EU Medical Device Labeling Regulation and the Unintended Consequence on Sterilized Product, the Environment, and the Health and Safety of People

The new European Union Medical Device Regulation (EU MDR) came into force in 2017 and following a three-year transition period, all the requirements were to be officially implemented by May 26, 2020.^*,1  Based upon the amendment that was published in the Official Journal of the European Union on April 24, 2020,²  May 26, 2021 is now the official date of full application of the MDR, which delays the start date by one year. All medical device manufacturers selling products in the EU must prepare to meet the terms of this regulation by the deadline.

There are many new guidelines manufacturers must follow before they can get their medical devices onto the market and the requirements for medical device instructions for use (IFU) are also impacted by the new language requirements. While individual EU states previously chose their own selection of languages, the new EU MDR stipulates that medical device content must be available in all 24 official languages to meet the needs of all EU members.

The consequence of this requirement is that the size of the IFU will increase in accordance with the number of languages. If a current IFU has eight languages, it will increase by 16 languages, thereby increasing the size and volume of material in packaging.

The increased IFU content and resulting change in the volume, density, and overall configuration of the package or sterilization load on a pallet will negatively impact the most commonly used sterilization methods. The amount of cellulosic material in a sterilization cycle will impact the density, the sterilant absorption characteristics, and the lethality of the process.

For radiation, the increase in size of the IFU will most certainly result in larger dose uniformity ratio (the ratio of the maximum dose divided by the minimum dose across the sterilization load), therefore requiring additional dose distribution studies to ensure the process will meet the minimum and maximum dose requirements.³  This increased dose uniformity ratio may make routine radiation processing more difficult as it may require a significant change to how the products are presented to the radiation source.

For ethylene oxide (EO), the increase in size of the IFU may impact the ability of the gas to penetrate the load and negatively affect the sterility of the products. Therefore, the amount of gas required to fill the sterilization load to achieve the same lethality will have to be increased because of the absorption of the gas by the IFU. The additional gas will result in an increase of EO residuals⁴  that need to be aerated before the product can be used on a patient. This also means more EO gas will need to be eliminated from the sterilization chamber and the sterilization facility before the load can safely be handled by people for distribution to healthcare facilities.⁵ 

Currently, EO is used to sterilize roughly half of all medical devices in the world,⁶  but health concerns have put it under scrutiny. With its future in question, medical device manufacturers, contract sterilizers, and regulators are working to reduce the amount of EO used in sterilization to ensure its sustainability. The significant increase in IFU size runs directly counter to this effort and will increase the amount of EO used to sterilize medical devices worldwide to meet the necessary sterility assurance level, potentially increasing EO fugitive emissions to the environment and negatively impacting worker health and safety.

We will review the impact of this change on four different medical devices to help better understand what impact this change will have on the package and sterilization load.

As we can see from Table 1, the impact may be very small (only 2.3% change in pallet weight), or it may be very large (a 71.1% change in pallet weight).

Figure 1 illustrates the effect of the additional paper. An IFU accompanies the product in each individual product package. There are 170 individual unit boxes per distribution case and there are 16 distribution cases per pallet. This means each pallet contains 2,720 IFUs. Considering a threefold increase in IFU size, the new total IFU weight will be 277 kg per pallet. This is a 185-kg increase in IFU paper when compared to the current state of a sterilizer pallet and requires a larger pallet volume.

Adding a significant amount of weight in the packaging system can also have an adverse effect in the packaging system design since this represents an additional 11.5 kg per distribution case.

Potential changes to the packaging system may modify the pallet configuration and require the use of stronger distribution cases that will further increase the paper content per sterilization load.

