Document KRMDN7DEREaN5Bwn44BxQy3j2

Confidential - Company Proprietary SECTION III. Non-confidential comments It is possible to provide both general comments on the Annex XV restriction report subject to this Consultation and answers to the specific questions posed. In both cases, it is necessary to provide supporting evidence to allow ECHA's Committees to take your comments into account. It is important not to leave the submission of any socioeconomic information until the consultation on SEACs opinion but already submit relevant comments at this stage. General Comments Select the relevant boxes that cover the content of your comments and provide your non-confidential comments below, (maximum 9 000 characters) General Comments The current analysis and proposal do not proportionally address the high industry impact on the life sciences and biopharmaceutical sectors. This initial response seeks to outline the high industry concern and key missing uses; we will also submit a further response with detailed data on the costs and impact to our industry by the consultation deadline to further inform ECHA's assessments. This response: Requests a 6 month extension to the consultation period to collect and provide data on the impact on the life sciences and biopharmaceutical sectors and the socio-economic risks this restriction poses to industries and their downstream users, including patients. Requests that fluoropolymers be excluded from the scope of the restriction; Requests that the critical equipment used to fabricate pharmaceutical and biopharmaceutical products be recognized as missing uses and proportionate derogations be considered; Responds to specific information request for the following 5 missing uses: o [1] Hydrophobic and/or Oleophobic Filtration Membranes in Pharmaceutical Processing o [2] Fluoropolymer-based bioprocessing materials (e.g. membranes, gaskets, seals, fittings, etc.) in which no PFAS (<C16) chemicals or processing aids are used to manufacture the polymer o [3] Fluoropolymer-based bioprocessing materials (e.g. membranes, gaskets, seals, tubing, O-rings, pumps, connectors) in which PFAS-processing aides may be used in the manufacture of the polymer. (e.g. PTFE filtration membranes, gaskets, seals, etc.) o [4] Fluoropolymer used as auxiliaries on sites to manufacture chemicals vital to the bioprocessing industry o [5] Membranes used in medical device-related applications, including oleophobic, PTFE, and PVDF It is crucial to approach the proposal with careful consideration of the impact on life sciences and biopharmaceutical manufacturing and the supply of critical lifesaving vaccines and medicines, the development and production of which involve complex processes requiring adherence to stringent quality standards, regulatory compliance, and extensive testing. Any significant changes in our Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary practices can have far reaching consequences for patients, innovation, and the ability of our industry supply chains to respond e.g. to future global pandemic threats. We are a supplier of hardware, specialized chemicals, consumables, and medical device products. Our products are used in applications ranging from fundamental biological research to making lifesaving vaccines, biologic drugs, and novel cell and gene therapies. We supply the tools and services that help our customers do their work better, faster and safer. Some of our products, such as filters and membranes, can also support a range of applications in industries outside of biological research and manufacturing. We have 16,000 associates across 41 countries worldwide including manufacturing sites in Sweden, Denmark, Germany, Belgium, the Netherlands, and Austria. Endorsement of Related ECHA Submissions. As a member of the bioprocessing industry committed to sustainable solutions, we also support related industry group sector responses, including those from BPSA (Bioprocess systems alliance), BioPhorum, ASME-BPE, and EFPIA. Extension to the consultation period due to supply chain mapping challenges Due to the breadth of the proposed restriction and the scale of the scoping challenge (detailed below), we request that ECHA considers extending its consultation period to enable more companies like ours to fully map out and quantify the risks this restriction poses to industries and the downstream users of these technologies including patients. Given the broad scope of this restriction (affecting over 10,000 substances and polymers), further time should be given to consult on its impact and to implement it. In addition, since most of these PFAS, including fluoropolymers are not currently under any restricted or controlled list requiring notification to the authorities or downstream users and given that polymers are exempt from registration requirements, fully mapping out the impact of this broad restriction for any industry's entire supplychain in 6 months is extremely challenging and requires the generation of massive amounts of new data. Furthermore, identification using CAS number is reduced given that most of the PFAS do not have CAS numbers, in particular polymers. For a complex company like ours, this means manually assessing 100,000+ components used to manufacture hardware and consumables to initially identify if they are high or low risk materials. Only then can we begin discussions with suppliers and R&D to