Pacemaker Investigation An example of Medical Device Testing at the TGA Arnie Riedl Biomaterials & Engineering Section, Office of Laboratories and Scientific Services, TGA Australian Biomedical Engineering Conference 20 August 2014
Jun 13, 2015
Pacemaker Investigation An example of Medical Device Testing at the TGA
Arnie Riedl Biomaterials & Engineering Section, Office of Laboratories and Scientific Services, TGA Australian Biomedical Engineering Conference
20 August 2014
Office of Laboratories & Scientific Services Testing at the TGA
• Part of the post-market monitoring & compliance system
• Risk-based
• Results in regulatory outcomes
Pacemaker Investigation 1
Office of Laboratories & Scientific Services Types of testing
• Responsive eg. Adverse event investigations
• Programmed Testing eg. Check compliance with technical standards – Surveys of product ranges to check for compliance with required standards – Lot release review of manufacturing and test data for marketing of individual batches of vaccines and
selected biological medicines
• Maintenance & External • Research and development of technical and regulatory standards and test methodologies
2 Pacemaker Investigation
3 Pacemaker Investigation 3
Type of testing
Responsive Problem reports
Programmed Proactive compliance testing
Maintenance QA, method development accreditation, standardisation
External WHO, other government, regional support
Type of testing (2012)
Safeguarding public health
Responsive 25%
Programmed 60%
Maintenance 10%
External 5%
Programmed Testing • Mandatory reporting by sponsors • Voluntary reporting by users etc • Testing projects chosen from:
– statistical analysis – specific events – international data
• Examples: – Ear thermometer accuracy – Surgical (vaginal) meshes cytotoxicity – AEDs time to deliver therapy – Wheat bag flammability
Pacemaker Investigation 4
Requires adverse event reporting!
Responsive Testing • Investigate the cause of specific events • Examples:
– Injuries from crutches that broke – Head injuries from a wheelchair that
tipped over – Fire in a battery powered wheelchair – Death while wearing a pacemaker
5 Pacemaker Investigation
Testing in OLSS • Done within a rigorous framework defined by our quality system • Some tests are NATA accredited (eg, examination gloves & condoms) • To local & international standards where possible • Other testing done to meet the needs of a specific incident
• Regulatory outcomes are more likely with more evidence – take away message is to submit more adverse event reports!
6 Pacemaker Investigation
Adverse Event – Pacemaker Investigation • A man passed away with a pacemaker implanted. The device was sent to the TGA to determine if
the pacemaker was working appropriately and if it may have played a role in the death of the user.
Pacemaker Investigation 7
Receipt • Incident logged into database
• Pacemaker sent for cleaning!
8 Pacemaker Investigation
Device
9 Pacemaker Investigation
Model
Serial #
Manufacturer
Device
10 Pacemaker Investigation
Electrical Testing – ISO 14708-2 • HP 54502B 200MHz Analog CRO • Fluke SigmaPace 1000 External Pacemaker Analyzer
11 Pacemaker Investigation
Measured bipolar output – 1000W load • 1.5V Peaks
• 60 malformed pulses
per minute
12 Pacemaker Investigation
Possible Issues • Lack of a square wave output may mean the battery is depleted
• Discolouration on back of device indicates significant localised
heating
• Has the device short-circuited and overheated inside the patient??
13 Pacemaker Investigation
Coroner Images • Supported our hypothesis
of overheating
14 Pacemaker Investigation
Coroner Images • Supported our hypothesis
of overheating
15 Pacemaker Investigation
Canberra Imaging - Mammogram
16 Pacemaker Investigation
Canberra Imaging – Standard X-ray
17 Pacemaker Investigation
Canberra Imaging – CT Scan
18 Pacemaker Investigation
• Computerised (Axial) Tomography (CT) Scan of pacemaker.
