ToxChats©

This podcast is part of a series on the different career paths in the field of toxicology. In this episode, we interview Dr. Alex Eapen on his career path to his current position as the Director of R&D Scientific & Regulatory Affairs – North America at Cargill. Dr. Eapen shares his experiences as a toxicologist in the food industry and the exciting opportunities this job brings to positively impact people's lives. In this episode, we also explore an overview of the responsibilities and the education requirements needed to pursue a career in toxicology in the food industry.

Not every drug that has reached human clinical trials has needed preliminary nonclinical studies to demonstrate safety. This podcast episode is a case study for replacing the use of animals during the safety testing that occurs prior to human clinical trials, in which our guest speaker reviews conversations with regulatory authorities regarding a modern nonanimal testing strategy utilized to bring a nonequine-derived antitoxin as a therapeutic product to a patient.

This ToxChats© episode is part of a series on the different career paths in the field of toxicology. In this episode, we interview Dr. Marcus Delatte on his career path to his current position as the Vice President of Regulatory Strategy at the consulting company, Allucent. Dr. Delatte also shares his experiences as a pharmaceutical consultant in toxicology.

In this podcast, recent findings from toxicological studies on the emissions produced during fused filament fabrication (FFF) 3D printing are discussed. The use of low-cost FFF 3D printers is on the rise in households, businesses, and educational settings, enabling the creation of 3D objects from digital models. However, this process releases volatile organic compounds, ultrafine particles, and metal oxides, which could potentially pose health risks to users. Of significant concern is the potential harm to children, who may be disproportionately affected due to uncontrolled exposure to ultrafine particles in confined spaces, such as classrooms and libraries. Dr. Kyle Mandler comprehensively addresses the characteristics and human health effects of these FFF 3D printer emissions and propose effective recommendations for mitigating exposure to these emissions.

This podcast is part of a series on different career paths in the field of toxicology. In this episode, Dr. Chuck Schwartz, PhD, DABT, shares the career path that led to his current position as the principal consulting toxicologist and managing member of a consulting practice that specializes in the fields of occupational and quality toxicology. Dr. Schwartz's experiences as a corporate director and then consultant in the field of toxicology will be discussed.

Drug-induced seizures are a major concern for central nervous system active pharmaceuticals during development. Currently, there are no guidelines for interrogating and mitigating seizure liability associated with new pharmaceuticals. Because of the risks to patient safety during clinical trials, the understanding of nonclinical characterization that informs the translation of risks to humans is an area of intense interest among drug developers and regulators. A Continuing Education course was held at the 2022 ACT Annual Meeting in Denver, Colorado, where Dr. Delatte presented on identifying seizure liability in nonclinical studies. In this interview with Dr. Delatte, we discuss nonclinical findings that are indicative of seizure liability and appropriate approaches to characterize risks. Many drug classes carry seizure liability which may trigger preliminary studies, such as kindling studies, to understand risks prior to conducting a repeat-dose toxicology study. A description of premonitory signs of seizure in dose-range findings and repeat-dose toxicology studies is also discussed. Finally, this talk briefly discusses when nonclinical EEG studies are warranted and how to leverage the data from general toxicology studies to design an informative EEG study. Learning objectives of this talk are: (1) set up a drug development program for drugs in a class with seizure liability; (2) identify seizure liability in nonclinical studies; and (3) examine the elements from general toxicology studies that inform the pivotal EEG study.

In this ToxChats© podcast, we spoke with Dr. René Meisner, Head of Safety Assessment at Denali Therapeutics, on using both transgenic and disease mouse models in a drug development program. Topics include considerations for program design, regulatory interactions, and the role of these mice moving forward. s for program design, regulatory interactions, and the role of these mice moving forward. 

Mentors meet with you, listen to you, and provide advice. Sponsors have influence, connections, and can speak to your talents, abilities, and potential in new opportunities. Learning how to distinguish between the two and identify a sponsor that can help support your key growth and access to future opportunities is a critical skill needed to support one's professional and personal development.

In this ToxChats© episode, we interview Dr. Lorrene Buckley, Vice President at Eli Lilly & Company. Dr. Buckley is a board-certified toxicologist with over 30 years of experience in the practice of toxicology. In her current position, she is responsible for the design and execution of a nonclinical safety program and global regulatory submissions and interactions of drugs in the development and commercialization phases. Her mentorship of early and late-stage professionals is an important contribution to the success and growth of toxicologists in our field. For this professional development podcast, Dr. Buckley discusses the importance of identifying an appropriate sponsor to support your growth and success in the workplace.

