Document KJ1k4BnB06xpKXvKxvED1KRxX

Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs Content 1 Summary ......................................................................................................................................... 2 2 Background...................................................................................................................................... 3 3 Chronology of the restricon .......................................................................................................... 5 3.1 PFOS......................................................................................................................................... 5 3.2 PFOA ........................................................................................................................................ 5 3.3 PFHxS ....................................................................................................................................... 5 3.4 PFAS ......................................................................................................................................... 5 4 PFAS in PharmaTech and Equipment of Sophiscated Chemical Analycs ..................................... 7 5 Content of the dra Restricon..................................................................................................... 11 6 Full ban .......................................................................................................................................... 12 7 Posions of Hamilton Bonaduz AG, Business Unit Process Analycs ........................................... 13 7.1 Role of PharmaTech and Sophiscated Laboratory Analycs in the Restricon Dra .......... 13 7.2 Abandonment of ,,essenal use" and specific risk assessment ............................................ 13 7.3 Fluoropolymere ,,of low concern" ......................................................................................... 14 7.4 Missing alternaves............................................................................................................... 16 7.5 Impact on PharmaTech and Equipment for Sophiscated Chemical Analycs ..................... 17 7.6 Emissions and emission prevenon ...................................................................................... 18 7.7 Assessments from outside the EU......................................................................................... 19 8 Literature reference....................................................................................................................... 21 12. September 2023 Author: Peter Pianegonda, Senior Quality Manager, Hamilton Bonaduz AG 1 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 1 Summary The European Chemical Agency (ECHA) has opened a comprehensive restricon procedure for per- and polyfluorinated alkyl substances, or PFAS. PFAS are extremely stable compounds that do not degrade under natural condions, accumulate in the environment and can enter the human body. Short-chain PFAS are classified as harmful to health; individual substances have already been banned in the EU under POP or REACH. The special properes have made long-chain PFAS important materials in various industries, the fluoropolymers and the fluoroelastomers. These include, for example, polytetrafluoroethylene, also known as Teflon. Fluoropolymers are also used in water-repellent texles, in firefighng foams, electronic equipment, in the automove industry, in medical products - and in plants for the producon of acve ingredients, medicines, vaccines or anbiocs, hereinaer referred to as PharmaTech, e.g. seals for aggressive chemicals as well as sensors, valves, pumps, pipes, tubes etc., for PharmaTech plants, which must be autoclavable (SIP) or cleaned inside the plant with strong alkali lye (CIP). Furthermore, fluoropolymers are used in equipment for sophiscated chemical analycs, e.g. to determine the threshold of traces of unwanted substances in a formulaon or in complex arcles. According to current knowledge, there are no alternave materials that could combine all the properes of fluoropolymers or fluoroelastomers. A ban would therefore have a significant impact on the producon of vital medicines, vaccines and anbiocs, even with the largest possible me exempon. In addion, it is important to ensure the availability of fluoropolymers/fluoroelastomers in the required quality. The first manufacturers of fluoropolymers/fluoroelastomers are withdrawing, reducing producon capacies or disconnuing them completely. This threatens new dependencies on manufacturers in China, India, etc., which may have lower standards in terms of environmental protecon than within the EU. This posion paper of Hamilton Bonaduz AG discusses the chemistry and properes of fluoropolymers/ fluoroelastomers, highlights their importance for pharmaceucal technology equipment and chemical analysis, and shows the consequences of a ban on these groups of substances for the supply of medicines, vaccines and anbiocs as well as for sophiscated chemical analyc equipment. The posions of Hamilton Bonaduz AG outline a more differenated, risk-based approach to PFAS to take into account paent welfare and safety as well as environmental and health protecon concerns. This includes allowing the connued use of low risk PFASs such as fluoropolymers and fluoroelastomers. This would also be welcome about other key European projects, as PFAS and fluoropolymers also play a decisive role in the manufacture of medical devices, semiconductors, hydrogen and batery, "green deal" technologies, among others. 