Ethylene oxide (EtO) is used to sterilize medical devices, pre-filled syringe barrels, and some elements of single-use system technologies. However, there are issues with the use of the gas: it is a recognized mutagen and is carcinogenic, as well as being an irritant and highly flammable.
For these reasons, the US Environmental Protection Agency (EPA) has proposed new rules to cut EtO emissions in the USA, targeting an 80% reduction in emissions from EtO sterilization facilities. There are also proposals to increase the requirements for personal protective equipment that operators must wear. These actions threaten to make the industry untenable for many sterilization service providers, which would threaten the surety of supply for a number of pharmaceutical products, many of which are biotherapeutics.
The pharmaceutical industry’s needs have not been considered by the EPA and disruptions to the current sterilization process proposed by this rule change have the potential to impact the availability of vital medications, even beyond the jurisdiction of the US.
We believe the result of these proposed changes presents a very serious risk to patients and shows that a thorough and more robust transition plan is required.
As a result, we have submitted a response to the proposed changes and have raised several concerns with the EPA:
- The proposed rule changes need to consider the impact of EtO cycle optimization, and the timelines associated with any changes
- There is a lack of capacity for alternative methodologies and not all methodologies are compatible with the components to be sterilized
- Any disruption or delay in the current sterilization processes may put biotherapeutic availability and patient safety at risk.
An achievable transition period
We suggest that any modifications to current EtO emissions standards must be introduced to allow an appropriate transition period. We think the EPA must consider the time required for biomanufacturers to adapt their operations and ensure continued compliance without compromising product quality or patient safety.
One member of the EtO response team who helped to author the response to the EPA states “As a major provider of life-impacting biopharmaceuticals, we support 50 million patients across 175 countries, to treat 75 medical conditions. We are heavily reliant on sterilization processes to meet the stringent requirements for product safety and quality. Without sterilization, we are not able to serve the needs of these patients. The proposal for change to EtO emissions must be dealt with in a manner that considers the impact to the biopharmaceutical industry and associated patient cohorts.”
The EPA suggests a five-year timeline for cycle redesign and compliance to reduce EtO used in existing products to 500mg/L, and two years for new products to market. However, we do not think either timescale is achievable. There is also an 18-month timeline for sterilization companies to act on the changes that directly impact them; once these are in place, companies are also required to reduce the amount of EtO utilized in sterilization activities to less than 500 mg/L.
As a comparison, the derogations linked to the European Union Chemicals Agency’s proposal to restrict the use of per- and poly-fluoroalkyl substances (PFAS) offered the medical device industry 12 years to develop and execute a transition plan out of PFAS. Considering product redesign and revalidation timelines, this seems a more appropriate period for EtO.
We have therefore made the following recommendations to the EPA:
- A comprehensive impact assessment should be completed for how these changes affect the biopharmaceutical industry
- Adequate transition periods should be established that allow biomanufacturers time to adapt their operations and implement the necessary changes to meet the revised emissions standards without compromising product quality or patient safety
- Collaboration between the EPA, biomanufacturers, and other stakeholders should address the challenges, focusing on a risk-based approach.
Working in partnership with regulatory agencies, we hope to help the transition happen at a pace that industry can handle and without concerns for the availability of the life-changing biopharmaceuticals that so many already rely on. We look forward to continued collaboration with the EPA and other stakeholders to achieve this balance. For more information, download the full EtO response team’s submission here and contact Ciera Clayton, Global Change Facilitator, at firstname.lastname@example.org