Educational Co-Support Provided by: Charles River and SciLucent, Inc.
This session will present interactive case studies from pharmaceutical development across the toxicology testing continuum. The aspects that will be presented will include CMC (i.e. formulation preparation), excipients, impurities/degradants, analytical chemistry/bioanalysis stability, study designs (species, exposure, metabolites, duration, route of administration, etc.), safety margins, novel modalities (e.g. cell and gene therapy), unexpected toxicity, regulatory meetings, in the context of the targeted patient population/indication and regulatory jurisdiction. The moderators in this session include representation from pharmaceutical industry, CRO, consultants, and regulatory agency toxicologists. Moderators will interact and discuss with participants for each case study presented as the various perspectives are considered.
Educational Co-Support Provided by: EPL, Inc. and American College of Toxicology
Pathology is one of the most critical pieces in a toxicology report and so communicating with the pathologist is essential to understanding a toxicology study. The pathology report is the primary means by which the study pathologist communicates the histopathological findings and how those findings relate to other data from the study including organ weights, clinical pathology findings, macroscopic (gross) and in-life observations. In addition, the pathology peer review and a pathology working group are additional steps that can be taken to improve or clarify the findings in a toxicology study. This session will cover how a toxicologist should approach the pathology report to be able to critically review the data and the narrative. It will also cover the peer review process, how it is performed, and when best to perform a peer review and then introduce the concepts of a pathology working group and what problems a PWG can and cannot address. Finally, the session will end with a regulatory perspective on the pathology report, the peer review, and the pathology working group.
Educational Support Provided by: AstraZeneca
Rapid advancements in science and technology have led to the emergence of novel tools in nonclinical drug safety assessment, and considerable excitement about the potential of these tools to improve human risk prediction. However, there are no regulatory guidance or a uniform industry-wide strategy for using these promising novel tools. The session will include transparent discussion regarding the use of these novel tools by biotech/pharma in nonclinical safety to advance drug discovery and development. The session will feature a global pharmaceutical company’s overview of their overall strategy in using these tools (such as microphysiologic systems, omics, AI, cell painting, imaging) and an FDA speaker discussing the regulatory perspectives on integrating these novels tools into nonclinical safety assessment. The session will also feature examples of how these novel tools are used successfully by several pharmaceutical companies to advance drug discovery and development, by supplementing and/or enhancing current testing methods. This session will be impactful in enabling productive discussions among regulatory, government, and pharmaceutical stakeholders. The session will inspire progress towards the development of consistent industry practices and regulatory guidances for implementing these novel tools in nonclinical safety assessment, and lead to meaningful reduction in animal use.
Educational Co-Support Provided by: Aclairo Pharmaceutical Development Group, Inc. and American College of Toxicology
One of the challenges when developing safe and efficacious pharmaceuticals is finding a way to deliver these molecules to target tissues or cells in a safe and effective manner. Lipid-based nanoparticle formulations can serve as carrier systems to transport and deliver diverse therapeutic agents including biotechnology products and small drug molecules. These drug delivery systems are an area of intense research because they can facilitate a payload’s penetration of cell membranes, improve drug stability, aid in resisting proteolytic degradation, control drug release, and target drugs to specific tissues based on their biochemical composition. Drug formulations containing lipid-based nanoparticles have been investigated in products with a variety of indications and routes of administration; but nanomaterials present unique challenges during safety evaluation. This session will provide an introduction to the latest developments in lipid-based nanoparticle technology, describe safety considerations during evaluation of these delivery systems from a regulatory perspective and provide case studies describing how evaluation of lipid-based nanoparticle formulations have been approached.