2 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 2 Background PFAS are organic compounds with carbon chains of different lengths in which hydrogen atoms are replaced by fluorine atoms: fully (perfluorinated) or parally (polyfluorinated). According to the OECD definion (OCED, 2021), this includes almost all substances that contain at least one fully fluorinated methyl group (-CF3) or methylene group (-CF2-) without further hydrogen, chlorine, bromine or iodine atoms. This group of substances comprises more than 10,000 compounds. The OECD disnguishes between long-chain and short-chain PFAS. Short-chain PFASs include, for example, perfluorinated carboxylic and sulfonic acids (and corresponding precursor compounds) with fewer than seven and six perfluorinated carbon atoms, respecvely (Umelt Bundesamt DE, 2020). They are excreted more rapidly aer absorpon into the human and mammalian organism than those with longer carbon chains. In addion, numerous so-called precursors are in use, for example PFASs interrupted by ether bonds (Bundesinstut fr Risikobwertung, 2023). Among other things, these precursors can be converted into PFASs that are difficult to degrade. The best known and best studied are PFOS (perfluorooctane sulfonic acid or perfluorooctane sulfonates) and PFOA (perfluorooctanoic acid). The PFOS and PFOA are already banned under the POP resp REACH regulaon and are not under discussion in this paper, .i.e. they are dangerous to humans and the environment and should remain banned. The various PFAS have been used in many areas since about the 1950s. Among them are or were: - Automove industry - Building Materials - Chemical industry - Electrical and semiconductor industry - Energy industry - Firefighng foams - Household goods - Laboratory and analysis technology - Aerospace industry - Medical technology - Pescides - Pharmaceucal technology for the producon of drugs, vaccines and anbiocs. - Transportaon of chemical and pharmaceucal bulk goods - Texle impregnaon - Packaging - Waxes/lubricants - Detergents The decisive factors are the special properes of PFAS: water-, grease- and dirt-repellent, chemically and thermally stable. The very strong bond between carbon and fluorine can only be broken with a very high energy input. Under natural environmental condions, neither bioc processes (bacteria) nor abioc processes (water, air, light) can contribute to the degradaon of PFAS. Once the substances are 3 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs introduced into the environment, they disperse, for example, in water and sediment, but are not degraded (are persistent). Accordingly, they are referred to as "eternity chemicals." Some PFAS, especially long-chain PFAS, accumulate in organisms and along the food chain (bio-accumulave). Short-chain PFASs are excreted more rapidly but are highly mobile. They are not retained in the soil and therefore quickly reach groundwater. Due to their low adsorpon potenal, short-chain PFASs can hardly be removed from water during treatment. In addion, short-chain PFAS are taken up and stored by plants, thus entering the food cycle and ulmately the human body. In humans, short-chain PFASs such as PFOA bind to proteins in the blood, liver and kidney. Decreased immune response to vaccinaons and increased cholesterol levels are cited as health effects. In 2020, the European Food Safety Authority (EFSA) set a new threshold for the main PFASs that accumulate in the human body (EFSA Panel on Contaminants in the Food Chain, 2020). This is 4.4 nanograms per kilogram of body weight per week. It is known from animal studies that many PFASs damage the liver and have a developmental toxic effect. However, they do not directly alter the genec material and in animal studies only have a carcinogenic effect at doses above those ingested by humans via food (Bundesinstut fr Risikobwertung, 2023). Parcularly crical is the transfer from mother to child during pregnancy and lactaon. However, only limited toxicological data are available on short-chain PFAS (Bundesinstut fr Risikobwertung, 2023). 4 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 3 Chronology of the restriction 3.1 PFOS In October 2006, the European Parliament decided to restrict the use of PFOS to a few areas of applicaon. The corresponding Direcve 2006/122/EC regulates the "approximation of the laws, regulations and administrative provisions of the Member States relating to restrictions on the marketing and use of certain dangerous substances and preparations (perfluorooctane sulfonates)" (Europische Union, 2006). On June 20, Regulaon (EU) 2019/1021 on "persistent organic pollutants" entered into force in a new version, the so-called "POP Regulaon" (EUR-Lex, 2019). 3.2 PFOA Under the European Chemicals Regulaon REACH, PFOA was idenfied as a so-called chemical of very high concern in 2013 and added to the REACH candidate list (Umwelt Bundesamt, 2017). Subsequently, the regulaons were transferred to the POP Regulaon1. Since July 2020, PFOA may no longer be manufactured and placed on the market. Delegated Regulaon (EU) 2020/784 "concerning the intake of perfluorooctanoic acid (PFOA), its salts and PFOA precursors" sets the upper limit in substances, mixtures or arcles at 0.025 mg/kg, for PFOA precursors at 1 mg/kg (EUR-Lex, 2020). 3.3 PFHxS Perfluorohexane sulfonic acid (PFHxS) was included in the Candidate List of substances of very high concern for Authorisaon (REACH) in 2017. PFHxS has been used, for example, in fire fighng foams, texle impregnaon, cleaning agents and detergents, and in the manufacture of semiconductors (Persistent Organic Pollutants Review Commitee., 2018). PFHxS is one of the most commonly detected PFAS in human blood and has a very long half-life in humans of 8.5 years (range 2.2 -27 years). Called effects on liver, serum lipids, cholesterol, thyroid hormones and nervous system development (Persistent Organic Pollutants Review Commitee., 2018). 2022 are PFHxS has been included in Annex A of the Stockholm Convenon. In Switzerland, the producon, placing on the market and use has been banned since October 1, 2022. In addion, the markeng, producon and use of perfluorinated carboxylic acids with nine to fourteen carbon atoms (PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA) have been restricted since February 25, 2023. Several other PFAS, such as perfluorobutanesulfonic acid and "GenX" (ammonium 2,3,3,3tetrafluoro-2-propanoate), have already been idenfied as Substances of Very High Concern (SVHC) under REACH and included on the associated SVHC list with the aim of substung them as well (Bundesministerium fr Umwelt, Naturschutz, nukleare Sicherheit und Verbraucherschutz, 2023). 