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Inhalation OctOber 2024 29 and Dry Powder Inhaler (DPI) Drug Products-- Quality Considerations. 2018. https://www.fda.gov/ regulatory- information/search-fda-guidance-docu ments/metered-dose-inhaler-mdi-and-dry-powder- inhaler-dpi-drug-products-quality-considerations. 3. International Organization for Standardization. Technical Report. ISO/TR 10017 Guidance on Sta- tistical Techniques for ISO 9001:2000. 4. Yu L, Kopcha M. e Future of Pharmaceutical Quality and e Path to Get ere. International Journal of Pharmaceutics, 528 (1-2), 354-359, 2017. 5. United States Food and Drug Administration. Nasal Spray and Inhalation Solution, Suspen- sion, and Spray Drug Products--Chemistry, Man- ufacturing, and Controls Documentation. 2002. https://www.fda.gov/regulator y-information/ search-fda-guidance-documents/nasal-spray-and- inhalation-solution-suspension-and-spray-drug- products-chemistry-manufacturing-and. 6. Sandell D, Bergum J, Hofer J, Larner G, Hauck W, Curry P, Skwierczynski R, Walfish S, Brown W. Batch Release Testing for Ensuring Compliance with Uniformity of Dosage Units <905>. Stimuli to the Revision Process. USP-NF Pharmacopeial Forum, 45(4) 2019. Acknowledgements e authors thank the IPAC-RS Board of Directors and the IPAC-RS Product Quality Demonstration Strategy (PQDS) Working Group for their support and helpful feedback on the manuscript. About IPAC-RS e International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) is an interna- tional association comprising pharmaceutical, biotech and medical device companies as well as providers of equipment and testing services that all work to help develop, manufacture and market drug and biologic medical products for delivery via the respiratory tract. For more information or to join, visit ipacrs.org. Helen Strickland, MSc, Statistical Consultant, GSK, Zebulon, North Carolina, US, helen.n.strickland@ gsk.com. J. David Christopher, MSc, Executive Direc- tor, Research CMC Statistics, Merck & Co., West Point, Pennsylvania, US, j.david.christopher@merck. com. Beth Morgan, PhD, Senior Director Digital Sci- ences, AstraZeneca, RTP, North Carolina, US, beth. morgan@astrazeneca.com. Greg Larner, MSc, Inde- pendent Statistical Consultant, Kalamazoo, Michigan, US, Greg.L.Larner@gmail.com. Svetlana Lyapustina, PhD, Principal, Faegre Drinker Consulting, Washing- ton, DC, US, svetlana.lyapustina@faegredrinker.com (corresponding author). Everyone must recognize that the dose measurement system (as any measurement system) is imprecise in absolute terms. In the context of ensuring product quality, it is also imprecise as a measure of an individual dose's safety and efficacy. One must change perspec- tive from "single dose management" to a "full treat- ment regimen." Consider the impact of a single dose over the entire treatment therapy course. A current default quality standard of "no more than one dose outside the 80-120% or 75-125% range for every 20 doses," translates to an out-of-range dose once every three weeks if therapy is used daily. Depending on the clinical profile, this might be acceptable and in the best interest of the patient to assure a successful health outcome without unnecessarily restricting the supply of safe and effective product. Establishing the overall (sample-independent) quality standard is the largest and most important challenge. In setting this quality standard, each sponsor should evaluate their product's data in light of its particular risk profile, which would take into account the type of medication, e.g., for maintenance vs. rescue use; and, ideally, clinically-guided or at least clinically- informed thresholds for efficacy (e.g., to prevent underdosing) and safety (e.g., to prevent overdosing). With an appropriately defined quality standard in place, a number of established guidelines could be consulted to design specific demonstration (release) tests (see Table 2). Conclusion Starting with the end goal (quality standard, expressed quantitatively, ideally based on clinical information) and setting sampling plans to demonstrate that qual- ity standard with specified levels of confidence, will mean that processes and methods can be developed statistically and intentionally to meet that standard. If the ultimate goal of health authorities, pharma- copoeial and industry organizations is to enable product sponsors to produce high-quality medicinal products that are readily available to the patient, free of contamination and reproducibly deliver the ther- apeutic benefit promised in the label, it is imperative all parties work together to identify and develop solu- tions that will address the underlying challenges that continue to reduce our ability as an industry to better serve patients. References 1. International Conference on Harmonisation of Technical Requirements for Registration of Phar- maceuticals for Human Use. ICH Harmonised Tri- partite Guideline. Pharmaceutical Quality System. Q10. http://database.ich.org/sites/default/files/q10 guideline.pdf. 2. United States Food and Drug Administration Draft Guidance for Industry Metered Dose Inhaler (MDI)