The Science of Safety
ASG’s biocompatibility expert Rylan Wolfe shares insights on the role and the future of biocompatibility in the medical device industry.
Rylan Wolfe is ASG’s resident expert in biocompatibility and the regulations that surround it. He’s also a specialist in injection molding and accelerated aging testing. Rylan’s background in chemistry and knowledge of materials science make him a nimble partner for both his colleagues and ASG’s clients, who praise him for his precise work and deep understanding of the ever-changing regulatory environment. In this Q&A, Rylan shares insights into what the future looks like for the field of medical devices and biocompatibility and how regulations play a part in the components we use.
Tell us what you do at ASG.
Most of the projects our team works on are based on a single device. My role is to meet with project teams to understand their timing needs and figure out how we can best jump in and fulfill those. Often, they’re looking to fulfill some sort of product or regulatory requirement, such as biocompatibility. My responsibilities include understanding the current regulation, ensuring the technical requirements of the regulation are met, and writing up the results in a clear and concise manner. I also do a lot of communication with our suppliers. Clients buy resins from major suppliers, and those suppliers don’t always disclose what’s in their products. We have to find a way to learn everything we need to know without disclosing proprietary information. Everything must be well-documented and traceable.
Where does chemistry come in?
Coming from a chemistry background helps a lot. I’m preprogrammed to think about the chemistry side of biocompatibility. As the field progresses and moves toward chemical-based testing, there’s more testing on individual chemicals and how they interact with the body. If we know what something is made out of or what will come out of that component, then we can evaluate that purely on its composition and previous knowledge from published literature and research. It’s also extremely useful to be able to communicate effectively with project teams composed of people who have background in chemistry too.
Tell us more about your work with regulatory requirements.
I work a lot with regulated substances. One example is California’s Proposition 65. This is the law that requires businesses to state, “This product contains a substance known to the state of California to cause cancer” on the labels of their products. The list contains substances of high concern, like mercury or BPA. We look at what the client’s devices contain (i.e. the plastics, metal components, etc.) and then cross-reference that with the Proposition 65 list. If there’s a match, we’ll perform a technical assessment on estimated exposure levels.
Then there are regulations that are more specific to medical devices. There’s a new regulation (European Medical Device Regulation or EU MDR) governing medical devices in Europe that was supposed to go into effect May 2020 but was pushed back a year due to the pandemic. One paragraph in the regulation deals specifically with substances that are carcinogenic, mutagenic, toxic to reproduction or endocrine disruptors. Similar to a Proposition 65 assessment, we’ll work with suppliers to identify any substances of concern in the device components and perform a technical assessment on user exposure.
How do these regulations relate to biocompatibility?
All of these regulations have the intent of protecting end-users or the environment. Biocompatibility has the same intent — protecting the end-user. Understanding all the substances that go into a device and their impact on the human body or environment is the key step in each process.
There’s an additional component besides determining whether devices are biocompatible. We have to make sure the digital thread (as Doug Koeneman would call it) is completely filled in. When you’re complying with regulatory requirements, you have to make sure the entire process is documented and traceable.
Why is biocompatibility so important in medical device manufacturing?
As consumers we have expectations that what we buy is safe for us. That’s why we saw such an uproar when there was evidence of BPA, an endocrine destructor, leaching out of hard plastic water bottles. I think there’s an even stronger expectation that medical devices are safe.
Having delved into this more over the past year, I’ve been surprised at how many regulations govern other aspects of products that we buy that I wasn’t aware of. For example, stainless steel cutlery is governed by ISO 8842 which specifies material composition and performance requirements.
My two-year-old son has a pack of crayons and the label says it conforms to ASTM D 4236. I have the ability to look up that standard and see what it says about the labelling and safety of art supplies. When you pick up a crayon, you don’t think that it might not be safe to use, but there are people out there who are working to make sure those crayons are safe.
This becomes more and more true with medical devices. You don’t want something that’s supposed to cure you to actually cause you harm. Patient safety is extremely important, and there are experts working to make sure they’re safe for consumers to use.
How do you test biocompatibility?
The ultimate knowledge of safety comes from how devices behave in the field. But you don’t want to test that directly on humans. There are clinical trials, but the amount of work and testing that goes into drug products before they’re used on humans is astounding. The same goes for medical devices.
For example, we test for sensitization and irritation in surface devices, which are both skin-level reactions. We can check for these types of reactions through either chemical or biological tests. Irritation is an acute or one-time reaction — think drain cleaner or repeated exposure to hand soap. Sensitization is an allergic reaction pathway where someone is exposed to low levels of something and overtime becomes allergic to it. One example is nickel, which can be found in cheap jewelry and belt buckles.
