Seal of approval

Packaging is the last major part of the manufacturing process, and the first thing medical professionals encounter when interacting with a device. Whether it’s the seemingly simple plastic wrapping that contains a set of pre-filled syringes or the hard clamshell case that encloses an implantable pacemaker, the sterile barrier is essential to offset the risk of infection. It’s for this reason that it is critical for medical device manufacturers to design products with the packaging in mind, rather than it being an afterthought. In fact, packaging and sterilisation can often be a process of several stages, stresses Dan Burgess, fellow of packaging engineering at Boston Scientific. “Viewing packaging as the final stage may not always be as simple as it sounds,” he says. “In some cases, packaging may happen in stages depending on sterilisation and device needs. For example, some products are sterilised at the sterile pack level and others at the final pack level. In addition, some sterile barrier designs may require multiple processing steps, including sterilisation, before the final seal is applied.”

In either case, Burgess is a strong advocate for packaging engineers being brought into the process right from the outset, when the initial concept of a device is being discussed. At this point, he says, many key questions must be asked: How large will the device be? How much will it weigh? Will it need to be stored in a specific position? Designers must also consider the potential hazards a device or packaged contents, such as assembly coils or mounting cards, may present to the sterile barrier. Common examples include sharp or abrasive surfaces, high mass devices or geometries that do not align with the seal profile. Another consideration is the ability of a medical device to be manipulated into different shapes for packaging without damaging them. This is especially important for devices that are long (>30in) such as delivery systems and catheters. “Without the ability to coil devices of this type the packaging design must allow for a straight device, typically requiring larger packaging than would be necessary if the device could be coiled,” Burgess explains. “If this need is not considered during development of the device, it may result in material or design choices that will not permit the use of smaller packaging without damage.”

Burgess adds that it’s important to decide whether a product is to be sterilised at the sterile pack level or the final pack level; both approaches have their pros and cons. “For example, in ethylene oxide sterilisation, if you sterilise at the sterile pack level, you can fit more units in a chamber, which is a big benefit,” he explains. “On the other hand, if you sterilise everything in the final pack, it is ready to go as soon as it’s sterilised.”

Understanding device sensitivities

Material compatibility is also crucially important, and sponsors must ask whether the material they are considering for the device has any environmental sensitivities – whether that be heat, cold, humidity, pressure or oxygen – that will require specific protection or mechanisms of assessment for the user, such as temperature indicator labels. “Since there are many different modalities of sterilisation, including steam sterilisation, radiation sterilisation and ethylene oxide sterilisation, it’s important for a development team to understand the characteristics of each material,” Burgess explains. “They must also take into consideration not only what materials may be used on the device, but also the packaging.” Nylon, for example, is a common material in both medical devices and packaging due to its strength and durability compared to other polymers, but it may have difficulty achieving the desired performance during radiation sterilisation. This is because ionising radiation can break the polymer chains and cause cross-linking, leading to a reduction in mechanical properties, like its strength and flexibility. This can compromise the integrity of the packaging material and increase the risk of packaging failure during storage or transportation. However, if steam sterilisation is the method under consideration, a different set of materials would be excluded. “In this case, high heat will be used, and many polymers in common use for packaging could be impacted since their glass transition temperatures are near temperatures employed for this method of sterilisation,” Burgess notes. DuPont Tyvek, for example, should not exceed 127°C or there may be an impact to part dimensions and porosity. The implications of not asking these questions could be severe project delays due to the substantial redesign work needed to resolve any issues. “In some cases, this could mean months or years of rework, resulting in a long delay to bringing new life saving technologies to the market,” Burgess says.

Logistical challenges

Beyond the functional, companies must also consider the logistical implications of their packaging choices. What will the annual volume be for this product? How important to the company is this device likely to be? This leads into how much effort will be needed to develop packaging for the various elements of a medical device’s ecosystem. For example, the primary device might be a pacemaker, which will be implanted into the patient. This product would also come with several accessories that facilitate implantation of the device, but are not themselves responsible for delivering therapy to the patient. “Because of the risk and importance of the pacemaker itself, it’s vital to understand that more time and energy will be required to develop packaging for the device, rather than the accessories – not from a safety standpoint, but in terms of appearance or marketing,” Burgess notes.

