Layer-by-Layer Assembled Systems for Localized Lung Delivery of Therapeutic and Diagnostic Agents
By Vivek Gupta Associate Professor, and Scientific Founder at St. John's University
12:00 - 12:30
Connected Health Opportunities and Complexities of for Inhalation Devices to Consider Prior to Starting Development
By Rita Lee Principal Consultant at Suttons Creek, Inc.
➡ When classification of connected software device is not clear: challenges, opportunities of 513(g) and Pre-Sub seen
➡ Key Considerations gathered from past experience working on software (including mobile apps) to US market: for example, potential FDA/FTC/HIPAA requirements, labeling, strategy of including in device or not (one example, integrated, one add-on), potential impacts of who consumes/is given access to collected data: payers, pharma sponsor, patients, HCPs, or all of the above?, etc
➡ Development of Internal process flow/framework/policy regarding any/all software product concepts for US market: when, which (internal stakeholders), FDA and non-FDA requirements
12:30 - 13:00
“Emergency-use” nasals: Technical and reliability considerations
By Kalpita Mehta Principal Combination Product and Medical Device Expert at Hikma Pharmaceuticals Inc.
13:00 - 14:00
RESCON Business Lunch
14:00 - 14:30
The Role of 3D Models of Human Intranasal Airways in Preclinical Studies of New Nasal Delivery Products
By Beth Laube Professor Emerita at the Johns Hopkins School of Medicine
➡ 3D models of the intranasal airways of adults and children provide for inexpensive and rapid preclinical investigations into optimal formulation and device design for new nasal delivery products prior to expensive in vivo studies.
➡ 3D models of human intranasal airways allow for preclinical testing of factors that could affect the total and regional dose of new nasal delivery products under controlled conditions.
➡ 3D models of human intranasal airways can be used in preclinical testing of methods to optimize local, systemic and CNS delivery of new nasal products.
14:30 - 15:00
Integrated in vitro/ex vivo assessment of efficacy and respiratory toxicity for accelerated respiratory drug development
By Katharina Schwarz Head Aerosol Technology and Aerosol Biophysics at Fraunhofer Institute
➡ Developing new (inhalational) anti-infective strategies for the clinical application is a very lengthy and difficult process. For a fast and predictive non-clinical development we established a integrative test-platform for evaluation of inhalational drug candidates In this platform we integrate state of the art human ex vivo methods like PCLS with the rat ex vivo isolated perfused lung system and in vitro cell-based inhalation assay in order to address different questions highly relevant for the assessment of safety and efficacy of new drugs. In this case we used Nafamostat, a repurposing drug with excellent anti-viral efficacy against SARS Cov-2 that is already is approved for systemic use against pancreatitis in Japan. Methods:
➡ In a highly integrative approach, we used state of the art in vitro/ex vivo and in vivo methods to determine the safety and efficacy of inhalational Nafamostat. First, using the Fraunhofer ITEM developed PRIT ExpoCube human epithelial cells were exposed to nebulized Nafamostat in order to define the NOAEL. For human proof of concept and to define a therapeutic window a Precision Cut Lung Slice (PCLS) model was used as an ex vivo organotypic infection model for investigation of the host-pathogen interaction in situ. The Isolated Perfused Rat Lung (IPL) providing a fully intact organ system with cellular, structural and functional integrity was established to investigate local organotoxic effects as well as for pharmacokinetic studies. In addition, a classical GLP 28-day regulatory inhalation toxicological study was performed in rats. Data integration was conducted using the Multiple-Path Particle Dosimetry (MPPD) model and the PBKit inhalation-focused PBK model developed by the Fh ITEM. Results and Conclusion:
➡ In-vitro inhalation studies with A549 cells indicate at a LOAEL value for Nafamostat Mesylate of ~2 µg/ cm2. For Nafamostat, a dose dependent efficacy could be demonstrated in Precision-Cut-Lung Slice infection models (SARS-CoV-2). Efficacy has been shown for 0.5 µM in PCLS, which is in a similar range with the assumed therapeutic range reported in the literature (30 – 240 nM). Determination of local toxicity revealed an excellent therapeutic window with efficacy being a factor of more than 100 lower than the toxic level. In Isolated Perfused Lungs, a LOAEL of 0.2 mg/kg bw was observed in an inhalation dose-escalation protocol with adverse effects observed in the upper airways only. Applying the MPPD-model for detailed dosimetry, a corresponding surface specific LOAEL of ~ 7 µg/cm2 was derived. In a 28-day in vivo inhalation study, animals showed adverse effects for a 0.3 mg/kg body weight dose in the larynx and upper airways (ulcer, necrosis) with locally deposited doses up to ~ 30 µg/cm2, while effects in the pulmonary region were smaller with locally deposited doses ≤ 2 µm/cm2. No toxicity was found in histopathological analysis of the nasal area though a high head deposited dose. Thus, in vitro/ex vivo and in vivo data point towards comparable LOAEL values. Furthermore, integration of IPL derived absorption parameters into the PBKit inhalation-focused PBK model supports a favorable lung concentration profile for inhalational application.