3.4 PFAS Whereas up to now mainly those PFAS were regulated that were detected in the environment in the highest concentraons and whose effects on the environment or human health could be jusfied, the planned procedure covers the enre group with about 10,000 substances (Bundesministerium fr Umwelt, Naturschutz, nukleare Sicherheit und Verbraucherschutz, 2023). 5 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs In its "Chemicals Strategy for Sustainability - Towards a Pollutant-Free Environment" (European Commission, 2020), the EU Commission outlined in October 2020 that PFAS require "special attention" due to the high number of contaminaons of soil and (drinking) water. Key iniaves therefore include "phasing out the use of the most harmful substances, including (...) persistent substances such as perand polyfluoroalkyl substances (PFAS), unless they are shown to be essential for the public good." Subsequently, the European Chemicals Agency (ECHA) has entered consultaon on a possible restricon of PFAS under REACH. At the request of the European Commission, a Member State or ECHA can iniate the restricon process if there is concern that a parcular substance may pose an unacceptable risk to human health or the environment. ECHA may also propose a restricon for arcles containing substances included in the list of substances subject to authorizaon (Annex XIV) (European Chemicals Agency, 2023). The date of intenon was published on July 15, 2021. The reason given by ECHA for the restricon is: PFAS are persistent substances or eventually transform into such, leading to irreversible environmental exposure and accumulation. Due to their water solubility and mobility, contamination of surface water, groundwater, drinking water and soil has occurred in the EU and worldwide and will continue. It has proven very difficult and extremely costly to remove PFAS after their release into the environment. In addition, some PFAS have been shown to be toxic and/or bio accumulative, both with respect to human health and the environment. If no action is taken, their concentrations will continue to increase; the toxic and environmentally damaging effects will be difficult to reverse (European Chemicals Agency, 2021). On July 19, 2021, the "Call for Evidence" was launched. The proposal dossier contains background informaon such as substance identy and jusficaons for the restricon. It provides informaon on the idenfied risks and alternaves for the substances and the costs and environmental and human health benefits of the restricon (European Chemicals Agency, 2021). Interested pares were able to submit comments and formulate arguments for exempons. The inial deadline for submission of the restricon dossier was mid-July 2022. In fact, authories from Germany, Denmark, the Netherlands, Norway and Sweden did not submit the dossier unl January 13, 2023. On March 22, the "Annex XV Restricon Report" was published. On this basis, the consultaon procedure was iniated, which ends on September 25, 2023. Subsequently, the opinion of the ECHA Commitees will be formed. It remains to be seen when the Commission will decide on the proposal and the restricon will enter into force. 6 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 4 PFAS in PharmaTech and Equipment of Sophisticated Chemical Analytics For years, fluoropolymers and fluoroelastomers have been used in PharmaTech (PharmaTech refers to all equipment that meets substances in the manufacture of drugs, API, vaccines and anbiocs). Likewise, the fluoropolymers and fluoroelastomers are needed for the equipment for cung edge chemical analysis to avoid any cross contaminaon with the substance to be analyzed. The special properes of the fluoropolymers and fluoroelastomers are decisive for the respecve field of applicaon (Banghard, 2023): - Chemically inert: PTFE, FKM, FFKM (see below) shows no reacon with the substances used in drug, vaccine and anbioc producon, as well as with the chemicals commonly used for cleaning and reprocessing; extremely resistant to all bases, many acids, alcohols, ketones, benzines, and others. - Thermally stable: The melng point of PTFE is 327C and can therefore be autoclaved (SIP) or used for in-line cleaning (CIP) of equipment without any problems. - Thermoplasc: Fluoropolymers and fluoroelastomers can be conformed or atached to complex geometries. - Biocompable: Fluoropolymers and fluoroelastomers pass biocompability tesng according to the applicable test from the DIN EN ISO 10993 series - Biostability: The material maintains its funcon over the enre period of use (producon of drugs, vaccines and anbiocs) even in aggressive cleaning agents. The following table shows typical fluoropolymers and fluoroelastomers used in PharmaTech and Chemical Analycs. The list does not claim to be complete: PVDF (Kynar, Solef); Polyvinylideifluorid Application in PharmaTech and Equipment of Sophisticated Chemical Analytics Biocompatible polymer with piezo-, ferro- and pyroelectric properties. Due to the hydrophobic surface, the material has high media purity and no leaching behavior. This is an important requirement for the use of these materials as materials in PharmaTech and equipment for chemical analyt- ics. High gamma radiation resistance, which is necessary for gamma sterili- zation. as coating: - Packagings - Hoses and tubes - Seals - Reaction vessels - Transport and storage tanks - Filtration plants - Pumps - Valves As design material: - Membrane in sensors - Luer locks and interfaces for tubing 7 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs PTFE/PFA (Teflon) Perfluoralkoxy, Polytetrafluorethylen