2021 AIT Webinars
Thank you if you have already registered for the AIT webinars.
Registration is still open for the AIT webinars 2021.
Below is the list of the remaining AIT webinar sessions scheduled for 2021 (with summaries where available). Please send an email to email@example.com detailing the webinars that you want to attend. I will send you a link to join your selected sessions in due course.
There are only 150 places available for each session. If the sessions are full a waiting list will be employed. Thank you.
The AIT would like to sincerely thank our Webinar Sponsors:
Level 1 sponsorship supporting all the webinar sessions:
Charles River Laboratories (Link)
ITR Labs Canada Inc (Link)
Intox Products (Link)
Regulatory Science Associates (Link)
Level 2 sponsorship supporting one of the webinar sessions:
Webinar 4: Product Safety Labs (Link)
Webinar 10: Lovelace Biomedical (Link)
2021 AIT webinars:
4. Monday 18th October 2021 at 1-2pm (UK time): David Jones (MHRA): The lung effects following COVID-19 and how “good” the animal models of disease are.
Summary: The talk will cover a brief introduction to the virus and its emergence into a global pandemic. David will then move on to a discussion on the disease itself, especially the host immune response and the pulmonary complications followed by looking at the animal models of disease looking at the pros and cons of each. The final part of the talk will look at treatments, focusing on those administered by inhalation, including products that were initially developed for other routes of administration.
5. Monday 1st November 2021 at 1-2pm (UK time): Mary McElroy (CRL): Development of Rat Models of Acute Respiratory Distress Syndrome (ARDS) for Efficacy and Safety Assessment.
Summary: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition associated with pneumonia, sepsis and trauma; the mainstay of treatment is to support lung function. ARDS is a little known but very severe lung disease which has been in the news a lot recently due to COVID19. Mary will provide background describing important features of ARDS vs other lung inflammation models and present data from a rat model developed by CRL with clinically relevant challenge agents.
6. Wednesday 3rd November 2021 at 2-3pm (UK time): James Randazzo (CRL): A Mighty Approach to Generating Aerosolized Cannabidiol.
Summary: Cannabidiol, or CBD, is one of hundreds of cannabinoids found in the cannabis plant. Unlike THC, CBD can be used for anti-inflammatory, anti-anxiety, and pain-relief effects without the accompanying psychoactive high. Emerging cannabis-based pharmaceuticals, such as Epidiolex, reaffirm legalizing its rich potential for medical use. Currently, the most common methods of ingesting CBD include oils (topical), pills (oral), candy and chocolates (oral, edibles), and tinctures (sublingual). However, the highest bioavailability for CBD is absorption through the lungs (inhalation).
While administration of CBD by inhalation may be a viable route for the patient, it does not come without its challenges and concerns. Given the potential that e-cigarette, or vaping, product use associated lung injury (EVALI) was associated with vitamin E acetate in some THC-containing vaping products, alternate methods for inhalation may be preferred by the user. In this webinar, we will discuss iterative process of adaptation of the Mighty Medic, a portable medical cannabis vaporizer, for use in a non-clinical setting.
7. Thursday 4th November 2021 at 1-2pm (UK time): Zachary Enlo Scott (final year PhD student within the Institute of Pharmaceutical Science, at King’s College London): A combined in vitro-in silico approach for the toxicokinetic prediction of inhaled pesticides.
Summary: Current European regulations make the unvalidated assumption that 100% of inhaled pesticide is absorbed into systemic circulation. This is in stark contrast to oral or dermal routes of exposure, which use established evidence-based in vitro and in silico methods to infer bioavailability and potential toxicity. Data-driven and evidence-based approaches for predicting pesticide respiratory bioavailability and toxicity are therefore urgently needed for future risk assessments, both for occupational and bystander population exposures.
Different in vitro models were assessed and optimised to study local toxicity, transepithelial permeability and potential in situ metabolism of unintentionally inhaled pesticides, using the following cells: nasally derived RPMI-2650, bronchially derived BEAS-2B, 16HBE14o-, Calu-3 and the alveolar derived A549 and TT1 cell lines. These were tested for their suitability to assess the cytotoxicity of 9 different pesticides with varying physicochemical properties and modes of action. Standard markers for xenobiotic metabolism (CYP1A1, 1A2, 2B6, 3A4, 3A5, NQO1 and GST activities) and permeability were assessed highlighting the Calu-3 cell line as the most suitable model. Additionally, lipid-based permeability models such as PAMPA and lung lipid extract were found to provide useful complementary information.
