Medical Device Blog

St. Jude's impressive product development time

2011-10-28T23:06:00.000-07:00

St. Jude has recently announced approval for its optical coherence tomography / fractional flow reserve (OCT / FFR) system called ILUMIEN (fyi: they have a cheese video of water with words flashing across on their site, the Light Years Ahead tagline is good though). The press release for FDA approval was on October 26, 2011. The press release for EU approval was on July 14, 2011. I'm sure the two extra months the FDA took was value added questions about colorant or something (assuming they did both submissions at the same time).

Anyway, I thought it would be fun to look at St. Jude's performance on this new medical device product development timeline from start to approval. In this case we have a unique opportunity because we know when St. Jude bought Radi (the FFR part), and when they bought LightLab (the OCT part). These dates are all approximate, since St. Jude could have waited a few days or weeks to make announcements, but ballpark is good enough for this blog. St. Jude bought Radi Medical AB for $250 million on December 21, 2008. St. Jude bought LightLab for $90 million on July 7, 2010. The EU review was probably 45 business days or about two months, giving a 10 month product development time line.

I will assume they couldn't really get started until July 2010, if so, I think it is impressive to combine these two systems, even if they added no features beside switching, and get approvals in basically a year. Sure they could have done some work on the cart, and presumably they have some hardware picked out before 2010, but most of the hardware and software will have to wait until you know the specifics- which a company won't give out until it is bought.

Maybe you can make your software modular and they can add in applications quickly as it grows, but it initially came from Radi, and smallish companies don't usually think that far ahead. Maybe they started on this in 2008. But more realistically, the software group was given two programs that had no intention of interacting and they managed to make it work in 6 months and 2 months of test. Oh yeah, the two teams are probably at different sites, so you have that difficulty to constantly work through as well.

There is another wrench to throw into the works, IEC 60601-1:2005 (3rd edition), which is scheduled for EU implementation on June 1, 2012, you'd be crazy not to build a new system to 60601 3rd edition and have to redo it in a year or so for the EU. So I'm guessing that there was also an update of at least LightLab's system and probably Radi's system to 60601-1 3rd edition included in this device as well. Now maybe these companies had already made the transition, but small companies I know are behind on this requirement. Yes, some of the changes are minor, but they still involve significant amounts of work. Additionally, the 60601 testing itself takes a reasonable amount of time that would have to be worked in.

Now this is assuming the quality of the product is adequate, they could have rushed out junk (although I have no reason to think this based on the water video), I am impressed that they were able to complete this new product and get it approved in such a short period of time, congratulations to them. Could your company pull this off?

Tech Talk – In Vitro Medical Device Verification Testing in Blood

2011-10-27T22:00:00.000-07:00

I previously discussed testing medical devices in blood here (in 2007!), but I think I did a poor job of it and I’d like to revisit it.

Why do you test in blood? Well for one, blood is hard to simulate, it’s a non-Newtonian fluid, and using glycerin and water don’t really do it justice, but these can work depending on the application. For another, a common blood test is to check for hemolysis, sure this is tested during a biocompatibility test, but biocompatibility tests are not performed during actual use conditions. Hemolysis may also be a part of an animal safety study that you want to check out beforehand.

Where do you get the blood from? At a slaughterhouse of course, if you can find a smaller or craft meat location in your area, they’ll probably work with you, one used to sell to us for $40 a week, and we’d take a couple gallon buckets and their workers would fill them up while we waited. They only slaughtered on certain days, so call ahead. You’ll probably find cows easier to find and work with, but there isn’t really a reason you couldn’t use pig blood.

Before we leave for the slaughterhouse we’ll set up a water bath at 37ºC to be ready when we get back. Then we’ll add anticoagulant to the blood collection bucket. We’ll use either heparin or Acid Citrate Dextrose (ACD).

Once we get the blood, we mix the bucket to ensure the anticoagulant is distributed in the blood. Heparin is prescription drug, so hit up your vet consultant or animal lab for some ahead of time. ACD you can make based on USP guidelines from commonly available chemicals (water, citric acid, dextrose, and sodium). We used around 10,000 to 20,000 units of heparin per liter of blood. Of note is heparin is used clinically (on people) more in the U.S. and ACS is used in Europe, so you could maybe argue for the use of one over the other, but you’re using animal blood, so I’m not sure if that really matters. I’ll assume we are using bovine blood for the rest of this post. If you don’t use an anticoagulant, you’ll end up with a clot bucket when you get back to the lab, just throw it away if this happens, it is not recoverable.

Time is generally of the essence so don’t stop by Chili’s on your way back to the lab. Also, just be aware that water will damage your blood cells, so it is preferable to rinse your lab ware with a bit of saline before use.

When we get back to the lab we first check the blood pH and temperature, ideally the pH is between 7.2 and 7.4. We then take a hematocrit (hct) measurement by collecting blood in a capillary tube with clay sealant to stopper the bottom (get blood before using clay). Then we centrifuge the capillary tube for a few minutes at high rpm. Once centrifuged, the capillary tube will look like this:

You’ll need a hematocrit chart. Below is a simple representation of how to measure hematocrit, you put the capillary tube on the chart, line up the clay on the baseline, you move the tube left or right until the fluid level matches the top line, then you find the line where the red blood cells stop and follow it over to read the percent hematocrit, in this case 50%.

We generally take two hematocrit measurements and average; you need two capillary tubes to balance the centrifuge anyway. 38 to 42% hct is a typical range for a study like this one, although it will vary depending on how much the animal drank before it was slaughtered, I’ve seen it come in in the low 20s, so don’t worry about the initial hematocrit too much.

We then pump the blood from the collection bucket through a saline primed arterial filter (pediatric filters have lower priming volumes) and line to remove hair and large clots and into a carboy with a plugged outlet at the bottom. We’ll set up a circuit from the bottom of the carboy to the top (through the filter) with a peristaltic pump to keep the blood circulating. Place the outlet in the blood and not above it or you’ll get a bunch of foam. At this point we’ll add saline to the blood to get the hematocrit where we want it, usually around 22% to 32%. Keeping hematocrit consistent is better than not. We’ll measure the hematocrit and adjust until we’re good, using the following formula:

S = [(H/F)-1]xV

Where:

H is the initial hct,
F is the desired hct,
V is the original volume of blood, and
S is the volume of saline to be added.

Once we get the hct where we want, we’ll measure pH and temperature again. At one point we were centrifuging the entire sample to remove the buffy coat layer between the serum and the cells, then mixing it back together but this proved pointless and didn’t really benefit our results or affect our testing any and it was a major pain, so I don’t recommend it.

