Document BRrqddwnDzmKEbLNGgxkLz8Z8

Honeywell Advanced Limited 25 May 2023 Riverview House Harvey's Quay Apartments Limerick V94R3DE Ireland 26 May 2023 PFAS REACH Annex XV Restriction Report 1ST Public Consultation (22 March - 25 September 2023) PCTFE fluoropolymers exclusion or unlimited derogation in the PFAS Proposal for Restriction 1. Executive summary Honeywell International Inc. (hereinafter - Honeywell)1 is a global manufacturer and importer of various fluorinated products into the European Union ("EU"), including Polychlorotrifluoroethylene (PCTFE)2 based materials (thermoformable films and resin) used as a non-contact layer in originator and generic prescription and over-the-counter (OTC) pharmaceuticals and animal health (i.e. medicinal) primary and secondary packaging, as well as medical device packaging applications. PCTFE is imported as a finished film for the above applications and is not produced in the EU/EEA. Hence, all tonnages of PCTFE fluoropolymers imported into EU for the above uses are Honeywell's products, marketed under the trademark Aclar. On 13 January 2023, the competent authorities of five EU/EEA states (Dossier Submitters) submitted the PFAS REACH Annex XV Restriction Report (Proposal) to the European Chemical Agency (ECHA).3 Although considered very persistent (vP) by design, PCTFE is a fluoropolymer that satisfies all internationally recognised criteria of Polymers of Law Concern (PLC).4 In particular, they do not exhibit hazards identified by the Dossier Submitters as "supporting concerns" applicable to all PFAS, i.e., bioaccumulation, mobility, long range transport potential (LRTP), accumulation in plants, ecotoxicity, endocrine activity/endocrine disruption, effects on human health and concerns triggered by a combination of these properties. In section 1.1.4 of the Proposal, the Dossier Submitters erroneously attributed these hazards to all substances in the "PFAS group", including PCTFE. Grouping PCTFE with all other PFAS for REACH read-across5 and restriction processes purposes is scientifically unjustified and contrary to the provisions of Annexes I, XI and XV REACH. PCTFE (Aclar) fluoropolymers are manufactured both from the respective non-PFAS raw materials and the non-PFAS monomer Chlorotrifluoroethylene (CTFE)6 and polymerized without involvement or addition of other PFAS substances such as processing aids, additives, or agents. PCTFE (Aclar) is a medical grade, high-purity, intrinsically stable, inert material, with extremely low levels of residues, impurities, and negligible leaching characteristics throughout its full life cycle. The combination of these properties, along with the excellent formability in both rigid and flexible packaging, makes it a premium material. Its end-of-life disposal in landfills and by municipal incineration are proven to be safe and 1 See the list of acronyms and abbreviations (aligned with the Proposal) in Annex I below. 2 ECHA Substance Inforcard - Chlorotrifluoroethylene polymer, CAS: 9002-83-9, EC: 618-336-7, (C2ClF3)n. 3 On 22 March 2023, ECHA published the PFAS REACH Annex XV Restriction Report in the Registry of restriction intentions until outcome and started the 1st Annex XV report consultation with a final deadline for comments on 25 September 2023. 4 Data analysis of the identification of correlations between polymer characteristics and potential for health or ecotoxicological concern, OECD Environment, Health and Safety Publications, ENV/JM/MONO(2009); A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers, Henry, B. J., et al. (2018).; A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers, Korzeniowski, S. H., et al. (2022) 5 See on relevant requirements inter alia in sections 3.2 and 4.2 of the ECHA's Read-Across Assessment Framework (RAAF). 6 REACH Registration information on the substances - Chlorotrifluoroethylene (EC: 201-201-8, CAS: 79-38- 9, C2ClF3). 1 recommended by national and international regulations7. Incineration at end-of-life above 800 C does not release PFAS-related materials nor detectable levels of TFA using ultra-high resolution mass spectrometry.8 Considering very small tonnages of PCTFE imported into the EU for uses in medicinal and medical devices packaging (app. 2.3% of the total PFAS uses in the medical devices sector and ca. 0,36% of the total polymeric PFAS tonnages used on the market in 2020),9 negligible emission levels (1%)10 and its PLC properties, the respective risks to human health and the environment, if any, could not be considered "unacceptable" under Articles 68 or 69 of REACH and are clearly disproportionate vis--vis the proposed REACH restriction. Furthermore, any potential in-use safety risks are adequately controlled by the applicable EU legislation, including EU medicines and veterinary laws,11 the requirements and procedures issued by the European Medicines Agency (EMA) and national medicines authorities12, EU Pharmacopoeia, Medical Devices Regulation (MDR)13, Food and Food Contact Materials (FCM) rules, EU waste and packaging laws14 and other regulations. All these provide, inter alia, enhanced risk management measures (RMM) for materials/packaging, (eco-)design and safe use standards, as well as disposal and end-of-life practices for PCTFE (Aclar). It is noteworthy that relevant RRMs cover both the final packaging and the starting (input) materials to fully ensure that all risks are adequately controlled. Hence, "double RMMs" on PCTFE-based inputs/materials for medicines and medical device packaging are excessive. These regulations could be strengthened at any time in the future, if warranted. There are no alternatives to PCTFE that provide similar moisture/chemical barrier and clarity properties, essential for preserving the quality, safety, and efficiency of drugs and medical devices over a range of temperatures as well as cryogenic conditions. Other materials will inevitably deteriorate and impact the 7 See e.g. Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas, K. Aleksandrov, 2019; Investigation of waste incineration of fluorotelomer-based polymers as a potential source of PFOA in the environment, P.H. Taylor, 2009; Per- and polyfluorinated substances in waste incinerator flue gases, Bakker, J., et al. (2021), RIVM report 2021-0143; Using mass defect plots as a discovery tool to identify novel fluoropolymer thermal decomposition products, Myers, A. L., et al. (2014). For landfills, see footnote 32. 8 Per- and polyfluorinated substances in waste incinerator flue gases, Bakker, J., et al. (2021), RIVM report 2021-0143 9 According to Honeywell's own estimates (i.e., based on relevant customs declarations), PCTFE (Aclar) annual import into the EU in 2015-2020 was ca 1000 MT per year. According to Table A.10, Annex A of the Proposal, total tonnages of polymeric PFAS put on the market in 2020 were 277 684 tonnes. Therefore, the share of PCTFE tonnages used in medicinal and medical devices packaging constitutes ca. 0,36% of the total polymeric PFAS tonnages used on the market in 2020. Considering very low PCTFE emissions through all life cycle (ca. 1%), its share in total PFAS emissions tonnages in the medical device sector in the same year (5 674 tonnes) was truly negligible ca. 0,18% (10*100%/5674, see Table E.107, section E.2.9., Annex E of the Proposal) and even lower (i.e., ca. 0,05%) as far as annual emissions of all polymeric PFAS in 2020 are concerned (19 958 tonnes, Table 1 of the Proposal). 10 "Emission estimates were derived from use/tonnage estimates. In case of polymeric PFAS it was assumed that 1% of PFAS use is emitted", last paragraph on page 316, section E.2.9.1, Annex E of the Proposal. 11 PCTFE-based fluoropolymers are only used as components of the "immediate packaging", "closed container" or "primary packaging" of final medicine products within the meaning of the EU legislation on regulation of medicinal products for human or veterinary use (i.e., Regulation (EC) No 726/2004, Directive 2001/83/EC, Directive 2001/82/EC). 12 Aclar materials also comply with the current World Health Organisation (`WHO') and EU Guideline on Plastic Immediate Packaging Materials (See Guidelines on packaging for pharmaceutical products, WHO Technical Report Series, No. 902, 2002), relevant European Pharmacopoeia Monographs as well as the Directive 2002/72/EC and Regulation (EU) 10/2011 on plastic foods contact materials. 13 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (MDR) 14 Directive 94/62/EC on packaging and packaging waste; Directive 2008/98/EC on waste (Waste Framework Directive). 2 stability characteristics of pharmaceuticals, increase packaging sizes, and exhibit dangerous features, e.g., PVC/PVDC15 polymers. In addition, when compared to cold form foil (CFF), PCTFE also improves patient/drug adherence due to the transparency and clarity of blister packaging. Therefore, the conclusions regarding the exposure assessment and risks characterisation, in sections 1.1.5 and 1.1.6 of the Proposal, are manifestly erroneous. Hence, the proposed REACH restriction on PCTFE (Aclar) fluoropolymers is not justified. Considering the above, Honeywell submits that PCTFE-based materials used as medicinal and medical devices packaging, and with food supplement and over-the-counter (OTC) medicines (including input materials (polymers), intermediate and final packaging (articles)) should be either excluded from the scope of the Proposal as such or made subject to an unlimited derogation (see in section 8 below). The derogation would be similar to those granted to active substances in biocidal, plant protection, or medicinal products already included in the Proposal (see point 2, in Column 2 of the proposed restrictions). This approach will also be in line with previous RAC/SEAC practices applied in similar situations/circumstances.16 2. Background information Honeywell manufactures Polychlorotrifluoroethylene (PCTFE) fluoropolymers used in pharmaceutical (i.e. medicinal) and veterinary primary and secondary packaging, and in medical device packaging applications (trademark Aclar), and imports them into EU/EEA. Upon importation, specialized EU processors laminate PCTFE films to other materials such as polyethylene, PVC, or polypropylene (as thermoformable films) into blister packaging, other laminates, bottles, vials, etc. If PCTFE (Aclar) is laminated at recommended temperatures, processing emissions remain at zero levels. Decomposition of the PCTFE polymer occurs at temperatures > 350 C, while the films are processed at temperatures up to 170 C according to Honeywell's recommended guidelines. Most pharmaceutical/medicinal or medical device packaging waste in the EU is collected and incinerated under municipal waste conditions (i.e., statutory recommendation) or disposed in landfills. Considering the low hazard profile as defined by polymers of low concern (PLC) criteria, the use of non-PFAS raw materials and monomers, the absence of processing aids/additives/impurities/residues, and the lack of water solubility for PCTFE, there are no PFAS emissions or mobility concerns for PCTFE (Aclar) within pharmaceutical or medical devices packaging when landfilled (please see in detail below in section 4 below). In addition, municipal or medical waste incineration does not create TFA or other PFAS-related compounds of concern. 