HESI Insights - November 2020

The PROPAGATE Network, which HESI launched in June 2020 in collaboration with clinical and research colleagues around the world, was recently highlighted in Chemistry World. Via an inter-laboratory ring trial, the PROPAGATE Network has engaged nine global sites to generate novel evidence about the practical utility and performance of a direct-PCR based method for SARS-CoV-2 testing from nasal swabs. Participating labs are based in the United States, South America, the Caribbean, and Africa.

The study will conclude in the next two to three weeks and results will be made available via a preprint. The initial results suggest that the method is robust and reproducible under most conditions. We hope that the results of this study will inform more efficient and actionable COVID-19 testing strategies as demanded by the global pandemic.

If you are interested in learning more about the study or helping us identify sites that might want to implement this method, please contact Ms. Connie Mitchell (cmitchell@hesiglobal.org).

Say hello to the new HESIGlobal.org! Our website has a new face, and we’d like you to be among the first to check it out. Now you can more easily discover upcoming events, read about featured collaborations, and learn more about ways to join us in developing science for a safer, more sustainable world.

The HESI Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee miRNA Working Group is seeking urine samples (minimum of 2 mL for each treatment) from renal toxicity studies treated with different toxicants (or controls) in rat, dog, or monkey. Samples need to be available to send to Dr. Peter Yuen at the National Institutes of Health. There are no specific requirements on sample collection, but donors should be able to share information on the compound with which the sample was treated. Replicate animals, as well as concurrent histopathology information, are preferred if possible.

Please contact Dr. Syril Pettit (spettit@hesiglobal.org) or Ms. Connie Mitchell (cmitchell@hesiglobal.org) if you have samples you are able and willing to share.

The HESI eSTAR Committee is exploring interest in starting a new working group that uses error-corrected sequencing (ECS)/duplex sequencing approaches to assess non-genotoxic carcinogens (the HESI Genetic Toxicology Technical Committee [GTTC] is exploring the use of the technology for genotoxic carcinogens). We are assessing interest in forming an exploratory group whose objective would be to develop a proposal for experimental work or other activities that might be adopted by the eSTAR Committee around the use of ECS to assess non-genotoxic carcinogenicity via the committee’s project proposal process.

We are seeking additional/new participants to help lead and populate this new group. Interested parties should reach out to Ms. Connie Mitchell (cmitchell@hesiglobal.org) and Dr. Syril Pettit (spettit@hesiglobal.org).

The HESI Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee is excited to announce the addition of two new participating organizations within the initiative launched in Fall 2019, “International Multi-Site Study – In Vitro Methods to Assess the Tumorigenicity of Human Cell-Based Therapeutic Products”. AstraZeneca and Imperial College London have joined the National Institute of Health Sciences (NIHS) in Japan and Takeda Pharmaceutical Co. to form a second arm of the study aimed at assessing the sensitivity of the “Highly Efficient Culture” (HEC) assay for detecting residual pluripotent stem cells in iPSC-derived cell therapy products. A kick-off meeting with the newly confirmed HEC Assay Team was held in September 2020 and technology transfer is underway.

The first arm of the multi-site study, focused on the “Droplet Digital PCR” assay, started in September 2019 with five sites (Cell & Gene Therapy Catapult, UK; NIHS, Japan; Novartis Institutes for BioMedical Research, Switzerland; Takeda Pharmaceutical Co., Japan; and Sumitomo Dainippon Pharma Co., Japan) after a public call for participants. Despite the global impact of the COVID-19 pandemic, preliminary experiments aimed at identifying relevant biomarkers have been completed at all sites and the team is preparing to move into the main phase of the study.

For more information, please contact Dr. Connie Chen (cchen@hesiglobal.org) and Dr. Lucilia Mouriès (lmouries@hesiglobal.org).

HESI THRIVE is a seed grant program that is innovating translational research and improving quality of life after cancer. By providing researchers with both seed funding and access to critical networks, THRIVE enhances the visibility of the patient need, the value of the research, and the reasons that larger funding entities might elect to incorporate these research streams into future funding priorities.

THRIVE provides seed grants for clinical and translational research and technology-based solutions that enhance our ability to predict when and how adverse effects may occur in patients who have received cancer treatment. The THRIVE grant program is designed to provide seed funding to investigators for the testing of initial hypotheses and collecting of preliminary data to help secure long-term funding by the National Institutes of Health and/or other major institutions. For details on eligibility, funding, the application process, and key deadlines, please click here.

The letters of intent deadline is 31 December 2020. For more information, contact research@hesithrive.org.

• Dystocia – toward understanding if reproductive performance in the rodents is waning/evolving.
• Male reproductive endpoints – determining the value of functional male reproductive toxicity endpoints (e.g., mating and fertility; sperm evaluations) relative to the profile generated by routine microscopic evaluation of male reproductive tract in repeat-dose toxicity studies.
• Defining an adverse DART effect – developing a training session or workshop that could address the differences between hazard ID and risk assessment.

