similar device to the fox mobile (510(k)) device.

• Brand Name: BREELIB INHALATION SYSTEM
• Type of Device: BREELIB
• Manufacturer (Section D): VECTURA GROUP LIMITED; one prospect west,; bumper's farm; chippenham, wiltshire SN14 6FH; UK SN14 6FH
• Manufacturer (Section G): VECTURA GROUP LTD.; one prospect west; bumper's farm; chippenham, wiltshire SN14 6FH; UK SN14 6FH
• Manufacturer Contact: one prospect west; bumper's farm; chippenham, wiltshire SN14 -6FH
• MDR Report Key: 16435474
• MDR Text Key: 310150945
• Report Number: 3008702754-2023-03948
• Device Sequence Number: 1
• Product Code: CAF
• Combination Product (y/n): N
• Reporter Country Code: GM
• PMA/PMN Number: K142059
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Foreign,Consumer
• Reporter Occupation: Other
• Remedial Action: Replace
• Type of Report: Initial,Followup,Followup
• Report Date: 07/13/2023

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?: Yes
• Device Operator: Lay User/Patient
• Device Model Number: BREELIB STARTER PACK EU1
• Device Catalogue Number: 08CD1042
• Was Device Available for Evaluation?: Device Returned to Manufacturer
• Is the Reporter a Health Professional?: No
• Initial Date Manufacturer Received: 09/10/2021
• Initial Date FDA Received: 02/24/2023
• Supplement Dates Manufacturer Received: 09/10/2021; 09/10/2021
• Supplement Dates FDA Received: 03/06/2023; 07/13/2023
• Was Device Evaluated by Manufacturer?: Yes
• Date Device Manufactured: 03/09/2020
• 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): Hospitalization
• Patient Age: 43 YR
• Patient Sex: Female