17 15 See e.g., Request to the European Chemical Agency to prepare an investigation report on PVC and PVC additives, ECHA's Call for evidence on alternative additives in PVC, and other plastics and respective Honeywell submission (Ref-Nr. b0bdd158-b0b6-4c8b-b97d-8e8648949bfe) on PVC and PVDC materials. 16 See e.g., Entry 51, Annex XVII REACH, restricting Phthalates such as DEHP, DBP, BBP, DIBP and providing time-unlimited derogation for "(i) the immediate packaging of medicinal products within the scope of Regulation (EC) No 726/2004, Directive 2001/82/EC or Directive 2001/83/EC, ... (g) medical devices within the scope of Directives 90/385/EEC, 93/42/EEC or 98/79/EC, or parts thereof, .... (f) materials and articles intended to come into contact with food within the scope of Regulation (EC) No 1935/2004 or Commission Regulation (EU) No 10/20111". See also Entries 28, 29 and 30 of Annex XVII REACH providing for time-unlimited derogations for use of certain carcinogenic, mutagenic or toxic substances in "(a) medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC; (b) cosmetic products as defined by Directive 76/768/EEC...", and other. 17 See e.g. Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas, K. Aleksandrov, 2019; Investigation of waste incineration of fluorotelomer-based polymers as a potential source of PFOA in the environment, P.H. Taylor, 2009; Per- and polyfluorinated substances in waste incinerator flue gases, Bakker, J., et al. (2021), RIVM report 2021-0143; Using mass defect plots as a discovery tool to identify novel fluoropolymer thermal decomposition products, Myers, A. L., et al. (2014). 3 On 22 March 2023, the European Chemical Agency (ECHA) published the PFAS REACH Annex XV Restriction Report (Proposal)18 and started the 1st public consultation on the Proposal. Hereby, Honeywell submits the following information and comments to the ECHA: - For more than 50 years, Honeywell' PCTFE Aclar thermoformable films are used in originator and generic pharmaceutical (blister packs), consumer health, and animal health primary packaging. - Aclar films are based on PCTFE fluoropolymer technology. They are crystal clear, biochemically inert, chemically resistant to a wide range of products, non-flammable, and plasticizer- and stabilizer-free. These films are produced from non-PFAS raw materials and ensure increased patient compliance with doctor prescriptions by enabling see-through, portable, and patient-friendly packaging presentations. - Aclar fluoropolymers provide the highest moisture barrier when compared to other extrudable thermoplastics films (ETF). These unique characteristics substantially increase stability, storage and usage life of medicinal products and devices and are consistent across a large range of temperature and humidity conditions. The latter attributes of drug packaging decrease medical waste and potentially reduce improper disposal of pharmaceuticals to the environment. - Aclar products do not require the use of additives and/or PFAS polymerisation or processing aids that may migrate into drug products, which help to ensure drug product safety, efficacy, and quality or functionality of medical devices. They fully correspond to European, United States and many other worldwide Pharmacopeia standards.19 - Aclar Accel is the trademark of the new line of the Honeywell's fluoropolymer films, designed for opaque laminates for human drugs (blister packs). Honeywell is also collaborating with pharmaceutical and bio-pharmaceutical companies on healthcare packaging for innovative therapies, medical devices, and vaccines. 3. PCTFE is a Polymer of Low Concern (PLC) Although PCTFE as a polymer is not registered under REACH, it satisfies all criteria of the internationally recognised OECD definition for a Polymer of Low Concern (PLC)20. It is scientifically proven to be a lowhazard, non-toxic, non-mobile, extremely inert material without chemical or biological reactivity, and with excellent stability under a range of environmental and normal-use conditions.21 Please see Annex II below for laboratory evidence demonstrating that PCTFE is insoluble in water, and therefore non-mobile and non-reactive in aquatic media. All available scientific data unequivocally demonstrates that PCTFE does not exhibit any of the hazards assessed in Section 1.1.4 of the Proposal and that its physicochemical, toxicological and ecotoxicological properties are very different from many other PFAS. It is apparent that PCTFE films do not exhibit PBT/vPvB equivalent concerns, contrary to the erroneous conclusions in section 1.1.6 of the Proposal. The Honeywell process does not start from PFAS raw materials, nor uses PFAS-related processing aids or additives, at any stage of the manufacturing process. In addition, during the use 18 On 22 March 2023, ECHA published the PFAS REACH Annex XV Restriction Report in the Registry of restriction intentions until outcome and started the 1st Annex XV report consultation with a final deadline for comments on 25 September 2023. 19 All Aclar fluoropolymer films comply with FDA regulation #21 CFR 177.1380, Drug Master File #1578. 