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40 April 2024 Inhalation variety of impactful publications [3-6]. Current article topics under active consideration include: 1) regulatory harmonization, 2) new approach methodologies (NAMs) for inhalation, 3) dosing approaches: time vs. concentration, 4) aerosol particle size distribution considerations and 5) AIT statement group on cannabinoids. 2024 Annual Meeting: Inhalation Toxicology Rocks e next AIT annual meeting will take place in Cleveland, Ohio, US during the week of September 16, 2024. Topics will include: • NAMs/in vitro toxicology (co-sponsored by e American Society for Cellular and Com- putational Toxicology; EU 2020 Horizon project HARMLESS), • inhaled biologics/cell and gene therapy, • aerosol generation in vivo/ in vitro, • computational disease models, • intranasal studies, • wildfires and smoke inhalation toxicology. For more information and to reg- ister: https://www.aitoxicology. org/conference-announcement. References 1. ICH Harmonised Tripartite Guideline M3 (R2). Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Market- ing Authorisation for Pharmaceu- ticals. https://www.ema.europa. eu/en/ich-m3-r2-non-clinical- safety-studies-conduct-human- clinical-trials-pharmaceuticals- scientific-guideline. 2. ICH Harmonised Tripar- tite Guideline S6 (R1). Preclini- cal Safety Evaluation of Biotech- nology Derived Pharmaceuti- cals. https://www.ema.europa. e u / e n / i c h - s 6 - r 1 - p re c l i n i c a l - safety- evaluation-biotechnology- while the administration method (pipette, syringe, micro-sprayer) will be influenced by the nature of the test material. Panel discussion e workshop chairs, Ben Forbes (King's College London), and Vik- toria McDonald (AlbaTox Con- sulting Ltd), facilitated a panel debate to complete the workshop. Delegates were curious about the following aspects of the topics discussed in the presentations: 1) whether the aerosol concentration and particle size need to be tai- lored to the test species or match the clinical aerosol characteristics, 2) what quality of test material is acceptable to support GLP toxi- cology studies, 3) how and when aerosol characterization, including API stability, should be performed over the course of a study, and 4) how long it will be before in vivo toxicology can be replaced by in vitro methods for drug develop- ment and accepted by regulators, particularly considering the FDA modernization act and approaches developed for the chemical/agri- cultural industry. e content of this workshop is being supplemented by reference to the literature and will be pub- lished in 2024 as a review article titled, "Non-clinical toxicology for inhaled and nasally adminis- tered excipients and drug prod- ucts: Regulatory requirements, current practice, emergent meth- odology and clinical translation." It will appear in Expert Opinion on Drug Metabolism and Toxicology. The AIT techno- regulatory workstreams Jo Kilgour, AIT President since 2011, also provided a brief history of the Association of Inhalation Toxicologists. e Society was established and held its first meet- ing in May 1981 and has held an annual meeting every year since, cycling between the UK, conti- nental Europe and US. e Soci- ety has a number of workstreams and has been responsible for a tion followed by an aerosolized antibiotic (amikacin or Fosfo- mycin) 1-hour post-infection with efficacy demonstrated by change in temperature or reduc- tion in bacterial load as colony forming units (CFU), • Neutrophilia—a lipopolysac- charide-induced model of acute pulmonary neutrophilia in rats was described, in which dexa- methasone (an experimental positive control) reduced both lung neutrophil count and the elevated cytokine levels in bron- choalveolar lavage fluid. Novel excipients for inhalation and nasal toxicology In response to pre-workshop feedback, Jo Kilgour (Regulatory Science Associates, Mereside Tox- icology Consulting and Apconix) addressed two additional topics: novel excipients for inhalation and preclinical nasal toxicology studies. Regulatory guidelines for qualify- ing an excipient are available. If a new excipient (or variation of type/concentration of an existing excipient) is for long term use, a 6-month rodent toxicity study is generally required; in addition, carcinogenicity studies (at least one of which should be by the relevant clinical route) will be conducted with the formulation for Marketing Authorization). In such studies, having an air con- trol is paramount and multiple novel excipients can be tested in a "to-be-marketed" formulation. e advice given was to keep for- mulations simple and seek guid- ance on safety data requirements from the appropriate regulatory authority. Nasally administered products have different safety consider- ations compared to orally inhaled products, both in terms of dose and safety margin. Practicali- ties dictate that dose is limited by nasal cavity size and the max- imum volume and frequency of delivery allowable for each species,