Once prepared, we can expect the blood to last for five or so hours before it gets questionable. If we’re testing an endovascular device, we’ll pump the blood around a tubing circuit (using a peristaltic pump) and then place the device in the tubing. Preferably the tubing is a similar inner diameter to the artery or vein the device will be used in. You probably want to place the blood reservoir above the test set up and the pump after the test area. Putting the blood reservoir above the test set up ensures a more consistent blood flow. A simple set up is shown below.

We can measure the device performance in blood directly, or we may be interested in something like how much does the device damage the blood, we’ll check the serum and see how red it is in simple terms. If it gets worse over time, then we’re damaging the blood. In this case, for an accurate comparison we need to run a control at the same time. For example, if we have an elaborate pumping system, we’ll run our pump system on one closed circuit and the control (with no device) in another closed circuit and track the hemolysis of both over time.

Tech Talk – Stroke Treatment with Medical Devices

2011-10-16T20:40:00.000-07:00

I thought I’d move into a newer area for medical devices, stroke treatment. Stroke affects more than 700,000 people a year in the US alone, of these, over 150,000 die. Most of the strokes are ischemic in nature. Unfortunately the treatment options are very limited and time to treatment is absolutely critical to a good outcome. Successful recanalization of the occluded cerebral vessel during the acute ischemic event is associated with lower three month mortality and improved functional outcome. [Source]

Intravenous Tissue Plasminogen Activator (tPA) is the FDA approved drug for acute ischemic stroke for up to three hours after the stroke. This drug can dissolve the clot and is sometimes applied right at the clot through a catheter. This is generally the first form of treatment; however, tPA is not effective in all cases and can cause bleeding in the brain, particularly in older patients.

Mechanical removal of the clot using a medical device is being performed more and more alone or in conjunction with tPA. These devices have some advanatges over tPA, including more rapid achievement, ability to treat large vessels, and lower risk of hemorrhagic events. Only two neurothrombectomy devices are currently cleared for use in the US. You don’t have to be a rocket science to figure this one out- 700,000 people affected and two cleared devices, stroke treatment is a screaming opportunity for medical devices.

The FDA defines these devices as neurothrombectomy devices, these are devices intended to retrieve or destroy blood clots in the cerebral neurovasculature by mechanical, laser, ultrasound technologies, or combination of technologies. The FDA has provided guidance on these devices, one note of interest is that a clinical trial must be performed due to the high risk of the device.

There are some general procedural steps common to both devices that I will cover quickly now. Both devices must have access to the clot itself. This means advancing a guide wire and catheter using angiography to the clot first. Don’t tell cardiologists, but this is more difficult in the head than in the heart- there are many more possible pathways and the vessels are generally smaller and more easily damaged. If the patient has been given tPA any damage can be catastrophic. Angiography is also used to measure the vessel diameter so the appropriate sized device can be chosen.

Another procedure common to both devices in certain situations is the use of a balloon guide catheter with aspiration. The balloon guide catheter is inflated, which blocks blood flow in the blood vessel with the clot. Aspiration is then applied, this means taking a large syringe (typically 60 ml) and pulling it back, sucking whatever you can out of the blood vessel, alternatively you can buy a pump to do this. Minimizing balloon inflation time is important because the lack of blood flow is what causes a stroke, you don’t want to compound the problem.

The two approved devices are shown below:

Merci Retreiver (left) and Penumbra System (right) Image source.

The first FDA approved neurothrombectomy device was the Merci Retriever by Concentric Medical. The device was approved through the FDA 510(k) process in 2004, the current indication for use is:

Merci Retrievers are intended to restore blood flow in the neurovasculature by removing thrombus in patients experiencing ischemic stroke. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment. Merci Retrievers are also indicated for use in the retrieval of foreign bodies misplaced during interventional radiological procedures in the neuro, peripheral and coronary vasculature.

The Merci Retriever system includes a flexible nitinol wire coil formed into what looks like a corkscrew. The latest version of the device has filaments (made of suture material – I would guess nylon) that provide an additional mechanism for securing the clot during removal.

Basically, the device is advanced distal to the clot, deployed, turned, and when pulled back through the clot it captures the clot in the corkscrew and the device is then removed from the artery while under balloon aspiration. The balloon aspiration (pulling a vacuum on the vessel while a balloon blocks it) minimizes pieces breaking off from the clot and causing additional issues. [source] You can watch a demonstration of the device here.

Concentric Medical was recently bought by Stryker for $135million, which goes along with Stryker's previous purchase of Boston Scientific’s neurovascular division. I don’t know what Concentric’s revenue was, but I think this sounds like a good acquisition, with the caveat that the Concentric team must remain focused on Stroke treatment and not get caught up in all the other things Stryker does.

The second device in use is the Penumbra System of Continuous Aspiration Thrombectomy by Penumbra. The Penumbra System is used for the “revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease…within 8 hours of symptom onset”. The device is first advanced to the blood clot, the Penumbra Catheter’s tip is then placed at the proximal end of the clot. The Penumbra “separator” is advanced to the clot, aspiration is started, then the separator is used to help to break up the clot (or “debulking”) and make it easier to suck into the guide catheter. The separator has a straight tip and a cone (purple cone shown in the picture). In theory, there should be less damage to the vessel with this system, this is important if the patient has received tPA and that has not worked.

As reported in a State of the Evidence article, the clinical effectiveness of the devices, defined as the having a good outcome (modified Rankin Scale score 0 to 2), rates ranged from 21 to 36% with the MERCI and 20 to 48% with the Penumbra System. These numbers are not necessarily comparable to each other as the devices can be used for different types of clot. Presumably the Merci retriever is typically used for “hard” clots and the Penumbra system is used for softer clots (This is just my guess).

Other types of devices sometimes used off-label in the US, such as snares, exist, but I would expect their use will decline as more devices get approval for stroke treatment. Additionally, stent retrievers are available in the EU, but not yet approved for the US, I assume these devices will be approved in the next year or so and if you were so inclined you could roadmap out which ones are doing well in the EU and make an investment on that. The EU is currently two or so years ahead in types of devices available for stroke treatment. Other devices are certainly under development, with ideas from coronary or peripheral vascular being expanded for use. Startups include Insera Therapeutics who is developing a snare type device. I wasn’t able to identify any more in a few minutes of Google searching- if you know of any, leave a comment and I’ll add them later.

