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2023 PQRI Comments to ECHA REACH on Annex XV Restriction Report for Per- and polyfluoroalkyl substances (PFAS) About PQRI The Product Quality Research Institute (PQRI) (www.pqri.org) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality, manufacturing, and regulation. 0 PQRI Comments on Annex XV Restricon Report Contents Glossary............................................................................................................................................................................2 Introducon .....................................................................................................................................................................4 Background - Medicinal product lifecycle ....................................................................................................................4 Scope of Evaluaon ......................................................................................................................................................5 Summary of Core Findings............................................................................................................................................6 ECHA Specific Informaon Requests.................................................................................................................................7 Request #1 Sectors and Sub-uses .................................................................................................................................7 Request #1 Summary - Sectors and Sub-uses.............................................................................................................13 Risk to supply of medicines in EU ...........................................................................................................................13 Regulatory Challenges ............................................................................................................................................13 Pandemic and Catastrophic Event Preparedness ....................................................................................................14 Future populaon...................................................................................................................................................14 Aging populaon ....................................................................................................................................................14 Societal Impact and Unintended Consequences .....................................................................................................15 Request #2 Emissions in the end-of-life phase - manufacture, use, end-of-life..........................................................15 Request #2 Summary - Emissions in the end-of-life phase - manufacture, use, end-of-life........................................18 Request #3 Emissions in the end-of-life phase - incineraon effecveness................................................................18 Request #4 Impacts on the recycling industry ............................................................................................................18 Request #5 Proposed derogaons - Tonnage and emissions......................................................................................18 Request #6 Missing uses - Analysis of alternaves and socio-economic analysis.......................................................18 Defining PFAS: Grouping, Properes and Hazard Assessment ................................................................................18 PFAS in the Pharmaceucal Supply Chain...............................................................................................................20 Raonale for Pharmaceucal Sector PFAS Usage and Sub-uses..............................................................................23 PFAS Used to Produce and Deliver Medicinal Products Alternave Potenal.........................................................29 Request #6 Summary Missing Uses Alternaves and substuon consideraons......................................................34 Request #7 Potenal derogaons marked for reconsideraon-Analysis of alternaves and socio-economic analysis. ...................................................................................................................................................................................34 Request #7 Summary - Potenal derogaons marked for reconsideraon current derogaons not feasible. ...........36 Request #8 Other idenfied uses - Analysis of alternaves and socio-economic analysis..........................................37 Request #8 Summary - Other idenfied uses Societal Cost of Ban for Pharma ..........................................................43 Request #9 - Degradaon potenal of specific PFAS sub-groups................................................................................43 Request #10 - Analycal methods..............................................................................................................................43 Closing Remarks: Bringing back points to consider and paent impact..........................................................................43 References......................................................................................................................................................................46 1 PQRI Comments on Annex XV Restricon Report Glossary AD API CCS COPD CSS DDS EC ECHA ECTFE EEA EiF EMA EPPA SEA ETFE EU FEP FFKM FIH FKM FVQM GMP HVAC IMPD IND IPAC IPAC-RS MAA Mab Mfg OECD OELs PFAS PFOA PLC pMDI PMT POC PPE PQRI PTFE PVDF QC R&D Alzheimer's Disease Acve Pharmaceucal Ingredient Container closure system Chronic Obstrucve Pulmonary Disease European Commission Chemicals Strategy for Sustainability Drug delivery system European Community European chemicals agency Ethylenechlorotrifluoroethylene European Economic Area Entry into Force European Medicines Agency European Public Policy Advisors Socioeconomic Analysis Ethylene tetrafluoroethylene European Union Fluorinated ethylene propylene Perfluoroelastomers First In Human Fluoroelastomers Fluorosilicones Good Manufacturing Pracce Heang, Venlaon, Air Condioning, Refrigeraon Invesgaonal Medicinal Product Dossier Invesgaonal New Drug Internaonal Pharmaceucal Aerosol Consorum Internaonal Pharmaceucal Aerosol Consorum on Regulaon & Science Markeng Authorisaon Applicaon Monoclonal Anbodies Manufacturing Organisaon for Economic Co-operaon and Development Occupaonal Exposure Limits Per- and Polyfluoroalkyl substances Perfluorooctanoic Acid Polymers of Low Concern pressurized Metered Dose Inhaler Persistant, mobile, toxic Proof of Concept Personal Protecve Equipment Product Quality Research Instute Polytetrafluoroethylene Polyvinylidene fluoride Quality Control Research and Development 2 PQRI Comments on Annex XV Restricon Report REACH Registraon, Evaluaon, Authorizaon and Restricon of Chemicals RO1 Restricon opon 1 in Annex XV Restricon Report on PFAS RO2 Restricon opon 2 in Annex XV Restricon Report on PFAS SBT Science-Based Targets SBTi Science-Based Targets iniaves TULAC Texles, Upholstery, Leather, Apparel and Carpets UK United Kingdom 3 PQRI Comments on Annex XV Restricon Report Introducon The Competent Authories of Germany, The Netherlands, Sweden, Denmark, and Norway submited a joint REACH Annex XV restricon proposal for a broad group of PFAS.

