Per- and Poly-fluoroalkyl substance (PFAS) exposure, emissions, and end of life management in the healthcare sector

Expected Impact:This IHI JU topic will enable and directly contribute to the EU health priorities, initiatives, and policies. Healthcare products containing PFAS are often essential for the health of citizens in Europe and worldwide. The proposed IHI JU topic would strengthen collaboration between healthcare system stakeholders to reduce emissions of, and exposure to PFAS, evaluate alternatives and therefore, contribute to the EU Chemicals Strategy for Sustainability of the EU Green Deal.

The action under this topic is expected to achieve the following impacts:

• contribute to IHI JU SRIA objectives, driving cross-sectoral health innovation for a competitive European health industry. Contribute to the objectives of the Industrial Strategy for Europe and Pharmaceutical Strategy for Europe;
• understanding human health and environmental risks from PFAS in healthcare from a life cycle perspective, i.e. mapping where PFAS is introduced in the healthcare industry and removal, where possible;
• manage PFAS risks with novel mitigation measures, including safe disposal, reuse, and recycling;
• develop methodologies and solutions for PFAS replacement that meet regulatory requirements without compromising efficacy, quality, safety, or environmental performance;
• position the EU as a leader in safe, sustainable PFAS alternatives through industry-academia collaboration; foster medicine supply in the EU, avoid non-EU dependencies, and keep R&D activities in Europe for active substances to address societal and political needs;
• strengthen stakeholder collaboration to reduce emissions and exposure until alternatives are found;
• share industry knowledge and best practices to inform future PFAS policy;
• improve business planning certainty for medical technology manufacturers, ensuring long-term sustainability and patient access.

Possible target groups: medical technology and medicines manufacturers and their supply chains, stakeholders involved in regulatory approval process (i.e., notified bodies, policy makers); waste management companies; hospitals and other healthcare settings and providers.

Expected Outcome:Per- and Poly-fluoroalkyl substances (PFAS) are a broad range of materials which have many uses within the scope of healthcare products, including as components of medicines, vaccines, medical devices, and diagnostics. These substances are currently critical to product quality, safety, and efficacy and essential to their manufacture and safe storage. PFAS make up a large group of persistent anthropogenic chemicals which are difficult to degrade and/or dispose of in an environmentally respectful manner. This IHI topic prioritises phasing-out PFAS of concern (specified below) as much as possible by using alternatives that maintain at least the same level of patient safety and product performance. Additionally, where it is not feasible to replace the use of PFAS, e.g. for technical or toxicological reasons, applicants should investigate how their use can be minimised / adequately controlled with respect to environmental exposure. The current knowledge needed to address these challenges is fragmented and incomplete.

The action under this topic must contribute to all the following outcomes:

• replace PFAS: new environmentally sustainable materials as alternatives to PFAS that maintain patient safety are developed for the benefit of the healthcare industry and the citizens;
• reduce / re-use PFAS: improved usage of PFAS materials and minimised exposure is achieved for the benefit of the environment and therefore citizens and society;
• a mapping of the types and applications of PFAS throughout the supply chain is available for healthcare technologies and products, including collaborating with upstream suppliers;
• a database of alternatives to PFAS is available;
• new disposal processes of PFAS are available for the benefit of the environment and therefore citizens and society.

Scope:To replace PFAS in medical technologies without risking human health, input from supply chain actors, scientists, and engineers is crucial. This includes assessing material availability, feasibility, and testing. Where current technology falls short, understanding PFAS environmental exposure and mitigation must improve. Standardised testing protocols and quantification methodologies are needed to measure exposure accurately. Effective mitigation requires knowledge of exposure routes and environmentally sensitive disposal methods. A scientific, data-driven approach that aligns with the safe and sustainable by design (SSbD1) framework is essential for lifecycle exposure management and ensuring alternative materials are safe and effective. Collaboration among scientists, policymakers, regulators, healthcare providers, chemical manufacturers, patient groups and trade associations and waste managers is vital to address technical, legal, and practical considerations. Proper scientific assessment of alternatives is necessary to maintain safety and quality.