understand potential alternatives and replacement timelines. The challenge of mapping the impact goes beyond intentionally added PFAS in products and requires an assessment of auxiliaries both in our own manufacturing processes (i.e. a fluoropolymer O-ring in a chemical plant), as well as auxiliaries upstream in our supply-chain. The proposed restriction could cause such auxiliary products to become unavailable, risking our customers' ability to manufacture biopharmaceuticals and other life science products in the EU. This means multiplying our abovedetailed product scoping and assessment work to complete the same exercise for all indirect materials used at our own manufacturing sites, and again for materials used by suppliers upstream in the supply chain. Therefore, the scope of the restriction extending to auxiliary and indirect products means it is impossible to fully assess the impact of the proposal while generating sufficiently accurate data. Given these time constraints as well as the urgency to give input while discussions are ongoing, we will continuously be giving input to this consultation as more data is being developed. There is also a disproportionate challenge of identifying PFAS when used as an additive in other plastics to add necessary product safety properties, such as adding PTFE in low amounts to add anti- Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary drip properties to polymers used in electronics and hardware. To capture all such cases, it would be necessary to test all materials with certified labs which is time prohibitive given the limited consultation period and the high demand for testing it has generated, creating large lead times. All input must be viewed as the current best knowledge, but not the complete picture of the impact of the PFAS restriction. As such, at a minimum, broad industry-wide exemptions and/or derogations that cover uses across the entire supply-chain will be necessary to avoid key materials becoming unavailable in the EU in the near term. Scope or restriction option analysis A. Fluoropolymers used in industry should be exempted from the scope of the restriction. We fully support efforts to minimize and mitigate the presence of substances which pose a threat to human health and the environment. However, restrictions to commonly used materials such as fluoropolymers pose a risk to the EU's ability to supply itself with lifesaving therapies, both due to material shortages as well as regulatory approval backlogs from having to revalidate the manufacturing processes of the biologicals due to material/tool changes in their manufacturing processes. The proposed broad restriction of PFAS covering fluoropolymers would have unintended consequences on the global manufacturing of life science and biopharmaceutical products using tools containing PFAS or tools manufactured using products containing PFAS. We will submit data on how the proposed restriction affects our products which are present in every step of the drug development process, from research and drug discovery, to the fill and finish for monoclonal antibodies, mRNA vaccines, viral vectors, and cell therapies; all therapies that are vital to the health of EU citizens. Even if many of these fluoropolymer components could over time be replaced with PFAS-free materials as described in response to sections 5 & 6 below, the workload of finding appropriate replacement materials and redesigning all products impacted by this restriction in a few years will not be feasible. In addition, re-designs to the product or material changes done by customers will in some cases result in the customer using the product to manufacture pharmaceuticals having to re-validate their process with competent authorities, resulting in additional years after the change before the new material can be put to use. This will also place a significantly demanding workload on the competent authorities given the number of manufacturing processes impacted by the restriction proposal. Given all these challenges, we request that fluoropolymers used in industry be exempted from the proposed regulation in a manner similar to how the restriction of microplastics was managed. This will avoid the risk of materials upstream in the supply chain becoming unavailable while still significantly reducing the amount of PFAS placed on the market in consumer goods. Industrial manufacturing environments and the disposal of their waste is well controlled and regulated. An example of this is that today filters used during pharma-manufacturing are incinerated at the end of life, reducing the hazard they pose to human health and the environment.1 It is also important to ensure manufacturing remains in EU countries to reduce dependency on supply chains located mainly outside of the EU. 1 Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas, Krasimir Aleksandrov et al. Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary B. Missing uses associated with Pharmaceutical and Biopharmaceutical Processing Although the PFAS regulations proposed by the ECHA mentions PFAS used as ingredients of pharmaceutical products, there is currently no proportional consideration of, or specific derogation for, the critical equipment (filtration membranes, gaskets and seals, fittings, etc.) used to fabricate pharmaceutical and biopharmaceutical products (i.e. medicines) needed for patient therapies. In fact, we estimate that 80% of biopharmaceutical manufacturing projects, including those developed for COVID therapies, use impacted materials as part of the pharmaceutical manufacturing process. It is important to balance the critical need for these impacted materials for production of highly-regulated medicinal products against the very low volume of plastics used within our industry, which contributes to no more than 0.01% of the world's total plastic waste ("The Green Imperative", BioProcess International 18(6), June 2020). The size of the bioprocess technology market (which is only a portion of where these materials are used in overall pharmaceutical processing), is reported of the order of $24B for 20232, and growing at approximately 15% CAGR. The cost and ultimate socio-economic impact would be immense if insufficient time is given to determine if alternatives are available or can be developed. The specific types of technologies supporting bioprocessing that are impacted by the proposed broadly-defined regulations include those listed in section 6. These materials are chosen specifically for their chemical resistance, thermal resistance, wear resistance, transparency and ability to repel both polar and non-polar substances. Given that these components are often used in the fluid path during pharma manufacturing there is both, successful biological reactivity data associated with these materials as well as chemical extractables data showing such materials not releasing substances that would be hazardous to human health. These components are used both as components in hardware systems as well as consumables. Specific Information Requests 1: Sectors and (sub-)uses: Please specify the sectors and (sub-)uses to which your comment applies according to the sectors and (sub-)uses identified in the Annex XV restriction report (Table 9). If your comment applies to several sectors and (sub-)uses, please make sure to specify all of them. 2 www.globenewswire.com/en/news-release/2023/01/04/2582694/0/en/Bioprocess-Technology-Market-Sizeto-Worth-Around-USD-79-BN-by2032.html#:~:text=04%2C%202023%20(GLOBE%20NEWSWIRE),USD%2020.8%20billion%20in%202022. Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary 2: Emissions in the end-of-life phase: The environmental impact assessment does not cover emissions resulting from the end-of-life phase. To get a better understanding of the extent of the resulting underestimation, (sub-)use-specific information is requested on emissions across the different stages of the lifecycle of products, i.e. the manufacture phase, the use phase and the end-of-life phase. Please provide justifications for the representativeness of the provided information. In particular: a. Please provide, at the (sub-)use level, an indication of the share of emissions (as percentages) attributable to these three different stages. An indication of annual emission volumes in the end-of-life phase at sector or sub-sector level would also be appreciated. b. If possible, please provide for each (sub-)use what share of the waste (as percentages) is treated through incineration, landfilling and recycling. Please provide information to justify the estimates as well as information on the form of recycling referred to. 3: Emissions in the end-of-life phase: With respect to waste management options, additional information is requested on the effectiveness of incineration under normal operational conditions (for different waste types, e.g. hazardous, municipal) with respect to the destruction of PFAS and the prevention of PFAS emissions. Based on input from our customers, the vast majority of PFAS materials used by them in membranes and products is incinerated at the end of life as the material has been in contact with biological material. According to some studies such as "Waste incineration of Polytetrafluoroethylene (PTFE) to evaluate potential formation of per- and Poly-Fluorinated Alkyl Substances (PFAS) in flue gas" published at ScienceDirect, PTFE, for example, can be effectively incinerated above 800C reaching complete thermal decomposition, demonstrating that effective disposal methods are available to prevent accumulation of waste fluoropolymer products in landfill. Similar to the microplastics restriction derogation for industrial use, reporting requirements on amounts of polymeric PFAS purchased annually combined with reporting requirements on disposal at end of life could be implemented to monitor the amounts placed on the market and reduce the release of these materials to the environment. Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary 4: Impacts on the recycling industry: To get an understanding of the impacts of the proposed restriction on the recycling industry, information is requested on: a. The impacts that the concentration limits proposed in paragraph 2 of the proposed restriction entry text (see table starting on page 4 of the summary of the Annex XV restriction report) have on the technical and economic feasibility of recycling processes (together with a clear indication on the waste streams to which the described impacts relate). b. The measures that recyclers would need to take to achieve the proposed concentration limits. c. The costs associated with these measures. N/A Cannot speak for the recycling industry 5: Proposed derogations - Tonnage and emissions: Paragraphs 5 and 6 of the proposed restriction entry text (see table