Document 6wqMxwNGJMDgGLq9rLO1Odr1g

The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Gambica laboratory technology sector Report No.2023-0695 Rev. 0 Project No. REG50040-001 Rev. Description Prepared by Controlled by Approved by Date 0 Issue 1 Antony Lord Emily Tyrwhitt Jones Paul Goodman 23rd August 2023 RINA Tech UK Limited I 1 Springfield Drive, Leatherhead, Surrey, KT22 7AJ, United Kingdom I P. @rina.org I www.rina.org Company No. 07419599 Registered in England and Wales All rights, including translation, reserved. No part of this document may be disclosed to any third party without written consent of RINA Tech UK Limited The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Note on report approval. The persons identified above have signed off each stage of this report in accordance with RINA's BMS/QA procedure. Disclaimer Whilst great care has been taken in the compilation of this report, use of the information contained herein is entirely at the risk of the client or recipient. It does not constitute legal advice and should not be relied upon as such. To the extent permitted by law, RINA Tech UK Limited ("RINA") accepts no responsibility or liability for loss or damage arising out of acting upon or refraining from action as a result of any material in this publication. FEEDBACK QUESTIONNAIRE As a valued client your feedback on this project is important to us. We would be grateful if you could spare a few minutes to complete the questionnaire found via the QR code or hyperlink below: Link: RINA Questionnaire Thank you. Issue and Revision Record Rev. 0 Description Issue 1 Prepared by Antony Lord Controlled by Emily Tyrwhitt Jones Approved by Paul Goodman Date 23/08/2023 Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 0 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment EXECUTIVE SUMMARY RINA Tech UK Limited (RINA) was requested by the laboratory sector of the trade association GAMBICA1 to prepare an impact assessment report in support of the stakeholder engagement currently being undertaken for Per- and Polyfluoroalkyl substances (PFAS) under the REACH restriction proposal (ECHA, 2023)2 (hereafter the Restriction). GAMBICA is the Trade Association for Instrumentation, Control, Automation and Laboratory Technology. GAMBICA laboratory sector member products include clean air equipment, biological decontamination equipment, and the use of oxidising chemicals used in professional settings such as the semiconductor industry, healthcare, life science (including pharmaceuticals and biopharma production and research facilities) and testing and research laboratories. The filters must meet the technical performance classification requirements set out in EN 1822-1:2019 (CEN EN1822-1:2019, 2022) or EN 13408-2:2018 (ISO/TC 198, 2018). These applications require PFAS to produce and support contamination free work environments some of which must conform to EU regulations such as Commission Directive (EU) 2017/1572 regulating the production of human medicinal products. Oxidising chemicals are used to decontaminate the surfaces of these critical facilities, and in some cases the chemicals can be used inside equipment which incorporates PFAS tubing and associated connectors. The PFAS containing polymers used are the only technically suitable materials, with alternatives affecting the ability to conduct bio-decontamination. A derogation of 6 .5 years after entryinto-force (EiF) is proposed for biological decontamination equipment to allow alternatives to be identified and qualified. The equipment described in this report require a unique combination or properties including chemical resistance, hydrophobicity, gas permeability, liquid impermeability, and non-catalytic activity, which at present, are only available using PFAS materials. There is a need to store and transport oxidising chemicals safely such that they can be used in the biological decontamination equipment. The transportation of such chemicals needs to be in accordance with the European Classification, Labelling and Packaging (CLP) Regulation (1272/2008) and the agreement concerning the International Carriage of Dangerous Goods by Road (ADR). PFAS is used as a safety feature in the vent which require gas permeability, liquid impermeability, chemical resistance, and non-catalytic activity which is only offered by PFAS membranes. Whilst textiles for filtration and separation media are included in the Restriction under technical textiles, laboratory sector member products incorporate media that are not textiles and so these would fall outside of the scope of the proposed derogation 5.e. The PFAS containing polymers used in these filtration and separation media have a unique combination of physical and chemical properties which PFAS-free alternatives such as polyurethane are not able to offer. These properties include water repellence, low pore size which retains microbes, high chemical resistance, permeability to air and impermeability to water. Field replacement is not technically possible for the filters currently used and the entire equipment would need to be scrapped and new equipment designed and manufactured. It is not possible for replacements to be designed and manufactured and currently installed equipment replaced in less than 13.5 years. The equipment is used in EU regulated applications and therefore, the exposure to humans and the environment during the service life is negligible. An estimated 490kg of fluoropolymers are used in clean air equipment (not including clean rooms) used in the Life Science sector, equating to less than 0.0015 ______ 1 GAMBICA | Homepage 2 Annex XV reporting format 040615 (europa.eu) Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 1 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment % of the annual fluoropolymer production. The end-of-life phase of the equipment is controlled under EU regulations, with parts containing the PFAS incinerated under the EU rules applicable to hazardous waste. Therefore, there is negligible exposure to humans or the environment at end-of-life. Time is required to replace affected parts, once PFAS free alternative materials become available. GAMBICA requests the following derogations to cover filtration and biological decontamination equipment. This report substantiates the need for these requested derogations. GAMBICA's recommendations for the wording of requested derogations 1. By way of derogation, paragraphs 1 and 2 shall not apply to textiles and other membranes for use in filtration and separation media used in high performance air and liquid applications in industrial or professional settings that require a combination of water and oil repellence or any combination of water repellence and chemical resistance, selective permeability, and microbiological retention until 13.5 years after EiF. 2. By way of derogation, paragraphs 1 and 2 shall not apply to oxidizing liquid tubing and associated connectors in biological decontamination equipment until 6.5 years after EiF. 3. By way of derogation, paragraphs 1 and 2 shall not apply to maintenance and repair of highperformance filtration and separation equipment and biological decontamination equipment put on the market before [18 months after EiF] and for which no drop-in alternative exists until endof-life. These suggested derogation texts ensure that: 1. Non textile high performance filtration membranes are unambiguously within the scope of a 13.5-year derogation. 