Application in PharmaTech and Equipment of Sophisticated Chemical Analytics Biocompatible fluoropolymer with outstanding non-friction properties and chemical inertness. as coating: - Antiadhesive coating - inert coating of manufacturing vessels for Active Phar- maceutical Ingredients As design material: - Seals (e.g. Luer-Lock) - Heat shrinkable tubing - Insulation of wires, cables and electronic components - Filters, pumps, valves - seals for transport containers of pharmaceutical precursors and substances - high purity transport lines and containers - lubricants ECTFE (HALAR); Ethylen-Chlortrifluorethylen Application in PharmaTech and Equipment of Sophisticated Chemical Analytics Biocompatible polymer with high dielectric strength (high resistance combined with high application temperature). As design material: - Heat shrinkable tubing - Seals Insulation of wires, cables and electronic components - Filters, pumps, valves FEP or PFEP Tetrafluorethylen- Hexafluorpropylen- Copolymer Application in Phar- As design material: - Injection molded parts maTech and Equipment - Low temperature applications of Sophisticated Chemi- - Pipes cal Analytics - Valves - Pumps - Filters - Heat Exchangers As coating: - Lining of reaction vessels - Lining of transport vessels 8 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs PCTFE Polychlortrifluoreth- ylen Application in Phar- As design material: - Injection molded parts for maTech and Equipment - cryogenic applications of Sophisticated Chemi- - Pumps cal Analytics - compressors - Tubes - Valves - Filters - Heat Exchangers as coating: - Lining of reaction vessels - Lining of transport vessels FKM und FFKM Fluorkautschuk Application in PharmaTech and Equipment of Sophisticated Chemical Analytics As an elastic co- or terpolymer, particularly resistant to mineral oils and lubricants; stable to temperature, chemicals and radiation. Many compo- nents exhibit a particularly high shrinkage rate. Application range from ap- prox. -25 C to 200 C As design material: - Pumps, Valves, Filters - Metrology & Analytics Instruments - Insulations - Heat shrinkable hoses - Drive Belts - O-rings - spacers - gaskets - washers/sealing tapes - in mechanical seals and screw connections Furthermore, the following PFAS are used (Banghard, 2023; European Chemical Agency, 2023): PBSF (Perfluoro-1-Butansulfonylfluorid) PFA Perfloaroalkoxy MFA (Methyl-Fluoroacetat) mPTFE (modified PTFE) Other applicaons for fluoropolymers/fluoroelastomers in PharmaTech and Equipment of Sophiscated Chemical Analycs include (European Chemical Agency, 2023): Hoses and containers for transport of ultrapure media Technical fluids for cleaning and heat conducon Gases (sterilizaon) 9 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs packaging Coangs for opcal sensors Parcle filters In addion, it should be noted that PFAS can be found not only in products, but also - across industries - in producon processes and logiscs processes. In parcular, PFAS can be found in raw materials, auxiliary materials and operang supplies, as well as in lubricants, insulators, fixings, seals, molds, assembly aids or hoses. Those materials are essenal for funcon in applicaons in PharmaTech and Equipment of Sophiscated Chemical Analycs. 10 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 5 Content of the draft Restriction The dossier looks at a whole range of applicaons for PFAS. Among these are. - Food contact materials and packaging - metal coangs - ski waxes - medical devices - fluorine-containing gases - transport sector - Electronics and semiconductors - lubricants There are significant gaps in this list. Only the Use Sector "Transport (Annex E.2.10.)" is menoned in Annex XV and a generic remark regarding "Fluoropolymer applicaons" in the Use sector "Petroleum and mining" (Annex E.2.15.), which in no ways considers the following missing applicaons: - PharmaTech equipment for the producon of drugs, vaccines and anbiocs - Laboratory technology and analycs, which in turn are used for the research of drugs, vaccines and anbiocs, etc. - Equipment for sophiscated chemical analycs and for the development of analycal methods to prove compliance with threshold values, e.g. 25pbb for the 10,000 PFASs - Transport and storage containers, pipe systems for substances for storage and transport of pre- cursors for the producon of drugs, vaccines and anbiocs - Acve pharmaceucal substances (biopharmaceucals) All of these applicaons are at stake if fluoropolymers and fluoroelastomers are banned. The socio-economic impact cannot be quanfied in the me available; it will be exceponally enormous: - Shi of manufacturing of drugs, vaccines and anbiocs to countries with lower environmental standards. - As a consequence, stronger dependencies even at normal mes - Sever botlenecks in mes of crisis or disrupted supply chains - Relocaon of innovave companies outside Europe - Reinforcement of deindustrializaon - Loss of highly skilled work places. At Hamilton, appr. 3000 employees are at concerned. If PharmaTech products are significantly modified - as is the case with the replacement of fluoropolymers and the fluoroelastomers - they must go through a new approval process with the Drug Administraon in order to maintain GMP requirements. The dossier says nothing about their use in the pharma tech/biopharma industry. Drug manufacturing is highly regulated, so the enre process from idenficaon of a possible alternave to an approved product could take decades, with the risk that at 11 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs the end of this process, approval for the manufacture of drugs, vaccines and anbiocs is no longer given (European Chemical Agency, 2023). 