Because of the increased absorption characteristics of cellulosic material, this change in pallet configuration is directly related to the increase in cellulosic material needed for IFUs to meet the new the language requirement. If a sterilization process uses EO gas to sterilize a load with the current IFU, and now the load has 185 kg more weight in cellulosic materials, the amount of EO gas used to sterilize that load is estimated to be more than double the previous amount of EO gas needed. The sterilization cycle would need to be revalidated for the substantial change in the configuration of the sterilization load. This will add significant time to the validation process and strain the already limited EO capacity, and will also require regulatory approval—which adds more time to any updates required. In addition, the EO residuals for the product that are in that load will require revalidation to ensure compliance with the ISO 10993-7 requirements.⁷ 

Depending on the number of sterilization loads processed each year, this would add a significant amount of EO into the environment with no added benefit to the sterilization or safety of the product to the patient.

In accordance with regulations (e.g., EU Regulation 207/2012⁸  and FDA Blue Book), medical device instructions can be provided in digital format (eIFU). However, some professional use devices are excluded from the regulation, including non-implantables, accessories that can be used for multiple purposes beyond implantation, movable capital equipment, patient materials, ablation devices, instruments not used for programming, temporary leads, and devices with a high risk of off-label use. This remains one of the primary challenges with overcoming the EO sterilization load burden increase that the device industry faces with new MDR compliance requirements. While the EU MDR doesn't require eIFU, it does make it a permissible form of distribution to all member states; therefore, one could argue that it should be a requirement for them to accept eIFU.

Instead of allowing member states to require physical IFUs, the European Commission should expand the existing eIFU Regulation 207/2012 to include all medical devices and allow organizations the opportunity to leverage eIFUs as a distribution method, if desired. This green alternative would help drive down the amount of EO gas used and help reduce the amount of paper being placed in our waste streams, as well as promote compliance without extensive time-consuming and capacity-limiting validation.

Digital instructions for medical devices make sense for several reasons:

• They provide the timeliest delivery of the latest version of an IFU, assuring that the customer always has the most updated information.

• Ease of accessibility makes viewing an IFU a capability from a variety of electronics: a phone, tablet, or a laptop, which makes it a convenient alternative for healthcare providers and field personnel who often may not be in an office setting with access to a paper copy.

• They are a more effective communication tool, leading to improved customer satisfaction.

• When digital instructions replace printed instructions, they allow manufacturers to reduce the waste stream for EO gas usage and the amount of paper used.

• The digital IFU also allows ongoing enhancement of instructions in the future without extensive and time-consuming validation that strains the market and timeline for compliance.

The unintended consequences of the increased languages for paper IFUs are significant and can impact the radiation and EO sterilization processes, add paper into the waste stream, and increase the potential for exposure to EO gas for people handling the product post sterilization.

The time to make this change is now, when medical device companies are required to increase the number of languages for IFUs to ensure the safe use of their products. Today these instructions are commonly provided in printed format in the package with the medical device because the current EU eIFU regulation excludes a great number of medical devices from being in scope for eIFU eligibility.

As we consider as an industry where to go from here, a couple of key opportunities stand out. First, we should engage with those geographies that are amiable and engaged with pursuing eIFU adoption for a significant portion of products in the medical device industry. Part of this objective specifically includes geographies where there is a specific language requirement for a single country, and where eliminating the need for that language in paper reduces the size of the IFU. However, one of the primary barriers for many of these geographic regions is accessibility to the internet and capability to obtain an electronic copy of an IFU.

Organizations should be open to exploring other packaging configurations (e.g., pack-to-ship where eIFUs are unavailable), significantly reducing package and operational elements. Another opportunity may also be to engage with geographies and determine whether it is possible to supply healthcare providers and hospitals with a paper copy of an IFU upon first order of a product, then fulfill subsequent orders with eIFUs.

The second primary opportunity lies in expanding the scope of existing eIFU regulations for geographies that have current device restrictions. As an industry, there is tremendous opportunity for us to provide risk assessments in geographical areas where the internet is an easily accessible and highly reliable method of information, and leverage expansion on the scope of devices eligible for eIFU. It is also possible to consider a hybrid alternative where the customer could select the media for their IFU—paper or electronic—much like many vendors allow a customer to choose whether or not they would like to receive a paper or electronic receipt.

These ideas are easily put down into text, but are more difficult to actualize. However, as a community, we can come together to enact broader change on a global scale.