Tech Talk – Anatomy Models and Medical Device Testing

2011-08-29T20:46:00.000-07:00

One important consideration to take into account while designing and testing medical devices is how they’re going to be used. In the case of vascular devices, they will be used in arteries and veins and I’ll describe some of the test considerations. While performing your verification testing, you want to ensure that you have a reasonable clinical model to perform testing under.

For example you might have a device that is intended to be used in the Right Coronary Artery (RCA) as shown below (image from Wikipedia):

How do you ensure your device works correctly without using it on a person? You find an appropriate model.

Models of various anatomies are available from Elastrat and Shelley Medical Imaging Technologies. ASTM F2394 also contains a schematic of a two dimensional (2D) model recommended by the FDA for some applications. Although it is best to ensure you pick a model based on the vessel characteristics that your device will likely see (such as vessel diameter and tortuosity). Using the ASTM or another off the shelf model can get you into trouble if for example you’re testing a guide catheter and pushing it into the smallest vessels when it is only intended to sit in the aortic arch.

A 2D model is easy to construct and use, but not necessarily the most accurate, it generally consists of just two pieces of machined plastic (bottom with a clear top) with a piece of tubing inserted. The easiest model consists of just a radius as shown below (by the way, I did the diagram myself in MS PowerPoint!).

Ask your clinical source what the tightest radius your device is likely to see in-vivo and simply machine a curve of that diameter. Insert a piece of silicone tubing into that radius to simulate a vessel wall more accurately than hard plastic and you’re ready to get started (you can use pig vessels to line your tortuous pathway, but this is no fun to set up). It is easy to create 2D models of various tortuous pathways. Creganna (Medical Device Technology, May 2006) shows an example tortuous pathway in some of their coronary block model simulated use testing:

You can see the simulated aortic arch as the large looping arch (start from the top most pathway) and then into tighter arteries as the model continues.

A 2D model obviously lacks some realism as it is possible that your device will need to turn multiple planes during use. Although it may be argued that the worst case scenario is actually the 2D model as it stresses only those two dimensions, adding the third dimensions allows additional flexibility in most devices as they are generally concentric. In the case of a non-concentric model, you can perform your testing to the worst case in the 2D model, setting your weakest side up to take the most abuse. The 2D model is also arguably tougher on your device than clinical use as the give is limited to the wall thickness of the tubing you insert.

For 3D models, you’re probably better off buying one from the companies listed above, although they can get expensive, and can be damaged so you need to be careful. An example heart model from Elastrat is shown below.

Once you have your anatomy model, you generally want to further simulate clinical conditions, either by flowing 37C saline through the model, or a mixture of glycerin and water to simulate blood flow.

Now you want to run whatever tests you can using the model. For example, a guide wire or catheter turns to failure test is simple enough, just hold the distal end and turn the proximal end until the device breaks. However, to really simulate use, you should put the device through the model, and while the device is still in the model, hold the distal end then turn the device until it breaks. The addition of the model adds a bit of complexity to the test, but is a better test system.

I have seen the FDA question models, so document your clinical justification why the model you use is appropriate in the protocol. If you’re using a model that you bought, you should ask them to provide you with the justification.

Tech Talk – Catheter Bonding

2011-08-01T22:07:00.000-07:00

Tech Talk – Medical Device Catheter Bonding

For my second tech talk I thought I’d briefly cover catheter bonding. The typical vascular catheter is made of several types of polymer; it is of obvious importance to connect them in a precise way. A typical bond will consist of two types of tubing; a popular choice is Arkema’s Pebax. Pebax is a USP class VI material that stands up well to sterilization and takes colorants well; it is widely used in current catheters. Bonding will consist of something like 72 durometer on the proximal end of a catheter to 63 durometer on the next step, then moving down the catheter until you reach 35 durometer at the tip. Ideally, the two pieces of tubing are the same size, but they can be of slightly different inner and outer diameters. Starting with your two pieces of Pebax tubing:

Since Pebax isn’t as smooth as most physicians desire, a PTFE or HDPE liner is usually used on the inside of the catheter. The liner allows for smooth delivery of other devices such as guide wires or other catheters down the catheter. A liner will not be required for something like an inflation lumen. Liners may also be multiple layers to better bond with the Pebax. A mandrel is placed inside the liner or lumen. The mandrel is usually coated with PTFE (by companies like Applied Plastics) or parylene for easy removal later on in the process.

Fluorinated ethylene propylene (FEP) tubing is then placed over the Tubing joint. FEP is available off the shelf in multiple diameters and wall thicknesses, it can also be custom made if required by companies such as Zues and Fluortek. Using FEP forms a more consistent and even joint.

Apply heat to the FEP tubing to shrink it and melt the Pebax. Pebax melts at around 174°C so usually 190°C is enough heat. To heat, Beahm Designs makes off the shelf heaters that apply a constant stream of air at a set temperature. Alternatively heat guns can be used, although long term you should look for a more controllable solution.

After heat is applied and the part is allowed to cool, cut off the FEP tubing with a razor blade (slice more parallel to the tubing, not straight into the middle of the FEP) and remove the mandrel and you have a very nice piece of tubing that is very difficult to tell where the transition is.

For a catheter you may actually have five or six transitions such as this depending on the stiffness you want and the number of lumens you want at each point. It is also possible, but not as desirable to join two types of tubing using adhesive, this may be required if the polymers are too different to heat bond. In this case, one piece of tubing fits into the other.

The adhesive used for medical devices is generally made by Dymax or Loctite and can be UV or heat/time cured. UV cure is superior for manufacturability as you can quickly pass it to the next operation, but it may not be possible to use UV adhesives in all cases. The geometry of this catheter is more difficult and the liner may have to be tapered.

Advanced Polymers also sells a polyester heat shrink tubing that can be left on the device and used in catheter bonding if these two methods don’t quite work for you.

After bonding you will want to validate your design and process using methods such as tensile test to ISO 10555 and burst pressure to ensure it is high quality. Catheter bonding is something that has been fairly extensively developed and you can get lots of support from suppliers, but it always turns out you need to know one extra trick that you have to develop yourself.

References for this post are Medical Device R&D Handbook by Theodore R. Kucklick, Beahm Designs, Arkema, and personal experience.

Working for the man

2011-07-24T17:44:00.000-07:00

I can't get enough of Seth Godin, I particularly liked this line from a recent post:

Work for a coal mine and make minimum wage. Discover a coal mine and never need to work again.

I think it probably hits home for every engineer in medical devices. A typical core team seems to be six or less engineers with two to three of them doing the heavy lifting for design and process design.