6 Full ban Aer transion period (RO1) resp. The derogaon me (RO2) a full ban is in force. This includes - the producon, use and import of PFAS as well as - the placing on the market and the use of PFAS as a constuent of (another) substance, in mixtures or arcles, if certain limit values are exceeded. The dossier lists the proposed thresholds (European Chemical Agency, 2023): - 25 ppb for all PFAS with targeted PFAS analysis (except polymeric PFAS), - 250 ppb for the sum of PFAS with targeted PFAS analysis, with degradaon of precursors where appropriate, - 50 ppm for PFAS including polymeric PFAS. If the total fluorine content exceeds 50 mg/kg, the manufacturer, importer, or downstream user must provide evidence of measured fluorine as a PFAS or non-PFAS content to enforcement authories upon request. To detect such very low thresholds, new sophiscated chemical analycal methods using adequate laboratory equipment using materials with no cross-contaminaon, e.g. fluoropolymers and fluoroelastomers. Therefore also Equipment of Sophiscated Chemical Analycs needs to be excepted by the PFAS ban. 12 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 7 Positions of Hamilton Bonaduz AG, Business Unit Process Analytics PFASs exhibit unique properes. These include temperature resistance and dielectric strength, very good autoclavability, chemical resistance, sliding properes and excellent biocompability. The use of PFAS contributes significantly to the advanced and safe treatment of paents in various fields of applicaon. Here - and in other industrial areas - the enormous stability of the substances has undeniable advantages. In nature, it causes problems when crical PFASs accumulate and enter the human body. On one side benefit, on the other risk. Unl now, this weighing has been done on a case-by-case basis. Now an enre group of substances is to be restricted. This is understandable in that, in the past, banned substances were replaced without further ado by compounds that were no less dangerous but were not regulated, which ran counter to the actual objecve. Therefore, reducing overall emissions and further regulang the handling of chemicals is undoubtedly to be welcomed. The concerns are not directed at the dossier. However, the current approach ensures that substances that can be used safely will also be subject to a ban. These points will be outlined below. 7.1 Role of PharmaTech and Sophiscated Laboratory Analycs in the Restricon Dra In the dossier, an atempt has been made to idenfy as comprehensive an overview as possible of the various areas of applicaon of PFAS and to relate the restricon in each case to, among other things, emission savings, alternaves and (follow-up) costs. Aer weighing the pros and cons, plant protecon products, biocidal products and pharmaceucals have been excluded from the further procedure. But to manufacture pharmaceucals, you need adequate PharmaTech equipment and sophiscated chemical analycs using special laboratory equipment to do so. in comparison with crop protecon products, biocidal products and pharmaceucals, the role of Pharmatech equipment and chemical analycal equipment for people and society must be appreciated even more and disnguished more clearly from other industries. 7.2 Abandonment of ,,essenal use" and specific risk assessment In the past, products and applicaons have been examined to establish "essenal use." This covers products that are necessary for health or to maintain the safety and funcon of society or for which there are no technically and economically viable alternaves. The main objecve of the approval procedure under REACH is to replace substances that have parcularly concerning properes in the near term if it is technically feasible and economically viable to do so. Users of these substances may connue to use them over a certain period of me if they show that they can handle the substance without risk, or at least with a low level of risk, and there are no comparable alternaves (Bundesanstalt fr Arbeitsschutz und Arbeitsmedizin, 2021). A general restricon on 10,000 substances represents a departure from this principle. What is more, the burden of proof as to why the use of PFASs is considered essenal for society now lies with manufacturers and users. 13 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs The menon in REACH of "substances that have parcularly concerning properes" above relates to ecological risk criteria (including endocrine substances) as well as effects on human health (including CMR substances). Previous restricon processes have targeted precisely these types of substance for removal from circulaon or aimed to impose strict regulaons on handling them, as has already been done with a number of PFASs. What is happening now, on the other hand, is that restricons are being imposed on substances even if their effects on humans and nature can be controlled and there are sll no alternaves in sight. No specific risk is being invesgated. Instead of a general restricon, PFASs should be evaluated using a risk-based approach and their "essenal use" should be assessed. 7.3 Fluoropolymere ,,of low concern" There are different grades of PFASs. The properties of short-chain PFASs are different from those of long-chain fluoropolymers. Although they match the structural definition of a PFAS, they have very different physical, chemical, ecological and toxicological properties compared to other substances. Fluoropolymers make up their own family within the group of substances. The study by Henry et al. (Henry, et al., 2018), shows, among other things, that fluoropolymers are thermally, chemically, photochemically, hydrolytically, oxidatively and biologically stable. They contain practically no monomer and oligomer residues and have minimal or no leachable components. Fluoropolymers are practically insoluble in water and are not transported over long distances. With a molecular weight of over 100,000 Da, fluoropolymers cannot penetrate the cell membrane. Fluoropolymers are not bio accumulative, as demonstrated by toxicological studies of PTFE (acute and sub chronic systemic toxicity, irritation, sensitization, local toxicity upon implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation and thrombogenicity). Clinical studies on patients who have received permanently implanted cardiovascular medical devices containing PTFE show no chronic toxicity or carcinogenicity. The conclusion reached by Henry et al. (2018) is that fluoropolymers meet widely accepted assessment criteria for classification as "polymers of low concern" (PLCs) and that they are significantly different from other polymer and non-polymer PFASs and should therefore be considered separately for risk assessment or regulatory purposes. The OECD criteria for "fluoropolymers of low concern" (OECD Enviornment, 2008) include high molecular mass, low persistence, nonsignificant bioaccumulation, low toxicity and negligible exposure. The substances investigated in detail were PTFE, ETFE (ethylene tetrafluoroethylene), FEP (fluorinated ethylene propylene) and PFA (perfluoroalkoxy). Korzeniowski et al. (Korzeniowski, et al., 2022) have examined several fluoroplastics, fluoroelastomers and special fluoroplastics in more detail and have set out criteria for "polymers of low concern" in each case: - Composition - Molecular weight - Ionic character - Reactive functional groups - Low-molecular-weight leachable components 14 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs - Particle size - Structural composition - Elemental composition - Water and lipid solubility - Stability - Abiotic stability - Biotic stability - Thermal stability All the substances that were examined met the requirements for classification as "polymers of low concern". Including the four fluoropolymers from the previous study by Henry et al., a total of 18 fluoropolymers can thus be rated as "polymers of low concern." - PTFE - ETFE (ethylene tetrafluoroethylene) - FEP (fluorinated ethylene propylene) - PFA (perfluoroalkoxy) - PVDF (polyvinylidene fluoride) - PVDF-HFP copolymer (vinylidene fluoride hexafluoropropylene copolymer) - ECTFE (ethylene chlorotrifluoroethylene copolymer) - ECTFE (ethylene chlorotrifluoroethylene hexafluoroisobutylene terpolymer) - PCTFE (polychlorotrifluoroethylene) - FEVE (fluoroethylene vinyl ether copolymer) - EFEP (1-propene, 1,1,2,3,3,3-hexafluoro-, polymer with ethylene and 1,1,2,2-tetrafluoroeth- ylene) - CPT (1,1,1,2,2,3,3-heptafluoro-3-[(trifluoroethenyl)oxy]propane polymer with chlorotrifluoro- ethylene and tetrafluoroethylene) - THV (1-propene, 1,1,2,3,3,3-hexafluoro-, polymer with 1,1-difluoroethylene and tetrafluoro- ethylene) - Perfluoro(alkenyl vinyl)ether polymer - Sodium or potassium salts of perfluorosulfonic acid/TFE copolymer or perfluorocarboxylic acid/TFE copolymer - FEPM (tetrafluoroethylene propylene polymer) - FKM (1-propene, 1,1,2,3,3,3-hexafluoro-, polymer with 1,1-difluoroethylene copolymer and terpolymers) - FFKM (tetrafluoroethylene trifluoromethyl trifluorovinyl ether copolymer) These are chemically stable, non-toxic, non-bioavailable, non-water-soluble and non-mobile materials that do not have unwanted effects on the environment or human health. There is therefore an urgent need to proceed with the restricon process using scienfically based evidence and to remove families of substances that do not have the potenal to pose risks to humans or the environment. PTFE 15 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs has been parcularly well studied. It can be considered neither carcinogenic (Radulovic & Wojcinski, 2014) nor genotoxic (Radulovic & Wojcinski, 2014) or toxic for reproducon (Davis, Rothmann, Tan, & Thomas, 1993). Likewise, no effects on the immune system are known (Kim, et al., 2013). Skin exposure to PTFE has also been considered safe for a long me. This is evident, for example, in the use of PTFE needles for intravenous access (Smith, Bell, Fulton, Quine, & Morden, 1993). In atempts to use PTFE as a filler for dietary products, it was found that the material cannot be absorbed through the digesve tract (Naalovich, Naalovich, & Greenway, 2016). For parcle sizes larger than 20 m, the insoluble polymer cannot enter the bloodstream with reasonable certainty. It is therefore imperave that the restricon process be based on scienfic evidence and exclude substance families that do not pose a risk to humans or the environment. These are substance families that have been used safely in PharmaTech and chemical analycs for decades. Fluoropolymers "of low concern," which present no potenal risk to humans or the environment and are essenal for PharmaTech and chemical analycs, should be excluded from the restricon process. 7.4 Missing alternaves The restricon proposal considers the availability of technically and economically feasible alternaves to decide on exempons. In the dossier, applicaons to PharmaTech and chemical analycs are not listed, and there are no comparable substute materials for fluoropolymers and fluoroelastomers in prospect. And the likelihood is high that none will be found. This is explicitly confirmed in Anne XV, sector Petroleum and mining, "Fluoropolymer applicaons": In light of the sufficiently strong evidence pointing to the non-existence of technically and economically feasible alternatives at EiF, a derogation is proposed for Fluoropolymer applications. The restricon dossier focuses in parcular on persistence, or the long-lasng nature of PFASs. It should be assumed that any alternaves will share this property. This makes it even more unlikely that it will be possible to use them. A broader view is needed in this context. A restricon will affect medical technology directly, but also indirectly. PFASs can be found in auxiliary materials and working materials (such as lubricants) or in producon system components (such as seals and tubes). PFASs are used in the producon of semiconductors, which in turn are used in acve medical devices. In those areas too, fundamental changes are expected that will impact on companies: they will need to invest in new assets and systems, which they will then need to integrate and validate in compliance with the regulatory framework. In