Lubricious Coating Biocompatibility - Verification

Posted by Josh Simon on Wed, Mar 28, 2012 @ 03:03

At the request of a fan of this site, I am devoting a post to Verification of biocompatibility of lubricious hydrophilic coatings.  Next article, I might talk a little bit about particulate and give an update on that, so stay tuned.

The first thing you need to do when looking into biocompatibility for a medical device, coated or not, is think about your application and categorize it on this chart:

biocompatibility chart

For most hydrophilic coatings, the application requires a Limited exposure (<24 hrs) in a Circulating Blood environment.  Therefore the chart reveals that you will need to do cytotoxicity, sensitization, irritation, systemic toxicity, in some limited circumstances genotoxicity, and finally, haemocompatibility.  If your application is different, look it up on the chart and see which tests you need.

First, make sure that your devices are tested exactly as they are delivered clinically, i.e. coated and sterilized.  You do not want to find out that your coating is fine but when sterilized it suddenly becomes cytotoxic, for example. 

The other thing you really should do is look at each bicompatibility test and understand how it works.  Do not just send out your samples with a checklist and rely on the results without thinking. 

For example, the cytotoxicity test can be complicated, and that's one of the simplest ones.  There are different variations on the MEM Elution test.  In the first phase, the test article is submerged in a fluid to extract substances into it.  This extraction can be done at different temperatures and for different lengths of time.  Obviously a longer extraction time at a higher temperature is the toughest test.  If you think you can pass the toughest test, go for it.  If you can't, then you just need to go for the test that is acceptable to the Regulatory body you work with.  In the second phase of the MEM Elution test, the extracted solution is exposed to cells, usually L929 fibroblasts.  This extraction can be done for different lengths of time too, from 24 hrs to 72 hrs.  The longer the exposure, the tougher the test.  Extractions can also be done with polar and non-polar solvents, and the tests can be run by weight or by surface area which has a big effect on the results.  Usually for hydrophilic coatings, you want to run the test by weight.

There are also vendor differences for these tests.  For example, they use different amounts of serum in their media, and some add antibiotics to the solution and some do not. Ask your testing vendor to see the protocols.  I am not able to conclude whether or not these protocol differences influence results but I can definitely tell you that different vendors give different results.  In my experience, Toxikon is really easy to pass, almost too easy, whereas Nelson Laboratories is tougher, but very reliable.  NAMSA is somewhere in between, and Apptec is probably on the tougher side.  Again, this is just my experience.  Your mileage may vary.

Generally, you should just figure out the minimum test protocol your Regulatory body will accept, and do that.  As long as in reality your device is not harmful to humans, you can rely on the results.

 

 

 

 

Tags: lubricious coating, biocompatibility, Regulatory, hydrophilic coatings, lubricious coatings, cytotoxicity

Verification of Lubricious Coatings on Medical Devices

Posted by Josh Simon on Wed, Mar 21, 2012 @ 10:43

I have hinted much on this blog about ways to go about verifying hydrophilic coatings on medical devices.  When I speak of "verification", I am talking about the first "V" in "V&V", i.e. the Verification step in Design Controls that may or may not precede a Validation step, depending on the device.  As you may quickly realize, speaking about specific verification steps for any device is a huge task, because verification is nothing more and nothing less than confirming that design inputs = design outputs.  Does your device prototype meet specification?  Since every device in the world has different specifications, it is impossible to come up with ways that apply to all devices.

However, for lubricious coatings there are some general themes that pop up which are widely applicable, even though specific verification tests may vary per device. 

 

Adhesion

In all but rare cases, if you are coating a device, you want the coating to stick, at least for a while.  You may not care if the coating ultimately resorbs, or you might care.  However, in most cases, you would not be satisfied if the coating flaked off and left material behind in the body.  Thus, some sort of adhesion test is necessary.  For flat surfaces, ASTM D3359-78 may be appropriate.  This is known as the "tape test". Modifications to this test would be necessary for curved or irregular surfaces.  Adhesion can also be tested with a pinch test indirectly.

Lubricity

If using a lubricious coating, you obviously want it to be slipperier than a device without the coating.  Thus, your verification process will require some testing of lubricity against a control, and/or to your spec.  Pinch testing is also an option for this, and you can click on the button below to get an article that goes into details on that.  There are also other tests you can rig up, such as an anatomical model for sliding your coated article through it and measuring force or ease of insertion/withdrawal.  The pinch test paper mentions four major kinds of lubricity tests. However, the limitation of most lubricity tests is that they do no correlate to clinical use.   Despite this limitation, they can still be a good basis for making an engineering decision.

 

Click me

Sterilization

Most sterilization testing involves bioburden analysis, i.e. making sure that you get a 4-log kill (or whatever your spec states).  The other thing to think about is how the sterilization method will affect your coating, so you will need to do coating performance tests after sterilization, as well as before (if that is still relevant to you).  Performance testing can be the same type of tests mentioned above for Adhesion and Lubricity.

Aging

Once you have a favored set of tests and output variables, such as lubricity via pinch testing, or adhesion via tape test, you can keep using those tests over and over for environmental effects, such as Aging.  Does your coating remain lubricious after aging?  This can be accelerated aging, but make sure the conditions of acceleration do not adversely affect the coating.  For example, if your coating is sensitive to water vapor, do not run an aging study at 100% Relative Humidity, because it will not correlate with real time.

Transportation and Handling

How will people treat your lubricious coating on the road, in the doc's office, during shipping, at the patients' houses?  The first step is to do a shipping study.  Send the coated article somewhere and test its performance.  Make sure it stands up.  From there, you can gradually get more nasty by subjecting it to harsher environments, mimicing the trunk of a sales rep's car on a hot day in Puerto Rico, for instance.  Again, you will be using your preferred performance output variables.

Differences in testing will be dictated by what your device actually is.  Is it an IOL Cartridge?  Is it a Jamshidi needle?  Is it a coronary guidewire? 

Also, this list is by far not exhaustive.  I have not even mentioned things like biocompatibility and particulate testing.  I wonder if I should make several parts to this post?

 

Tags: medical device, medical device coating, lubricity, medical device development, medical device coatings, hydrophilic coatings, lubricious coatings, lubricity testing