20 Data analysis of the identification of correlations between polymer characteristics and potential for health or ecotoxicological concern, OECD Environment, Health and Safety Publications, ENV/JM/MONO(2009). 21 Please find detailed assessment of PLC criteria of fluoropolymers in A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers, Barbara J Henry et all, Integrated Environmental Assessment and Management -- Volume 14, Number 3--pp. 316-334, 2018. 4 phase, our material is processed at temperatures up to 140 C, well below those needed to initiate thermolysis or partial degradation (more than 2X). Therefore, grouping PCTFE with all other PFAS for REACH restrictions and/or read-across purposes is not supported by available scientific data and ECHA RAAF requirements.22 Furthermore, according to the RAC/SEAC opinions in the Restriction Proposal of microplastics (see the RAC opinion), it is only when a "polymer", as defined in Article 3(5) REACH, has specific intrinsic properties of "microplastics" (i.e. particles size, (bio)degradation and water solubility thresholds), that these properties may affect its hazard characteristics, resulting in vPvB equivalent concerns.23 It is evident that PCTFE-based materials (e.g., laminate films, blister packs, etc.) do not satisfy the above definition of microplastics. Therefore, the blanket application of conclusions regarding PBT/vPvB and non-threshold properties of microplastics, as proxies to unacceptable risk to all fluoropolymers (and PCTFE, in particular) without the adequate and comprehensive risk assessments of their respective hazards and exposure, is not justified.24 The adequate scientific assessment of PCTFE, which is required to demonstrate the level of "unacceptable risk" under Article 68 REACH, is missing in sections 1.1.4., 1.1.5 and 1.1.6 of the Proposal. 4. Regulation of packaging of medicinal products and medical devices PCTFE based Aclar fluoropolymers are used as non-contact components of the "immediate packaging", "closed container" or "primary packaging" of final medicine products, within the meaning of the EU legislation on the regulation of medicinal products for human or veterinary use.25 Goods subject to EU medicinal regulations are explicitly excluded from the scope of most REACH requirements and procedures because all components of medicinal products, including packaging/containers, are subject to comprehensive and strict safety/quality assessment procedures and data requirements, including on traceability and testing of each component. Their safety for humans, animals, and the environment, including at the waste stages, are vigorously scrutinised/approved by EMA and the EU national authorities prior to obtaining the marketing authorisation (including at the production and disposal stages). 22 See in Conclusions of A Critical Review of the Application of Polymer of Low Concern and Regulatory Criteria to Fluoropolymers, Barbara J Henry et all, Integrated Environmental Assessment and Management -- Volume 14, Number 3--pp. 316-334, 2018. 23 In this context RAC concluded in section B.1.2.2 of the Opinion on the Restriction Proposal of microplastics that "although there are uncertainties in the understanding of the hazard and risk of microplastics, there is sufficient evidence to conclude that that they constitute an intrinsic hazard because of their long-term persistence in the environment in combination with their particulate form and potential to cause adverse effects". 24 See e.g., on three elements of risk - hazard, exposure, and risk based on the hazard manifesting themselves in the exposure in the specific case, Fidenato v Comune di Padova, Case C-442/14, Commission v Germany, Case C-47/90. Etimine SA v Secretary of State for Work and Pensions, C-15/10. 25 I.e. Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency; Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use; Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products. 5 PCTFE (Aclar) materials also comply with the current World Health Organisation (WHO)26 and EU Guideline on Plastic Immediate Packaging Materials27, relevant European Pharmacopoeia Monographs, as well as Directive 2002/72/EC and Regulation (EU) 10/2011 on plastic food contact materials28. In these circumstances, according to the Memorandum of Understanding on Working Arrangements Between the European Medicines Agency (EMA) and the European Chemicals Agency (ECHA) from 14 May 2014, in order to ensure coherence in scientific opinions/evaluations as well as to avoid potential contradictions and "double regulation", RAC/SEAC must consult, exchange information and coordinate with EMA assessments of PCTFE during the PFAS REACH restriction process.29 Moreover, medicinal packaging is subject to EU regulations on packaging and waste.30 These laws establish comprehensive "essential requirements" on composition, safety, and eco-design of packaging materials31 and their environmentally friendly waste treatment (collection, disposal, recycling, etc.). All medicinal products packaging in the EU shall comply with these rules when produced, placed on the market, used, and disposed of within the EU. It is noteworthy that due the high purity of PCTFE, absence of additives and impurities, and extremely low leaching characteristics, its landfill disposal under normal conditions is safe due to the lack of water solubility (see Annex II), and together with municipal incineration32 is "highly recommended" for