In the previous article, I focussed on getting a lubricious hydrophilic coating to market in spec, and what goes into specifications. I gave references to other articles that can help with finding out more about coating selection. In this article I want to focus on time, as in, the time to market for a medical device with a hydrophilic coating.
The first thing to do here is point you to an article from this blog called Why You Won't Get Your Coated Medical Device to Market in 6 Months. This article explains exactly that.
Next I want to elaborate on some of the points I made in that article about time to market. The biggest killer of timelines is not taking into account the time it takes to set up and validate a coating process. I have experienced several cases where a customer has Biocoat do some test coatings for a client successfully, to then have the client say, "Ok, so let's just have you make another 10,000 and we'll be set." Hold the phone! That is not how it works, even if we were a contract manufacturer. "But why doesn't it work like that? You made some great samples, just make more!", says the customer.
Understandable question if you are not working for a hydrophilic coating company, so let me explain.
As I have said before, hydrophilic coatings are not trivial. They are a sophisticated component that forms a substantial piece of the manufacturing process. There is a big difference between whipping up 4 or 40 samples versus producing 10,000 GMP-grade medical devices suitable for use in vivo. If I am doing research samples, I can put a coating onto a device anyway I know how, and as long as it works on a small scale, that is all I care about in the initial stage because I just want the customer to successfully test it on an animal or mechanical tester. Once the device is to come into contact with human subjects, a whole new world of laws and regulations apply.
To make a GMP-grade medical device, a GMP-grade (Good Manufacturing Practice) process is needed. That requires that each device or lot of devices has a batch record and full set of SOP's for the creation of the device, and all of that made on a process that has itself been validated for its installation, operation, and performance (IQ, OQ, PQ). There is no magic validated process anywhere in the world for applying a hydrophilic coating to any device that it may come across, even "easy" devices. Every new device that comes along requires new SOP's and a new process. That requires time to set up. Contract Manufacturers make their living by doing this very thing, but even they need time.
Moreover, the scaleup from making 10 to 100 devices is not a one-to-one thing when making 10,000 devices or 100,000 devices. In each level of production there will be different degrees of automation. There will be different numbers of each piece of equipment, and different numbers of operators. This all has to be planned out.
Medical Device Engineers are so focussed on the processes for extruding their tubing and drawing their wires, and validating those processes, that they forget all about the fact that they need to do the same thing for their hydrophilic coatings. Except here it is worse, because there ARE magic machines and validated processes for making some kinds of tubing and wires, but that is not so for lubricious hydrophilic coatings.
So, again, if you want your coated device on time, make sure you factor in the process development time. You will need anywhere from 6 months to a year to do this properly.
Ultimately on this blog, I try to keep the marketing of my own products to a minimum because what I am trying to do here is provide an educational resource. The title is deceptive, therefore, because I am actually thinking broadly and more literally about how any lubricious coating can be applied in spec, on time, and on budget. I do this because I was recently presented with a marketing piece from a medical device development company that broke their services down into precisely those three categories.
So, what is involved with getting a hydrophilic coating onto a commercial device in spec, on time, and on budget, and how much of that is dependent on the vendor versus just plain old reality?
Let me focus on specs in this article. Maybe later I will cover the others.
A couple of years ago, I posted a checklist for hydrophilic coatings. That post explained many of the questions a potential client should answer before contacting a vendor. Like the coatings white paper I wrote on the same basic subject, it explains that you need to at least know what the device will be used for, i.e. what industry, what procedure, as well as what the materials used in the device are, among other things.
Once those things are known, there is another layer below that. For example, lubricity is a broad term to mean slipperiness, but just how slippery should the medical device surface be? What coefficient of friction do you want? 0.1? 0.01? Teflon is a great hydrophobic coating that can go as low as 0.1, but true hydrophilic coatings are needed to get to 0.01.
After understanding the friction (or lack thereof) at the surface, what sort of use will the device experience? Is it going to be quickly inserted in vivo and then removed after a few seconds, or is it going to abrade against the inner lumen of a blood vessel, or maybe even another hard plastic catheter?
