Ethylene oxide (EtO) is one of the most widely used sterilization methodologies in the biopharmaceutical industry. A survey completed with BioPhorum members found that 69% of members use EtO sterilization for semi-finished inputs, components, and terminal products and devices. The US Environment Protection Agency (EPA) has issued proposals for 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.
The biopharmaceutical industry fully understands the rationale for the proposed changes and agrees with the EPA on the emissions and dosage reduction goals. However, the implementation timelines are too short for industry to plan a safe, appropriate, and economically viable transition.
We therefore set up an EtO Response Team, consisting of various member companies from throughout the BioPhorum community, to gather industry’s views on the proposed changes and develop a consensus response. A sub-team was then selected to be a delegation to the EPA. This is a great example of BioPhorum’s ‘One Voice’ approach in action.
The delegation met with the EPA in October 2023 to share industry’s position and help educate the Agency on why the current proposals would severely impact the supply chain and patient access to critical biotherapeutics and vaccines. The reasons include sterilization capacity constraints for any components used to manufacture biologic pharmaceuticals, that industry cannot ‘lift and shift’ into different modalities, and the delays caused by regulatory filings.
To help the EPA better understand the impact of its proposals, the BioPhorum team presented the basics of EtO use in the biopharmaceutical industry. This included process maps for different regulatory pathways and where they are impacted by EtO, sterilization modalities and how they are selected, and cycle optimization.
The meeting was also used to set out BioPhorum’s position and ‘asks’ in support of the wider biopharmaceutical industry, which were for:
- A comprehensive impact assessment to be completed on how these changes impact the industry.
- Maximum transition periods to allow component suppliers and biomanufacturers time to adapt their operations to meet the revised emissions standards.
- Collaboration between the EPA, biomanufacturers, and other stakeholders to address the challenges, focusing on a risk-based approach.
Although the EPA has carried out impact and qualitative benefit assessments (and has no plans to carry out more), BioPhorum is concerned that these did not focus specifically on biopharmaceuticals and offered to help the EPA understand the specific risks for our industry.
We also stressed the need for maximum transition periods and exemption processes, and that delivering the proposals within the suggested timelines is unachievable. The EPA clarified the proposed timelines, noting that the Office of Air and Radiation can give a maximum timeline of four years, but typically this would be two to three years. However, the Office of Pesticides Programs has no specified time limit and has more flexibility around timelines. BioPhorum offered to follow up with the Office of Pesticides Programs to ensure the proposed timelines minimize the risk to the supply chain and patient access to medicines.
We asked the EPA what justification and level of rigor is needed for products to be exempt. The EPA said it has not looked in-depth at this but noted it has previously allowed exemptions for reasons relating to technical feasibility, so it would not be a new concept.
We also emphasized the need for clear guidance and processes that leverage alternative modalities or bring more sustainable use of EtO to market. We offered to work with the required regulatory bodies to develop this guidance and have requested discussions with the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to explore these matters further.
The EPA noted that there has been regular collaboration with the FDA, but said expertise there is limited due to the extremely technical nature of the subject, so it encourages the EPA to speak with industry and those with technical knowledge. We have offered the EPA and FDA our subject matter expertise to help in any way possible and will follow up separately with the FDA to progress this.
The complexity of our industry demands a thoughtful and collaborative approach to regulatory changes. We look forward to ongoing discussions with the EPA and FDA to help the transition away from EtO happen at a suitable pace while minimizing the effects on the supply chain, patient safety, and product availability.
In June 2023, the EtO Response Team submitted its comments on the proposed changes to the EPA; these can be read here. The October 2023 presentation to the EPA and the BioPhorum event report can be downloaded here.
For more information, contact Tori Crawford, Regulatory & External Partnership Manager, at email@example.com