Another area where the FDA has spent some of their focus is on particulates generated by medical devices. A particulate is defined by USP 788 as “Particulate matter consists of mobile, randomly-sourced, extraneous substances, other than gas bubbles, that cannot be quantitated by chemical analysis due to the small amount of material that it represents and to its heterogeneous composition.”
The FDA guidance (PTCAballoons and stents) points out that particulate matter can be generated by the manufacturing process or from the breakdown of any coating (e.g., hydrophilic coating) on the device or from the device packaging. If particles are introduced in the bloodstream during use, they may present an embolic risk to the patient. Measurement of the total quantity and size of particulates a device may generate is an indication of embolic risk.
It used to be that medical devices didn’t have hydrophilic coatings and particulate really wasn’t an issue. Then hydrophilic coatings came along and for a while USP 788 specification was adopted for use with medical devices. If a small volume injection could have 6,000 or less particles 10 um (micrometers) or larger and 600 particles 25 um or larger, it seemed reasonable that if a medical device generated less than that it was okay. A general note, particle counts are binned as 10+ um, 25+ um, etc. The count for the 25+ um bin is included in the 10+ um bin, so the particle count will always decrease as the bin size increases, binning other ways may confuse people.
This worked for a while until people thought about it more and some of the coatings turned out to generate large numbers of particles. The USP 788 specification has a significant issue, there is no discussion of upper limit of particle sizes, i.e. you could have a bunch of particles half an inch in diameter and still meet the adopted USP 788 specification. The specification may work for injectables because you will not get half inch particles in a liquid and certainly can’t inject them anyway, but with a medical device you just might be able to. Since that question has come up, AAMI TIR42:2010
was released with a section on the clinical significance of particulate matter which basically concludes that particulates less than 100 um are not a major concern. There is less evidence showing any particles larger than 100 um are safe (although they may be). This just further highlights the inadequacy of using USP 788 as a particulate specification for medical devices.
So while you may still use an adoption of USP 788 as your specification, you do so at your own risk and you’ll probably need some further explanation for the FDA. What specification you do choose is tricky though, as you probably do not want to set a specification of zero particles 100 um or larger. First, is this clinically significant? Second, in my experience every now and then you will get a particle that large, it may not even be from your device, but it will show up in your environment results. If you have a history of using USP 788 for other devices on the market, you can probably use that if you’re comfortable with it, along with a clinical evaluation of your results on the larger particles. However, the FDA has left the door open here for you to accept larger numbers of particles than USP 788, which for some coatings may be required, the AAMI TIR42 standard references plenty of literature saying large numbers of small particles are unlikely to do harm. Alternatively, you could compare your results to results from a similar device on the market, but this method is riskier, expensive, and is going to be less repeatable.