Following model optimisation, the in vitro ADME properties of the 3 fungicides azoxystrobin, chlorothalonil and propiconazole were tested, revealing significant differences in their transepithelial permeability, airway surface liquid binding and plasma protein binding, based on the physicochemical properties of the fungicides. This in vitro data was then combined with in silico modelling to predict the bioavailability of the respective fungicides for a range of occupational exposure scenarios, highlighting toxicokinetic differences dependent on regional deposition within the respiratory tract and the influence of physicochemical properties of the particular fungicide. In all realistic exposure scenarios respiratory bioavailability was less than 100%, due to regional aerosol deposition and the interplay between transepithelial permeability and non-absorptive clearance.
In conclusion, this study highlights that in vitro data combined with an in silico approach has the potential to improve predictions of respiratory toxicity and bioavailability and optimise future occupational risk assessments for respiratory exposure to xenobiotics.
8. Monday 8th November 2021 at 1-2pm (UK time): Alison Wolfreys (UCB Pharma) and Jo Kilgour (Regulatory Sciences and AIT): Review of the Technical, Toxicological, and PKPD Considerations for Conducting Inhalation Toxicity Studies on Biologic Pharmaceuticals — The Outcome of a Cross-Industry Working Group Survey.
Summary: The inhaled route is still a relatively novel route for delivering biologics and poses additional challenges to those encountered with inhaled small molecules, further complicating the design and interpretation of toxicology studies. A working group formed to summarize the current knowledge of inhaled biologics across industry and to analyze data collated from an anonymized cross-industry survey comprising 12 inhaled biologic case studies (18 individual inhalation toxicity studies on monoclonal antibodies, fragment antibodies, domain antibodies, oligonucleotides, and proteins/peptides). The output of this working group provides valuable insights into the issues faced when conducting toxicology studies with inhaled biologics, including common technical considerations on aerosol generation, use of young and sexually mature nonhuman primates, pharmacokinetic/pharmacodynamic modelling, exposure and immunogenicity assessment, maximum dose setting, and no observed adverse effect levels determination. Although the current data set is too small to allow firm conclusions, testing of novel biologics remains an active area and is likely to remain so for molecules where delivery via the inhaled route is beneficial. In the future, it is hoped others will continue to share their experiences and build on the conclusions of this review to further improve our understanding of these complex issues and, ultimately, facilitate the safe introduction of inhaled biologics into clinical use
9. Wednesday 10th November 2021 at 1-2pm (UK time): Peter Hall (UCB Pharma): Challenges of Inhaled Biologics – Pathology, Immunogenicity and Mechanisms of Toxicity.
Summary: The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this presentation, 12 case studies, comprising 18 toxicology studies are presented, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies. Analysis of the data revealed that many of these molecules were associated with characteristic patterns of toxicity associated with high levels of immunogenicity. Microscopic changes in the airways consisted of a predominantly lymphoid perivascular/peribronchiolar (PV/PB) mononuclear inflammatory cell (MIC) infiltrate, whereas changes in the terminal airways/alveoli were characterized by simple (“uncomplicated”) increases in macrophages or inflammatory cell infiltrates ranging from mixed inflammatory cell infiltration to inflammation. The PV/PB MIC changes were considered most likely secondary to immunogenicity, whereas simple increases in alveolar macrophages were most likely secondary to clearance mechanisms. Alveolar inflammatory cell infiltrates and inflammation were likely induced by immune modulation or stimulation through pharmacologic effects on target biology or in one case, type III hypersensitivity (immune complex disease).
10. Thursday 11th November 2021 at 1-2pm (UK time): Jake McDonald (Lovelace Biomedical) Title and summary: TBC
11. Monday 15th November 2021 at 1-2pm (UK time): CANCELLED
12. Wednesday 17th November 2021 at 1-2pm (UK time): Simon Moore (LabCorp formerly known as Covance): Primate animal welfare / exposure system design.
Summary: The requirement for NHP studies by inhalation has been on the increase over the last years in line with the growth in the development of biopharmaceuticals. Inhalation has always been technically challenging, however, with the use of both of standard and mature primates, administration and study conduct poses additional challenges from an animal welfare perspective. This webinar will provide detail of the initiatives that Labcorp have been undertaking over the last few years to improve study conduct and make the studies a success.
13. Thursday 18th November 2021 at 1-2pm (UK time): Helen Palmer (LabCorp formerly known as Covance): Bronchial lavage (BAL) in different species (specifically primates and dogs).
We hope you will be able to join us.
Date(s) - 18/10/2021 - 17/11/2021