plastic materials inter alia by the WHO Guideline on Plastic Immediate Packaging Materials.33 In addition, incineration at municipal or medical waste incinerators able to reach temperatures above 800 C, well below the requirements of best available technology (BAT), eliminates all PFAS-related degradation products as well as TFA34. Honeywell believes that RMMs targeting end-of-life risks is a more appropriate risk mitigation option for the pharmaceutical and medical device sectors than blatant prohibitions on all uses of PCTFE, especially because our raw materials are not PFAS-related and our film material is inert by design during the usage-phase of its life. Coupled with voluntary production initiatives of EU fluoropolymers producers, these RMMs could be the most effective risk mitigation as well as economically, technologically, and societally neutral measures to put in practice. Although Honeywell is not a producer of pharmaceutical or medical device packaging as such, the company provides customers (producers/processors of primary packaging) with all required information on traceability and safe use of Aclar, including at the waste stage. We also collaborate across the industry to build-out and expand a future network for blister collection and proper disposal (e.g. Sustainable Medicines Partnership), in addition to funding university 26 Guidelines on packaging for pharmaceutical products, WHO Technical Report Series, No. 902, 2002 27 Guideline on Plastic Immediate Packaging Materials, EMA, London, 19 May 2005, CPMP/QWP/4359/03, EMEA/CVMP/205/04 28 For instance, Commission Regulation (EU) No 10/2011 on plastic FCM materials and articles establishes in Annex I a Union List of substances that are permitted for use in the manufacture of plastic FCMs. Starting monomer CTFE (chlorotrifluoroethylene, CAS 79-38-9) of PCTFE fluoropolymers is included into the above Union List (entry 148). 29 Sections 1-4 of the Memorandum of Understanding on Working Arrangements Between the European Medicines Agency (EMA) and the European Chemicals Agency (ECHA), 14 May 2014. 30 European Parliament and Council Directive 94/62/EC of 20 December 1994 on packaging and packaging waste; Directive 2008/98/EC of the European Parliament and of the Council of 19 November 2008 on waste 31 See Annex II Directive 94/62/EC - Essential Requirements on the Composition and the Reusable and Recovered and Recoverable, including recyclable, nature of packaging. 32 See e.g. Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas, K. Aleksandrov, 2019; Investigation of waste incineration of fluorotelomer-based polymers as a potential source of PFOA in the environment, P.H. Taylor, 2009. 33 See for Plastics Material, Table 2 (Methods of disposal of uncontaminated packaging), page 140, Guidelines on packaging for pharmaceutical products, WHO Technical Report Series, No. 902, 2002 (see also on PVC and released dioxins at page 142). 34 See footnote 8. 6 studies and industrial partnerships to develop chemical recycling technologies whereby PCTFE can be converted back into CaF2 feedstock. The latter program is set to run through 2026. In this respect, the proposed ban on production, placing on the market and use of PCTFE (Aclar) products in the pharmaceutical and animal medicines sectors is disproportionate and excessive. These materials are already subject to vigorous statutory RMMs and strict prior marketing authorisation requirements, aiming to ensure that potential risks are adequately controlled. If warranted, the European Commission can clarify and enhance these measures at any time, as explicitly stated in Article 20 of the Directive 94/62/EC. Under these circumstances, the REACH restrictions on PCTFE (Aclar) are excessive and disproportionate. The same is true regarding the regulation of medical device packaging under EU Medical Devices Regulation (MDR)35, which requires that medical device packaging must be designed and constructed in a way that ensures "stability, and functionality of the device during its shelf life". In this respect, packaging materials used for medical devices should be non-toxic, non-reactive, and non-absorbent, and they should maintain the functionality of the device throughout its shelf life. These requirements are thoroughly assessed within certification and other conformity assessment procedures mandatory for all medical devices in EU.36 PCTFE is the only fluoropolymer which can satisfy all technical specifications required for primary and secondary packaging of many critical medical devices under the MDR (see section 6 below). In addition, the primary packaging for drugs is explicitly tied to the pharmaceutical active in order to ensure stability and efficacy of medical formulations and solid dosages through market authorisations. Furthermore, in previous REACH restrictions, RAC/SEAC and the European Commission repeatedly provided time-unlimited derogations for immediate packaging and materials thereof that are already regulated under the respective medicines, veterinary, cosmetic and/or food contact (FCM) laws based on similar considerations as discussed above. For example, the Entry 51, Annex XVII REACH, restricts Phthalates such as DEHP, DBP, BBP, DIBP and provides a time-unlimited derogation for "(i) the immediate packaging of medicinal products within the scope of Regulation (EC) No 726/2004, Directive 2001/82/EC or Directive 2001/83/EC, ... (g) medical devices within the scope of Directives 90/385/EEC, 93/42/EEC