This document summarizes a pacemaker investigation conducted by the TGA following a patient's death. Electrical testing found the pacemaker was functioning within specifications. Analysis of the pacemaker and autopsy images did not reveal any abnormalities. While pacemaker-induced arrhythmias can sometimes occur, there was no evidence this pacemaker malfunctioned or contributed to the patient's death. The investigation concluded the device had performed normally but could not determine its role around the time of death.

1. 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

2. Office of Laboratories & Scientific Services
Testing at the TGA
•
Part of the post-market monitoring & compliance syst
em
•
Risk-based
•
Results in regulatory outcomes
Pacemaker Investigation 1

3. 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
Pacemaker Investigation 2

4. 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%

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!

6. 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 Pacemaker Investigation 5

7. 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!
Pacemaker Investigation 6

8. 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

9. Receipt
•Incident logged into database •Pacemaker sent for cleaning!
Pacemaker Investigation 8

10. Device
Pacemaker Investigation 9
Model
Serial #
Manufacturer

11. Device
Pacemaker Investigation 10

12. Electrical Testing – ISO 14708-2
•
HP 54502B 200MHz Analog CRO
•
Fluke SigmaPace 1000 External Pace
maker Analyzer
Pacemaker Investigation 11

13. Measured bipolar output – 1000W load
•1.5V Peaks •60 malformed pulses per minute
Pacemaker Investigation 12

14. 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??
Pacemaker Investigation 13

15. Coroner Images
•
Supported our hypothesis of overheating
Pacemaker Investigation 14

16. Coroner Images
•
Supported our hypothesis of overheating
Pacemaker Investigation 15

17. Canberra Imaging - Mammogram
Pacemaker Investigation 16

18. Canberra Imaging – Standard X-ray
Pacemaker Investigation 17

19. Canberra Imaging – CT Scan
Pacemaker Investigation 18
•
Computerised (Axial) Tomography (CT) Scan of pacemaker.

20. Image Analysis
Pacemaker Investigation 19
•Battery is not at location of overheating
•No internal damage evident
Mammogram
X-Ray
Manufacturer’s documented x-ray image

21. Canberra Hospital – Pacemaker Interrogation
•
The device was initially hard to interrogate (comms problems)
•
Cardiologist advised discolouration was
caused by external defibrillation (typical of devices subjected to shocks from external defibs)
•
Battery life “OK“ (over 7 years remaining)
Pacemaker Investigation 20

22. 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)
Pacemaker Investigation 21

23. Electrical Testing – back to the drawing board
•
The device was programmed to Unipolar Mode
Pacemaker Investigation 22

24. Electrical Testing
Pacemaker Investigation 23
•
Nice square wave apparent

25. 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
Pacemaker Investigation 24

26. 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
Pacemaker Investigation 25

27. 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
Pacemaker Investigation 26

28. 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
Pacemaker Investigation 27

29. 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
Pacemaker Investigation 28

30. 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
Pacemaker Investigation 29

31. 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
Pacemaker Investigation 30

32. 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
Pacemaker Investigation 31

33. 32
PLEASE REPORT THE INCIDENT…
it could save a life!
http://www.tga.gov.au/safety/problem.htmiris@tga.gov.au 1800 809 361