starting on page 4 of the summary of the Annex XV restriction report) include several proposed derogations. For these proposed derogations, information is requested on the tonnage of PFAS used per year and the resulting emissions to the environment for the relevant use. Please provide justifications for the representativeness of the provided information. * Compulsory Fields6: Missing uses - Analysis of alternatives and socio-economic analysis: Several PFAS uses have not been covered in detail in the Annex XV restriction report (see uses highlighted in blue and orange in Table A.1 of Annex A of the Annex XV restriction report). In addition, some relevant uses may not have been identified yet. For such uses, specific information is requested on alternatives and socio-economic impacts, covering the following elements: a. The annual tonnage and emissions (at sub-sector level) and type of PFAS associated with the relevant use. b. The key functionalities provided by PFAS for the relevant use. c. The number of companies in the sector estimated to be affected by the restriction. Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary d. The availability, technical and economic feasibility, hazards and risks of alternatives for the relevant use, including information on the extent (in terms of market shares) to which alternative-based products are already offered on the EU market and whether any shortages in the supply of relevant alternatives are expected. e. For cases in which alternatives are not yet available, information on the status of R&D processes for finding suitable alternatives, including the extent of R&D initiatives in terms of time and/or financial investments, the likelihood of successful completion, the time expected to be required for substitution (including any relevant certification or regulatory approvals) and the major challenges encountered with alternatives which were considered but subsequently disregarded. f. For cases in which substitution is technically and economically feasible but more time is required to substitute: i. the type and magnitude of costs (at company level and, if available, at sector level) associated with substitution (e.g. costs for new equipment or changes in operating costs); ii. the time required for completing the substitution process (including any relevant certification or regulatory approvals); iii. information on possible differences in functionality and the consequences for downstream users and consumers (e.g. estimations of expected early replacement needs or expected additional energy consumption); iv. information on the benefits for alternative providers. g. For cases in which substitution is not technically or economically feasible, information on what the socio-economic impacts would be for companies, consumers, and other affected actors. If available, please provide the annual value of EU sales and profits of the relevant sector, and employment numbers for the sector. [1] Hydrophobic and/or Oleophobic Filtration Membranes in Pharmaceutical Processing These membranes, which are coated in PFAS-related chemistries to alter their surface tension properties, prevent the passage of microorganisms such as bacteria and endotoxins. The membrane coatings function to repel moisture and various liquids, thereby preserving the functional properties of the membrane itself. Such membranes are heavily used in aseptic pharmaceutical processing to maintain the sterility of connectors while connecting unit operations. Alternatives are not yet available. In the past 10 years, many of these membranes have been redeveloped to move away from PFOA-based chemistries but are now impacted by the newly proposed regulations. Whereas it is expected that many (~80%) of these membranes formulations can be redeveloped to be PFAS-free (per ECHA definition), these R&D development projects Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary typically require approximately 4 years per membrane type. Also please note that the resources developing alternatives, cannot simultaneously be developing alternatives to these and the other impacted materials indicated further below. Once developed, implementing any novel alternative membranes in validated and regulated pharmaceutical manufacturing processes can take anywhere between 6 months to 2 years, and can require extensive resources from the pharmaceutical manufacturer, which would divert resources from other patient therapies or impact the cost of medicines. Requested derogation. We request a derogation of 13.5 years for development and transition to PFAS-free oleophobic filtration membranes for bioprocessing where such alternatives can be developed (expected 80%). We request an indefinite derogation for those smaller number of applications where suitable alternatives cannot be produced (expected 20%). [2] Fluoropolymer-based bioprocessing materials (e.g. membranes, gaskets, seals, fittings, etc.) in which no PFAS (<C16) chemicals or processing aids are used to manufacture the polymer. Many of the fluoropolymer materials deemed in scope of the ECHA definition and used to support bioprocessing are already made without the use of small molecule (<C16) PFAS chemicals or processing aids (e.g. PVDF), as investments to move away from PFAS processing aids were implemented many years ago. To group these types of fluoropolymers together with lower grade materials where such