Drug discovery and development is a complex, lengthy and expensive process that takes on average 10–15 years and approximately $1–2 billion for the approval of a new drug. While the studies needed to support clinical development are generally outlined in guidance documents, there is much less guidance on how to translate the nonclinical data into clinical designs. Nonclinical studies are performed to conduct the First‐in‐human (FIH) clinical trial which is the first major milestone to advance new promising drug candidates and are conducted primarily to determine the safe dose range for further clinical development. Resolving how to move forward and even whether to move forward requires significant cross‐functional collaboration with pathologists, ADME scientists, biologists, and clinical staff. There are many reasons why drug candidates might fail, these could be as simple as insufficient understanding of the nature of the translational process, failure to effective integrate the data coming from different pharmacologically relevant species or erosion of margin of safety during chronic toxicology studies. This continuing education (CE) course is aimed to help participants improve their skills at “Managing translational challenges from nonclinical to clinical program” encountered during drug development by providing case study examples for various modalities. Speakers will briefly review the key principles of translation development and will provide case studies from multiple therapeutic areas and involving several types of toxicology challenges.
Educational Support Provided by: Society of Toxicologic Pathology
We will present an overview of the mechanisms of action, toxicologic liabilities, and safety risk assessment approaches for novel biotherapeutics for use in treating nervous system disorders and neuromuscular diseases. These modalities include vector-based therapies such as lentiviral and adeno-associated viral vectors (AAVs), cell-based therapies such as stem cells and CAR-T cells, nucleic acid-based therapies such as antisense oligonucleotides (ASOs) and mRNAs, and novel antibody-based therapeutics. The session will begin with an overview of the mechanisms of action for each of these therapeutics, how they can specifically target the nervous system and the unique aspects of safety risk assessment for these novel biotherapeutics. Additionally, there will be a presentation on the methods for investigating biodistribution, pharmacokinetics and pharmacodynamics to enable clinical/human dose prediction of these novel therapeutics. Finally, there will be 2–4 short case studies to demonstrate the importance of an informed safety assessment for novel biotherapeutics that target the nervous system. The goal of this session is to provide a well-rounded overview of the rapidly emerging biopharmaceutical research that is focused on developing novel therapeutics for the treatment of nervous system disorders and neuromuscular diseases.
Educational Co-Support Provided by: Burleson Research Technologies and American College of Toxicology
The last several years have witnessed several advancements within the field of immunotoxicology. These include, but are not limited to, a greater understanding of the mechanisms underlying various immune-mediated diseases including cancer, new therapeutic options to treat inflammatory and autoimmune diseases, and the development of new immunotoxicity assays (including in vitro alternatives for the evaluation of dermal sensitization). This past year also saw the publication of the revised FDA guidance, “Nonclinical Evaluation of the Immunotoxic Potential of Pharmaceuticals”, which covers several aspects of immunotoxicology that have arisen since the publication of ICH S8, “Immunotoxicity Studies for Human Pharmaceuticals”. This session will provide an overview of the new guidance and address three areas that are key to this guidance and of increasing interest within the immunotoxicology community – dermal sensitization, immunostimulation/immunomodulation, and developmental immunotoxicity.
Educational Support Provided by: SciLucent, Inc.
Toxicology assessment is an important part of the manufacturing process of pharmaceuticals to ensure that impurities are managed to acceptable levels. Impurity management is multi-disciplinary requiring interaction of the toxicologist with different parts of the Chemistry, Manufacturing and Control (CMC) organization. Several ICH Quality and Multidisciplinary guidelines are set up to guide pharmaceutical sponsors in ensuring high quality and safe medicines for patients. This session will discuss how toxicological principles are used to ensure that impurities are controlled to safe levels for patients. The ICH Q3A/B guidelines discuss when impurities need to be qualified, which is done by generating biological data (clinical or nonclinical) to understand the safety of the impurity. DNA-reactive (i.e., mutagenic impurities), require specific control, often- times lower than the ICH Q3A/B thresholds because of their innate hazards. Biological drugs involve different syntheses than traditional “small molecules” and require some alternative approaches to toxicological assessment of impurities. Finally, information generated by the toxicologist in incorporated into a CMC regulatory submission to demonstrate the hazards and control strategies of impurities. This course will outline and discuss the basic strategies for toxicological assessment of impurities as well as showcase practical case studies.