Title: ISAM Webinar: Inhale-Predict: Integrated ex vivo/in silico platform for predictive testing of inhalable anti-infectives

Tuesday, 18th July  2023, 8 am – 9 am (San Diego, CA); 11 am – 12 am (New York, NY); 5 pm – 6 pm (Paris, France)

Follow this link to register for the zoom webinar

Presenter: Dr. Katharina Schwarz and Msc. Norman Nowak

Dr. Katharina Schwarz leads the department of Aerosol Technology and Aerosol Biophysics at the Fraunhofer Institute for Toxicology and Experimental Medicine. ITEM, Hannover, Germany

MSc. Norman Nowak is a PhD student at the Fraunhofer Institute for Technology and Experimental Medicine. ITEM, Hannover, Germany

Facilitators:

• Jessica Oakes
• Carsten Ehrhardt
• Barbara Rothen-Rutishauser (ISAM president)

Webinar content

• 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 an integrative platform aiming at an early assessment of efficacy, toxicity and respiratory pharmacokinetics of new inhalational drug candidates. Here, we used ciprofloxacin and tobramycin, two well-established antibiotic drugs for treatment of respiratory infections.  

• To define the local therapeutic window for ciprofloxacin and tobramycin in the lungs, a Precision Cut Lung Slice (PCLS) model was used as an immunocompetent ex vivo organotypic infection model for investigation of the host-pathogen interaction in situ.

• Besides knowledge of efficacy and toxicity, information on pharmacokinetics after inhalation, especially in the lung as site of the infection is crucial. Isolated Perfused Rat Lungs (IPL) providing a fully intact organ system was established to investigate respiratory pharmacokinetics.

• Data integration was conducted using the PBKit PBK model developed by the Fh ITEM, a new generic PBK model focused on the inhalational route. The new model divides the lung into several sub-compartments according to its heterogenic structure and different particle related clearance and uptake mechanisms determining the fate of inhaled pharmaceuticals.

• As shown for the two antibiotic agents and also for an anti-viral agent, application and combination of different methods can provide data, that can be incorporated into the non-clinical development of inhaled drug candidates. Therefore, newly developed platform can contribute to a faster and more effective early pre-clinical development and can help to refine regulatory studies.

About the presenters

Dr. Katharina Schwarz

• Leading the department “Aerosol Technology and Aerosol Biophysics” at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) in Hannover

• Expert at the interface between aerosol/inhalation research, respiratory pharmacokinetics, toxicology/physiology, and inhalation exposure science with a special focus on particle lung dosimetry and biophysical particle-lung interactions

• Responsible for the aerosol aerosol/inhalation and dosimetry-related aspects in drug development programs and toxicological or inhalation exposure studies including GLP/GCP-compliance in her institutional role

• Interfacing with interdisciplinary teams from pre-clinical and clinical airway research as well as toxicology/risk assessment from Fraunhofer ITEM and the corresponding sponsors from chemical/pharmaceutical industry or governmental institutions to meet the sponsor’s needs

• In particular she has overlooked the development of the inhalation-focused “PBKit” PBK model as well as the derivation of quantitative in vitro to in vivo extrapolations (QIVIVE) resulting in powerful tools in in particular for respiratory toxicity and efficacy studies

• One of the chairs of the working group “Environmental/Occupational Health/Toxicology” of the International Society for Aerosols in Medicine (ISAM) and actively engaged in the working group “Respiratory Toxicology” of the German Society of Toxicology

• Member of the Scientific Program Committee for the 24th congress of the Society held in 2023

MSc. Norman Nowak

• Obtained master’s degree in material and nanochemistry at the Leibniz University in Hannover, GER

• It was during his master’s thesis working at the Fraunhofer Institute for Toxicology and Experimental Medicine that he was first introduced to PBK modelling

• Continuing his work at the Fraunhofer Institute, he now works on an inhalation-focused PBK model applicable to gases/vapours but also airborne particles or droplets

• Is part of various projects (Cefic LRI, Riskhunt3r (Horizon 2020), InhalAB/InhalPredict)

• He was awarded the “Best trainee abstract” in the biological modeling specialty section at Society of Toxicology meeting ’22 and

• He expects to finish his PhD this year