Educational Support Provided by: GSK
Nonclinical safety assessment of a new molecule is a critical component prior to initiation of clinical trials. According to GLP regulations, the Study Director is the single point of study control and is responsible for study conduct and interpretation. The Study Director must be a scientist, project manager and great communicator, and possess regulatory knowledge for nonclinical study conduct. Study Directors and their projects are successful when they have support and coordination within the laboratory and collaboration and support from the Sponsor/Study Monitor and any external laboratories that might be involved. This course will provide an innovative forum for learning and sharing details of study conduct and the roles of Study Monitors and Study Directors. It will focus on practical approaches to real-life challenges faced during study conduct and will provide insight on anticipating and analyzing potential problems to develop solutions to issues that arise during the conduct of a nonclinical study. Participants will advance their understanding of the roles of the Study Director and Study Monitor, the concepts of study design, protocol development, handling study issues, expectations for monitoring study conduct, and best practices for interpreting and communicating study data.
Each participant will follow a general toxicology study, from the initial design to reporting. Real-life examples and experiences will be used to build a base of knowledge and to manage expectations. This is a hands-on course, and attendees should be prepared to solve study-related problems in small groups, interpret data, and interact with course faculty and attendees.
Educational Co-Support Provided by: EPL, Inc. and American College of Toxicology
Nonclinical safety evaluation studies are essential to identify potential hazards, to determine an initial safe dose for first-in-human (FiH) trials and to develop subsequent dose escalation schemes. These studies aim to identify potential on- target or off-target toxicity and provide signals for clinical monitoring plan. According to the ICH S6 regulatory guidelines for biotherapeutics, species/model selection is crucial for performing safety assessment studies. A relevant species is defined as one in which the test material exhibits pharmacological activity due to the presence of the receptor or epitope. Commonly, cynomolgus monkeys, rats, or mice are used as relevant species for safety assessment of biotechnology-derived drugs. However, in cases where traditional species are unsuitable, engineered (usually transgenic and/or huMouse) models expressing human targets may be employed. Several huMouse or disease rodent models have been successfully used for early discovery and/or efficacy studies and have been used for FiH-enabling safety assessment studies along with the cynomolgus monkey for establishing margin of safety. By providing case study examples, this continuing education (CE) course is designed to help participants improve and enhance their skills on the factors to consider when selecting an appropriate transgenic and/or huMouse models for FiH-enabling programs.
This CE course will offer a comprehensive examination of the application of Artificial Intelligence (AI) in toxicology, emphasizing its transformative potential and challenges within regulatory decision-making. Participants will gain foundational knowledge of AI concepts, explore state-of-the-art methodologies for toxicology predictions, and examine case studies showcasing successful AI applications. Additionally, the course will address current barriers to AI adoption and discuss strategies to integrate AI innovations into regulatory practices. By the end of this course, participants will: Understand foundational AI concepts and methodologies as applied to toxicology; Evaluate the strengths and limitations of AI tools in regulatory contexts; Critically assess AI-based toxicology predictions and their implications; Explore ongoing developments, ethical considerations, and collaborative opportunities in AI-driven toxicology. The course aspires to empower attendees to leverage AI for improved toxicological assessments while addressing regulatory challenges, ultimately driving safer and more efficient decision-making processes.
Educational Co-Support Provided by: Charles River and SciLucent, Inc.
At the 2023 ACT meeting, a basic CE course on Juvenile Toxicology described the added value of ICH S11 in defining the need, timing and design of juvenile animal studies (JAS) to support the pediatric development of novel therapeutic candidates. Building on this foundation, the proposed advanced CE course on JAS will delve deeper into several key areas. The regulatory processes for Pediatric Investigation Plans (PIPs) by the European Medicines Agency (EMA) and Pediatric Study Plans (PSP) by the US Food and Drug Administration (FDA) will be compared, including options for seeking pediatric regulatory deferrals and waivers. The Weight of Evidence (WoE) approach will be discussed. The course will also focus on the key drivers that determine the depth of evaluations on developing organs in JAS. There will be a deep dive into specialized approaches to bone evaluation in juveniles, supported by a case study illustrating how nonclinical data led to the inclusion of specialized bone examinations. In addition, possible designs for neurotoxicity assessments in JAS will be discussed, covering options for neurobehavioral testing and both routine and enhanced neuro-histopathology evaluations. Before the course concludes with an interactive panel discussion, both EMA and FDA will give their regulatory perspective. EMA will present the regulatory alignment with pharma regarding JAS for 127 medicinal products and FDA will talk about case studies where ICH S11 recommendations had a significant impact on the regulatory outcome as well as examples of JAS with both aligned and divergent regulatory perspectives between EMA and FDA.