or 98/79/EC, or parts thereof, .... (f) materials and articles intended to come into contact with food within the scope of Regulation (EC) No 1935/2004 or Commission Regulation (EU) No 10/20111". Also Entries 28, 29 and 30 of Annex XVII REACH provide for time-unlimited derogations for use of certain carcinogenic, mutagenic or toxic substances in "(a) medicinal or veterinary products as defined by Directive 2001/82/EC and Directive 2001/83/EC; (b) cosmetic products as defined by Directive 76/768/EEC...". In the current Proposal, the Dossier Submitters also applied the same approach to the regulation of PFAS as active substances in biocidal, plant protection and pharmaceutical products. In Honeywell's view, the use of PCTFE-based materials in final packaging (blister packs, films, containers, bottles, vials, etc.) in medicinal and medical devices packaging applications should be excluded or made subject to an unlimited derogation from the PFAS restriction in question. 5. Information on PCTFE tonnages PCTFE (Aclar) is not produced in the EU/EEA and is only imported by Honeywell for uses in medicinal and medical devices packaging applications in the EU. There are no other PCTFE producers or importers in the EU/EEA for the above uses. 35 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices (as amended) 36 Similar approach is envisaged in the Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and other relevant laws. 7 According to Honeywell's customs data and estimates, annual imports of PCTFE fluoropolymers into the EU was ca. 1 000 tonnes in 2015 - 2020. This constitutes app. 2,3% of total tonnages of PFAS used in the medical devices sector in 2020 (i.e., ca. 43 899 tonnes).37 Moreover, a share of the above PCTFE uses constitutes app. 0,36% of total polymeric PFAS uses put on the market in 2020 (i.e., 277 684 tonnes).38 Moreover, PCTFE is an expensive material, with very low levels of emissions during the manufacturing/processing and use phases (i.e., 1%).39 Therefore, total PFAS-related material from PCTFE (Aclar) production, use, and disposal/end-of-life stages did not reach 10 tonnes in 2020, which is ca. 0,18% of PFAS-related emissions in the medical device sector during the same year (5 674 tonnes)40 and 0,05% of estimated annual emissions of all polymeric PFAS in 2020 (19 958 tonnes)41. Thus, PCTFE tonnages placed on the EU market for uses in pharmaceutical/medicinal and medical devices packaging applications, its total emission tonnages, the potential exposure to humans and the environment, as well as all associated risks are genuinely negligible. In these circumstances, and also considering the physicochemical characteristics of PCTFE as a polymer of low concern (PLC), the REACH restrictions in the Proposal that suggest banning PCTFE uses in medicinal/pharmaceutical and medical devices packaging are disproportionate to the alleged current and/or potential risks and may inadvertently damage supply and accessibly to critical medications across the EEA. 6. Absence of suitable alternatives As correctly highlighted in the Proposal and submitted by many participants of the two Calls for Evidence (CfE) on the PFAS restriction, fluoropolymers (and PCTFE, in particular) are premium products and are only used when their unique combination of properties are required to ensure safety, quality, efficacy, durability, and stability of drug formulations and medical devices. Because PCTFE is an extremely inert material and is categorized as a polymer of low concern (PLC), it is used in numerous critical applications and is indispensable in the delivery and preservation of safe pharmaceuticals as well as the functional integrity of medical devices. In addition, drugs and primary packaging materials are linked in both the EU Market Authorizations and US-FDA Drug Master Files. Our primary packaging materials are used in a broad range of markets, including originator and generic pharmaceuticals, over-the-counter (OTC), pharmaceutical and animal health packaging, in vitro diagnostics (IVD) or medical devices packaging, and others. In the pharma (medicines) sector, PCTFE is used in over 600 oral solid therapies, across all therapeutic areas, including the nervous system, cardiovascular, metabolic, hormonal, antipsychotic, and oncology treatments. PCTFE does not interact with the environment, humans, or broader organisms. Unique PCTFE film properties relevant for medicinal and medical device packaging are: The best moisture barrier of any clear thermoplastic film (highest WVTR protection)42 Bio-chemical inertness (very low leaching/migration) Chemical-resistance (practically to a broad range of chemicals) The highest crystal clarity of any thermoforming film on the market43 37 Table E.107, section E.2.9., Annex E of the Proposal. 38 Mean value Table A.10, Annex A of the Proposal. 39 See last paragraph page 316, section E.2.9.1, Annex E of the Proposal. 40 Table E.107, section E.2.9., Annex E of the Proposal. 41 Total mid value for polymeric PFAS in Table 1 of the Proposal. 42 Including, polyethylene terephthalate (PET) & ethylene vinyl alcohol (EVOH). 43 In applications where dosage, timing, and potential abuse are critical (children, elders, etc.), patients must be able to use colourless transparent packaging formats to ensure compliance and patient safety. 