Tech Talk – Guide Wires

2011-07-12T22:56:00.000-07:00

I sometimes enjoy The Oil Drum’s tech talks, so I thought I’d give one a try.

Guide wires, or guidewires, are used in the vasculature to act as a guide for other devices, an example video shows guide wire and stent. Guide wires are generally more flexible and steerable than devices used to treat or diagnose patients. Typically, once access to an artery is gained, the guide wire is inserted and steered under fluoroscopy to the location of interest. Then one or more devices (usually catheters) are delivered over the guide wire to diagnose and treat the condition.

Guide wires usually come in diameters of 0.010” to 0.035” with 0.014” being the most common (0.013” is equivalent to one french or 1/3 of a mm – so the typical guide wire is slightly over 1 french in size). Guide wire lengths vary up to 400 cm, depending on the anatomy you want to reach and the work flow. The flexible distal tip portion is usually 3 cm long, the slightly less flexible portion is usually 30 to 50 cm long, the less flexible proximal portion makes up the balance.

The user requirements of a guide wire are can it quickly get to where it needs to go and then can I reliably deliver devices over it without patient safety issues.

A typical guide wire construction is shown below:

In this diagram, the blue proximal section is the hypotube, similar to a syringe needle (minus the sharp end). The hypotube is generally coated in PTFE- but other coatings are also used. The PTFE coating allows devices to more easily slide over the guide wire and is probably the major component in device “deliverability” on the guide wire side. It is easier to slide a catheter over a guide wire with PTFE than it is to slide a catheter over a guide wire without PTFE. The PTFE coating of the hypotube can be a tricky part of manufacturer and is usually outsourced. Just as your pans vary in quality of the non stick surface, so do guide wires and different variations in processing and materials can affect how well your guide wire delivers devices.

The core wire material is usually nitinol or stainless steel and tapers from the proximal end to the tip. At the tip it is generally flattened. The core wire affects the torquability of the device; you want the tip of your guide wire to turn in a 1:1 ratio with the proximal end. The torquability affects the steerability of the device, can it get to where you want to go. Nitinol core wires are harder to kink, but can lose some torquability. The core wire is attached to the proximal end of the hypotube using solder or adhesive.

Alternative guide wire construction can look like this:

In this design there is no hypotube, the core wire is the proximal portion of the device. Coating is applied directly to the core wire and you have better torquability because you are turning the core wire directly, instead of turning the hypotube, which turns the core wire.

In both designs, the next section is a more flexible distal section, usually consisting of a wire coil. The connection is made to the hypotube or core wire by solder or adhesive at this point. The coils are more flexible than the hypotube and the distal portion of the device is suited to navigate to the desired portion of the anatomy. There may be several types of coils attached together or one long coil where the coil spacing changes. The more proximal section of the coil is generally made of stainless steel for cost savings. The distal tip coil of the guide wire is made of radioopaque metal, generally a platinum alloy, but a palladium alloy may also be used. Some hospitals recycle these religiously for the $4 in platinum they can get in the tips.

At the very distal tip, the wire coil is soldered to the core wire using tin - silver solder, although in some older wires the core wire may be attached using adhesive.

The tip itself is rounded into a ball shape, which the solder or adhesive naturally forms when applied to the tip. This allows the guide wire to follow the curve of the vessel and is generally called an atraumatic tip. From a manufacturing point of view, manufacturers are very careful to not allow any burrs in the tip assembly for fear of vessel damage, but I have not seen any direct reports of vessel damage caused by badly made tips.

The tip itself is always shaped by the user to aid in steerability, usually to around 45 degrees. Usually the tip is shaped by using an introducer or needle. Here is a video of a shaped tip, although this method isn’t encouraged. Some manufacturers offer tips pre-shaped. One notable alternative tip construction is shown below:

In this case an extra wire has been attached to the core wire and the tip to allow better tip shapeability and can give a softer tip. Depending on where you want to go in the vasculature different tip softness is desired, for example in the cerebral vasculature usually the softer the better. Tip softness can be measured as tip load, the amount of force (or load) it requires to bend the tip a certain amount. Obviously you want the tip to flex instead of damage the vessel wall.

The distal portion of the wire is coated with a lubricious coating, generally a hydrophilic coating, older wires used hydrophobic coatings, but they are becoming rarer. The hydrophilic coating is a proprietary coating that manufacturers generally outsource and pay a considerable amount of money for. There is some skill in developing a coating that does not come off of the guide wire, and retains its lubricity over time.

When building a guide wire you want to start at one end and work your way down, starting at the tip and working to the proximal end. Making guide wires is not that labor intensive with the most skill you need is to be decent at solder and soldering cleaning. You need to work at keeping them undamaged in manufacturing due to their small size and the less flexing of the wire you do the better.

There are other variations on guide wires, such as plastic coatings and different combinations of coils and hypotubes, but I’ve covered the major ones. Guide wires are basically a commodity at this point and only the regulatory barriers to entry and the fact that physicians aren’t typically price sensitive are keeping it as a reasonably attractive market to pursue.

When performing performance verification testing on a guide wire, some common tests are turns to failure (you clamp the distal tip and turn the device until it breaks), particulate / adhesion tests (of the coating), tip tensile strength, torquability (which you turn the proximal end of the guide wire a set amount and measure how much the distal end turns), tip load, radioopacity, and deliverability (where you measure the force it takes to move a catheter along the guide wire). DDL has uploaded this video on testing a guide wire to ISO 11070, but I’ve never used that particular test.

For validation testing you generally request feedback on navigating a guide wire to the desired location in a bench or animal model and delivering a device over the guide wire.

I was unable to find the size of the guide wire market, but every endovasculature procedure uses at least one guide wire, many times more. Many companies outsource the manufacture of guide wire to a contract manufacturer; it is difficult to enter the market fresh at this point. However, as a company, you want to sell a guide wire so you can get your 40% margin on an outsourced guide wire instead of the competitor getting 60%. Also, it is generally beneficial to sell a whole suite of devices when selling to a hospital, if you sell only catheters you will have a harder time getting shelf space unless you can bundle it with other products.

More information is available at: PCI equipment: Guidewire selection. And the FDA chimes in with helpful guide wire tips on device safety- always read those IFUs.