2. Biological decontamination equipment (not currently included in Table 9 of the Restriction) is within the scope of a 6.5-year derogation. 3. Spare parts may be used to allow existing equipment to continue in service until end-of-life of the existing equipment. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 2 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment TABLE OF CONTENTS EXECUTIVE SUMMARY 1 INTRODUCTION 1.1 Profile of GAMBICA 2 DESCRIPTION OF THE EQUIPMENT 2.1 Clean air equipment 2.1.1 High volume air filters 2.1.2 Low volume air filters 2.2 Liquid filters 2.3 Bio decontamination equipment 2.4 Bottle vents 3 DESCRIPTION OF THE END USE EQUIPMENT 3.1 Clean air equipment 3.2 Bio-decontamination systems 4 TECHNICAL AND QUALFICATION REQUIREMENTS 4.1 High volume air filters 4.2 Low volume air filter membranes 4.3 Liquid filters 4.4 Decontamination equipment tubing and connector. 4.5 Chemical bottle vents 5 REDESIGN QUALIFICATION AND REPLACEMENT TIMELINES 6 SOCIO ECONOMIC IMPACT ASSESSMENT 6.1 Importance to society 6.2 Economic impacts 7 PFAS EMISSIONS FROM USE OF THE EQUIPMENT 8 ENVIRONMENTAL AND END-OF-LIFE AND CONSIDERATIONS 9 PROPOSED DEROGATIONS 9.1 Suggested amendment to derogation 5.e. 9.1.1 Textiles and other membranes 9.1.2 Requirement for a combination of additional properties 9.2 New derogation for biological decontamination equipment 9.3 New derogation for spare parts 10 REFERENCES Page 1 6 6 7 7 7 8 9 10 11 12 12 14 15 15 16 18 18 20 20 21 22 22 23 23 25 25 25 26 26 26 27 Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 3 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment LIST OF TABLES Table 1: PFAS components and end equipment they are used in. 7 Table 2: Property requirements of high-volume air filter membrane materials. 15 Table 3: Pressure drop (frictional air resistance) across filter types. 16 Table 4: Property requirements of low volume air filter membrane materials. 17 Table 5: Comparison of polypropylene and PVDF filter performance 18 Table 6: Compatibility of tubing and associated connector PFAS free alternatives 19 Table 7: Timeline to test and validate PFAS-free materials 21 Table 8: Current consumption by filter material type. 23 Table 9:Estimated weight of PFAS polymer used per year 24 LIST OF FIGURES Figure 2-1 Example of a high-volume air filter 8 Figure 2-2 Close up of high-volume air filter 8 Figure 2-3 Example of Low volume air filters 9 Figure 2-4 Example of the liquid filter 9 Figure 2-5 Example showing tubing installation in equipment. 10 Figure 2-6 Example showing tubing from storage bottle into vaporiser hotplate. 10 Figure 2-7 Bottle cap Type A 11 Figure 2-8 Bottle cap Type B 11 Figure 3-1 Microbiological Safety Cabinet 12 Figure 3-2 Laminar Airflow unit (LAF) 13 Figure 4-1 Selective permeability property of the air filter 17 Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 4 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment ADR BMS CLP EEA EiF EPDM ePTFE ETFE EU GF HEPA MCE NBR PEEK PES PFAS PP PTFE PVC PVDF QA QC REACH RABS SDS TPE Tygon UK ULPA ABBREVIATIONS AND ACRONYMS International Carriage of Dangerous Goods by Road Business Management System Classification, Labelling and Packaging Regulation European Economic Area Entry into Force Ethylene propylene diene monomer Expanded PTFE Poly(ethene-co-tetrafluoroethene) European Union Glass Fibre High Efficiency Particulate Air filters Mixed Cellulose Ester Nitrile butadiene rubber Polyether ether ketone Poly Ether Sulfone Per and Perfluoroalkyl Substances Polypropylene Polytetrafluoroethylene Polyvinyl chloride Polyvinylidene fluoride Quality Assurance Quality Control Registration, Evaluation, Authorisation of Chemicals Regulation Restricted Access Barrier System Safety Datasheet Thermoplastic elastomer PVC polymer specialist grade United Kingdom Ultra-low penetration air filters Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 5 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 1 INTRODUCTION RINA Tech UK Limited (RINA) was requested by GAMBICA to gather information to support the stakeholder engagement currently being undertaken for Per- and Polyfluoroalkyl substances (PFAS) under the REACH restriction proposal3 (the Restriction) relating to filtration and biological decontamination equipment. Owing to the unique combination of essential physical and chemical properties required in the equipment which currently only PFAS materials offer, derogations are proposed with supporting technical and socio-economic reasons as outlined in this report. 1.1 Profile of GAMBICA GAMBICA is the UK Association for manufacturers of Instrumentation, Control, Automation and Laboratory equipment which serves the following industrial sectors: Process Instrumentation and Control Factory automation Test and Measurement Laboratory Technology GAMBICA's mission statement is to strive to increase knowledge, improve best practice, develop, and promote policy, standards, and regulation, remove barriers, and maximise the market potential in these industrial sectors. The membership encompasses more than 240 organisations employing 1,200 employees comprising 75 % of the industry sectors. The total market sector represented is valued at 4.5 billion. GAMBICA4 is itself a member of Orgalim, a trade association representing Europe's technology industries that together comprise the EU`s largest manufacturing sector of 770,000 innovative companies across the engineering, electrical engineering, electronics, and metal technology sectors with a combined annual turnover of 2,906 billion, manufacturing one-third of all European exports and providing 11.19 million direct jobs. ______ 3 Annex XV reporting format 040615 (europa.eu) 4Additional information on GAMBICA and its mission and membership can be found on their website: https://www.gambica.org.uk/about-us.html Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 6 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 2 DESCRIPTION OF THE EQUIPMENT In order to fulfil their intended function, PFAS components, as shown in Table 1 below, are required and discussed in more detail in the following sections. Table 1: PFAS components and end equipment they are used in. Component High volume air filters Low volume air filters Liquid filters Oxidising solution transport & storage bottle pressure vent Tubing for accurate dispensing of oxidising chemicals onto hot plates End products Clean air equipment that provide a controlled work environment clean air equipment that provide a controlled work environment Microbiological contamination free liquid Bottles Decontamination equipment PFAS Expanded PTFE (ePTFE) ePTFE Polyvinylidene fluoride (PVDF) ePTFE PTFE with poly(ethene-co-tetrafluoroethene) (ETFE) connector 2.1 Clean air equipment Clean air equipment describes equipment used to create an environment which has extremely low particulates as defined by ISO 14644-1, and zero viable organisms. The following are some of the most common equipment in the class: Microbiological safety cabinets as defined by EN12469:2000 Laminar Airflow Units Pharmaceutical Isolators