Addressing industry challenges through collaboration: What the BioPhorum EtO Response team achieved!

How did it all start?

In May 2023, I started to facilitate a team in the Supply Resilience Phorum, called the EtO Response team. It was an intense 10 months from the day the response team was kicked off, until March 14th when the final ruling was announced.

Back in April 2023, The US Environment Protection Agency (EPA)? 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 application of EtO in the BioPharma industry and the impact on supply of critical medicines to patients had not been sufficiently considered or recognized in the EPA’s proposal. It was highlighted by the EtO response team that any disruption or delay in the current sterilization processes may put biotherapeutic availability and patient safety at risk due to shortages or delays in the delivery of life-saving medications to patients in need.

What did we do?

The team submitted comment to the EPA in June 2023, attended public hearings and had their own 1-1 meetings with the EPA and the FDA to discuss these concerns and start to develop an exemption process.?

?In a face to face meeting with the US EPA , the BioPhorum EtO Response team educated the EPA on the differences between the Medical Device Industry and the Biopharmaceutical industry. They described the complicated and timely process to adopt EtO alternatives?and complete cycle optimisations.

Originally the EPA suggested a 5-year timeline for cycle redesign and compliance to reduce EtO used in existing products to ≤500mg/L, and 2 years for new products to market. However, it was believed that development time and approval from the regulatory bodies, i.e., FDA, would mean 2 years, is not achievable and 5 years is not guaranteed either. The Biophorum EtO response team had requested a thorough and more robust transition plan for this industry as a decreased concentration could lead to:

?·???????? Significant variability in timelines to execute

·???????? Sterilization process is normally outsourced, those who own the products/cycles are at the mercy of??CMO support amongst competing initiatives.?

·???????? Unintended trades offs (All-in-one' processing will have a significant decrease capacity)

·???????? All-in-one' processing will have a?significant?decrease capacity) Not feasible for many facilities/cycles

·???????? Insufficient guidance

·???????? There is significant risk in undertaking an approach to optimize a sterilization cycle/process.? Customers need to know what the trade-offs are with regards to cost, timing, regulatory impact, etc.

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It was suggested by the EtO Response team that further investigation be performed by the EPA regarding the impact of these changes on the biopharmaceutical industry and the following recommendations are to be considered in the final rule:

• Comprehensive impact assessment to be completed for how these changes impact the biopharmaceutical industry, including an evaluation of capacity and feasibility of alternative sterilization methodologies.?
• Maximum transition periods to be established that allow component suppliers and biomanufacturers the time to adapt their operations and implement the necessary changes to meet the revised emissions standards, without compromising product quality or patient safety. This transition period will help to reduce the risk of product shortages during the adjustment phase.?
• Collaboration between the EPA, biomanufacturers and other stakeholders globally to address the challenges, with a focus on a risk-based approach. The EPA should defer to, or closely collaborate with, the FDA and the ISO/AAMI committees to provide industry guidance related to cycle optimization or alternatives to EtO. This guidance should be practical and ensure continuity of supply while maintaining product sterility and original product performance, as well as align with other governmental agencies (i.e. US FDA).

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What did we achieve?

On March 14th the final ruling was announced. EPA announces final rule to slash toxic emissions of ethylene oxide and reduce cancer risk | US EPA

In developing the final rule, the EPA had considerable feedback.? Based on all this input, EPA improved the risk assessment and strengthened the standards to ensure risk reductions for surrounding communities.

Key takeaways from the ruling:

• Through the installation of proven and achievable air pollution controls, commercial sterilizers will reduce emissions by more than 90%. These are the strongest measures in U.S. history to reduce emissions of EtO.
• 3 different phases of implementation dependent on the scale of EtO use. If facilities need, they will have an additional 180 days to demonstrate compliance. Also, the Clean Air Act provides that under certain standards facilities can apply for a 1-yr extension.
• Based on the scope of the final ruling, there is no longer a requirement to meet the 500 mg/L for cycles and (therefore) there is no exemption process.?However, Biomanufacturers are still interested in understanding what the facilities are required to do that will then have a knock-on impact to their customers: potential for the team to develop guidance on this.??

The EtO Response team were able to influence what was in scope for the biomanufacturers. The EPA fully agreed and acknowledge the EtO teams input, which has changed the scope of the ruling to eliminate the risks associated with cycle redesign. The majority of the risk for their products and supply chain impact was tied directly to the prospective cycle redesign.

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The EtO Response team believe without BioPhorums engagement these initial requirements for customers and risks to supply chain would still exist in the final proposal. One team member said "I hadn't been part of a group before that was able to make such an impact so quickly and aligned on a topic to try to get in front of decision makers and have an impact. I can't emphasise enough how big of a relief that is with respect to the amount of work and impact that that could have had and risks it could have increased with regard to the availability of products. " ?

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What wonderful words to hear as this underpins the very heart of what BioPhorum is about for the Supply Resilience Phorum. The involvement and the collaboration across functions teams, whether it's the sterilisation companies we worked with or the Biomanufacturers and suppliers in the team, they are all to be thanked for their contribution to this huge industry achievement. It was a pleasure working with you all and I am incredibly grateful to have been part of the journey to change.

Case study from one of these team members is coming soon!

Ciéra