作者: Ugur, Nurcin ; Kuehl, Philip J ; Lyapustina, Svetlana ; Rehmann, Franz-Josef K ; Mao, Lei ; Kadrichu, Nani ; Mansour, Heidi M ; Singh, Gur Jai Pal ; Rossi, Irene ; Li, Bing V ; Cipolla, David ; Suman, Julie D ; Gruenloh, Christopher J

Background: Delivering large molecules and biologics via inhalation or intranasal routes allows these innovative therapies to directly target the respiratory tract, access the richly vascularized lymphatic tissue in the nose for vaccination, bypass gastro-intestinal and first-pass hepatic metabolism for systemically active drugs, and provide a convenient alternative to injections. These advantages are driving significant growth in research and development within this field. However, before such products can reach the market, they must undergo rigorous nonclinical studies and clinical trials and address challenges related to formulation, manufacturing, analytical testing, quality standards, and regulatory review. Methods and Results: This report summarizes discussions among leading experts from industry, academia, and regulatory bodies on how to apply general Chemistry, Manufacturing, and Controls (CMC) principles, alongside bioequivalence (BE) considerations, to the development of inhalable and nasal biologics (INBs). It also explores the balance between these requirements and the established techniques for medical aerosols. In the absence of explicit regulatory guidelines for the development of INBs, this article reviews applicable literature, including guidelines from the US FDA and EMA for biologics, on the one hand, and for small-molecule inhalation and nasal drug products, devices, and combination products, on the other. The original discussions reflected here took place at the 2023 workshop co-organized by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS). Subsequent recent developments have also been added. The article describes regulatory expectations, the selection of delivery systems and formulation types, and analytical techniques for assessing product quality attributes of INBs. Several specific cases are presented in detail, including regulatory considerations for generic peptides, the approval package for one of the first marketed biologics for inhalation, and analytical detection strategies for viral-based products delivered to the lungs. Conclusions: Looking ahead, the future of INBs includes opportunities to treat and potentially cure diseases that currently have no effective treatment or that require repeated injections. Continued collaboration among researchers, developers and regulators will be key to advancing these therapies, ultimately benefiting patients and improving health outcomes. The future of INBs looks promising!.

2024-08-27·Journal of Alzheimer’s Disease

First Biodistribution Study of [⁶⁸Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys

Article

作者: Gandhi, Reenal ; Jorgensen, Mathew J. ; Register, Thomas ; Krizan, Ivan ; Craft, Suzanne ; Solingapuram Sai, Kiran Kumar ; Gollapelli, Krishna K. ; Miller, Mack ; Suman, Julie ; Cazzola, Charles ; Erichsen, Jennifer M. ; Bansode, Avinash

Background: Intranasal insulin (INI) is being explored as a treatment for Alzheimer’s disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes. Objective: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system. Methods: To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans. Results: We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq. Conclusions: The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans.

2023-10-24·European Journal of Public Health

Impact of a digital therapeutic on adult asthma

作者: dOrsay, G ; Bijlani, A ; Goodheart, C ; Suman, J ; Mauger, D

AbstractBackgroundAsthma impacts 334 million people globally. Medication adherence is estimated at 50% worldwide. Digital therapeutics (DTx) may improve medication adherence and health outcomes.MethodsProspective, single cohort observational study of 104 adults with asthma managed on inhaled corticosteroids. Subjects had 90-day access to Aptar Digital Health respiratory platform: HeroTracker to monitor adherence, spirometer for lung function, and BreatheSmart mobile app with real-time alerts. Primary outcomes: asthma control, rescue medication use. Secondary outcomes: controller medication adherence, patient feedback.ResultsSubjects completed Asthma Control Test (ACT) at baseline (T0); 96% (N = 100) completed ACT at 90 days (T1). Between T0 and T1, ACT scores increased significantly (baseline: 16.5 ± 4.7; ΔT0 to T1: + 2.8, 95% CI (2.0, 3.6), p-value <0.001); rescue medication use decreased 44% ((95% CI: 14.1, 63.5), p-value = 0.008); adherence to controller medication decreased 10.7% ((95% CI: 6.4, 15.1), p-value <0.001). 82.5% of subjects reported platform very/somewhat easy to use, 97.5% rated spirometer very/somewhat easy to use, 92.5% reported alerts very/somewhat helpful. Platform rating mean score = 7.825/10 (1-10; 10=high).ConclusionsDTx may improve asthma control and decrease rescue medication use. T1 medication adherence was 17% higher than global medication adherence. Patient feedback was positive.References1. Enilari, O., Sinha, S. (2019). The global impact of asthma in adult populations. Ann Glob Health, 85(1), 2, 1-7.2. Kim, J., et al. (2018). Medication adherence: the elephant in the room. US Pharm, 43, 1, 30-34.Key messages• DTx promoted improvement in ACT scores and decreased rescue medication use.• DTx platform feedback was positive.

项与 Aptar Pharma Japan Ltd. 相关的新闻（医药）

2022-06-09

·GlobeNewswire-Health Care

Opiant Pharmaceuticals and Aptar Pharma Expand Long-Term Collaboration for the Manufacture of Unidose Nasal Spray for OPNT003, Nasal Nalmefene

SANTA MONICA, Calif., June 08, 2022 (GLOBE NEWSWIRE) -- Opiant Pharmaceuticals, Inc. (Opiant) (NASDAQ: OPNT) today announced a capacity investment agreement with Aptar Pharma (Aptar), a leading provider of drug delivery systems, to expand production of Aptar’s nasal Unidose device, which will be used in the production of commercial supply of OPNT003, nasal nalmefene. The agreement includes an investment by Opiant of €2 million (approximately $2.1 million) and a commitment by Aptar to install and maintain equipment in support of increased future production of its Unidose device to meet the potential commercial demand for OPNT003, nasal nalmefene. “This capacity investment with Aptar demonstrates Opiant’s commitment to ensure adequate supply of OPNT003, nasal nalmefene, to communities and emergency responders as quickly as possible, if approved,” said Roger Crystal, M.D., President and Chief Executive Officer of Opiant. Opiant has initiated rolling submission of a New Drug Application to the U.S Food and Drug Administration (FDA), for OPNT003, nasal nalmefene, for the treatment of opioid overdose, using the 505(b)(2) pathway. It intends to complete its application in the second half of 2022. Opiant was granted Fast Track Designation in November 2021. About Opiant Pharmaceuticals, Inc. Opiant Pharmaceuticals, Inc., the company that developed NARCAN® Nasal Spray, is building a leading franchise of new medicines to combat addictions and drug overdose. For more information visit: www.opiant.com. For Media and Investor Inquiries: Ben Atkins, Opiant (310) 598-5410 batkins@opiant.com