Note: This is the final part of the medical devices particle testing tech talk, see part 1 and part 2.
Once the particulate test method has been validated, it is appropriate to start product testing. The FDA guidance documents suggest testing finished devices subjected to sterilization, performing testing on the extremes and an appropriate intermediate size for the product matrix, and assessing both inter- and intra-lot variability. A common way to meet these requirements is to perform testing on samples from design verification, aging, and three lots of process qualification.
The best practice would be to also test lots produced under worst case coating process conditions, which is the thickest allowable coating applied using the minimum cure time, although the FDA did not mention this. If you do particulate testing as part of lot release testing, it is in your best interest to test the worst case coating process conditions.
It is desirable to finish as much testing as much as possible in one day; this makes the results more consistent and minimizes the amount of time spent cleaning.
A typical test format is:
- Perform test on water with glassware
- Perform test on water through the model without test device
- Perform test on water through the model after test device is cycled
To test, first ensure the water and glassware to be used are acceptably clean. For these examples it is assumed the validated particle method used 50 ml of water. For example, if the test includes using a syringe to inject water into your model then collecting the effluent in a beaker, use the syringe to inject 50 ml of water into the sample collection beaker and test it. The result should show a small number of particles in the 10+ um bin and very few (i.e. 0, 1 or 2 per ml) in the larger bins. If necessary, clean your test glassware some more and then retest.
Next, get baseline results. This can be done by injecting 50 ml of water through the model, collecting it in the test collection container, and then performing the particulate test. This is the baseline and should be subtracted from your test device results. Typically, the baseline has more particulates than the glassware test, but it should still not be that many. If you see more than 5 large particles (i.e. 50+ um), I would rinse the model with water and perform the test again. The baseline test may be performed before every sample test, per sample group, or per day. Any of these methods is defensible. You should also re-determine the baseline if a test condition changes, such as a new bottle of water is used.
Then you’ll perform your test to typical use conditions.
As before, a typical test might be:
a. Fill model with 10 ml water, collect any effluent in sample container
This step ensures the model is hydrated prior to use, very few endovascular procedures are performed with a system that is not hydrated. If the system is not hydrated the devices will likely generate extra particulates.
b. Fill guide catheter with 1 ml water, collect any effluent in sample container
This step ensures the guide catheter interior is hydrated prior to use, for the same reasons as listed above.
c. Perform simulated use with your device which takes 4 ml of water (obviously varies by device volume), leave device in model, collect any effluent in sample container
This step is the meat of the test. Simulated use should match the IFU and typical use. For example, if you have a guide wire and the IFU states to hydrate it for 30 seconds, you should hydrate it for 30 seconds prior to insertion into the RHV, through the catheter and into the model (the water used to hydrate is not used in the test). Continuing the guide wire example, the guide wire should be advanced to a clinically relevant position in the model, and then retracted, the advance and retractions should be performed a clinically significant number of times. For a PTCA catheter, the FDA guidance suggests inflating to the maximum labeled diameter.
d. Flush guide catheter with 10 ml of water, remove device from model, collect any effluent in sample container
This is a typical example; the guide catheter is often flushed during endovascular procedures. Using the guide wire example, you would flush through the guide catheter because it is standard practice and you will capture any particles removed from the outside of the guide wire. Flushing through the guide catheter ensures you collect the most particles. Alternatively you can perform a flush through the model with the guide wire in place, but the particles generated by the guide wire in the guide catheter will not be captured. One could also perform both flushes to be conservative.
e. Flush model with 25 ml of water, entirely empty model into sample collection container
Flushing after the device is removed from the model ensures that any particles generated during device removal are captured.
f. Perform particulate count matching the validation conditions
Perform the test using the method previously validated.
g. Flush the model with water
To ensure the model is clean for the next test, flush with water. You can determine how much water is required by testing the effluent after a flushing, or you can perform a baseline test prior to every test as mentioned above.
h. Identify particulate (as necessary)
Identifying the type of particulate can be done to determine the source of the particulates. It is generally only attempted when an unexpected number of large particles are detected. TIR42 lists typical methods for particulate matter determination. To identify the particulate you have to retain the remainder of the sample, or collect it from the particle counter effluent. Collecting the sample from the particle counter effluent can be challenging due to the particle counter volume.
To analyze your results, subtract the baseline the sample test results. If the baseline had a higher result than the test (resulting it a negative number) it is generally acceptable to change that bin to zero, how to deal with this situation should be discussed in the protocol. Finally it is generally desirable to convert the results to a per device basis and determine if the results met the specification.