Educational Support Provided by: Charles River
This CE course will present interactive case studies from pharmaceutical development across the toxicology testing continuum and with a focus on neurotoxicology. Attendance will be organized into tables of 6-8 attendees, and volunteers will be requested to present their perspective to the audience. Participants will have the opportunity to discuss each case in subgroups and the moderators will then provide case outcomes from the various perspectives. The aspects that will be presented will include general toxicology study design for centrally delivered antisense oligonucleotide (ASO), developmental neurotoxicology, safety pharmacology, neuropathology, CNS biomarkers and regulatory strategies. The session will explore a wide range of therapeutic modalities and represent commonly encountered challenges in neurotoxicology. A strong emphasis on regulatory toxicology will allow session participants to gain practical knowledge in this rapidly involving space.
This CE course will focus on examining the various modalities, documents and timelines when submitting preclinical safety studies to enable clinical studies. Every year unsuccessful IND submissions result in delay of clinical onset, often due to lack of experience when submitting safety packages or due to inexperience of writing applications. Furthermore, several companies lack strategies and miss opportunities to advance translational research models, tools, and technologies to enable R&D efficiency. A robust regulatory strategy is essential to ensure development activities are aligned with regulatory requirements. The role of the toxicologist in this process is to ensure the nonclinical development program supports the proposed clinical trial. The International Conference on Harmonisation provides a framework for recommendations and regulatory expectations for the United States, Europe, Japan, Canada, and Switzerland. However, there are regional differences in requirements even within ICH regions. This course will provide an overview of regulatory expectations and recommendations for nonclinical safety assessment to support clinical trials in the United States as well as Europe, the United Kingdom, Australia, and Canada. We will review nonclinical submission requirements and opportunities for seeking regulatory input via formal meetings in these regions. In addition, we will highlight some common pitfalls that may lead to a clinical hold and best practices to ensure a successful regulatory submission.
Minipigs are a well-established nonrodent species in nonclinical safety assessment and device biocompatibility evaluation. However, many toxicologists have little, if any, first-hand experience designing and conducting toxicology studies in minipigs. This session is intended to improve our understanding of minipigs by 1) reviewing regulatory acceptance of their use; 2) providing basic information on their use in toxicology and safety pharmacology, and 23) offering forward-looking perspectives that could expand the use of minipigs as an alternative to dogs and NHPs in the future. The session will begin with basic descriptive overviews of technical and logistical considerations when working with minipigs (including micropigs and nanopigs) in repeat-dose toxicology studies and safety pharmacology studies. Comments on the current status of regulatory acceptance as well as on use with various drug modalities (small molecules, biologics, etc.) will be included. After this foundational instruction, the session will shift to more forward-looking discussions that will challenge attendees to consider potential future directions and opportunities for minipig use. This will include a description of hurdles that must be surmounted to assess the suitability of minipigs as a model for DART studies. The session will close with a talk highlighting the importance of immunology issues with minipigs in toxicity testing and a discussion of the value humanized minipigs could bring to nonclinical safety assessment programs. In summary, this session is intended to be both instructive and provocative. The initial talks will provide foundational knowledge for toxicologists seeking to gain familiarity with the current state-of-the-art with minipigs. The subsequent talks will be more thought-provoking for those who are looking to future possibilities for minipigs in drug discovery and development.
Educational Co-Support Provided by: Aclairo Pharmaceutical Development Group, Inc. and American College of Toxicology
The 2024 Nobel Prize in Physiology and Medicine was awarded to Victor Ambros and Gary Ruvkun for their discovery and description of microRNAs. This session will tell the story of the discovery of microRNAs and their broad gene regulatory functions, conservation across species, and their contribution to normal physiological processes. Importantly, the session will review their dysregulation, it's contribution to different pathological states and opportunities for therapeutic intervention. We will provide therapeutic context from a regulatory perspective and will discuss FDA guidance on Nonclinical Development of Oligonucleotide Therapeutics with a focus on small RNAS. Lastly two industry speakers will discuss their experience within the field of microRNA therapeutics; topics include microRNA therapeutics (mimics and microRNA inhibitors/anti-microRNAs), development of small interfering RNAs (siRNA, therapeutically similar to microRNA), and upregulation of microRNAs by antisense oligonucleotides.
Developmental and reproductive toxicity (DART) studies are generally not needed to support first-in-human clinical trials but are typically conducted to support continued clinical development and marketing approval. Animal studies used to support DART safety assessments include male and female fertility, embryo-fetal development (EFD), and pre- and postnatal development (PPND). Initial safety evaluation of male and female reproductive organs in nonpregnant animals are included as part of most general toxicity studies to inform risk of infertility prior to and throughout clinical development, as well as potential for clinical monitoring. Functional fertility studies and developmental toxicity studies (EFD and PPND) are usually conducted later to support enrollment of individuals of reproductive potential on clinical trials and to inform patient safety in the package insert of approved products. DART and genetic toxicity data is used to inform recommendations on egg and sperm preservation, pregnancy testing, contraception, and potential restrictions on egg and sperm donations in clinical protocols, informed consent documents and/or package inserts. This course will review when, what, and how DART data are used to support clinical trials and labeling from different perspectives including a nonclinical team representative, DART subject matter experts, pharma clinical lead and a FDA deputy director of safety