8  Non-flammability; Plasticizer and stabilizer free Highly flexible, enabling deep draw packaging designs; Cryogenic stability PCTFE (Aclar) films have also very good machineability and can be used on existing thermoforming lines alongside other materials like PVC, PVC/PVDC, COC and PP, without the use of additional tooling. Therefore, it is a drop-in solution for thermoforming that offers best-in-class moisture barrier and clarity while working alongside existing infrastructure. They are also sealable against all aluminium lidding foils with PVC heat-seal lacquers, as well as lacquers for sealing against Aclar films. Moreover, primary packaging of any medicinal product is critical to preserving drug stability and shelf life which dictates the extent to which an active substance or a final drug maintains its quality, safety, and efficacy throughout its storage period, shelf life and use. The latter refer to the extent to which an active substance or a final drug preserves its quality, safety, and efficacy throughout its storage period and use. Stability characteristics are an integral part of the "marketing authorisation" conditions specified by EMA or national medicines authorities for each medicinal product (analogue of a mandatory "technical specifications"). Changes in these specifications require extensive and costly testing and approval by the authorities (see in more details in section 7 below). None of the potential alternatives for blister or other primary medicine packaging match the properties of PCTFE materials relevant for the stability of drugs. Aclar is particularly effective with the best barrier at lowest material use, while also exhibiting unparalleled performance in high barrier moisture protection when compared to any other polymer. Some drugs may be packaged with varying levels of moisture protection, but PCTFE-film is unmatched in high-barrier applications that require clarity along with maximum protection needed to meet the marketing authorisation specifications approved for drugs packed using Aclar products. Alternatives such as cold form foil (CFF) do not meet transparency needs and increase packaging sizes up to 55% compared to thermoformed blisters using Aclar. The same is equally true for stability and functional characteristics of medical devices during their entire shelf life. In addition, there is a potential for a higher risk of exposure to hazardous substances from substitutes aiming to meet the high standards of PCTFE fluoropolymers in many applications. This brings higher safety risks, increases in hazardous emissions resulting from technical regression, and could put the EU goals for climate and energy at risk. For instance, other plastic materials, inter alia PVC and PVDC, discharge significant amounts of hydrochloric acid, dioxins, and furans during incineration and thus are more harmful for the environment than PCTFE. It is noteworthy that, in May 2022, the European Commission requested ECHA to investigate in-depth PVC materials and additives, while considering the preparation of the Annex XV REACH report44. In the meantime, cold form foils (CFF) in comparison to PCTFE, are not transparent (opaque) and increase packaging sizes up to 55%, negatively affecting the EU's Grean Deal and resource efficiency goals. Non transparent packaging has been shown to decrease the efficacy of treatment regimens due to decreased patient adherence.45 Creating a smaller pack size with PCTFE fluoropolymers directly reduces raw material (film/foil) usage, waste production, warehousing expenses, and transportation/energy costs along with CO2e emissions. According to Honeywell's knowledge, and submissions of other stakeholders during the two Calls for Evidence (CfE) for the PFAS restriction proposal, there are no acceptable chemical or functional substitutes to PCTFE films for use in medicinal and medical devices packaging available on the market. Other materials do not provide the required properties/benefits and characteristics specified in the respective marketing authorisations/certificates. Use of substitutes (like PVC, COC, COP, etc.) will 44 See e.g., Request to the European Chemical Agency to prepare an investigation report on PVC and PVC additives, ECHA's Call for evidence on alternative additives in PVC, and other plastics and respective Honeywell submission (No Ref-Nr. b0bdd158-b0b6-4c8b-b97d-8e8648949bfe). 45 Global Trends in Child-Resistant Pharmaceutical Packaging Proven Strategies for Preventing Injury, Green, M., Honeywell International, March 2014. 9 inevitably result in shorter storage time and use periods of medicinal products and reduced functionality of devices, which are crucial characteristics for many drugs and medical equipment. Material substitutes like PVDC offer similar storage times, but yellow over time and the moisture barrier properties differ depending on environmental temperatures and relative humidity levels. 