improvements have not been made is not proportional to the risk they pose and punishes industries that have invested in preemptively phasing out small molecule PFAS. Our understanding is that these fluoropolymers still fall under the broad scope definition of PFAS by ECHA, but pose no meaningful level of PFAS-related environmental pollution during manufacturing, use, or end of life. At a minimum, any references suggesting a meaningful PFASrelated environmental impact from these materials are highly specious, and warrants additional review given the enormous socio-economic impact to the pharmaceutical manufacturing industry and patients who require medicines that these materials enable. Examples of these materials used in biopharmaceutical processing can include but are not limited to PVDF gas/air filtration membranes, PVDF liquid filtration membranes for removal of bacteria, PVDF filtration membranes for removal of viruses, PVDF tubing fittings, PVDF gaskets and seals, PVDF bearing races, PVDF tubing clamp, etc. Substitutions & Alternatives [2a] For bioprocessing applications such as fittings, and tubing clamps, it is expected similar devices made from polypropylene or PBT may be available or could be developed over 2 to 5 years. The number of impacted designs means these could not all be done simultaneously, and hence staggered implementation over a longer 10+ time frame may be required. [2b] For gas filtration membranes used in bioprocessing (typically PVDF or PTFE), few to no validated alternatives are available which can be readily sterilized in a way acceptable to biopharmaceutical manufacturing processes, and which can yield similar or acceptable performance characteristics. Development of economically-feasible alternatives is questionable, may depend strongly on the various chemistry and temperature of individual pharmaceutical processes, and can require extensive time (6 months to several years) to validate for individual pharmaceutical processes. Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary [2c] For liquid filtration membranes used to remove particulates and bacteria (i.e. sterilizing grade filtration), these filters are frequently used both throughout, and also during the final steps of the biologics manufacturing process. In some cases, such as with some types of buffer filtration, these membranes may be substituted for a similar membrane made of PES (polyethersulfone). However, in many cases, depending on the drug formulation and processing conditions (flow rate, throughput, temperature, etc.), the alternative PES membrane does not provide adequate bacteria retention properties. This is specifically why pharmaceutical regulatory requirements require costly performance validation using conditions reflecting the specific drug formulation and manufacturing process. In addition, some impacted filtration membranes require layers of both PES membrane and PVDF membrane in order to ensure adequate performance characteristics for removing bacteria from pharmaceutical manufacturing processes. The cost of revalidating a substitute membrane where alternatives do exist, can require months to years for each pharmaceutical process, and frequently requires additional pharmaceutical studies beyond membrane performance evaluation, including drug product stability, drug matrix adsorption, and leachables analysis to evaluation other chemical compounds that can migrate from the materials into the drug. [2d] Virus retention filters. These membranes (e.g. PVDF) are required in many biopharmaceutical manufacturing processes to ensure any potential contaminating virus are removed from the drug manufacturing process stream. In some cases, alternative PES membranes may be suitable alternatives, and in other cases, the substitutes may have performance (retention, flowrate, compatibility) challenges that make such alternatives unsuitable. Moreover, the resource requirements to revalidate a virus retention membrane are often far more complex than those for sterilizing grade filtration ([2c]) requiring specialized testing laboratories capable of handling mammalian virus and controlled drug substances. [2e] Gaskets, seals, ball bearing seats, etc. These bioprocess materials are used for chemical compatibility and ensuring integral seals in the pharmaceutical manufacturing process that prevent risks of contamination into the process, prevent leakage and loss of medicines during processing, and various individual technical functions. Replacement of these types of bioprocessing materials depends strongly on how well candidate alternatives perform within the chemical and process conditions of each pharmaceutical manufacturing process. There are no universal substitutes that readily replace these materials, as each would require evaluation on a case-by-case basis. Requested Derogation. Given what is understood to be a low toxicity concern of fluoropolymers manufactured without the uses of small chemical (<c16) PFAS processing aids, the enormous socioeconomic impact to industry and patients, and how materials that contact drug substances must be handled, we request such materials be removed from scope or given a permanent derogation. [3] Fluoropolymer-based bioprocessing materials (e.g. membranes, gaskets, seals, tubing, O-rings, pumps, connectors) in which PFAS-processing aides may be used in the manufacture of the polymer. (e.g. PTFE filtration