view of the high degree of uncertainty as to whether alternave substances with comparable properes can be found at all, the use of non-crical, essenal PFASs such as fluoropolymers must connue to be authorized beyond the 12-year period. Manufacturers of PharmaTech and equipment for chemical analycs urgently need legal certainty in this area. 16 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 7.5 Impact on PharmaTech and Equipment for Sophiscated Chemical Analycs As there is neither reporng nor labelling obligaon for PFAS materials in place, the industry as a downstream user needs to conduct complex invesgaon across the supply chain to idenfy the components impacted by the PFAS restricon to have a complete overview. The current proposal bans the use of PFAS in PharmaTech and other applicaons in pharmaceucal producon processes where substuon has to be assessed individually. Without equipment containing fluoropolymers and fluoroelastomers, EU manufacturing plants cannot operate. Manufacturing processes are qualified and validated processes covered by sectorial legislaons and global markeng authorizaons. These are severely impacted by the restricon. The regulatory oversight over equipment and the validaon for operaon is necessary to assure a consistently manufactured product; one that had been proven to be safe and effecve during clinical development. The manufacturing equipment must demonstrate that it will not introduce an unacceptable impurity into the product authorized for market. Concerns exist around the meframe for idenficaon, tesng and validang alternaves for components that need to be replaced, in the rare case that alternaves are feasible and available. A ban of these substances or even a me-limited derogaon will create a serious compeve disadvantage for the EU in global manufacturing. In pracce, such a ban would impact all human and veterinary medicinal products including biopharmaceucals, vaccines and anbiocs and would seriously affect medicines availability in the longer term. This is another reason why an exempon for fluoropolymers and fluoroelastomers must be thought in a wider scope. Without supply chains that connue to funcon, socially relevant industries such as pharma tech will not be able to survive. Those PFASs that are absolutely necessary for the producon of polymers (emulsifiers, etc.) must not be forgoten. To ban these and other starng materials would be tantamount to a de facto ban on the producon of fluoropolymers. The example of Chemours shows that emissions-neutral producon is possible: the company is invesng 75 million euros in its plant in Dordrecht (Netherlands) to reduce PFAS emissions by 99 percent by 2030 compared to the 2017 fiscal year. Above all, it is important to keep and strengthen these supply chains in the EU. In recent years, it has become painfully clear how dependent the European family of countries is on non-European suppliers. For example, the European Chips Act is a direct result of this realizaon. In 2023, the European Commission published a study on the extent to which key industries have unrestricted access to important raw materials. Fluoropolymers are among the processed materials menoned, for example in energy technology, robocs and chip manufacturing. One conclusion is that the EU is heavily dependent on third countries, and China in parcular, at various stages of the value chain. An allover PFAS ban runs counter to all well-intenoned efforts. Instead of bringing value creaon back to Europe, dependence on non-European manufacturers is growing. 17 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 7.6 Emissions and emission prevenon The proposed restricon aims to reduce the discharge of PFASs into the environment to as close to zero as possible. To this end, it looks at manufacture, use and disposal. For medical technology, a 400% increase in emissions is expected between 2025 and 2050. The largest component in the dossier is fluorinated gases, followed by fluoropolymers and non-polymer PFASs (including precursors of perfluoroalkyl acids, PFAAs). In the case of polymer PFASs, it is assumed that 1% of the PFASs used are released. For fluorinated gases, discharge percentages of between 10% (gases used in industrial processes for medical applicaons) and 100% (e.g. propellants, anesthecs, contrast agents) are used. It remains to be seen whether this forecast is completely accurate. However, it should be noted that significant contribuons to emissions reducons are possible even at the manufacturing stage for PFASs. Medical technology, the PharmaTech and equipment for chemical analycs procures these materials, but does not manufacture them. With a uniform European standard, it would be possible to achieve the highest level of "containing" even at the manufacturing stage. Steps have already been taken to achieve this (in the Netherlands, for example). Pharmatech and equipment for chemical analycs are intended for professional use by specialists in the respecve industry and research. This also means that the products follow a ghtly defined flow of goods (manufacturer - user - disposer) and that uncontrolled discharge of materials containing PFAS into the environment is virtually impossible. The requirements for the disposal of waste from pharmaceucal producon are already strict, both from a hygienic point of view and for environmental reasons. In the meanme, the disposal of fluoropolymers has also been scienfically invesgated38. To show that PTFE can be converted almost completely and in order to establish the possible formaon of lowmolecular-weight PFASs, the incineraon of PTFE was invesgated under typical waste disposal condions at the BRENDA pilot plant at the Karlsruhe Instute of Technology (KIT). Within the methodological limits, no stascally significant indicaons were found that any of the detected PFASs were produced in the incineraon of PTFE. For this reason, the municipal incineraon of PTFE using the best available technologies is not a significant source of the PFASs invesgated and should be considered an acceptable form of waste treatment. Raw and starng materials, intermediates, auxiliaries, equipment, and consumables required for manufacture of pharmaceucals and medical devices should also be exempt, as these are handled under controlled condions and without them, manufacturing of medicinal products and devices is impossible. Any emission of industrial manufacturing into environments is controlled and regulated via other exisng EU legislaon. Any risk posed by emissions of these substances can be further migated through waste management or circularity regulaons. Brand new research indicates novel approach to destroy PFAS based on kinec mechanical forces (Gobindlal, Shields, Whitehill, Weber, & Sperry, 2023). 