Google health shuts down and the FDA approves a device in 30 days

2011-06-30T20:44:00.000-07:00

Google Health is apparently shutting down, too soon, we're just getting ramped up in fact. Although they didn't seem to embrace the key to making their system widespread and more popular, user input, not just physician input, the two would be easy to separate. The aps are already out there, they just need to be linked to health records, blood pressure, workout data, smoking, drinking, drugs, diet, etc. The whole state of California would love to upload their workout history to their health record, with the user invested in their health record, the health record becomes more useful and valuable. Someone will put this together and it will be awesome.

Anyway, enough on that, I did say that I had something good to say about the FDA a post or so ago, from Mass Device: "The system was submitted for Food & Drug Administration 510(k) review in mid-May and is available for sale in the U.S. just one month later." They managed a 30 day 510(k) review, which is probably nothing impressive for a blood pressure device, but it is on the iPhone which is probably somewhat more difficult to show that it wouldn't be corrupted, do you apply for the Ap from Apple or for approval from the FDA first? So, good work.

New product turn over

2011-06-26T22:31:00.000-07:00

MedCity News has an article on J&J exiting the coronary drug eluding stent business: End of J&J stent business carries lessons for medical device innovators. It is very surprising to me that they are just leaving the market, surely with $400 million revenue this year they could make something happen. I know they were getting their clock cleaned, but what kind of signal does this send to their R&D organization as a whole? We're not afraid to throw in the towel? Obviously J&J has a lot of smart people and I've never run a Fortune 500 company.

The take away message from the article is you need to keep innovating... I have no idea why you wouldn't, you need to turn over your devices regularly to stay competitive, plus each time you do it you can raise prices and increase margin. Plus you're paying those engineers anyway (hopefully)- don't let them get distracted on non value added side projects. How often you turn over your devices with new models depends on the devices, guide wires and catheters, every 1-2 years you should have a new model or at least a respectable line extension. Other devices can take longer depending on their complexity and regulatory approval time, obviously for drug eluding stents you need a more significant investment.

That being said, don't do it just for the sake of having something new, if the device isn't actually improved a reasonable amount they customer will notice. I was part of one launch with really good immediate sales, then a huge fall off because the customer realized this new product didn't meet any need the old one didn't, in fact it was worse (from their point of view, from the company point of view it was cheaper.) After the initial buys, the customers didn't reorder, they saw right through it despite the best efforts of marketing. If you're investing in a medical device company this is one thing you want to look for, are they launching new products at a reasonable rate, or are they just sitting back and letting things happen?

Anyway, congratulations to Abbot, Boston Scientific, and Medtronic enjoy your extra sales.

How to help

2011-06-20T20:05:00.000-07:00

From a recent FDA press release:

The FDA is helping advance the development of an artificial pancreas system...

I think they should be more clear. What they are really doing is releasing a new guidance document which "will help provide clarity for manufacturers, investigators and reviewers in the development of the artificial pancreas system. It proposes safety and effectiveness goals that the FDA may require researchers and industry to meet when developing a type of artificial pancreas system". Some other things are listed (like a workshop...), but they aren't actually advancing the science.

It is quite a stretch to say this actually helps to advance the development of anything, it just sets expectations, which is great, but lets call it like it is. To advance the development, you need to be working on the device itself, not what you may require as the regulatory pathway. This is probably oversimplifying, but if we were to say all cars must get 50 mpg meeting a defined criteria, I don't anyone would claim that we were helping to advance the development of high mileage cars. (I have some FDA praise slated for a future post, so don't feel bad for them)

Not that this is limited to government. This is a fairly common response when a project team runs into an issue. The project manager calls a meeting to help resolve the issue and the theory is we all pitch in and solve it. In reality there is one guy doing 90% of the work on this problem and it takes too long to really bring another person up to speed on all the required details and anyway they have their own stuff to do. The meeting (or workshop...) just serves to piss the person doing all the work off by either suggesting common sense things he's already done or doing, giving him unnecessary work, or suggesting unnecessary work that he has to fend off. If he is your subject matter expert, trust him, who else is going to solve the problem, the Sr. Director?

If you're the project manager- one on one the guy doing the work, figure out what he wants. Also know his weaknesses and compensate. If he's great at solving the problem, but can't write a report or presentation that passes management muster, then get your ace report writer primed and ready to take over. If he doesn't have the attention span to stand around in the lab for 14 hours straight and supervise testing, make sure the lab guys know what is expected and fill in to keep them running.

I've seen projects delayed for months because everyone was too busy solving the problem with meetings (Why don't we look at this... How about a build that does this.... Did you write that PO yet...) to get hands on time to actually solve the problem. If you're not working on the device, on the manufacturing floor, in the test lab, you're not advancing the development of the device.

Update 1: If you'd like to read more on the FDA and company responses on the artificial pancreas, try here or here.

Catheter recall - tip detachment due to embrittled material

2011-06-15T21:10:00.000-07:00

Boston Scientific is getting a bit of attention for an IVUS catheter Class I recall, to be honest a smaller company probably wouldn't get the same attention. What I thought was interesting was that they published a rate for the catheter tip detachment, from Cardiovascular Business:

The corrective action, announced May 27, is being taken due to eight confirmed cases of catheter tip detachments caused by the embrittlement of catheter material. The Natick, Mass.-based company confirmed a rate of 0.027 percent of catheter tip detachments in the U.S. and Puerto Rico from April 1, 2010, to May 10, 2011.

I don't think I've seen a rate published before and a quick search didn't turn up anything. Presumably this is their complaint rate, of 0.027% or about 1 in 3700, so their recall of 30,000 devices prevented 8 tip detachments. No more details are available, so we don't know if it is a design issue or a manufacturing issue, although an "embrittlement of catheter material" sounds like a design issue- but it is not impossible to imagine something done incorrectly in manufacturing that could cause this. That being said, storage conditions or sterilization effects (if it is not EtO) would be where I would start.

From a risk point of view, if there is one thing you don't want to happen is for parts of a catheter to fall off inside of someone, the severity is obviously high. Tip detachment is generally detectable at least when you remove the catheter from the body, if not sooner, depending if the part detaching is radiopaque or if the catheter stops functioning when the tip detaches. In this case the bar has been set, a rate of 0.027% is too high, which I would agree with, especially for a large company and this type of diagnostic device with suitable alternate diagnostic methods available. Boston Scientific is doing the right thing with the recall and hopefully they are able to address the issue and move on.

SonoChief predicts the costs of the recall:

Boston Scientific’s voluntary recall of the iCross Coronary Imaging Catheters will be disruptive to their ultrasound division. With an average street price of [private]$800 dollars a recall of nearly 30,0000 catheters equates to a loss of 2.4 million inventory.
...
Boston Scientific customers are being told all iCross Coronary Imaging Catheters are being replaced with Atlantis SR Pro Coronary Imaging Catheters, which will operate with Boston Scientific’s IVUS imaging consoles and are immediately available. The Company does not expect this recall to have a material financial impact.