As shown for Nafamostat, application and combination of different methods can provide data, that can be incorporated into the non-clinical development of inhaled drug candidates. Therefore, these studies can contribute to a faster and more effective early pre-clinical development and can help to refine regulatory studies by e.g. supporting dose selection.
In Vitro Testing/Inhalation
15:00 - 15:30
Solving Problems in Aerosol Delivery: Breath Enhanced Jet Nebulization
By Gerald Smaldone Professor of Medicine, Physiology and Biophysics at Stony Brook University Medical Center
15:30 - 16:00
Inhalation Drug Products and Packaging Quality: Exploring USP General Chapters and Future Developments
➡ The United States Pharmacopeia (USP) contains a number of General Chapters and General Information Chapters directly addressing key quality attributes required for components and delivery systems for inhalation drug products. The content and recent updates to General Chapters <5> and <601> will be reviewed covering inhalation drug product product quality and inhalation delivery systems performance quality tests respectively, followed by an overview of the inhalation performance quality tests contained in the General Information Chapters <1601> to <1604>.
➡ A new USP General Chapter <662> Metal Packaging Systems and Their Materials of Construction and its accompanying General Information Chapter <1662> are in the process of being developed to complete the series on primary packaging systems that currently covers glass containers <660> and plastics containers <661> for pharmaceutical use. Metal primary packaging materials are used in a wide variety of drug products including aluminum and stainless steel inhalation canisters. The presentation will provide an overview of progress to date in developing these two chapters that will include inhalation canisters.
16:00 - 16:30
16:30 - 17:30
Panel Discussion: Future Trends and Collaborations in Inhalation Technology and Drug Delivery
By Carolyn Berg Vice President, Business Development at Catalent Pharma Solutions, Dujuan Lu Manager/Global Leader-E&L at SGS, David Cipolla VP of Research at Insmed Incorporated, Jeffry Weers Chief Technology Officer at cystetic Medicines, Inc., John Patton Head of Kindeva's Scientific Advisory Board, Rita Lee Principal Consultant at Suttons Creek, Inc.
➡ Exploring emerging trends and technologies in the field of inhalation drug delivery.
➡ Discussing the potential for cross-industry collaborations to drive innovation.
➡ Analyzing the impact of regulatory changes on the future of inhalation technology.
➡ Identifying opportunities for research and development in inhalation drug delivery.
Closing Remarks & End of the RESCON Summit 1st day
19:30 - 22:00
RESCON Cocktail Dinner at Ophelia Lounge NYC
09:00 - 09:30
Registration & Morning Coffee
09:30 - 10:00
Inhalation delivery for respiratory and systemic indications using Cyclops™, an innovative patient-centric high-dose DPI
Mitigating Nitrosamine Drug Substance Related Impurity Risks with Novel Active Material Science Innovations
By Matt Riccio Director of Business Development at Aptar CSP Technologies
➡ Understand the landscape of emerging concerns regarding the presence of N-Nitrosamines (a class of organic compounds known for their potential carcinogenicity) in pharmaceutical products and the resulting investigations and recalls prompted by regulatory bodies.
➡ Explore how pharmaceutical developers are working to mitigate risk in current drug products and new APIs in development to assure they meet new, strict guidelines related to N-Nitrosamine presence or formation.
➡ Discover innovations in active material science that can be deployed in active packaging solutions to reduce or prevent nitrosamine formation and/or eliminate nitrosamines post-formation in the packaging headspace, minimizing the need for reformulation and reducing risk of recalls.
13:00 - 14:00
RESCON Business Lunch
14:00 - 14:30
Pipeline Overview and Trends in Inhaled Pulmonary Delivery
By Carolyn Berg Vice President, Business Development at Catalent Pharma Solutions
14:30 - 15:00
The role of cascade impactors in the design of dry powder inhalers
By Jeffry Weers Chief Technology Officer at cystetic Medicines, Inc.
15:00 - 15:30
Inhaled Insulin: from dry powder to liquid connected device
By John Patton Head of Kindeva's Scientific Advisory Board