Restricted Access Barrier Systems (RABS) 2.1.1 High volume air filters Clean air equipment is used for a variety of applications, including, critically, in the pharmaceutical industry concerning workplace air quality for the preparation of sterile medicinal products (European Commission, 2022)5. These are defined in Annex 1 of the legislation under Manufacture of Sterile Medicinal Products" 4.27 Table 1 and 4.31 Table 2. The ePTFE air filters used in the clean air equipment to achieve this high air purity working environment allow few non-viable biological particles as defined by ISO 14644-1 and zero biologically viable particles (bacteria, spores, viruses etc) in the enclosed workspace. High-volume air filters are referred to as High Efficiency Particulate Air filters (HEPA), or Ultra-low penetration air filters (ULPA). These filters must comply with the standard EN18221:20196. They are classed as H13, H14 or U15 according to the Standard, they must have an integral efficiency of 99.95%, 99.995% and 99.9995% respectively of the most penetrative particle size. Examples are shown in Figures 2-1 and 2-2 below. ______ 5 https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en#annexes 6 https://standards.iteh.ai/catalog/standards/cen/dc543da7-38c7-4354-aa68-d73b542caece/en-1822-1-2019 Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 7 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Figure 2-1 Example of a high-volume air filter Figure 2-2 Close up of high-volume air filter The properties of these filters must include a combination of water repellence, chemical resistance, and performance that meets the requirements outlined in EN1822-1:2019. 2.1.2 Low volume air filters These are classed by the pore size according to EN 13408-2:2018 and are referred to in Directive (EU) 2017/1572 under Annex "1 Manufacture of Sterile Medicinal Products, Gases and Vacuum Systems" section 6.19" (European Commission, 2022)57. There are a variety of sizes of ePTFE filters used in clean air equipment, typical examples are shown in Figure 2-3 below. The properties of these filters must include a combination of achieving the performance requirements set out in the EN standard, water repellence and resistance to oxidative chemistries. They are used to give a microbiological barrier between the clean air zone and the outside environment where there is movement of a low volume of air, e.g., when measuring the pressure. ______ 7 https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en#annexes Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 8 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Figure 2-3 Example of Low volume air filters 2.2 Liquid filters Filters are required to remove contaminants such as micro-organisms and endotoxins from oxidising liquids before they can be used in a pharmaceutical production facility. The filters meet the requirements of EN 13408-2:2018, which identifies a pore size of 0.22m. The oxidising chemical is then used for the cleaning, disinfection, and decontamination of the rooms, either by hand or by use of equipment. PVDF filters are used to filter strongly oxidising solutions to comply with the EU requirement for the pharmaceutical industry to remove contaminates from solutions. Where an organisation holds a licence from a member state national medicinal products regulator to produce a medicinal product (drug, vaccine etc), a requirement may be in force that all liquids entering the manufacturing facility must be sterile and contaminate free. This requirement arises depending upon a particular manufacturing facility's production process, and their interpretation of the Good Manufacturing Practice applicable to the end product. An example is shown in Figure 2-4 below. Figure 2-4 Example of the liquid filter The properties of these filters must include, water repellence, compatibility with oxidising chemicals and ability to achieve the EU filtration performance requirements in the medicinal and veterinary products legislation (See Section 4.3). Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 9 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 2.3 Bio decontamination equipment These systems are required to apply disinfectant chemistries as part of their authorisation under the European Biocidal Products Regulation (EU 528/2012) and operate by turning liquid chemicals into a vapour or mist. They are used to create bio-decontaminated environments in a variety of industries, most critically in hospitals and the Life Science sectors. The equipment comprises a storage bottle for the oxidising chemical (typically 12-35 % w/w aqueous hydrogen peroxide CAS No: 7722-84-1) and tubing and associated connectors to deliver the solution to a heated surface within the equipment where it is evaporated into a stream of air and conveyed to the target environment. Due to the proximity of the PTFE tubing to the evaporator hotplate, the temperature of the tubing may reach 150C. In addition, in order to join the tube (at the opposite end to the evaporator) to a delivery pump, a connector is required. This is manufactured from ETFE and operates at room temperature. The combination of properties required in these parts are, compatibility with hydrogen peroxide (both chemical resistance and absence of catalytic activity with the peroxide, which would cause it to decompose and become ineffective) and rigidity whilst retaining flexibility and wear resistance. The tubing must also resist temperatures up to 150C without any alteration in the other properties. Figure 2-5 Example showing tubing installation in equipment. Figure 2-6 Example showing tubing from storage bottle into vaporiser hotplate. Entry point onto hotplate To source chemical Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 10 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 2.4 Bottle vents Where oxidising chemicals need to be transported and stored it is critical that this is accomplished safely and in accordance with the European Classification, Labelling and Packaging (CLP) Regulation (1272/2008) and the agreement concerning the International Carriage of Dangerous Goods by Road (ADR). Some oxidising chemicals break down naturally, and the volume of the resultant chemicals can be many times the original volume. The vent membrane is therefore a critical and mandated safety feature as it prevents the liquid from escaping while allowing the liberated oxygen to escape. The oxidising liquid may be used by equipment to clean, disinfect, or decontaminate in the healthcare, life science or laboratory applications where having a high level of cleanliness is critical. The vent membrane maintains a high performance separation between the external environment and the internal environment of the bottle. The properties of the vent material must include permeability to air, water repellence and compatibility with oxidising chemicals (both chemical resistance and absence of catalytic activity with the peroxide). There are two types of bottle vent caps with associated vents which are shown in Figure 2-7 and Figure 2-8. Figure 2-7 Bottle cap Type A Non PFAS containing parts. ePTFE Vent membrane shown in situ. Vent membrane also shown separately. Figure 2-8 Bottle cap Type B Non PFAS containing parts. ePTFE Vent membrane shown in situ. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 11 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 3 DESCRIPTION OF THE END USE EQUIPMENT Typical applications for the above four types of equipment include: Production facilities preparing and filling healthcare and veterinary products. (True for clean air equipment and decontamination equipment and liquid chemicals) Decontamination of surfaces in hospitals, ambulances and other healthcare environments following a contamination event. (True for decontamination equipment and liquid chemicals) Hospitals where the decontamination of patient rooms, operating theatres and other spaces are done on a routine basis or as part of a targeted campaign. (True for decontamination equipment and liquid chemicals) Laboratories working with live organisms. (True for clean air equipment and decontamination equipment and liquid chemicals) High purity working environments such as semiconductor manufacture. (True for clean air equipment) This is discussed in more detail below for each type of equipment. 3.1 Clean air equipment Clean air equipment maintains a particulate free environment. The device includes high performance filtration and separation membranes to achieve the required workplace environment. Figure 3-1 to Figure 3-5 show several types of clean air equipment. One application for the membrane filters (0.22 m) is on clean air equipment where a filter barrier is required, as an example at the start of a pressure measuring tube. Figure 3-1 Microbiological Safety Cabinet Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 12 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Figure 3-2 Laminar Airflow unit Figure 3-3 Pharmaceutical Isolator System Figure 3-4 Restricted Access Barrier System (RABS) Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 13 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Figure 3-5 Schematic of a pharmaceutical isolator showing air flow 3.2 Bio-decontamination systems These systems are used to apply disinfectant chemistries as part of their authorisation under the European Biocidal Product regulations (EU 528/2012). They convert a liquid oxidising chemical so that it fills the enclosure/room with the chemical causing the decontamination of the space to generate an aseptic environment. An example is given in Figure 3-6 below. Figure 3-6 Example of a Generator Vents used to disperse the vapour in the target enclosure. Tubing is used within the equipment to convey the oxidising chemical to a hot plate located within the equipment to create a vapour. This vapour is expelled out of the equipment (shown as a set of pipes above the Generator in Figure 3-6). The equipment ensures the bio-decontamination of localised environments such as hospital rooms, laboratories, pharmaceutical facilities, and equipment where an aseptic environment is required to be maintained or where the removal of dangerous pathogens is required. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 14 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 4 TECHNICAL AND QUALFICATION REQUIREMENTS This section describes the technical challenges that make substitution with currently available PFAS free materials impossible. 4.1 High volume air filters The high-volume air filters, referred to as High Efficiency Particulate Air filters (HEPA), or Ultra Low Penetration Air filters (ULPA) as defined by EN1822-1 are only available in two different materials, glass fibre matrix and ePTFE. These filters must have the following properties: Compatible with oxidising chemicals otherwise the filter would disintegrate upon exposure to the substances which is expected during the lifetime of the filter. Low water absorption. Meet the requirements of EN1822-1:2019. Low friction resistance to air (pressure drop), as explained below. Table 2 below shows the filter materials available on the market currently and their compatibility with the requirements needed to replace the current PTFE filters. Table 2: Property requirements of high-volume air filter membrane materials. GF - Glass Fibre Requirements for isolator filters Chemical resistance Water absorption (%)8 PTFE GF 0.019 - 0.110 0.59 Meet the requirements of EN1822-1:2019 Low air friction (pressure drop) Low friction resistance to air is critical as an air flow rate of the following is required in the following applications: 0.36-0.54m/s for RABS and pharmaceutical isolators as required by Rules Governing Medicinal Products in the European Union (European Commission, 2022).11 0.25-0.5m/s as required by EN 12469:2000 for Class II Microbiological Safety Cabinets. ______ 8 With the specific values depending upon the method of measurement. 9 https://omnexus.specialchem.com/polymer-properties/properties/water-absorption-24-hours 10 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400541/ 11 Annex 1 Manufacture of Sterile Medicinal Products" 4.30. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 15 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment The glass fibre material filters have nearly double the pressure drop of ePTFE. Table 3 below is a comparison of the two different materials tested at 450m3/hr using the most common H14 filters. Table 3: Pressure drop (frictional air resistance) across filter types. Filter size 305 x 915 x 68 915 x 457 x 68 Pressure drop Glass Filter Pa 100 110 Pressure Drop ePTFE Filter Pa 56 62 As a result of the increased pressure drop, glass fibre matrix filters require larger fans resulting in more energy consumption. To change from an ePTFE to a glass filter in an existing piece of equipment is in most cases technically not possible. To maintain the same flow rate as required by the EU regulations (European Commission, 2022) a larger more powerful fan would be required. The space in the existing structure and interface will usually not be available, and thus replacement or re-working of major parts or replacement of the whole equipment will be required. The Restriction states that there is some evidence for a substitution potential as alternatives are in development and polyurethane has been cited by one stakeholder in the Restriction consultation process as a substitute to PFAS. In the PFAS Restriction proposal Annex E under E.2.2.4. Substitution potential page 40 it states the following: "As for outdoor technical textiles, one of the seven alternative substance groups, i.e., polyurethane, is furthermore deemed to be applicable for high performance membranes based on a submission to the 2nd stakeholder consultation reporting the proven use of polyurethane membranes as an alternative to PTFE membranes in relation to this application". At the time the Annex E was drafted, there was insufficient stakeholder information available (a single submission, extrapolated to cover all possible membranes for all possible applications). Polyurethanes cannot be manufactured into filters which meet the requirements of EN1822-1. In addition, there is no other material manufactured which has similar low air resistance to ePTFE. Low air resistance is important because larger fans would be required for which internal space in current equipment is not available. Therefore, glass fibre filters could only be used in newly designed equipment and could not be used as replacement filters in the vast majority of existing air filtration equipment. The restriction in the Annex XV report is evaluating high performance membranes with only two properties, oil, and water repellence. The reasons given in Section 4 above demonstrate that when the technical requirements of high-performance filters are widened to include those filters relevant to this impact assessment, ePTFE is currently the only available filter material. The only filters having the required combination of properties are PTFE or PTFE coated membranes. 