Educational Co-Support Provided by: Neurocrine Biosciences, Inc. and American College of Toxicology
Artificial intelligence (AI) is revolutionizing toxicology, transforming it from an observational science into a data-rich discipline capable of addressing complex challenges in drug and chemical safety assessment. By leveraging advancements in machine learning, deep learning, and the growing availability of toxicological data, AI is enhancing predictive toxicology, risk assessment, and mechanistic research. This session provides an overview of key developments in AI-enabled toxicology, from early expert systems and quantitative structure-activity relationships (QSARs) to recent breakthroughs with deep neural networks. It highlights emerging trends and opportunities while addressing critical limitations, such as sparse datasets, high-dimensional challenges, and the risk of overgeneralization in AI models. The responsible integration of AI—through interpretable, human-centered tools and multidisciplinary collaboration—offers immense promise for advancing toxicology and regulatory science. However, it must complement ongoing efforts to strengthen primary evidence generation and critical appraisal. By thoughtfully navigating these advancements, AI can accelerate safer outcomes for human health and the environment. This session is a follow up to the keynote talk given by Dr Weida Tong in 2024, and is designed to address some of the questions raised by attendees during that opening session.
Educational Support Provided by: Roundtable of Toxicology Consultants
Many toxicologists consider consulting an alluring and viable career option with work-from-home benefits, flexibility, and perceived freedom for early- to late-career professionals. Toxicology consulting is a rewarding career, but it is not for everyone. Dedication and persistence are required along with motivation to solve problems and work diligently with clients, laboratories, the regulatory community, non-toxicologists and project teams. In this interactive workshop, we will compare career options for toxicologists as independent consultants or members of consulting organizations. The challenges for independent consultants can be daunting but are surmountable. This workshop will outline how to start and build a consulting practice to ensure success. This workshop will answer common questions: “how do I start”, “how much should I charge” and “what do I need to do?” The initial presentation will describe “how do I begin” with real-world challenges for a consulting practice and will address consulting rate, fees, liability insurance, bank accounts, accounting, and day-to-day operations. Subsequent presentations will describe consulting for solo practitioners, a small group practice, and a large consulting group, as well as developing niche consulting practices. A final presentation will discuss myths and misconceptions that keep toxicologists from choosing consulting – mostly marketing. A panel discussion will address questions, case studies, dealing with clients, and providing regulatory and scientific feedback to clients.
Educational Support Provided by: Eli Lilly and Co., Inc.
Recent advancements in molecular targeting technologies have led to a renewed interest in radiopharmaceuticals, particularly radioligand therapies for oncology, due to the potential to deliver cytotoxic radiation selectively to cancer cells while minimizing damage to healthy tissues. Compared to other targeted therapies, radiopharmaceutical therapies can be personalized by radionuclide imaging and deriving individual patient tumor and normal organ radiation absorbed doses. Radiopharmaceuticals generally require fewer cycles to elicit a response and are generally well tolerated relative to traditional chemotherapies. Unfortunately, the relatively short half-lives of radionuclides, measured in hours or days, make their deployment for cancer therapy challenging. This symposium will explore the unique safety, logistical, translational, and regulatory considerations associated with the development of this oncolytic modality. The goals of this session are to 1) provide a basic overview of various radiopharmaceutical constructs and commonly used radionuclides in cancer therapy, 2) discuss nonclinical studies required for the registration of a novel radiopharmaceutical product, 3) present study design considerations for the safety evaluation of non-radioactive constructs, 4) discuss the design and conduct of biodistribution studies with the radioactive construct and the logistical challenges associated with their execution, 5) present how organ-level dosimetry estimates are extrapolated to humans based on dosimetry data obtained from nonclinical biodistribution studies, and 6) discuss the regulatory requirements for the development of radiopharmaceutical products. The audience will gain a basic understanding of the development of radiopharmaceuticals and translational dosimetry. The speakers will elaborate on terminology associated with radiation wherever applicable and present case studies wherever possible.
