Society of Toxicology Annual Meeting 2018: Physicians Committee Continues to Promote Modern Test Methods

It’s that time of year again! The Society of Toxicology (SOT) annual meeting—the world’s largest gathering of toxicologists—is taking place March 11-15 in San Antonio, Texas. Just like last year, Physicians Committee scientists are actively participating in sessions throughout the conference to advance their work in promoting more effective, nonanimal toxicological test methods. 

We are again sponsoring events to engage and train toxicologists and regulatory scientists with scientific and policy initiatives to replace animal tests with more human-relevant methods, including our Adverse Outcome Pathway seminar. We are also participating in multiple poster sessions to inform attendees of current topics in predictive toxicology and alternative test methods. 

Here is a select list of Physicians Committee-sponsored sessions or events. If you are attending SOT, we invite you to attend these sessions. Please contact Kristie Sullivan (ksullivan [at] pcrm.org (ksullivan[at]pcrm[dot]org)) for more information. 

You can also download a curated list of other SOT scientific sessions and events of interest to scientists working with in vitro and computational methods. 

Monday, March 12

Poster Session:  Regulatory Policy and Policy Evaluation

The Preclinical Innovation and Patient Safety Initiative: Recommendations for Modernizing Preclinical Testing

Presenting Author: Elizabeth Baker

9:15 a.m. – 4:30 p.m. (Author Attended: 10:45 a.m. – 12:15 p.m.)

Convention Center Exhibit Hall

Abstract: Preclinical drug testing is critical to understanding the toxicity, pharmacology, and pharmacokinetics of candidate drugs. The Preclinical Innovation and Patient Safety (PIPS) Initiative fosters collaboration among drug development stakeholders—including federal agencies, patient, research and health organizations, academia, technology companies, and the pharmaceutical industry—to implement modern human-focused preclinical approaches. Participants recognize that more predictive approaches are fundamental to the timelier delivery of safe and effective medicines. This presentation highlights the scientific, regulatory, policy, training and educational recommendations made by a group of stakeholders during the kick-off roundtable in January 2017, and explores three projects identified by PIPS participants as likely to provide high impact on the field of toxicology. First, modern approaches to validation should incorporate human data. This is the only way to overcome the challenge of comparing human in vitro approaches to currently available animal safety data. The legislation 21^st Century Cures and the Prescription Drug User Fee Act mandate that FDA make real world human data/evidence more accessible. PIPS identified that implementation of the mandates should include making real world evidence available to method developers for validation purposes in order to better understand a method’s predictive ability. Second, researchers must have access to human cells and high-quality tissues in order to use human-focused approaches. Currently, there are no guidelines for collection and care of human cells and tissues intended to be used for research. PIPS is coordinating efforts to develop guidelines to ensure the increasing demand is met. Third, despite significant private and public investment in the development of human-focused approaches, many FDA regulations require animal data. While industry may use modern approaches for internal decision-making, the regulatory requirements prioritize animal data and dis-incentivize use of modern approaches. PIPS has identified the regulations and coordinated multiple projects to push the agency to update the regulations to reflect flexibility that allows for evolving science. 

Tuesday, March 13

Hands-On Seminar: Creating an Adverse Outcome Pathway in the AOP Wiki

5 – 7 p.m.

Grand Hyatt Rooms Bowie A – B 

The Human Toxicology Project Consortium and the Physicians Committee for Responsible Medicine invite you to deepen your understanding of the AOP Wiki and gain experience entering an Adverse Outcome Pathway in a structured, hands-on seminar Tuesday evening. 

Version 2.2 of the AOP Wiki was released in January 2018.  This seminar will be ideal for those wishing to gain some hands-on experience with the new version as well as those who are new to the AOP concept. We will also present an available online course on AOPs, and course attendees will work through a case example in small groups

See full agenda and please register in advance to ksullivan [at] pcrm.org (ksullivan[at]pcrm[dot]org). Registration is appreciated, but not required. Please indicate whether you will bring a laptop.

Thursday, March 15

Poster Session:  Late-Breaking 01: Model Systems

Title: Towards an IATA for Chemical Respiratory Sensitization: Establishment of Reference Chemicals to Evaluate In Vitro and In Silico Approaches

Presenting Author: Kristie Sullivan

8:30 – 11:30 a.m.

Convention Center Hall 1

Abstract: Public health and regulatory needs require approaches to detect and discriminate respiratory sensitizers from dermal sensitizers; however no single method or strategy is generally accepted. An Adverse Outcome Pathway (AOP) for respiratory tract sensitization by low molecular weight organic chemicals identifies several promising in vitro methods. Most of these methods have only been assessed with a few well-known respiratory sensitizers (e.g., toluene diisocyanate or trimellitic anhydride). To further evaluate the utility of these in vitro methods, we have set out to build a more comprehensive list of reference chemicals, including known respiratory irritants, non-sensitizers, and dermal sensitizers. The ideal list of respiratory sensitizers should cover a range of chemical classes and include “challenging” chemicals, such as respiratory sensitizers thought to elicit effects through dermal exposure and those for which specific-IgE has not been detected in humans. To build the list, we are conducting a review of established structure-based profilers, recent literature, and human clinical reports, focusing on data verified in humans for translatability to human health outcomes. We are also making use of the Abstract Sifter literature review tool (Baker et al., (2007)) to identify additional potential respiratory sensitizers. Briefly, a set of PubMed MeSH terms describing adverse effects (AEs) for 92 known sensitizers was used to query a large database of chemicals and AEs, yielding over 7000 chemicals of potential interest. The top 500 ranked chemicals (based on article counts) are currently undergoing manual review. This reference chemical list is an important step towards an assessment of potential test methods and creation of internationally-harmonized integrated approaches for the detection of chemical respiratory sensitizers.