Being able to tell your coating vendor what you want is important, and that is independent of the coating vendor. In some ways, most hydrophilic coatings on the market are the same, but they do differ in other important ways as far as processing, composition, and business models. They also can influence the other two pieces of this puzzle: time and budget.
Over at the Medical Design Perpectives blog, I have a guest article there about a trip I took to visit almost 50 medical device companies over the last three months. The trip was ultimately for the purpose of selling our hydrophilic coatings, but what wound up happening is I got a great set of answers to some questions about where the medical device industry is heading.
Medical device companies are heading outside the US, to put it simply.
I've been locked in my office all day today working on the slides for this upcoming webinar. You can registor for it by clicking this link:
Depending on how you test a hydrophilic coating, you will get different outcomes, for the same coating, and some may be "good" and others not. Moreover, companies that sell hydrophilic coating frequently "massage" the data, usually by leaving out some particulars, to make their coatings seem more lubricious or durable than they really are.
What I aim to do here is not directly attack printed data, but rather educate the public on the proper questions to ask about data, so they can think critically about it themselves. I will go over several different types of lubricity and durability tests, as well as their pro's and con's, and then focus on a particularly common coating test called a Pinch Test. From there, I will talk about how you can get different results from that test depending on how you run it, and what things you should look out for when trying to make "apples to apples" comparisons between lubricious coatings.
The slides should be informative and I at least try a little to make them entertaining as well, so come on by!
If anyone has ever been starry-eyed, it's me. "I am going to get my PhD in only three years!" "I will have all this extra money with this new job!" "I will probably retire at 55!" Of course, at that point reality rudely awakens me. Shucks.
I am not old yet, but I am old enough to try and catch myself now when I start convincing myself about things like this. I smile it away and shake my head. Back to reality.
So it goes for other people, too. In my job, the one I hear most often is, "I will get my medical device with a hydrophilic coating through clinical trials and to market in six months!"
Well, if today is the first day you have talked to me about a hydrophilic coating on your medical device, no you won't. Sorry! Maybe six months from now, if all goes well, you can say that, but certainly not in our first conversation.
I have written similar articles on this blog before, and I still need to get the word out: Hydrophilic coatings are not trivial. They are sophisticated and advanced additions that add real value to some medical devices, and they require an entire level of attention to detail, all their own.
If you are coming to me with a six-month deadline to market, you are TOO LATE. My next line to you will be, "Can you extend your timeline?" By the way, this does not only occur with inexperienced startups developing their first medical devices. This sometimes happens with veteran engineers too.
So, why then?
It breaks down into a few reasons:
- Coating equipment always needs customization
- The coatings themselves often need customization
- Ordering machinery has a lead time
- IQ, OQ, PQ take time
- Devices with coatings must go through Verification and Validation, as per Design Controls, at least in the US
- Clinical trials, at least in the US, require an IDE if they are significant risk, which takes time to get
- FDA Clearance or Approval always takes at least 60 days
So, just do the math. A proper aging study on a hydrophilic coating takes 4 months if you want a three-year shelf life. You can do other things in parallel with that, certainly. The lead time on the equipment alone can be four to six months, so even if you get the equipment in just three months, you still need to do IQ, OQ, PQ on it. Also, this is if the type of equipment is exactly known from day one. That never happens because every catheter shaft has holes at different spots, or different diameters, or shapes, etc, or maybe it is not even a catheter so it needs a different kind of machine invented entirely. However, will that be possible if you still do not have your coating formulation nailed down yet? If you are assuming that you will get a perfect coating on your first sample run and simply scale things up from there, you are mistaken most times.
These things take time. Believe me, I would also love it if you could get to market in six months. It makes the money come in a lot faster. Reality is different. Usually all of these things take the better part of a year, if everything goes smoothly, and in many cases they take the better part of two or three years.
I do not want to discourage anyone from trying a coating. It can add real value to your device, and some devices may not be able to exist without one. I do want to educate people about how long this stuff can take, however.