“Manufacturers must also consider the risk associated with what they are packaging; if it’s a device that is going to live in a person for a long time, there’s a lot more risk involved; if it’s not going into the body, it’s a much lower risk product. This risk is managed by regulations medical device manufacturers must follow, including the type of regulatory submission required for low (Class I) versus high-risk (Class III) products. Just like the device itself, these regulations dictate how much scrutiny and time you are going to spend developing the packaging for that product.”

These considerations will also impact supplier selection – a far greater issue for medical device manufacturers today than it was before the pandemic. “Three years ago, there was never a concern about making sure we had enough parts to make a product; supply wasn’t really an issue,” Burgess says. “Now we’ve recognised that if you have a really important product, you should have at least one alternative source for materials, so that if your primary supplier fails, you have a back-up plan.” This process brings up a whole new set of questions. How stable is the back-up supplier’s manufacturing process? Can they maintain the same level of quality in two years’ time, or three? “Unfortunately, these are things that tend to show themselves over time that you might not notice right away,” Burgess says. “But these kinds of discussions are certainly taking place more frequently.”

The future of sterile packaging

With net-zero targets drawing closer, medical device manufacturers are also under increasing regulatory pressure to reduce their emissions and the amount of energy used during the packaging process. This is leading to the development of new sterilisation methods, as well as the adaptation of existing ones.

For example, ethylene oxide sterilisation is one of the most common medical device sterilisation methods. In fact, more than 20 billion devices sold in the US every year are sterilised with ethylene oxide, accounting for approximately 50% of devices that require sterilisation. These devices range from wound dressings to more specialised devices, such as stents, as well as kits used in routine hospital procedures or surgeries that include multiple components made from different materials. However, there are widespread concerns about the environmental impact of this popular sterilisation method. Following a risk assessment conducted by the Environmental Protection Agency (EPA) last year, the agency is proposing to limit the application rate for ethylene oxide to no more than 500mg/L of air, which would help to reduce ethylene oxide gas that these facilities release by 80%, bringing emissions below the Clean Air Act standard for elevated cancer risk, and forcing medical device manufacturers to reconsider their sterilisation processes. “If manufacturers consider sterilising at the sterile pack level, that will potentially allow them to use less ethylene oxide gas, because they would only have to get through one barrier to sterilise the contents of the package,” Burgess explains. “However, if a company has always done their sterilisation process at the final pack level, moving to sterilisation at the sterile pack level is a big change, because it will require new methods of handling the product.” There are many factors to consider: Do you have the right equipment? Is there going to be extra handling that might lead to a sterile barrier breach? “You need to evaluate your manufacturing process to assess whether or not that’s going to be a concern if you change where and when you’re doing the sterilisation,” Burgess advises. To help manufacturers address these challenges, the FDA has been proactively working with medical device sterilisers to reduce the amount of ethylene oxide they use while still effectively sterilising products to help ensure they meet the EPA’s standards – for example through an Innovation Challenge. Early observations suggest that some facilities have cut emissions from between 20–35%. Challenge participants are also exploring the potential for using alternative sterilisation methods, such as vaporised hydrogen peroxide, supercritical carbon dioxide and nitrogen dioxide for certain types of medical devices.

Technological innovations

Another development Burgess believes could impact the sterile packaging process in the coming years is computational modelling, which has high potential to reduce development time and packaging waste. “The traditional approach of physical prototyping, build and test is still prevalent in the industry,” he notes. “And while it’s a time tested and proven method, supply chain challenges and lead times mean it is taking an increasingly long time to do.” If manufacturers were able to model their designs virtually and iterate them hundreds of times to find the optimal design before building a physical sample, the time and energy saved could be enormous. “Other industries are using this technology; it’s been prevalent in cosmetics and food packaging for a long time. We have examples out there to pull from; it’s time we got started,” Burgess stresses.

Industry developments aside, for Burgess the bottom line remains: packaging and sterility must be considered from the very outside of any medical device development process. “The best way to overcome the common challenges associated with this process, from material selection to supply chain issues, is to avoid them all together,” he concludes “And the only way to achieve this is through communication and upfront design characterisation work.”