4.2 Low volume air filter membranes The filters are classed by the pore size as required by (European Commission, 2022)12 and defined in EN 13408-2:2018. This is determined by the diameter of the particle that it can be expected to retain with a defined, high degree of efficiency. The filter must not absorb any cleaning, disinfection or ______ 12 Annex 1 Manufacture of Sterile Medicinal Products section 6.19. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 16 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment decontamination chemicals or atmospheric water, whilst allowing air movement through the filter. Figure 4-1 below illustrates the selective permeability to gases required of the filter membrane. Figure 4-1 Selective permeability property of the air filter The filter must have the following properties: Chemical resistance to oxidising disinfectant solutions. Water repellent to avoid water absorbance (blinding) reducing filtration efficiency. Compliant to EN13408-2:2018 (0.22 m). Can be sterilised by irradiation, ethylene oxide, or other recognised method. Table 4 below shows the filter materials available on the market currently and their compatibility with the requirements needed to replace the current PTFE filters used in low volume air filters used in isolators. Table 4: Property requirements of low volume air filter membrane materials. Requirements for isolator filters PTFE PES (PTFE coated) PES Nylon MCE GF GF (PTFE coated) Chemical resistance13 Water absorption (%)14 0.018- 0.19 0.018 1.708 1.59 - 3.08 1.98 0.59 0.018 Pore size (0.22 m) PES - Poly Ether Sulfone, MCE - Mixed Cellulose Ester, GF - Glass Fibre The only filters having the required combination of properties are PTFE or PTFE coated membranes. ______ 13 Known to chemically react with hydrogen peroxide to give reduced physical properties such as tensile strength. 14 With the specific values depending upon the method of measurement, Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 17 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 4.3 Liquid filters To remove biological and particulate contaminates, chemicals must be filtered. The requirements of the liquid filters are: EU requirements (Commission Directive (EU) 2017/1572) for endotoxin removal. Water repellent to avoid water absorption reducing filter efficiency. Compatible with oxidising chemicals used as disinfectants. Not catalytic in their interaction with disinfectant solutions. Meet the classification requirements set out in EN 13408-2:2018. The only suitable and available materials for the filter construction which meet the above requirements are polypropylene (PP) and PVDF. The other available filter materials either do not meet the requirements of Commission Directive (EU) 2017/1572 and EN 13408-2:2018 or undergo chemical reactions with the sterilising fluids. A series of trials relating to the removal of endotoxins were undertaken with PP and PVDF materials with a solution containing a concentration of 1.32 EU/ml endotoxins (One Endotoxin Unit (EU) is equivalent to approximately 0.1 to 0.2 ng endotoxin/ml). As shown in Table 5 below, the measured concentration of endotoxins for PP is 11 times higher than PVDF and will usually exceed the limit value. The limit value for the maximum allowable endotoxin concentration in a medicinal product depends upon the product formulation (dictated by the method of drug delivery either parenteral such as injection or infusion or enteral route such as liquids that can be swallowed) and must be calculated according to the rules set out in the European Pharmacopoeia. This means that for many medicinal products, PVDF filters are the only ones capable of achieving this calculated limit value. For applications not involving medicinal products, such as bio decontamination equipment, there remains the requirement to filter disinfectant solutions. This requires all of the properties listed above. Table 5: Comparison of polypropylene and PVDF filter performance Filter Polymer type PP PVDF Measured concentration EU/ml before filtration 1.32 1.32 Measured concentration15 EU/ml after filtration 1.13 <0.1 At present there is no PFAS free material on the market which meets all of the property requirements. 4.4 Decontamination equipment tubing and connector. The tubing must meet the following requirements: ______ 15 The units are endotoxin units per millilitre. One EU is equivalent to approximately 0.1 to 0.2 ng of endotoxin/ml of solution. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 18 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Compatible with oxidising chemicals used as disinfectants. Compatibility with oxidising chemicals includes both chemical resistance and the absence of any catalytic activity with the chemical that would result in its break down and hence reduce its efficacy. Not catalytic in their interaction with disinfectant solutions. Rigid enough to not alter in internal volume (resistant to being crushed or expanded so that the internal bore diameter is not altered) during equipment operation to an extent that would affect the accuracy of the volume of disinfectant being delivered to other parts within the equipment by more than 1.5%. The reason for these requirements is to maintain an accurate flow rate to ensure that the validated delivery cycle is reproducible. The cycle may use as little as 15g per cycle and the rate of delivery as low as 1.5g/min, but it is critical that the parameters are maintained as deviations could affect the efficacy of the bio-decontamination. Cycles where the amount of chemical required is not delivered may result in not all the viable organisms being destroyed. Flexible enough to pass through tight internal areas of the equipment without a change in the internal bore dimensions. Mechanically hard wearing. Resistant to chemical degradation and physical property alterations at temperatures up to 150 C The tubing must have the properties given in Table 6 below, which only PTFE or ePTFE offer all of the necessary properties. Table 6: Compatibility of tubing and associated connector PFAS free alternatives Property code Compatible with highly oxidising chemicals Accurate 1.5% delivery from the pump at very low volume rates, down to 1.5g/min* Able to resist temperatures up to 150 C Mechanical wear resilience and rigidity Flexible with a minimum bend radius of 10 mm whilst maintaining the other physical properties PEEK NBR Tygon 2075 / 2375 NT NT NT NT Silicone and TPE EPDM PVC Tygon ND 100-80 NT NT NT Stainless steel Aluminium ePTFE PTFE Table key NT PEEK NBR PVC Not Tested Polyether ether ketone Nitrile butadiene rubber Polyvinyl Chloride Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 19 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Tygon Silicone EPDM TPE Polymer specialist grades with different base resin and plasticizers and additives Polysiloxane polymer Ethylene Propylene Diene Monomer rubber Thermoplastic Elastomer The connector must be compatible with highly oxidising chemicals and have good wear resilience and rigidity allowing a leak free seal with the tube. The only available connector material meeting all of the requirements is ePTFE. 