I would like to draw your attention to a new video available that details a new lubricious coating called Hydrosleek2. To access the video click on the button below, and enjoy.
Within the presentation, you will find information on coefficient of friction and processing of the coating, both before and after sterilization and aging. In previous posts I have talked about the importance of this sort of data: a company displaying friction data must qualify whether the data is for aged and/or sterilized coating or virgin coating. They must also talk about the nature of the testing that was performed on the coating to obtain the friction data, especially for durability. Recall a study we did on the effects of pinch testing parameters on hydrophilic coatings.
I have not mused about the business in several posts, so let me get back to that for a bit.
When it comes to coatings for customers, the focus is on the customer, and rightly so. Naturally, for such a deal to occur the customer must be interested in the hydrophilic coating (or other coating) company, but what is on the other side of the coin?
This is: the coating company must be interested in you too.
We do not talk about this enough, and openly, but doing so will save a lot of people a lot of wasted time on both sides of the relationship. Every slippery coating company wants to land the gigantic medical device suppliers of the world, and they also want to land a good many of the smaller players too! When speaking of catheters, guidewires, introducers and other "conventional" devices, those people have nothing to worry about. A coating company will nearly always welcome you with open arms.
What about the less obvious devices that may or may not benefit from a coating? I generally go by these criteria when thinking about taking on a customer:
1) Application of the coating onto the device should be achievable, and with minimal manufacturing nightmares.
2) The volume produced should be significant, on a yearly basis.
3) The customer should be an established, if not reputable, business, not a university, not a lone physian, not a retired consultant with no resources, not a grad student, etc..
4) The application should be in the medical or diagnostic field, or at least if not in the medical field, the forces and environmental conditions where the coating is used should be along the same lines as medical forces/conditions.
5) The customer must undestand that coatings are not free. (Don't laugh! I have been asked to give our services gratis!)
Much of this is talked about in this paper on hydrophilic coatings. If you have a medical device with an odd shape, the best thing to do is ask someone like me or another person working at a hydrophilic coating company. Anyone with some coating experience will do. I have seen great ideas and great devices foiled by the simple fact that getting the coating onto the darned thing is nigh impossible.
I have a large family. One day I will probably go broke from the number of college educations I need to pay for. In order to have any hope of staving off bankruptcy, I need to keep the high-value customers rolling in. A high-value customer is quite simply a customer that brings in much more money than we spend on maintaining them.
If your company is in India (or another faraway land), and you want to buy $10,000 worth of material every year, and my company needs to spend $12,000 to visit you and provide customer service to you every year, guess what? We are not interested. That is not high-value.
If you are a lone-actor that wants to coat 5 pieces of stainless steel, once, ever, that prospect really holds no hope for a coating company. It is wonderful that a century from now your device will be the greatest thing since sliced bread with a volume of millions per year, but our outlook is more toward the 2 to 8-year time scale. Unless your device is already in a company an under initial stages of Design Control, it is probably not less than 8 years out.
Honestly, this is more related to the previous two points than anything else. It takes a serious company to A) know how to develop a medical device in today's world and B) be capable of producing the volumes necessary to make us both successful.
Physicians (and occasionally Professors) do provide great design ideas for medical devices, but they themselves have often dedicated little time to understanding how a device is designed and commercialized. Going it alone is not an option. If you come to me as a lone physician unattached to a company, I will thank you for your time and point you to Coatings2Go.
I will also say the same to graduate students, and consultants that just want to try something out, and for the same reasons.
Simply having a company to work from is not always a guarantee either. It is necessary to demonstrate a knowledge of product development in the medical field, if this is a medical device.
Medical Devices and Non-Medical Uses
I do not want to make it seem like trying to coat non-medical devices with hydrophilic coatings is pointless. It is not, IF you know what the characteristics of the coating are. Nevertheless, I still get calls from people that want to coat valves for the crude oil industry and truck parts, etc. They usually do not bother to read (and admittedly it may not be that easy to find) the material that talks about the impermanent nature of hydrophilic coatings, especially under high abrasion and repeated use. High abrasion and repeated use are two phrases that sum up the vast majority of non-medical uses, and thereby eliminate most of those uses with medical grade hydrophilics.