membranes, gaskets, seals, etc.) Fluoropolymers (including those which may use small chain PFAS precursors). Fluoropolymers, including PTFE, FEP, FKM, FFKM, PVDF, PFA are widely used to support bioprocess applications with most data indicating that any low level, intentionally-added PFAS residuals are biologically unavailable and not impactful to human health. The assumption that PFAS molecules within these polymers may be liberated in meaningful levels over the product lifecycle and become Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary bioaccumulative, rely largely on speculation, and at a minimum require further evaluation given the relatively small volumes used in the bioprocessing industry and the enormous socio-economic impact. Based on input from our product and material experts, there are today no good PFAS-free replacements for these materials. [3a] PTFE filtration membranes (e.g. removes bacteria from gases and fluids) used in pharmaceutical applications are critical for chemical, temperature, and oxidation compatibility. Given the uniqueness of fluoropolymers such as PTFE, there are no universal substitutes readily available, and in most cases, suitable substitutes for most of these applications are not available. It is envisioned that given sufficient R&D investment and time (10+ years), different membranes may be able to be developed for up to 50% of these applications. However, this would likely result in multiple unique membranes developed for a single membrane today, and the viability of developing economically viable alternatives is also highly speculative. [3b] Gaskets and seals. Similar to [2e], candidate alternatives would need to be evaluated on a case-by-case basis. In addition, given that this category [3] largely includes PTFE, which has unique chemical resistance properties, the likelihood of finding and validating suitable alternatives for each application is low, based on input from internal material experts. Other applications. There are likely similar impacted applications as those described in [2]. However, given the unique nature of fluoropolymers in this class (e.g. PTFE, PFA, etc.), restrictions on these materials used in bioprocess applications will likely pose significant hurdles to current and evolving pharmaceutical innovations, including cell and gene therapies, where extremely low temperature freezing of augmented cells benefits strongly from the malleable low temperature flexibility and compatibility of fluoropolymer storage bags. Other examples include valve rotors currently using PEEK CF30+PTFE15 material which will not work without PTFE due to wear. Today we have no alternative materials to replace these rotors. Glues containing PFAS which form fluoropolymers while hardening used to glue optical components will also be challenging to replace, today there are no PFAS-free alternatives that are known to work for our applications. Requested Derogation. Given what is understood to be a low toxicity concern of fluoropolymers including those manufactured with PFAS processing aids, the enormous socio-economic impact to industry and patients, and how materials that contact drug substances must be handled, we request that such materials be removed from scope or given a permanent derogation. [4] Fluoropolymer used as auxiliaries on sites to manufacture chemicals vital to the bioprocessing industry. In the same way fluoropolymers are used as components in products described in section [2] and [3], components like O-rings, pumps, gaskets and seals are also used on chemical manufacturing sites to create chromatography resins and other chemical products that are vital to the bioprocessing industry. PTFE coatings are also standard in reaction vessels for highly oxidative reactions. At this point suppliers have indicated they would need at least 10 years to develop PFAS-free alternatives to these types of reactor coatings. Collective socio-economic impact of restricting missing uses Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary If, at the very least/minimum, derogations are not offered to the 4 above uses, we estimate that more than 80% of biopharmaceutical manufacturing campaigns in the EU will be impacted, resulting in impact on the scale of 20+ billion a year for an industry whose polymer usage contributes to no more than 0.01% of the world's total plastic waste. The cost in finding and revalidating alternatives, which will be unique and specific to different drug manufacturing processes, will impact availability of resources to bring current and new drugs to market thereby potentially resulting in drug shortages. In addition, it is likely taht such enormous costs will ultimately be passed down to patients. Even if derogations are offered for these uses there will be a massive risk of these materials becoming unavailable as the Life Sciences industry represents as a small fraction of the overall use which may otherwise be restricted. Exemptions for fluoropolymers used in industry would minimize these risks. [5] Membranes used in medical device-related applications, including oleophobic, PTFE, and PVDF Membranes and seals with similar technical and performance properties to those described above in [1], [2], [3] and [4], are also heavily used for patient therapies as part of medical device applications. Our interpretation of Annex XV, including annex A.3.10, Table A.99, is that it does not specifically