18 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs 7.7 Assessments from outside the EU The fact that PFAS emissions need to be reduced can be seen as a global consensus. However, countries outside the EU have different and in some areas much more nuanced processes, especially for fluoropolymers. Australia In 2017, an Expert Health Panel for PFASs was set up in Australia to advise the Australian government on the available knowledge, including important internaonal reports and opinions from the public and other stakeholders. The panel concluded that although the scienfic evidence is limited, the previous reviews and research have provided consistent reports of a connecon with various health effects. The Environmental Health Standing Commitee (enHealth) has published guidelines intended to help assess public health risks. As a precauonary measure, enHealth recommends that exposure to PFASs be minimized as far as possible while further invesgaons into the potenal health effects are carried out40. The declaraons contain informaon on the possible health effects of exposure to PFOS, PFOA and PFHxS. With regard to PTFE, it states that although the polymer is part of the PFAS family, it has a different structure and therefore different properes to PFOA, PFOS or PFHxS: - PTFE is not water soluble - PFOA, PFOS and PFHxS are water soluble. - PTFE is too large and too insoluble to be absorbed by organisms - PFOA, PFOS and PFHxS are easily absorbed by organisms. - PTFE is not toxic to animals - PFOA, PFOS and PFHxS have a range of toxic effects in animals. These differences mean that the regulatory authories do not consider PTFE to be a chemical of concern for human health or the environment41. United Kingdom In 2021, the UK government set the first restricons to be introduced under the new chemicals regulaon system, the UK REACH system42. A restricon is introduced when there is evidence of an unacceptable risk to human health and the environment. The review is carried out by the Health & Safety Execuve (HSE) with the support of the Environment Agency (EA). Those bodies also examine the risk from PFASs. In the UK's most comprehensive analysis of these chemicals to date, HSE has idenfied the most common and harmful uses of PFASs and demonstrated what measures could be taken to control and deal with them. According to the Regulatory Management Opon Analysis (RMOA), restricons do not need to be applied to low hazard groups or low risk uses. The "low hazard groups" category includes fluoroplascs and fluoroelastomers. These could be highlighted as derogaons from a proposed restricon (Health and Safety Execuve, 2023). 19 / 23 Position of Hamilton Bonaduz AG, Business Unit Process Analytics on the draft for a restriction of PFASs USA The U.S. Environmental Protecon Agency (EPA) published an Advance Noce of Proposed Rulemaking (ANPRM) in April 2023. It focuses on the potenal idenficaon of hazardous material discharges of PFASs as part of the Comprehensive Environmental Response, Compensaon, and Liability Act (CERCLA) (United States Enviromental Protecon Agency, 2023). Dabei sollen die neuesten wissenschaliche Erkenntnisse und Informaonen zu PFAS gesammelt werden. Der Schrit folgt dem Regelungsvorschlag aus dem September 2022 zur Einstufung von PFOA und PFOS als gefhrliche Stoffe. aims to gather the latest scienfic findings and informaon on PFASs. This step follows the regulatory proposal from September 2022 on classifying PFOA and PFOS as hazardous substances. The EPA's roadmap sets out the concrete steps to be taken by 2024 (Unites States Enviormental Protecon Agency, 2021). It defines three pillars: Research (investments in research and development and innovaon to gain a beter understanding of PFASs and their impact on health and the environment), restrict (comprehensive approach to proacvely prevent PFASs from reaching quanes in the air, soil and water that are crical for humans and the environment) and remediate (expanded and accelerated remediaon of PFAS contaminaon to protect human health and ecosystems). The producon and processing of PFASs, metal finishing, airports, pulp and paper, landfill sites and the manufacture of texles and carpets are all named as key industries with significant documented emissions. Under "restrict," the objecves described are as follows: - To use and harmonize all the available legal measures to control and prevent PFAS emissions and minimize the exposure of consumers and industry to PFASs. - To entrench the responsibility of manufacturers, processors, dealers, importers, industry and other important users for liming PFAS discharge and for dealing with risks. - To set up programs to reduce PFAS use and discharge. - To avoid or minimize PFAS discharges and emissions in all communies. The EPA also plans to review past PFAS regulatory decisions. In this context, addional noficaon obligaons may be imposed so that it can examine PFASs before they are used in a new, potenally quesonable way. Outside the EU, countries are taking a nuanced atude and allowing the use of fluoropoly- mers and fluoroelastomers to connue in some areas. 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