4.5 Chemical bottle vents The requirements of the vents are: Allow the passage of air, liberated oxygen, and other gases. Block the passage of water or oxidising solution. Water and chemical repellent to avoid saturation of the vent and a consequential drop in gas permeation efficiency. Chemically resistant to highly oxidising chemicals. Non-catalytic activity in contact with the disinfectant chemicals resulting in loss of concentration of the chemical. At present there is no PFAS free material on the market which meets all of the above combinations of property requirements. It is not possible to do a comparison of alternatives as there is no alternative material having suitable properties that is on the market to compare it with. 5 REDESIGN QUALIFICATION AND REPLACEMENT TIMELINES Clean air equipment and biological decontamination equipment are used in highly regulated applications. They have to undergo a detailed testing and qualification process both before and after they have been installed at the site where they are operated. This is to ensure that both the equipment and the workplace environment conform to the applicable EU standards. When a design is altered, testing and qualification work must be undertaken to ensure that: Performance characteristics are met (examples include, flow rate, liquid delivery volume accuracy, pore size, particle size retention etc). Specified service life and sustained performance are maintained against the EU standards. Chemical, mechanical and heat resistance are achieved over the service life. Table 7 below summarises the estimated time required from a PFAS free alternative material becoming available on the market to qualifying an alternative solution. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 20 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Table 7: Timeline to test and validate PFAS-free materials Activity Time (years) Decontamination equipment tubing and connector Liquid filter High volume air filter Low volume air filter Chemical bottle vent Design 1 1 2 2 1-3 Dpreovdeulcotpiomnetnritaalsnd 1 1 2 2 2 Testing 2 2 2 2 3-4 Ivnaslitdaalltaiotinononansdite 1 1 6* 6* N/A Notified body approval N/A N/A N/A N/A 2-3 Total time from replacement availability 5 years 5 years 12 years 12 years Up to 12 years * 6 years is the estimated time required to manage all of the existing in-field equipment due to the quantity of equipment and limitations on the specialist trained resource required. It is important to note that the total timescales in Table 7 can start only when a suitable substitute has been identified and Gambica is not able to predict when this will occur. Validation can be viewed as being divided into four sub-categories (Jindal, 2020). These are: Analytical method validation Process validation Cleaning validation Equipment validation The rules for the validation requirements for medicinal and veterinary products are set out in the Good Manufacturing Practice and these requirements are enforced in the EU (European Commission, 2022)16. These will vary between clients and installation sites depending upon the work conducted using the equipment. 6 SOCIO ECONOMIC IMPACT ASSESSMENT The importance and benefits to society derived from the availability of the equipment are described, together with negative effects that the proposed restriction of PFAS in the EU would have, without the derogations requested in this submission. ______ 16 Annex 15: Qualification and Validation. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 21 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 6.1 Importance to society Decontamination chemicals and equipment are used in healthcare environments. Hospital acquired infection is a significant problem worldwide (World Health Organisation , 2022)17. The WHO report conclusions for the EU were: 7% of patients in acute care hospitals in high income countries (EU) will contract at least one health care associated infection with 24% of all hospital treated sepsis cases being health care associated. 4.5 million episodes of hospital acquired infections occur each year in acute care hospital settings. The three antibiotic-resistant microorganisms accounting for 70% of anti-microbial resistance resulting in disability or death are typically acquired in health care settings. Mortality among patients infected with resistant organisms is 2 to 3 times higher than among patients not infected with these organisms. The equipment allows automated decontamination of surfaces. Manual decontamination can be problematic, be less effective and may spread contamination to other areas, patients, and workers. It also frees up staff time, thereby providing cost savings. The clean air and bio decontamination equipment is used in the manufacture of health care products including pharmaceuticals and vaccines and in health care settings. All aseptically manufactured products have to be made in an environment which can only be achieved by use of clean air equipment. The new era of cell and gene therapies which is starting to revolutionise the prevention and cure of cancers, genetic diseases, vaccines, and other conditions is highly reliant on this technology. These therapies are starting to save lives within the EU which has not been possible up to now. The clean air equipment is also used in work settings where high purity air is required. These include high value and high production volume products such as electronics and semiconductors. These products could not be manufactured without the use of the clean air equipment. It is also critical in laboratories and R&D for the discovery and development of medicinal products as well as handling of organisms for test and other purposes. 6.2 Economic impacts The cost of qualifying a PFAS-free system has been unable to be estimated due to the lack of availability of alternative materials with suitable properties. The cost of replacing all installed equipment with equipment manufactured using PFAS free parts cannot be calculated because of insufficient information, for example, the number of installed equipment units is not known. This equipment has been installed over many years and may have a service life of up to 20 years depending upon the equipment type. This means that there is a large quantity of equipment items that would have to be replaced. Some types of equipment have parts which are replaced at service intervals such as filters. This equipment would have to be replaced with equipment manufactured with PFAS free materials if these PFAS free alternative parts cannot be installed in the existing equipment which will be true in most cases. The cost to validate the installed equipment is estimated to be at least 5 times the installation and equipment cost. There would be additional cost arising from the value of lost production