cover the medical device-related applications summarized below, and any potential derogations may be insufficient. Such applications include but are not limited to syringe filters, IV-line fluid filters, vent filters for IV sets, urinary drainage bags, oncologic/hazardous drug transfer devices, organ transplant carrier system, medical drug packaging, surgery kits (e.g. cardiovascular, eye surgery, etc...), and insulin pumps. In our position as a leading membrane manufacturer for medical applications, many of our membranes are subsequently incorporated into different types of medical devices, and hence the full breadth of applications is expected to be far larger. In most cases, our understanding, is that alternatives for these wide variety of applications are not available, and that any potential future alternatives would not be universally applicable, but instead requires multiple alternatives that would need to be tested and verified for each unique application. 7: Potential derogations marked for reconsideration - Analysis of alternatives and socio-economic analysis: Paragraphs 5 and 6 of the proposed restriction entry text (see table starting on page 4 of the summary of the Annex XV restriction report) include several potential derogations for reconsideration after the consultation (in [square brackets]). These are uses of PFAS where the evidence underlying the assessment of the substitution potential was weak. The substitution potential is determined on the basis of i) whether technically and economically feasible alternatives have already been identified or alternative-based products are available on the market at the assumed entry into force of the proposed restriction, ii) whether known alternatives can be implemented before the transition period ends (taking into account time requirements for substitution and certification or regulatory approval), Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary and iii) whether known alternatives are available in sufficient quantities on the market at the assumed entry into force to allow affected companies to substitute. A summary of the available evidence as well as the key aspects based on which a derogation is potentially warranted are presented in Table 8 in the Annex XV restriction report, with further details being provided in the respective sections in Annex E. To strengthen the justifications for a derogation for these uses, additional specific information is requested on alternatives and socio-economic impacts covering the elements described in points a) to g) in question 6 above. 8: Other identified uses - Analysis of alternatives and socio-economic analysis: Table 8 in the Annex XV restriction report provides a summary of the identified sectors and (sub-)uses of PFAS, their alternatives and the costs expected from a ban of PFAS. More details on the available evidence are provided in the respective sections in Annex E. For many of the (sub-)uses, the information on alternatives and socio-economic impacts was generic and mainly qualitative. In particular, evidence on alternatives was inconclusive for some applications falling under the following (sub-)uses: technical textiles, electronics, the energy sector, PTFE thread sealing tape, non-polymeric PFAS processing aids for production of acrylic foam tape, window film manufacturing, and lubricants not used under harsh conditions. More information is needed on alternatives and socio-economic impacts to conclude on substitution potential, proportionality, and the need for specific time-limited derogations. Therefore, specific information (if not already included in the Annex XV restriction report or covered in the questions above) is requested on alternatives and socio-economic impacts covering the elements listed in points a) to g) in question 6 above. 9: Degradation potential of specific PFAS sub-groups: A few specific PFAS sub-groups are excluded from the scope of the restriction proposal because of a combination of key structural elements for which it can be expected that they will ultimately mineralize Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction. Confidential - Company Proprietary in the environment. RAC would appreciate to receive any further information that may be available regarding the potential degradation pathways, kinetics or produced metabolites in relevant environmental conditions and compartments for trifluoromethoxy, trifluoromethylamino- and difluoromethanedioxy-derivatives. N/A 10: Analytical methods: Annex E of the Annex XV restriction report contains an assessment of the availability of analytical methods for PFAS. Analytical methods are rapidly evolving. Please provide any new or additional information on new developments in analytics not yet considered in the Annex XV restriction report. N/A Company Proprietary 2023 - ISSUED TO EUROPEAN CHEMICALS AGENCY This document contains proprietary and confidential commercial information of the submitting company and/or its affiliated companies. This document includes data that shall not be disclosed or used outside of ECHA's formal consultation process and shall not be duplicated, used, or disclosed - in whole or in part - for any purpose other than to evaluate this information. This restriction does not limit the European Chemical Agency's right to use the information contained in this data if it is obtained from another source without restriction.