If you are from a non-medical company, think long and hard before calling up a supplier of something that is impermanent and mostly geared for disposable single-use devices.
Coatings Cost $$
See the first paragraph under Production Volume. The good news about this is that although coatings cost money, the goal here is to make the customer money as well. Both parties must benefit.
This rules out charities that produce medical devices, unless of course they find a vendor willing to donate. It is not so prevalent for people to ask for lifetime free coating supplies, but often they can be taken aback by the costs associated with coatings. Often, hydrophilic coatings, drug delivery coatings, and antimicrobial coatings are more epxensive than non-stick PTFE coatings, and other sorts of barrier coatings.
I would like to point out a great talk given by my friend Mikki Larner over at Plasma Blog which gives an easy-to-understand rundown of the basics of plasma treatment of surfaces. For those new to this whole thing, not all hydrophilic coatings will stick to all surfaces. In order to get a hydrophilic coating to adhere to a surface, some materials require that you treat them with energized plasma (i.e. the fourth state of matter), which functionalizes or at least charges the surface to provide the chemistry necessary to make the coating stick.
The paragraph above is greatly simplified, but this video describes the process in more detail.
Often, some sort of test will follow the coating process, such as pinch testing.
This year is the first year that MDM East is in Philadelphia, which is essentially my own backyard. I had a chance to spend two days at the show (and it is not over yet by the time of this writing.)
Many of the regular crowd members of the hydrophilic coating industry were present at the show. I saw booths for Advansource, Hydromer, BioInteractions, DSM, Surmodics, Harland, and that company that owns Medi-Solv. Absent were booths for AST, Coatings2Go, and my own employer, Biocoat. (Forgive me, please, if I forgot anyone.)
Not having to man a booth gave me a lot of time to wander and meet with people. Interestingly, I had the impression from just about all of the hydrophilic coating companies that the show was "meh". (That would be an onomontopeia for the sound you make when you are generally NOT impressed.)
Really that all boils down to number of leads obtained at the show. The comment I heard most often, multiple times, was that the show was great for catching up with current customers and seeing people that you already know, but not so great for meeting new faces. Comments went on to suggest that the MDM/BIOMED show circuit is saturated, i.e. there are too many of them in too many places that are not so far away from each other (like Chicago vs. Minneapolis, anyone?). Coating companies are hungry for new blood, and frankly a little tired of fighting over the same customers time after time.
As promised to one reader, I am putting a little bit more information here on particulates and particulate testing with regards to hydrophilic coatings.
The first thing I want to do is point you to some great information on general theory and the regulatory status of particulates for medical devices. There is an excellent article by Susan Reynolds and Ryan Lunceford on the basics of particulate testing. It talks about the prevalent use of USP 788, as I have done in my previous article on medical device particulates here, including some specifics on the differences between laser counting versus microscopic counting of particles.
The article is a few years old, and at that time, the AAMI was not yet finished writing its report on setting medical device particulate limits. However, now that report is out, and you can find it here. Personally, I found it a little vague. It does not give any sort of concrete limits to follow, and is not any sort of draft guidance. It is good for figuring out how to think about this when going about your own particulate tests, however.
One item touched on by both the AAMI report and the article is composition. Specifically for hydrophilic coatings and/or lubricious coatings, these particles have characteristic identities. Like anything else, a major consituent of particulate could be clean room dust, which originates from human skin or clothing, or other particles tracked in from the outside. However, after abrasion, it can also be due to coating wear particulate. In fact, one method of testing durability for a hydrophilic coating is to run it through a tortuous path test and then measure the amount of particulate in the path after multiple cycles. For increasing number of cycles, you can track the increase in particle count.
Again, this is just an idea and not a standard. There are no suggested limits for a test like this right now. Everything in this field is at this point "unregulated", and we are all concerned about what the FDA will eventually do to throw a wrench in the innovation in the name of hypersensitivity.