Which is actually $24 million (incorrectly multiplied above), if you use street value, but presumably Boston has a margin of 60% or more, and no one buys list price, which would put the cost closer to $4 million. Although the recall is being expanded beyond the original 30,000 catheters. The cost to their reputation as competitors gain is obviously significantly higher.

I'm not sure what the take away from this is other than do a thorough job on your verification testing, Boston Scientific surely documented and tested for the tip detachment risks and thought they were acceptable, but the rate came out higher than predicted. I would like to know the material and conditions that lead to the issue, I have a few guesses, but its doubtful we'll ever see that level of detail.

Lean Product Development

2011-06-06T23:12:00.000-07:00

I've been working on lean product development lately, but haven't made much progress. For the most part we're able to turn over prototypes quickly enough, the addition of a simulated sterilization cycle would help, but we don't have the equipment for decently controlled humidity. The two areas we seam to have the most problem is fixing very minor product problems and document control.

The minor problems are usually software bugs or nagging fit or packaging problems that we can make work, but we wouldn't release with. No one is really excited about tackling these because they have the tendency to turn into a lot of work. Someone just needs to grind them out before we get to verification.

The document control delays are the delays that really get under my skin. I've worked with both paper and electronic systems now and I by far prefer electronic- especially if the team is split geographically. By electronic I don't mean the team signs a paper and scans it in and someone compiles it, I mean an approved online signature method. The problem almost always turns into we all agree on everything when we're talking, but putting it down on paper makes people weird, especially if you have a bad system where it is all or nothing and no one read anything ahead of time so you end up with several restarts. Now if you have a change you want to make that is 100% fine-by-me just do it in a timely manner and we're square. Try to avoid being one of the following types:

Double-dipper - bring up everything you want changed the FIRST time through, don't keep coming up with new issues. Second rounds of comments should be very rare.
Nit-picker - does adding that re-formatting really add value?
Delayer - doesn't read anything until its past due then has to find some issues to make the delay seem appropriate
2 center - can't let anything go without adding more work no matter what, 90% of the time adds no value. You want a hold order on this engineering product even though it is labeled "Not for Human Use" and the part number isn't active in the distribution or customer service systems so there is no possible way it could ship on an order?

Not that I'm perfect, but I try to come back to value added when making comments. Most of the time it is quicker and better for relationships to just suck it up and put up with whatever to get to the next step, but that doesn't really create a culture of improvement. Every cycle through the documentation system probably costs $500 when you have a bunch of Californians involved. For now I've decided to gently nudge people in what I consider the right direction, hoping to change the culture over the long run. If we can just focus on what is important maybe we don't have to work so many late nights, etc. I don't really know of another way to approach it.

BTW, there are a ton of great lean blogs out there, here are a few:

Evolving Excellence
The Lean Thinker
gemba panta rei
Gemba Tales

Biocompatibility Testing - Needles

2011-01-09T10:53:00.000-08:00

A reader asks:

I am new at medical devices biocompatibility. I've been asked to perform a MEM cytotoxicity assay on an arteriovenous fistula needle. I am not really clear on how to perform the extraction of the device; as I've been asked to do it on the final device which has the needle plus the tube. Would it be appropriate to calculate the volume for the extraction based on surface for the tube and weight for the needle, and sum up both volumes, and submerge the device in that volume?

You want to test the fluid pathway of the device and any other part of the device that is inserted into the body, i.e. the route the fluid would take as it enters the body and exterior of the needle. As you said, in your case it sounds like the area comes from the interior of the tube (and plunger surface), the needle, and some extra for the exterior portion of the needle that is inserted into the body. I would stick to the ISO 10993 standard and just use the surface area calculation, I'm not sure if the standard allows a combination of the weight and surface area calculations.

It sounds like you may be performing the testing yourself, but the easiest way for me to get answers or at least some direction for medical device biocompatibility testing (assuming you end up using them) is to call Nelson Laboratories, NAMSA, Pacific Biolabs, or WuXi Apptec. If this is your first time getting testing done- call all four (or at least the first two) and see which one you like, if this is not the first time, generally someone in the company has some strong opinions on which one is best.

Good luck with your testing.

510(k) Approval Timeline Part 2

2011-01-02T04:57:00.000-08:00

My original 510(k) approval timeline is my post popular post ever! I didn't even follow up with my latest project information. We extended the disposable product line and it was 30 day FDA review, no questions asked / response required, approval in April to May 2010. We justified not doing sterilization, biocompatibilty, shelf life, and packaging. All in all it was about as good as it can get time wise. Timeline went something like this:

August to December 2009: Concept and prototype to design
Jan to March 2010: Product build and verification / validation testing
April to May 2010: 510(k) Approval

Our validation was an animal study using a physician, who filled out a questionnaire like one to ten, how much is this better than the predicate device after he or she used it, oh boy did I learn something there, I'll go over that some other time.

Now we just have to sell them...

Medical Device Blog Email

2010-12-04T19:51:00.001-08:00

Just a quick note- I updated my email address on the right, meddeviceblog@yahoo.com.

The Attribute Gage R&R

2010-11-26T19:52:00.000-08:00

There is not that much information about the attribute gage (gauge) R&R readily available online (that I was able to find), so I thought I'd cover what I've done. First the basics, an attribute is something you can't quantify, generally a visual inspection- is this part "red" or something like that. While it generally seems simple, especially to the technical leads, operators can often get tripped up trying to pass or fail parts based on a description or a couple pictures. In the red example, can operators compare against the Pantone effectively and is this repeatable? You want to have your acceptance criteria and how you are proposing to test it with trained operators set up beforehand.

Your gage R&R should mimic what you do on the line and should be set up that way. If the operator does an inspection on the attribute before passing the part, then a final QC does that same inspection, you have two inspections and this should be part of your testing. You should present this as the entire package when possible. QA types tend to freak out when they hear you would accept a 10% possibility of passing a bad part, when in reality its 0.1%. Having the two (or more) inspections will be really helpful when you get to the acceptance criteria portion.