In this podcast, Dr. Tetyana Cheairs gives a detailed overview of the fertilized egg model and how it is currently being used in safety assessment studies. She then describes important ways in which toxicologists and drug development programs could benefit from utilizing the fertilized egg model. This podcast is incredibly informative and is tailored to be understood and enjoyed by a broad scientific audience. Dr. Cheairs is an Assistant Professor of Pathology, Microbiology, and Immunology at New York Medical College, where she leads an innovative research program focused on using nonanimal models to study the hazardous effects of chemicals. As a result of her active involvement in teaching activities, she was appointed as Assistant Dean for PhD Programs at the Graduate School of Biomedical Sciences in 2019.

In this ToxChats© podcast, Dr. Elise Lewis provides a thorough background on the use of rabbits in DART and the future direction of their use as alternative species for other types of nonclinical safety studies. Topics include advantages and challenges, sourcing, behavior, physiology, and the practicality of rabbits, and the translatability of rabbit data to other nonclinical species and humans. Dr. Elise Lewis is currently the Principal Director of Toxicology at Charles River Laboratories and has significant experience in reproductive, developmental, and juvenile toxicology.

In this ToxChats© episode, we interview Dr. Chris Christou, Director of Preclinical Imaging and Research Laboratories at the South Australian Health and Medical Research Institute. Dr. Christou discusses the history of sheep as a preclinical species for medical device testing, novel groundbreaking neurological disease models, and the use of sheep as an alternative model in general toxicology studies. Critical regulatory standards and international guidelines are discussed to ensure successful submissions with the US Food and Drug Administration, the Australia Therapeutic Goods Administration, and the Australia New Zealand Therapeutic Products Agency.

During the COVID-19 pandemic, there was a reduction in the availability of nonhuman primates available for conducting nonclinical toxicity assessments, and as a result, the FDA released a guidance in 2022. This sparked interest in evaluating the feasibility of performing safety studies with alternative nonrodent species or other models. This podcast is the first in a series of several podcasts sponsored by ACT, in which experts in the industry are interviewed about their experiences working with these nontraditional models.

In this ACT ToxChats© episode, Dr. Shayne Gad and Samantha Gad of Gad Consulting Services host a question and answer follow-up discussion to the ACT Signature Webinar, The Role of Chemical Characterization in Biological Risk Evaluation of Medical Devices. During the first part of the podcast, they discuss diverse medical device categories for safety evaluation, explore novel aspects of biocompatibility evaluations accepted by the FDA, and address differences in safety assessments for regulatory bodies in the US and other countries. During the second part of the podcast, they provide career advice for ACT colleagues interested in transitioning from the pharmaceutical industry or academia to medical devices in toxicology.

In this ACT ToxChats© episode, Dr. Meredith Steeves and Mr. Terry Leyden share their perspectives on the current hiring landscape for toxicologist roles in industry, how to find the right fit, tips for transitioning from a bench-based position, and how to prepare for and successfully navigate the interview and negotiation process. Dr. Steeves and Mr. Leyden have complementary roles in the hiring process for toxicologists in the biopharmaceutical industry. Dr. Steeves is a Senior Director of Toxicology and hiring manager at Eli Lilly and Mr. Leyden is a Certified Personnel Consultant and President of The Leyden Group, a Colorado-based professional recruiting and search firm. This podcast is of interest for toxicologists at all career stages, with a specific focus on trainees and early career professionals and is presented by the ACT Early Career Professional Subcommittee.

In this new ACT ToxChats© episode, Dr. Jeffrey Foy, Vice President of Toxicology at Pepgen and Dr. Scott Henry, Vice President of Nonclinical Development at Ionis Pharmaceuticals are interviewed. Drs. Foy and Henry discuss the past, present, and future of oligonucleotides. Their focus is discussing the development and challenges that oligonucleotides face as a class of drugs.