7. Socio-economic impact of the proposed PCTFE REACH restriction The costs associated with changes to packaging formats (technology, machinery, tooling, etc.) are borne by producers of packaging, pharmaceutical and medical devices companies and ultimately patients. If PCTFE materials were to be banned, pharmaceutical producers would be required to identify, develop, and qualify potentially inadequate human and veterinary alternative packaging formats, resulting in additional R&D costs, stability testing, and other regulatory costs for each drug currently packaged in PCTFE materials. These costs would inevitably be passed on to national healthcare systems, insurance companies, and end-use patients. In the meantime, the inferior moisture barrier and migration properties of other packaging materials will decrease quality, storage and use periods of medicinal products and devices. This will directly affect the safety, health, and environmental characteristics of medicines, as well as elevate costs on the industry and undermine patient affordability of medical treatments due to medicine expiration and increased product returns. These consequences could have significant impacts on the population in specific situations (emergency stocks, highly sensitive formulations/devices, transportation, and cryogenic storage conditions for vaccines, etc.). For instance, REACH restrictions on PCTFE uses in medicinal packaging (for humans and animals) will require addition "stability testing" and approval of changes/variations by EMA and/or national medicines authorities for each existing active substance and dosage of final medicinal product (currently over 600). This will not only require substantial development time (i.e., tests normally performed for long time periods with regular intermediate controls) but also considerable human resources from the industry and authorisation authorities. According to available information, the costs of "stability testing" for each medicinal product could reach 100.000 - 500.000 Euro, excluding EMA and/or national authorisation authorities fees (26.000 - 86.000 Euro per product/dosage) for the approval of potential variations. All of those costs will be passed on to final consumers and public budgets. In cases where alternative packaging would not provide satisfactory stability characteristics to active substances or final medicinal products, this will require changes to the medicinal formulations as such implying considerable costs and time for developing new medicinal products and obtaining marketing authorisation (additional testing, preparation of valid applications, evaluations by the authorities, etc.). This will also trigger costs for processors/producers of packaging materials to retool and refit their machinery for other barrier materials. According to Honeywell's dedicated estimates, new packaging changes alone will potentially add over 3 mln. Euro of additional costs for one drug and 1,896 bln. Euro for the entire Aclar product portfolio.46 Considering the average annual PCTFE (Aclar) supply tonnages in the EU (ca. 1 000 tonnes), substitution costs would reach over 18 mln. Euro per kg. of PCTFE. However, the overall socioeconomic impact of the REACH restriction on PCTFE uses in pharmaceutical and medical devices sectors, but also on medicinal products and devices diversity, are difficult to estimate. These restrictions would considerably limit the innovative capacity of the EU pharmaceutical industry, including the development of vaccines and other new drugs/devices/implants. It will also undermine the EU's economic goals and would hinder or jeopardise goals within the EU Green Deal. 46 Estimated conversion costs per drug - 3.034.000 Euro; Current number of drugs - 625, Total conversion costs - over 1,896 billion Euro, see detailed calculations in Annex III below. 10 8. Conclusions and proposal for exclusion or a new derogation Honeywell submits that the potential REACH restrictions on the use of PCTFE (Aclar) products in the pharmaceutical/medicinal and medical devices industry are not justified under Title VIII REACH. PCTFE is a well-studied Polymer of Low Concern (PLC) for which the grouping with other PFAS for REACH restrictions and read-across purposes is not scientifically justified. The Proposal reaches erroneous conclusions on PCTFE's hazardous properties, tonnages/emissions (which are negligible in practice) and risk characterisation. Moreover, PCTFE uses in medicinal and medical devices packaging applications are adequately controlled by comprehensive RMMs mandated under relevant EU Governing Agencies for Pharmaceutical Development and national laws during its entire life cycle. The proposed REACH restriction on PCTFE would result in disproportionally higher costs for society, due to decreased availability of vital drug products and higher medical costs, when compared with any possible risks due to the persistency of PCTFE-based fluoropolymers that are not made from PFAS monomers and are inert in the use-phase and at end-of-life. The most preoccupying of these possible future risks is decreased medical safety and increased cost or efficacy of medical treatments. In line with previous RAC/SEAC practices in similar situations/circumstances, PCTFE-based materials in medicinal and medical devices packaging (including PCTFE input materials and the final packaging) should either be excluded from the scope of the Proposal or provided with an unlimited derogation on similar practical grounds as other unlimited derogations already considered by the Proposal. In this respect, the following unlimited derogation should be added as the point 4.d. to Column 2 of the Proposed restriction: "d. PCTFE-based materials for the packaging of human and veterinary medicinal products, medical devices and in vitro diagnostics medical devices within the scope of Regulation (EC) No 726/2004, Regulation (EU) 2019/6, Directive 2001/83/EC, Regulation (EU) 2017/745 and Regulation (EU) 2017/746" ___________ Annex I - List of acronyms and abbreviations Annex II - PCTFE PLC status (OECD 120) Annex III - Honeywell cost analysis and calculations for the PCTFE (Aclar) substitutions scenarios 11