Antibody-drug conjugates (ADCs) are a promising cancer treatment that expands the therapeutic index of conventional chemotherapy agents by conjugating potent cytotoxic agents to highly specific monoclonal antibodies (mAbs) to increase efficiency and delivery of cytotoxic agents to targeted cancer cells. The Food and Drug Administration (FDA) have approved 13 ADCs covering 16 indications, including several types of breast cancer, non-small-cell lung cancer, bladder cancer, classic and non-Hodgkin lymphoma, and more. While ADCs are designed to minimize damage to healthy cells, side effects are still common in patients, and many ADCs have failed during the clinical development phase due to their adverse toxicities which might be missed in the non-clinical phase testing. Common side effects observed in the clinics, such as peripheral neuropathy and multi-organ toxicities (e.g. eye, lung, liver), are largely recapitulated in preclinical models, and analysis indicates that certain types of payloads are related to certain types of toxicities. Further analysis demonstrates that toxicities are often shared by different ADCs that deliver the same cytotoxic payload, independent of the targeted antigens (i.e., off-target toxicity) or cancer types. This mini-symposium will (1) highlight the nonclinical to clinical challenges of ADC treatment-related common adverse events (ie. peripheral neuropathy, ocular, lung, and liver toxicities); (2) summarize current in vivo non-clinical study requirement and alternatives from regulatory aspect, and (3) examine fundamental mechanisms contributing to ADC-related adverse effects and explore the suitability of various animal models and new approach methodologies to understand and mitigate ADC toxicity in nonclinical development.
Educational Co-Support Provided by: SciLucent, Inc. and American College of Toxicology
FDA interactions are an important part of the drug development process. Several formal meetings between sponsors and FDA are available to provide an opportunity for the Agency to provide input on drug development plans or to discuss any issues that may have arisen during development. Successful meetings take time and planning. Understanding the goals of the meeting is a first step. Questions should be clearly defined and the information to support the data should be available and provided in the Briefing Package to enable FDA to respond. This mini symposium will discuss best practices for a successful FDA meeting from both an industry and a regulator’s perspective. Case studies will be presented that highlight successful meetings and ways to avoid common pitfalls.
A traditional part of the final afternoon of the ACT Annual Meeting is the Hot Topics Symposium. Each year this session includes a variety of topics from leading experts focusing on late-breaking regulatory or scientific advances related to toxicology.
Educational Support Provided by: Eli Lilly and Co., Inc.
Endogenous substances are often present as impurities in biologic therapeutics due to the nature and method of manufacturing. There are many classes of endogenous compounds, including fatty acids, amino acids, nucleic acids, sugars, vitamins, enzymes and others (e.g., urea). While these compounds may be present endogenously, increased levels can lead to adverse effects; thus, appropriate exposure thresholds are necessary. Thresholds are not readily available for many of the endogenous compounds. Due to the number and diversity of compound classes, a single threshold is not appropriate. This session will present the different types of exposure thresholds including permitted daily exposure (PDE), acceptable daily exposure (ADE), acceptable daily intake (ADI) that are often used interchangeably to describe daily exposure limits, general approaches used when setting an appropriate exposure thresholds and their importance. Specific considerations for setting exposure thresholds for endogenous compounds will be discussed. After a discussion of methodology and special considerations for setting exposure thresholds for endogenous compounds, four example endogenous compound classes will be presented: 1) fatty acids; 2) amino acids; 3) sugars; 4) enzymes. Some of the classes like fatty acids and amino acids have been studied more extensively and other classes are a work in progress. Specifically, special considerations for each class and class- or compound-specific limits where available will be discussed. Following discussion of class-specific thresholds, challenges and limitations to the proposed approach will be presented. Useful links for the reference materials will be provided. While the scope of the presentation is for parenteral route of administration, other routes of exposures will be touched upon.
Educational Support Provided by: AstraZeneca
Intranasal therapies and vaccines have been around for centuries and regained interest during the SARS-CoV-2 pandemic. In addition to being a site of disorders and infections, the nasal cavity offers access to the rest of the respiratory system, vasculature, brain, and immune system. The nose poses an interesting challenge specifically for immune-activating conditions because it first serves as a barrier to the external environment. It is by ‘putting the nose to the grindstone’ that intranasal therapies are advancing. This symposium will address in vitro and in silico models for nasal drug development; how allergens affect the interplay between neural and immune systems; and the case study of a recent intranasal program for influenza vaccination.