Image Analysis
19 Pacemaker Investigation
• Battery is not at location of overheating
• No internal damage evident
Mammogram
X-Ray
Manufacturer’s documented x-ray image
Canberra Hospital – Pacemaker Interrogation • The device was initially hard to
interrogate (comms problems)
• Cardiologist advised discolouration wascaused by external defibrillation (typical of devices subjected to shocks from external defibs)
• Battery life “OK“ (over 7 years remaining)
20 Pacemaker Investigation
Canberra Hospital – Pacemaker Interrogation • Analysis of stored data did not
provide any information indicating abnormal device behaviour
• Best data was possibly approximate date of death (impedance increases)
21 Pacemaker Investigation
Electrical Testing – back to the drawing board • The device was programmed to
Unipolar Mode
22 Pacemaker Investigation
Electrical Testing
23 Pacemaker Investigation
• Nice square wave apparent
Electrical Testing – Final Results Programmed Mode SSIR
Amplitude 2.4 V
Refractory Period 300 ms
Rate 60 ppm (rate adapting)
Width 0.40 ms
Energy
Battery Unipolar
Connector N/A
24 Pacemaker Investigation
Electrical Testing – Final Results Programmed Specifications Mode SSIR SSIR
Amplitude 2.4 V 2.4 +0.1/-0.5V
Refractory Period 300 ms 300 +10/-20 ms
Rate 60 ppm (rate adapting) 60 ±1.5 min-1
Width 0.40 ms 0.42 ± 0.02
Energy
Battery Unipolar Bipolar/ Unipolar
Connector N/A IS-1
25 Pacemaker Investigation
Electrical Testing – Final Results Programmed Specifications Measured Mode SSIR SSIR SSIR
Amplitude 2.4 V 2.4 +0.1/-0.5V 2.08 V
Refractory Period 300 ms 300 +10/-20 ms 300 ms
Rate 60 ppm (rate adapting) 60 ±1.5 min-1 60.0 ppm
Width 0.40 ms 0.42 ± 0.02 0.424 ms
Energy 3.79 mJ
Battery Unipolar Bipolar/ Unipolar Unipolar
Connector N/A IS-1 OK
26 Pacemaker Investigation
Electrical Testing – Final Results Programmed Specifications Measured Manufacturer Mode SSIR SSIR SSIR SSIR
Amplitude 2.4 V 2.4 +0.1/-0.5V 2.08 V 2.11 V
Refractory Period 300 ms 300 +10/-20 ms 300 ms
Rate 60 ppm (rate adapting) 60 ±1.5 min-1 60.0 ppm 60 ppm
Width 0.40 ms 0.42 ± 0.02 0.424 ms 0.43 ms
Energy 3.79 mJ 3.5 mJ
Battery Unipolar Bipolar/ Unipolar Unipolar 2.79 V
Connector N/A IS-1 OK OK
27 Pacemaker Investigation
Electrical Testing – Final Results Programmed Specifications Measured Manufacturer Result Mode SSIR SSIR SSIR SSIR OK
Amplitude 2.4 V 2.4 +0.1/-0.5V 2.08 V 2.11 V OK
Refractory Period 300 ms 300 +10/-20 ms 300 ms OK
Rate 60 ppm (rate adapting) 60 ±1.5 min-1 60.0 ppm 60 ppm OK
Width 0.40 ms 0.42 ± 0.02 0.424 ms 0.43 ms OK
Energy 3.79 mJ 3.5 mJ OK
Battery Unipolar Bipolar/ Unipolar Unipolar 2.79 V OK
Connector N/A IS-1 OK OK OK
28 Pacemaker Investigation
Electrical Testing – Final Results Programmed Specifications Measured Manufacturer Result Mode SSIR SSIR SSIR SSIR OK
Amplitude 2.4 V 2.4 +0.1/-0.5V 2.08 V 2.11 V OK
Refractory Period 300 ms 300 +10/-20 ms 300 ms OK
Rate 60 ppm (rate adapting) 60 ±1.5 min-1 60.0 ppm 60 ppm OK
Pulse Width 0.40 ms 0.42 ± 0.02 0.424 ms 0.43 ms OK
Energy 3.79 mJ 3.5 mJ OK
Battery Unipolar Bipolar/ Unipolar Unipolar 2.79 V OK
Connector N/A IS-1 OK OK OK
29 Pacemaker Investigation
Pacemaker Investigation – concerns • Pulse width measured at 0.424 ms. • Programmed settings 0.40 ± 0.02 ms (ISO Standard gives a 5% tolerance) • Documentation states the pulse width is 0.42 ± 0.02ms
• Manufacturer responded that the programmer output is only accurate to 1 decimal
place, although it displays 2 decimal places • TGA though this was potentially misleading • BUT has no real clinical relevance and no action recommended
30 Pacemaker Investigation
Pacemaker Investigation – Conclusions • Patient’s symptoms had been ventricular fibrillation
• A known medical complication of pacemakers is the small risk of pacemaker-induced arrhythmias including ventricular fibrillation
• At the time of testing, the device had performed normally
• Nothing conclusive could be said about its performance around the time of the patient’s death other than that it was unlikely to have played a role in its cause
31 Pacemaker Investigation
32
PLEASE REPORT THE INCIDENT…
it could save a life!
http://www.tga.gov.au/safety/[email protected] 1800 809 361