Why are these kinds of tests so important?
Medical devices are getting more and more intricate as the number of disease states we treat increases and as medical technology improves. It’s important that the science of safety keeps up with the innovation so patients have access to safe, cutting-edge treatments.
For example, five years ago I had heart ablation surgery to correct a heart arrythmia. Thirty to 40 years ago, they would have either left it untreated or cracked open my ribcage and burned out the nerves that were overexcited. For me, it was a four-hour procedure and I got to go home nearly the same day. That advancement relied on medical innovations, material innovations, and rigorous safety testing.
How has technology improved biocompatibility over the years, and what will change in the future?
Our understanding of the human body is always changing. So is our understanding of the ways the body interacts with the environment. The interactions can be very complex, even when you’re trying to isolate a very specific reaction. The field of biocompatibility is trying to stay on top of some of the new technologies that might be implemented in medical devices. Nanoparticles is one example. When you get to the nano scale, the way that material behaves and the way the body reacts to it can change.
There’s also more focus on device degradation. As a device degrades, whether that’s inadvertently through repeated sterilization processes or on purpose like implantable stitches that degrade after a certain amount of time, it’s important to study how these processes affect device and the human body. The future will be about keeping up with new technologies that might be implemented in the medical device manufacturing industry.
Anything exciting you’re working on now that we can discuss?
There’s an ongoing effort to move away from animal testing whenever possible if it doesn’t affect patient safety. We’re looking forward to a new test method that uses reconstructed human epidermis cells that are cultured in a petri dish. It’s approved for individual chemicals right now. So, if you wanted to find out if a particular chemical is an irritant, this method is agreed upon internationally as an effective test. There’s currently work ongoing to qualify and regulate this method for use in the medical device field.
Tell us about your work with molding and accelerated aging.
My experience in molding is related to my work in accelerated aging testing and how plastics behave. With medical devices you want to make sure they still work after being on the shelf for many years. But you don’t want a product sitting on the shelf for seven years before bringing it to market just to make sure it works at the end of those seven years. One way we accelerate that process is to use accelerated aging or highly accelerated lifetime testing. You basically heat something up and any reactions that happen are going to happen at an accelerated rate at that higher temperature. We’re doing testing on plastic components and a lot of those are injection molded.
One of our clients has an in-house developmental injection molding lab that helped me and a few other ASG team members learn how to operate an injection molding machine, how to set it up and develop a process.
There’s effort that goes into understanding how materials behave at the end of a lifetime (after accelerated aging) before we select them for components. Once you go through the entire design process and you find out your material isn’t going to last more than four years, it’s quite expensive to go back and pick a new material and potentially change the design.
We’re working on filling out a database on understanding how different classes of resins and other materials behave and their appropriate test conditions. For example, there are certain materials that you can’t heat as high as others. You want to make sure the testing you’re doing is relevant and valid.
To tie that in with injection molding, there’s something called a process window where there are a whole bunch of settings that go into injection molding. There’s a high and low condition, and as long as you’re within those, the process will give you the part that you want. The question we’re looking at is: How does something that’s molding at the low end of that process window behave versus something that’s molding at the high end? How does it behave at time zero versus end of life?
We’re working with our colleague who is an expert at injection molding and designing those process windows so we can determine what to expect to happen to the material and what mechanical testing we need to prepare for. I hope that, once the pandemic lifts, we’ll be able to get back and do more in the injection molding lab.
What do you do when you’re not at work?
It took me a few years after graduate school to realize that spending more time at work or thinking about work doesn’t make you more productive. Recently, I’ve been spending more time reading. I’m currently reading “Crime and Punishment.” And I’m doing some woodworking — I just finished a live edge desk for my home office.
With the pandemic, it’s hard to compartmentalize work and home life when all my work is done at home. One thing that’s helped me with this is having a young son, because spending time with him or picking him up from daycare signals the end of a workday.
I’ve heard you like crosswords and puzzles. How do your puzzle-solving skills come into play at work?
One thing I love about crosswords is how sometimes you have to view things through a different lens in order to solve them. I used to write crosswords for an undergraduate newspaper at North Dakota State University, and part of the fun in writing the clues is to purposefully make people think a different way. I try to bring that same mindset to ASG and our clients. How can we look at difficult problems from a different perspective? And how do we ask the right questions to change our perspective?