The key challenges in the field include:

• obtaining information on PFAS uses in healthcare due to a complex global supply chain and limited data sharing;
• many specific use requirements and potential exposure routes exist due to the ubiquitous nature of PFAS use in the healthcare sector, including in production equipment, consumables, packaging, delivery devices, medical devices, complex machinery and cleaning agents;
• identifying alternatives for high-performing PFAS like polytetrafluoroethylene (PTFE) while ensuring product quality and safety;
• end-of-life management of healthcare products is underdeveloped, with inconsistent approaches to multi-component waste management;
• current wastewater treatment technologies struggle to eliminate complex PFAS;
• consideration of PFAS guidelines and regional policy disparities that may impact the global utility of this study.

The overall aim of this IHI JU topic is to provide world-leading, fully integrated and globally applicable solutions to address PFAS emission and exposure concerns, for example by substitution.

To fulfil the IHI JU’s topic aim, the applicant should address the following objectives:

Objective 1: Cross-sector solutions to develop PFAS alternatives

• Activities:

• Establish public-private collaboration to increase knowledge about PFAS applications and alternatives with a focus on prioritised PFAS chemicals listed in Table 1;
• Document key performance characteristics for PFAS used in healthcare products, manufacture, and testing;
• Exploit industry, academic and manufacturing collaborations, incorporating skills such as chemical synthesis, material sciences and analytics to develop PFAS alternatives;
• Test and validate PFAS alternatives generated by this project and, in addition, PFAS alternatives developed through research external to this project against performance characteristics and applications.

• Outputs:

• Reporting system to label PFAS-containing raw materials or medical device components;
• Technology on optimised materials capable of replacing PFAS in specific applications;
• Reliable data on alternative materials that could replace PFAS and corresponding design and performance characteristics;
• Technology for replacing PFAS chemicals in chemical synthesis or excipients in drug manufacturing;
• Replacements for trifluoroacetic acid (TFA) in chromatography and other analytical methods;
• Development of PFAS-free process aids (tubing, gaskets, fittings);
• Searchable database of validated PFAS alternatives.

Objective 2: Understanding PFAS in the medtech sector

• Activities:

• Identify and map PFAS types and applications in the medtech sector and align with those already identified in previous mappings of PFAS in the pharmaceutical industry;
• Develop a methodology for risk-benefit analysis of PFAS use;
• Establish public-private collaboration to gain knowledge about PFAS applications, alternatives, risks, and risk management options;
• Identify suppliers to raise awareness of PFAS alternatives and secure continuous supplies of raw materials and parts;
• Collect data on PFAS materials used in the supply chain, emissions, and mitigation options.

• Outputs:

• Increased knowledge of PFAS types and applications throughout the medtech and diagnostic process supply chain;
• Robust evaluation of PFAS alternatives;
• Enhanced stakeholder information sharing between medtech and the manufacturers of equipment, devices, disposables, PPE manufacturers and other activities identified by this mapping exercise.

Objective 3: Sector-specific solutions to reduce and reuse PFAS materials

• Activities:

• Map and calculate PFAS exposure from different categories of applications;
• Develop end-of-life management options across the sector in line with the SSbD framework;
• Evaluate and leverage PFAS removal technologies;
• Evaluation of sector specific circular economy principles for applications where removal is not yet possible;
• Evaluate sector-specific solutions to minimise PFAS exposure in partnership with healthcare facilities and waste management companies.

• Outputs:
• End-of-life management guidelines for PFAS components/chemicals, including circularity aspects and waste treatment;
• PFAS-specific removal, decontamination or environmentally responsible disposal technologies for TFA from wastewaters.

PFAS application

PFAS materials

Films/plastics (primary contact material) for final drug product sterile packaging:

• Cap or stopper coatings/liners
• Vial stoppers
• Syringe stoppers
• Seal linings
• Blister packs

ETFE (cap or stopper liners)

Other coatings (proprietary) e.g., OmniFlex stopper coatings

PTFE (coating for vial and syringe stoppers and seal linings)

Films/plastics (primary contact material) in manufacture and containment of drug intermediates (drug substance):