whilst the installation and revalidation work are carried out. ______ 17 https://www.who.int/publications/i/item/9789240051164 Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 22 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Decreased air filter performance on energy consumption The use of PFAS free alternative filters in clean air equipment will result in increased energy consumption because of the greater pressure drop resulting from a friction resistance with air. This additional electrical current consumption is illustrated in Table 8 below for a pharmaceutical isolator. Table 8: Current consumption by filter material type. Current Drawn at 527m3/hr Positive pressure isolator Current Drawn at 527m3/hr Negative pressure isolator Glass fibre Amps 2.12 2.10 ePTFE Amps 1.93 1.96 Difference Amps 0.19 0.14 The current drawn can then be calculated in units of energy in kilowatt hours. The additional energy when glass filters rather than ePTFE filters are used is expected to be 15,320 kWh over the course of a small isolators' life.18 This equates to an additional power consumption of 7.2 GWh over 20 years assuming that 470 units are placed on the market on average per annum. Pharmaceutical Isolators represent only a small segment of the total clean air equipment market, thus the actual figure for all equipment will be many times larger. This increased energy consumption is contrary to the objectives of the European Green Deal. 7 PFAS EMISSIONS FROM USE OF THE EQUIPMENT The PFAS used are all polymeric polymers that are thermally stable with negligible volatile emissions in the operating temperature ranges of the equipment. All of the PFAS material is contained within the machine. The equipment is operated and maintained to strict EU legislative requirements (European Commission, 2022). The decontamination equipment tubing is the only PFAS material that is suitable at temperatures above room temperature. PTFE is extremely inert and stable up to 250C (Huber, 2009). Above this temperature, it decomposes very slowly, with a reported weight loss of 0.004%/h at 371C (Huber, 2009)19. The estimated maximum likely maximum temperature of the PTFE tubing is 150C. The other PFAS materials are similar to PTFE in their loss of volatiles. There is no loss of PFAS via evaporation or skin contact during use of the equipment. There are, therefore, no significant emissions of PFAS to the environment and no exposure to animals or humans during the service life of the equipment. 8 ENVIRONMENTAL AND END-OF-LIFE AND CONSIDERATIONS The quantities of fluoropolymers used are estimated in Table 9 below based upon an industry estimate of the number of machines installed, service intervals and service life. ______ 18 A small isolator is determined to be 0.45m3 being used in a two-chamber positive pressure system as it is the most common device type which uses 87.4W. With a service life of 20-years. 19 Page 20 https://www.nilu.com/publication/24739/ Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 23 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Table 9:Estimated weight of PFAS polymer used per year Component Mass per unit (g) Items per year Total mass (kg)** Tubing 250 560 140 Liquid filter 320 10 3.2 Bottle vent membrane (A) 0.0064 98,000 0.60 Bottle vent membrane (B) 0.0002 98,000 <0.1 Low volume air filter* 0.88 750 0.66 High volume air filter* 45 7,500 340 Total weight per year 490 *Clean air equipment (not including clean rooms) used in the Life Science sector. ** Figures rounded to two significant figures The total quantity of fluoropolymers sold in Europe, the UK, and the EEA in 2020 was 40,000 tonnes (Croad B, 2022)20. The amount used in the manufacture of the filtration and biological decontamination equipment was less than 500kg which represents less than 0.0015 % of the annual fluoropolymer production. At end-of-service-life, or at service intervals if required, all of the PFAS material is removed under tightly regulated requirements (European Commission, 2022). The equipment falls under the EU WEEE Directive 2012/19/EU which ensures that the equipment is disposed of in accordance with EU legislation. The Generator tubing, bottle vent, liquid filter and high and low volume air filters are incinerated at high temperature in accordance with the EU rules that apply to incineration of waste (Commission, European, 2019). The environmental impacts from incineration of the PFAS materials have been considered in Annex A of the Restriction under A.3.18.2.7. Incineration. This recognises that "incineration of PFAS containing waste is currently seen as the most effective treatment option for destroying PFASs. The fluorine in the PFASs will end up in either the bottom/fly ash or the flue gas." This conclusion is supported by numerous studies (OECD, 2015)21 and (K, 2019).22 ______ 20 https://fluoropolymers.plasticseurope.org/application/files/1216/5485/3500/Fluoropolymers_Market_Data_Update__Final_report_-_May_2022.pdf 21 http://www.oecd.org/chemicalsafety/ 22 http://www.elsevier.com/locate/chemosphere Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 24 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment 9 PROPOSED DEROGATIONS GAMBICA requests the following derogations. 1. By way of derogation, paragraphs 1 and 2 shall not apply to textiles and other membranes for use in filtration and separation media used in high performance air and liquid applications in industrial or professional settings that require a combination of water and oil repellence or any combination of water repellence and chemical resistance, selective permeability, and microbiological retention until 13.5 years after EiF. 2. By way of derogation, paragraphs 1 and 2 shall not apply to oxidizing liquid tubing and associated connectors in biological decontamination equipment until 6.5 years after EiF. 3. By way of derogation, paragraphs 1 and 2 shall not apply to maintenance and repair of highperformance filtration and separation equipment and biological decontamination equipment put on the market before [18 months after EiF] and for which no drop-in alternative exists until end-of-life. 9.1 Suggested amendment to derogation 5.e. GAMBICA request that the derogation be adapted to: Allow membranes which are not defined as textiles. Allow membranes with a combination of properties of water repellence, chemical resistance, selectivity in permeability of gas over liquid and microbiological retention to also be permitted. 