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Annex I - List of acronyms and abbreviations Acronym AC B CAS CF2 CF3 CfE CF3C(O)F CFF CLP CO2 COC COP CSR CTFE DNEL EC ECHA EEA EEAP EFCTC EFSA EINECS ELV EMA EPA ETF EU EV EVOH F-Gas FCM FP GLP GWP HCFC HCFO-1233zd(E) HF HFC HFC-125 HFC-134a HFC-143a HFC-227ea HFC-236fa HFC-245fa HFC-32 Explanation Airconditioning Bioaccumulation Chemical Abstracts Service Methylene Fully fluorinated methyl Call for Evidence Trifluoroacetyl Fluoride Cold Form Foils Classification, Labelling and Packaging Carbon dioxide Cyclic olefin copolymer Cyclic olefin polymer Chemical Safety Report Chlorotrifluoroethylene Derived No-Effect Level European Commission European Chemicals Agency European Economic Area Environmental Effects Assessment Panel European Fluorocarbons Technical Committee European Food Safety Authority European Inventory of Existing Chemical Substances End of Life of Vehicles Directive European Medicines Agency Environmental Protection Agency Extrudable thermoplastics films European Union Electric Vehicle Ethylene vinyl alcohol Fluorinated Gas Food Contact Materials rules Fluorinated Products Good Laboratory Practice Global Warming Potential Hydrochlorofluorocarbon (1E)-1-chloro-3,3,3-trifluoroprop-1-ene Hydrogen Fluoride Hydrofluorocarbon Pentafluoroethane 1,1,1,2-tetrafluoroethane 1,1,1-trifluoroethane 1,1,1,2,3,3,3-heptafluoropropane 1,1,1,3,3,3-hexafluoropropane 1,1,1,3,3-pentafluoropropane Difluoromethane 1 HFC-365mfc HFO HFO-1233zd HCFO-1233zd(E) HFO-1234yf HFO-1234ze(E) HFO-1336mzz(E) HFO-1336mzz(Z) Honeywell HSE IUPAC IVD IVDR LRTP MAC MDI MDR Mln MoE NOAEL NOEC OECD OTC P PBT PCTFE PET PFAS PFC PFOA PFOS PLC PNDT PNEC PP PTFE Proposal PVC PVDC RAC RAAF R&D REACH RHVAC RMM RMOA RO RRM SAP SEAC 1,1,1,3,3-pentafluorobutane Hydrofluoroolefin (1E)-1-chloro-3,3,3-trifluoroprop-1-ene Trans 1-Chloro-3,3,3-trifluoroprop-1-ene 2,3,3,3- tetrafluoroprop-1-ene Trans-1,3,3,3-tetrafluoroprop-1-ene Trans-1,1,1,4,4,4-hexafluorobut-2-ene (2Z)-1,1,1,4,4,4-hexafluorobut-2-ene Honeywell International Inc.

8/25/23, 12:06 PM Maximum Continuous Service Temperature - Plastic Properties The material selection platform Plastics & Elastomers Max Continuous Service Temperature 1.