• Containers/films/bottles
• Single-use processing bags
• Single-use bioreactors
• Probes/inserts
• Sterile liquid filtration membranes
• Liquid filtration – virus clearance
• Vent and/or gas filtration (of bioreactors/carboys) – filter membranes
• Devices
• PTFE thread sealing tape in engineering systems
• Biopharma drug cryostorage bags and cell culture cryostorage bags
• Support filters (e.g., HEPA/HVAC air purification)

PVDF

PTFE

PTFE bottles

FEB bags/bottles

Films/plastics (primary contact material) for final drug product non-sterile packaging – blister packs

PCTFE

• Analytical HPLC methods
• Intermediate, raw material or ancillary material used in manufacture or purification of protein-based drugs

Use TFA in the mobile phase

PTFE filters

PTFE seals

Tubing and tube fittings (manufacturing engineering systems and transfer of drug material intermediates and final product) incl. gaskets and O-rings

Hardware systems (lined pipes, TFF cassette seals/components/solvent exchange systems/lined valves/gaskets

Pumps and components (diaphragm)

PVDF (tubings and fittings), PTFE, FKM (tubing/O-rings/gaskets), FEP, PFA

Heat and/or chemical resistant components, nonreactive coatings/insulation/lubricants/refrigerants

Additive of ABS

Additive in polycarbonates

ETFE: Ethylene tetrafluoroethylene; PTFE: Polytetrafluoroethylene; PVDF: Polyvinylidene fluoride; FEP: Fluorinated ethylene propylene; PCTFE: Polychlorotrifluoroethylene; TFA: Trifluoroacetic acid

Table adapted from EFPIA response to the ECHA consultation on the proposal for a universal ban on PFAS, Annex 3: ISPE_Industrial Use of Fluoropolymers & Fluoroelastomers in Pharmaceutical Manufacturing Facilities

Table 1 – Types of PFAS in use in healthcare industry. The project scope includes exploring alternatives to the PFAS materials listed here. (Table adapted from EFPIA response to the ECHA consultation on the proposal for a universal ban on PFAS, Annex 3: ISPE_Industrial Use of Fluoropolymers & Fluoro-Elastomers in Pharmaceutical Manufacturing Facilities).

In addition to the critical uses in Table 1, the following high-priority PFAS use cases in the healthcare sector are core to this project’s scope:

• production equipment and consumables (filters, tubing, seals/gaskets);
• primary and secondary packaging;
• medical devices (with and without patient contact) e.g. catheters, implants, needles, contact lenses; in vitro diagnostics (IVD), device handles;
• medical technology processing aids;
• complex machinery (diagnostic, imaging, research equipment);
• healthcare cleaning agents;
• healthcare consumables (surgical drapes, gowns, packaging, tapes, sutures, wound dressings, personal protective equipment (PPE));
• wastewater treatment.

The proposal should aim to collaborate with the following actors and initiatives:

• Industry associations and task forces with PFAS focus, such as EFPIA PFAS task force, Biophorum PFAS response team, Innovative Quality (Pharma) Consortium, American Chemical Society ACS) Green Chemistry Institute Pharmaceutical Roundtable, Pharmaceutical Supply Chain Initiative (PSCI), Animal Health Europe (AhE);
• IMI/IMI2 JU and IHI JU consortia (past and ongoing), including Prioritisation and Risk Evaluation of Medicines in the EnviRonment (PREMIER) and Intelligent Assessment of Pharmaceuticals in the Environment (iPiE) (on waste treatment), and the project resulting from IHI Call 4 topic 5 Safe & sustainable by design (SSbD) packaging and single use device solutions for healthcare products;
• Ongoing Horizon 2020 projects and future Horizon Europe calls comprising a PFAS focus;
• The Partnership for the Assessment of Risk from Chemicals (PARC);
• Regulators (to inform, align expectations, assess impact on regulatory pathways and ensure data and results produced will be fit-for-purpose); for the pharmaceutical and medical device industries including the European Medicines Agency (EMA), European Directorate for the Quality of Medicines & HealthCare (EDQM) & Official Medicines Control Laboratory (OMCL) network as well as additional national competent authorities. In the scope of this specific topic, engagement with the European Chemicals Agency (ECHA) should also be included.

Applicants should consider developing and implementing a strategy and plan to support relevant regulatory interactions.

1 https://publications.jrc.ec.europa.eu/repository/handle/JRC128591