Test Method: You need to determine the number of operators, parts and trials. Trials is easy, just use three, everyone does, obviously more is better, but three is generally good enough and you don't want to be looking at parts all day. For operators, you need two, but if you have three or more lines or shifts, you can include those easily enough. The number of parts is where it gets tricky and you're going to have to make a judgment call. Generally medical device companies rely on some sort of confidence and reliability based on the severity or RPN of the potential failure, however, in the case of gage R&R everyone seems to follow auto industry guidelines which are usually a smaller quantity, 30 is generally defensible either way.

The Acceptance Criteria: The key one medical device companies are concerned with is the probability of a miss, which is defined as:

Probability of a Miss = (# times a bad part was passed) / (# of opportunities) [i.e. number of inspections]

You need to base this on what is acceptable and preferably tie this back into your risk analysis (you may have to increase sample size). The good news is, if you're doing two of the same inspection, you can set it up so that your acceptance criteria can be something like:

Probability of a Miss (2 inspections) = (# of times a miss by one operator that were missed by another operator) / (# of opportunities)

In that way you can argue that different types of misses will be caught by different operators, but you are only concerned with the fact that it is caught at some point in the process. Setting it up this way significantly lowers the likelihood of a miss and allows you some flexibility.

Other Information: I recommend keeping it simple and only requiring a certain probability of a miss in your protocol (maybe effectiveness as well). You'll want the rest of the information you can collect documented, but that is a business decision, not a safety decision. You can cover:

Effectiveness - (# of parts correctly identified) / (# of opportunities) [a low effectiveness indicates your process is probably not robust and will give you trouble over time, greater than 70% is generally acceptable]
Probability of a false alarm = (# times a good part was rejected) / (# of opportunities) [waste]
Repeatability = (# agreements) / (# parts inspected) [calculate per operator and total, if an operator has low repeatability, less than 80% or so, he or she needs retrained]
Reproducibility = (# agreements among all operators) / (# parts inspected)
Bias = (Probability of a false alarm) / (Probability of a miss) [calculate per operator and total]

The Test Setup: For this you'll need two experts in the attribute being inspected, the experts will sort out the good parts from the bad, label them in some fashion, and randomize them. In my experience you should have at least 25% bad parts, even though your process isn't likely to have 25% reject rate (hopefully). It is nice to include some very marginal parts, but those can be hard to find and agree on. Don't have the operators performing the test make the parts if you can avoid it.

The Test: You want to set it up so an operator makes a determination and someone else records it, don't let the operators know the sample being given to them, previous results, or talk amongst themselves. Do the testing on the line and try to keep the production pace. During a gage R&R I find the operators tend to err on the cautious side.

The Results: There you go, you can now say your test method is qualified and have the data to back it up. You can also make operator decisions based on the results, maybe move one around to catch things earlier in the process, which one is the go to person, etc. I find the attribute gage R&R easier to perform than the variable one, yet it is generally more important than a dimensional one from a safety perspective because there are more things I can't measure easily.

Latex Free Labeling

2010-08-10T18:21:00.000-07:00

For a new device we spent a bit of time working on "Latex Free" labeling. From the FDA point of view (801.437), the key point is natural rubber. The term "natural rubber" includes natural rubber latex, dry natural rubber, and synthetic latex or synthetic rubber that contains natural rubber in its formulation. So while your label coatings may contain latex to give them that glossy look, its most likely synthetic latex (although not always), and you're off the hook.

ASTM D6499 (LEAP assay) can be used to determine if your device tests positive for natural latex and is reasonably cheap insurance that your product is safe.

Recently BS EN980 added a Latex symbol for devices that contain latex. However, there isn't a corresponding recognized symbol for latex free, so the words Latex Free seem like the way to go. Many companies, including GE and 3M, use the Latex symbol with an X through it.

While it is easy enough to lay off the latex gloves in your assembly area, what are your suppliers or their suppliers doing? Although it seems far fetched, a polymer resin handled with someone wearing latex gloves could make its way into your molded part. I can assure you, tracking down this information is a pleasant way to spend a week. Updating your Certificate of Conformance requirements from the product development seems like the easiest way to go.

On the Job Advice

2010-07-18T16:28:00.000-07:00

A few non specific business links I thought were interesting to read, mostly about getting things done. Not necessarily the safe approach.

Seth Godin asks: "Why am I here?"

This is a simple mantra that is going to change the way you attend every meeting and every conference for the rest of your life.

You probably don't have to be there. No gun held to your head, after all. So, why are you spending the time?

Boston Globe on: Why setting goals can backfire

IN THE EARLY years of this decade, General Motors had a goal, and it was 29. Determined to boost its flagging profits and reverse a long, steady fall from postwar dominance, the automotive giant did the natural thing: it set a goal. The company pledged to recapture 29 percent of the American market, the share it had ebbed past in 1999.

...industry analysts argue that one of the most damaging things the company did was to set that goal.

In clawing toward its number, GM offered deep discounts and no-interest car loans. The energy and time that might have been applied to the longer-term problem of designing better cars went instead toward selling more of its generally unloved vehicles. As a result, GM was less prepared for the future, and made less money on the cars it did sell.

And one I don't like from Best Life and Career: 5 Tips to Get Unstuck When You Hit a Plateau I won't quote it, but Take a Class? Really, this is the best we can do?

I suggest re-evaluating what is actually value added work and focusing on those items and working to eliminate the rest. I find that when I get bogged down and don't seem to be making any progress its usually due to overwork which doesn't allow me to focus on what I really feel needs to be done. Drilling down I find that much of the overwork is due to various individuals' preferences that helps the individual, is marginally useful for myself, but overall bad for the company. Yeah, you'll get that report reformatted from the database standard, that compliance memo drafted to supplement a non-conformance or corrective action, or that inspection annotated with extra details, but why do you want this from me? No one else can write a memo? Choose to do work that matters. Engineers make more than $50 an hour and you want me to do this several times a week at the expense of work non engineers can't do.

510(k) Infographic

2010-07-07T22:55:00.000-07:00

I tried my hand at making an infographic full of 510(k) information. Well I really only collected the facts and let a graphic designer do the rest, he fixed up some stuff from yesterday so I'm happy. Click to enlarge!

The perception of risky process changes

2010-04-27T21:33:00.000-07:00

Now that we have an approved device we're spending at least some time on process improvement instead of all out research and development. Unfortunately, even though everything is fairly new some of it is already difficult to change.

We have a piece of test equipment that displays pass or fail, prints out a page of results, and writes them to a database. The operator runs the test, marks pass or fail in the traveler, then staples the results to it. During a sort of related process change I suggested we take out the print out of the results. This was met with quite the uproar and doubt about how we could ever do it.