If you are interested in learning more about or participating in one the scoping projects or other DART Committee activities, please contact Dr. Connie Chen (cchen@hesiglobal.org) or Dr. Shermaine Mitchell-Ryan (smitchell-ryan@hesiglobal.org).

The HESI Protein Allergens, Toxins, and Bioinformatics (PATB) Committee hosted a virtual workshop from 21-23 October 2020 in collaboration with the Society of Toxicology (SOT) Food Safety Specialty Section titled “From Protein Toxins to Applied Toxicological Testing” in the context of safety assessment of novel foods and feeds.

The event brought together international experts from the academic, regulatory, and industry sectors. Eight speakers presented recent advances in protein toxins biology, the use of computational biology for protein toxins identification and characterization with in silico approaches, and discussed the applicability of existing tools and resources for safety assessment of novel food biotechnology products.

With an impressive outreach and audience engagement (200 participants from four continents and 20 countries registered), the event ended with a consensus on concrete, tangible next steps, which will be described in a publication reporting on the event. The HESI PATB Committee looks forward to continuing this interaction with the global scientific community.

For a full description of the event, please visit the event webpage, or contact Dr. Lucilia Mouriès (lmouries@hesiglobal.org). The final event program and speakers’ slides will be added soon.

The HESI GTTC is sponsoring an Environmental Mutagenesis and Genomics Society (EMGS) workshop on 3 December 2020. Event details can be found below or on the EMGS website.

• Workshop Title: Quantitative Interpretation of Genetic Toxicity Dose-Response Data for Risk Assessment and Regulatory Decision-Making: Current Status, Persistent Challenges, and Emerging Priorities
• Co-Chairs: Dr. Paul White (Health Canada) and Dr. Andreas Zeller (Hoffmann-La Roche)
• Date: 3 December 2020
• Time: 9:00 AM to 1:30 PM EST
• Cost: Free to HESI GTTC members and EMGS members; $75 for others. Attendees who are not EMGS members can join the EMGS for $75.
• Registration: Registration is open until 2 December 2020 and is free to HESI GTTC members and EMGS members by using this registration link.

The workshop will provide:

• A brief overview of the state of the science regarding quantitative interpretation of genetic toxicity dose-response data, including a brief overview of the BMD combined covariate approach for potency ranking and MOA investigation,
• A summary of recent genotoxicity risk assessment case studies, particularly those related the pharmaceutical impurities such as NDMA,
• An in-depth overview of issues pertaining to developing consensus CES values for genotoxicity endpoints,
• An in-depth overview of issues pertaining to the determination of effective AF values for routine interpretation of genotoxicity dose-response data for establishment of HBGVs, and
• A brief overview of issues pertaining to interpretation of in vitro genotoxicity dose-response data in a risk context.

The workshop will include two one-hour time slots for structured discussion aimed at delineating action items and next steps.

For more information, please view the event page or contact Dr. E’Lissa Flores (eflores@hesiglobal.org).

The HESI eSTAR Committee has co-organized a webinar with the American Association of Pharmaceutical Scientists (AAPS). This webinar is free and open to the public, so please feel free to share the link! Webinar details can be found below or on the AAPS website.

• Webinar Title: Development of Next-Generation Biomarkers for Detecting Kidney Toxicity
• Presenter: Dr. Alison Harrill (National Institute of Environmental Health Sciences)
• Date: 11 February 2021
• Time: 12:30 PM to 2:00 PM EST
• Cost: Free and open to the public
• Registration: Register here.

For more information, please contact Dr. Syril Pettit (spettit@hesiglobal.org).

It is hard to believe as the year is coming to an end that nearly all us have learned to live a new normal due to the COVID-19 pandemic. Even though COVID-19 prevention methods vary greatly worldwide, we are now looking at a second wave of infections. Unfortunately, this second wave is projected to continue throughout the cold season. The good news is that current vaccines in development show good outlooks and may offer the protection needed sometime in 2021.

This means that HESI’s annual Board of Trustees meeting in January will still take place online. Due to HESI’s long-standing “virtual teams” model, HESI staff, as well Trustees, adapted efficiently to a fully remote work environment. At the meeting in January, Trustees and staff will look at HESI’s organizational activities throughout the last year in addition to focusing on the post-COVID-19 period. Right now, it is uncertain if HESI’s Annual Meeting in June will take place in person or online.

One blessing is that HESI’s financial situation has remained very healthy, allowing us to continue advancing existing initiatives. Pursuing the increased involvement of academic members in HESI activities and extending our global reach – initiatives which slowed during 2020 – will remain priorities in 2021. In addition, HESI leadership encourages members to submit ideas for new scientific projects as emerging issues in human or environmental health, which are equally important for a successful HESI in the years to come. Please don’t hesitate to contact us with new ideas or suggestions.

Martin van den Berg, PhD, ERT
HESI Chair