One of the most common misconceptions about the opioid crisis is that it only affects people with a long history of drug abuse. Today, more than ever, a more diverse population is affected, potentially due to illicit fentanyl on the black market. In this ACT ToxChats© podcast, joined by Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, we discuss the history of opioid abuse, the factors that might have contributed to the current crisis, and other drugs that have played a role. We also discuss ways pharmaceutical and regulatory toxicologists may intervene.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), Multisystem Inflammatory Syndrome in Children (MIS-C), Adults (MIS-A), Neonates (MIS-N), and some Vaccinees (MIS-V). These are all considered clinically distinct diseases; however, the MIS-X diseases have overlapping symptoms and treatments with Kawasaki Disease (KD). MIS-C, MIS-A, MIS-N, and KD occur with increased frequencies several weeks following increased numbers of COVID-19 and for KD other pathogens. The incidence rate for MIS-C, MIS-A, MIS-N, and KD are typically a factor of roughly 5,000 lower than COVID-19 and for KD other pathogens. In this podcast, Dr. Darrell Ricke advances the hypothesis that MIS-C, MIS-A, MIS-N, MIS-V, and KD all represent a novel type of antibody-dependent enhanced (ADE) diseases associated with hyperactivation of granulocytes or mast cells. Symptoms for these diseases overlap those of histamine intolerance (HIT) coupled with pathogen associated symptoms. This ADE model proposes that antibody titer levels higher than primary immune response levels can hyperactivate granulocytes or mast cells to release inflammatory molecules including histamine; MIS-X and KD disease symptoms onset when histamine levels exceed the individual’s tolerance level. The proposed ADE model purports that patient treatment with intravenous immunoglobulin (IVIG) is successful in treating the MIS-X disease because IVIG compete with pathogen antibodies for binding to Fc receptors on immune cells, thereby reducing the immune responses to the pathogen or vaccine protein. This model is further supported with the vaccine spike protein activating immune cells via envisioned Fc receptor binding. This ADE model proposes additional antihistamine and diamine oxidase (DAO) adjunctive treatments combined with current standard of care treatments for investigation.

The severity of COVID-19 varies by individual spanning from asymptomatic, mild, moderate, severe, critical, and chronic disease. Prior to the availability of vaccines, high antibody titers correlated with disease severity. This was also observed for SARS disease. These high antibody titers on initial infections result from memory B cell responses with cross-reactive antibody responses from previous infection of likely other betacoronavirus family members. In general, family members of the betacoronavirus family leverage Fc receptor antibody uptake of viruses by phagocytic cells to infect these innate immune cells. This extended cellular tropism of phagocytic immune cells is dependent upon Fc receptors and antibodies. It is hypothesized that SARS-CoV-2 with higher antibody titers can infect phagocytic immune cells; SARS-CoV-2 infection of these cells has been observed in some patients with severe COVID-19. This proposed antibody-dependent enhancement (ADE) of disease has been proposed to a key transition of infection from respiratory infection to multi-organ disease in some severe COVID-19 patients. While the main medical community believes that there is no ADE associated with SARS-CoV-2 infections, multiple clinical studies are consistent with SARS-CoV-2 infection of monocytes and macrophages in some severe COVID-19 patients. The podcast discusses data available in the summer of 2022.

Dr. Thomas Hartung is a Professor at Johns Hopkins University and University of Konstanz in Germany, as well as the Director of the Center for Alternatives to Animal Testing. Dr. Sushant Kamath is a Senior Manager of Risk Assessment at Abbott Healthcare. In this podcast, Drs. Hartung and Kamath give a high level overview of the history and evolution of artificial intelligence (AI), different models used in AI, and also case examples of the use of AI in toxicology. We also discussed updates on the regulation of AI use in healthcare and toxicology and its ethical aspects. Last, we discussed challenges faced with AI and strategies to improve AI use. This podcast is incredibly informative, with general and high-level information about AI in toxicology—the future of AI is bright!

Dr. Cynthia Rohde is a Research Fellow at Pfizer, Pearl River, New York. As a drug safety representative on various project teams, she is responsible for developing and implementing nonclinical safety strategies for oncology products and vaccines. In this podcast, Dr. Rohde gives a high-level overview of the history and benefits of vaccines, and how they work. She then dives into innovative mRNA vaccines and discusses the important Emergency Use Authorization process that was utilized for mRNA vaccines against COVID-19. This podcast is incredibly informative, with general and high-level information about vaccines and regulatory processes, tailored to be understandable and enjoyed by a wide audience.