9.1.1 Textiles and other membranes Filtration and separation media are considered in detail in Annex A of the Restriction which establishes the concept of a membrane as a separation medium, recognising ePTFE as one such example. There are no EU legislative definitions of membrane, but the restriction proposal includes high performance membranes as a subcategory of technical textiles in Annex A.3.3.1.1. Regulation (EU) No 1007/2011 defines textiles as follows: (a) `textile product' means any raw, semi-worked, worked, semi-manufactured, manufactured, semimade-up or made-up product which is exclusively composed of textile fibres, regardless of the mixing or assembly process employed. (b) `textile fibre' means either of the following: (i) a unit of matter characterised by its flexibility, fineness, and high ratio of length to maximum transverse dimension, which render it suitable for textile applications. (ii) a flexible strip or tube, of which the apparent width does not exceed 5 mm, including strips cut from wider strips or films, produced from the substances used for the manufacture of the fibres listed in Table 2 of Annex I and suitable for textile applications Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 25 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment As such, the PTFE membranes described in this report, whilst being high performance membranes, fall outside of this EU textile definition. Due to this, there is the risk a legal interpretation of the derogation, once in force, might conclude that the filters are outside the scope of the 5.e. derogation. Unambiguous inclusion of non-textile membranes within the scope of the proposed derogation 5.e. would be achieved by including the words "other membranes." 9.1.2 Requirement for a combination of additional properties Annex A of the Restriction (A.3.3.1.1) restricts the scope of the derogation to materials having a combination of water and oil repellence. The filters used in this sector primarily conform to EN 18221:2019 or EN 13408-2:2018. These standards set performance criteria for classifying filters so that end users of the equipment are assured of a defined level of performance so that they can in turn comply with the requirements applicable to their applications. Depending upon the equipment model, they must also have the following combination of properties: Compatibility with oxidising chemicals (chemical resistance and absence of catalytic activity promoting the decomposition of the chemical) Low air friction Low water absorption Performance criteria in accordance with BS EN 1822-1:2019: or EN 13408-2:2018 9.2 New derogation for biological decontamination equipment There are no proposed or potential derogations in the Annex XV report Restriction that cover the necessary uses of PFAS in decontamination equipment tubing and connection fittings because biological decontamination equipment was not included as a use sector. The combinations of properties required for the components are as listed below. Tubing and associated connector These must have the following combination of properties. Compatible with oxidising chemicals Accurate 1.5% delivery from the pump at extremely low volume rates, down to 1.5g/min* Able to resist temperatures up to 150C Mechanical wear resilience and rigidity Flexible with a minimum bend radius of 10 mm whilst maintaining the other physical properties. 9.3 New derogation for spare parts To maintain the same flow rate in clean air equipment as required by the EU Regulations and EN norms a larger more powerful fan would be required when using PFAS-free alternatives. This is because the ePTFE has a much lower frictional resistance as illustrated in Section 4.1 Table 3. The space in the existing equipment is not sufficient for a higher-powered fan as they typically have a larger footprint. Therefore, the replacement of the filters and the replacement of the fan is only possible by replacing the entire piece of equipment. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 26 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment If the replacement of the ePTFE filters is not permitted, this will result in the premature end-of-life and scrappage of the entire equipment. Clean air equipment can have a typical service life of 20 years. Service, maintenance, and repairs are crucial for the success of the European Green Deal when it comes to better resource efficiency. Replacing equipment which still has a lot of life left also removes capacity from the industry encouraging companies to move production out of the EU, as well as diverting resource which could be used for new medicine discovery, development, and production, depriving the EU population of new medicines. It could easily result in medicine shortages as production facilities have to be closed and re-fitted with new equipment. A maintenance and repair derogation is requested to ensure that this equipment can continue in service to end-of life. 10 REFERENCES CEN EN1822-1:2019. (2022, June 8). High efficiency air filters (EPA, HEPA and ULPA) - Part 1: Classification, performance testing, marking. Retrieved from CEN Standards: https://standards.iteh.ai/catalog/standards/cen/dc543da7-38c7-4354-aa68-d73b542caece/en1822-1-2019 Commission, European. (2019, November 19). Establishing the best available techniques (BAT) conclusions, under Directive 2010/75/EU of the European Parliament and of the Council, for waste incineration. Retrieved from Oficial Journal of the European Union: https://eurlex.europa.eu/legalcontent/EN/TXT/?uri=uriserv%3AOJ.L_.2019.312.01.0055.01.ENG&toc=OJ%3AL%3A2019% 3A312%3ATOC Croad B. (2022). Update of market data for the socio-economic analysis (SEA) of the European fluoropolymer industry. London: Wood Group UK Ltd. DY, C. (1983, 1). Fluid dynamics model of air filter. Mech Eng, pp. 34-37. ECHA Q&A June 2023. (2023, June). Restriction of PFAS under REACH Questions and answers by five national authorities to questions on the content of the proposed restriction . Retrieved from ECHA: https://echa.europa.eu/documents/10162/2156610/230405_upfas_webinar_qa_ds_en.pdf/3f4 7fdcc-17c5-4b37-b758-720bb7e462f3#msdynttrid=HNlxhuwPKCeiaLmaod2PYhIBlvaMeQh2Ehjzy_hSYo ECHA. (2023, March 22). Annex XV Restriction report Proposal for a restriction per- and perfluoroalkyl substances (PFASs). Retrieved from ECHA: https://echa.europa.eu/documents/10162/1c480180-ece9-1bdd-1eb8-0f3f8e7c0c49 ECHA. (2023). Consultation on a proposed restriction on the manufacture, placing on the market and use of per- and polyfluoroalkyl substances (PFAS). Retrieved from ECHA Europe: https://echa.europa.eu/documents/10162/aea5537d-b698-3b75-4b67-0cadd0fd11d3 European Commission 20 June 2023. (2023, June 20). Proposal Amending Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council as regards undecafluorohexanoic acid (PFHxA), its salts and PFHxA-related substances. European Commission. (2022, August 22). The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Brussels, Belgium. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 27 The impact of a per- and polyfluoroalkyl substances PFAS restriction on filtration and biological decontamination equipment Huber. (2009). Emissions from incineration of fluoropolymer materials A literature survey. NILU (Norwegian Institute For Air Research. ISO 13408-2. (2018). Asceptic processing of health care products-Part 2:Sterilizing filtration. ICS. Jindal. (2020). Validation - In pharmaceutical industry: Equipment validation: A brief review. Adesh Univ J Med Sci Res, 2(2): 94-98. K, K. (2019). Waste incineration of PTFE to evaluate potential formation of PFAS in flue gas. Chemosphere, 226 (2019) 898 - 906 . OECD. (2015). WORKING TOWARDS A GLOBAL EMISSION INVENTORY OF PFASS: FOCUS ON PFCAS - STATUS QUO AND THE WAY FORWARD. Paris: OECD. World Health Organisation . (2022). Global report on infection prevention and control. WHO. Report No.2023-0695 Rev. 0 RINA Tech UK Ltd Page 28 RINA Tech UK Limited I 1 Springfield Drive, Leatherhead, Surrey, KT22 7AJ, United Kingdom I P. @rina.org I www.rina.org I Company No. 07419599