Apparently removing a redundant step that no one ever looked at was a big deal. Engineering and complaints thought it might be useful, even though they never used the printouts two years in- but someday they might. The change would save some minimal amount of money on supplies, transferring of materials into and out of the clean room and storage, along with associated labor. I was able to finally make headway when I pointed out that we do plenty of visual inspections that do not have another record and in this case we still had a record in the database. Everyone initially thought it sounded like a risky change based and we could be out of compliance, but it was all our own perception.

While this isn't the most impactful example, I think I may have learned the value of taking time up front to set this all up efficiently, but I'm not sure I'll be able to convince anyone to add extra time for these activities the next time around. "We can take care of that stuff during validation!"

Annual review of received parts' dimensions

2010-04-25T21:31:00.000-07:00

Many companies perform an annual review of every dimension or 100% inspection on all received parts. While this may serve as a halfway decent preventive action, I'm not convinced it is worth it. If you have automated inspection methods, maybe then it is not too much effort, but we're still using hand tools or manual adjustments for the majority of our parts.

You could argue that you have a critical device, we have to check for dimension drift. Well why aren't you checking for that anyway? And if it is so critical shouldn't you have insured that the supplier's process was capable before you even signed up with them? If it is truly critical and you're not checking it but once a year, good luck with that.

Additionally, if you do find something out of specification, nine times out of ten it is going to be on a non-critical dimension, or else you would have caught it in receiving inspection or manufacturing anyway. Once you find the out of spec item, you have to go back to your inventory, check it, then justify why it is either okay and change the specification, or send it back, and jump through hoops to justify why it was okay to use on the ones sold, but not okay to use going forward, or whatever other contortions QA wants.

In my experience these generally boil down to unclear or unnecessary specifications or measurement issues, where to start measuring a curve, a hole over specified, etc. Another argument for doing it right the first time and checking your supplier's process.

However, this if often a difficult battle, as new parts are generally part of R&D efforts and the team from R&D is behind schedule and they always try to make up schedule time by trying to get either quality or manufacturing to compromise on one issue or another (I *may* have pointed this out at a meeting once). If this happens and you don't have time to ensure supplier process capability, it is not the worse thing in the world, you can always blame the vendor and shop around for a new one that has no familiarity with the part and uses the same process that can't meet the specification. Sometimes the best you can do is make the risks clear.

Things I never thought I'd have to worry about

2010-04-22T21:32:00.001-07:00

A volcano in Iceland slowing shipments to and from Europe, since we ship everything by plane now. Inventory costs money but so do lost sales.

The longshoreman strike on the west coast about five years ago also slowed me down, back when we shipped by boat. Then it was product development and not production so it wasn't as urgent. We just moved to another piece of the project.

Everyone loves the idea of second sources, but small companies don't have time. Each new supplier of a custom part generally requires dozens of hours of training. "If you don't take that burr off, its not going to meet the specification. Please mask those holes next time like it clearly states on the drawing, etc." I can only improve the products or the business at once, take your pick. Improving products improves the business, although that is no good if you're out of business.

So you pick critical parts and go from there. A machine shop, you can get up to speed fairly quickly if you spend the time. Extruded tubing, not so fast, there is a 12 week material lead time, better plan for that. And even better is that some regulators want to be notified of a supplier change or even an alternate. We also implemented a finance check based on the current economy, but that has been a waste of time, our suppliers should do a finance check on us!

Pot and Medical Device Manufacturing

2010-04-19T22:31:00.000-07:00

California is set to vote on marijuana legalization later this year. I'm pretty much a live and let live guy, but how is this going to effect California's fairly large drug and medical device industry? I'm sure people will debate this, but lets cut right to how companies will see it:

In California you will have a much higher chance of someone stoned building your product and on average stoned people make worse decisions than non stoned people.

This probably doesn't matter if you're renting movies at BlockBuster, but small mistakes in medical devices can cost lives and / or millions of dollars. Right now most companies mitigate the risk of drug use by screening on hire and periodic screening. How would you mitigate in the future, or is my fear overblown? I don't think legalizing pot will help manufacturing in California, obviously that is not the only consideration, but an important one I think.

Finding Owners

2010-04-18T15:01:00.000-07:00

More and more I'm learning one of the keys to making good devices that meet quality and regulatory standards is finding people who will take ownership. Lately I've been working in the packaging area a lot and almost every time I'm in there I find discarded labels without lines drawn through them. Of course these are always discarded by the other shift. Everyone already knows the labels need lined out when questioned, so the basic training is there.

If you're an owner, you walk into your area and you own it top to bottom. You don't not fix things because you weren't around. You correct the issue and take it up with the supervisor on shift change. These are the types of people you want, and why many large medical device companies pay way over what they could for manufacturing labor. Pointing out the same non conformance over and over to the same people is ridiculous.

I've been involved with contract manufacturing in China and they were excellent at following instructions. They picked up GDP about 3 times faster than anyone else and have maintained it. This is not to say everything is perfect, but the basics were taken care of. Some of the more complicated situations that came up with the contract manufacturer were really botched up before we were notified, but at least I know the easy stuff is covered.

I'm not sure that me telling the 19 year old putting labels on boxes that this is the era of global competition and she has to work smarter and harder than they are really sinks in. Hopefully, we have a chance to develop the skills necessary because you only get so many chances.

Labeling for Reuse of Single Use Medical Devices

2010-04-14T21:33:00.000-07:00

Another relatively new EU requirement effective March 21, 2010 per the revised Medical Device Directive (MDD) (93/42/EEC) M5 is the following:

Where appropriate, the instructions for use must contain the following particulars:
...
If the device bears an indication that the device is for single use, information on known characteristics and technical factors known to the manufacturer that could pose a risk if the device were to be re-used. If in accordance with Section 13.1 no instructions for use are needed, the information must be made available to the user upon request;

Now it is not good enough (in the EU anyway) to just put single use device in your instructions for use (IFU), but you also must identify the risks associated with reuse (sepsis/infection is probably common). I'm sure these are already documented in your risk analysis already, just cut and paste them into your IFU. Apparently anyone already using the device off label by reusing it will be deterred by the listing of potential risks, a new mitigation is born.

This seems like a potentially slippery slope to me, why not have every warning list potential risks if not followed? Is it okay to exceed the shelf life? After all, there are no risks listed- how bad could it be? If it was really bad wouldn't they list more than just a rule like they do with reuse?

Anyway, it is not hard to comply with this requirement and we like to sell stuff in Europe, so we're in.

See my previous post on the new MDD phthalates labeling requirement.