HESI Insights - November 2022

The non-human primate (NHP) is an important animal model to assess drug safety in development and reproduction, but it should only be used as a last resort based on unique pharmacologic or toxicologic attributes, heightened ethical concerns using NHP compared to other animal models, and limited availability. Recent survey data also indicate NHP use is higher than expected for drug safety assessments overall. This is at a time when there is also a shortage of NHPs available for research use, including sexually mature NHPs which are important for developmental and reproductive toxicity (DART) testing for biopharmaceuticals. A heightened regulatory awareness of this issue has prompted renewed interest in minimizing NHP use for DART safety assessment whenever scientifically appropriate.

The current HESI DART working group is reviewing NHP use in DART packages of approved products in US and EU but recognize that there may be important examples of when NHPs were or were not used to support DART safety assessment for products not currently approved and for which publicly available information is unavailable.

If you or your company have unusual case studies of drug development programs/products that would be informative of how to minimize use of sexually mature NHP for DART safety assessment (fertility assessment and/or pregnancy/developmental toxicity assessment) in the future, we would be very interested to hear about that example for the purposes of potentially including it in a white paper on this topic. Of particular interest would be case studies where an alternative assessment of DART safety (e.g., use of a surrogate molecule in the rodent or genetically modified rodents, etc.) failed to detect liability that was later identified. Please provide example by 31 Dec 2022.

Please contact Chris Bowman (christopher.j.bowman@pfizer.com) for scientific questions and Shermaine Mitchell-Ryan (smitchell-ryan@hesiglobal.org) to submit information on the case study.

The Health and Environmental Sciences Institute (HESI) DART Technical Committee is attempting to understand how and when dystocia is identified and reported in laboratory rodents and to identify how these calls may differ between organizations. As such, we are gathering qualitative data from various laboratories and animal facilities that conduct or support DART studies to understand laboratory practices and standard operating procedures (SOPs). Information gathered via this forum will be used to inform a best practices manuscript which will serve as a useful industry-wide tool to standardize the identification of dystocia and improve animal welfare practices.

On behalf of the committee, we would like to invite you to participate in this electronic survey by answering questions about your laboratory’s practices regarding identifying and reporting dystocia in the rodent. Should you be interested, we would also be happy to schedule a 1-hour teleconference to conduct the survey in an interview style format. (* Please note, the electronic survey contains a set of reference responses to assist you in understanding the expected responses).

We appreciate your assistance and value your contributions to this effort. Please note that all survey responses will be blinded from member company representatives and access to original submissions will be restricted to the HESI scientific program managers assigned to this project.

Questions regarding the aims of the project or the survey should be directed to the either of the project co-chairs: Rashin Ghaffari (Rashin.Ghaffari@corteva.com) or Pragati Coder (Pragati.Coder@crl.com).

If you are willing to participate, please complete the survey by Monday, February 6th, 2023, or submit a request for an interview style survey.

Sincerely,

Shermaine Mitchell-Ryan PhD,  HESI Scientific Program Manager (smitchell-ryan@hesiglobal.org) &
Connie Chen, PhD, MPH, HESI Senior Scientific Program Manager (cchen@hesiglobal.org)

On behalf of the HESI DART Dystocia Working Group. Please don’t hesitate to contact us should you have any questions.

The HESI DART – Dystocia Working Group

Pragati Coder (Charles River Laboratories)*
Rashin Ghaffari (Corteva Agriscience) *
Catherine Jaussely (Bayer)
Christopher Bowman (Pfizer)
Curtis Grace (Merck)
Edward Dere (Genentech)
Isabelle Leconte (Charles River Laboratories)
Jason Manton (Exponent)
Narinder Barraclough (LabCorp)
Nicola Powles-Glover (AstraZeneca)
Sheila Wason (Bayer)
Sonya Sobrian (Howard university)
Warren Foster (McMaster University)

*Denotes WG co-leads

The HESI Cardiac Safety Committee seeks Postdoctoral or Early Career Researchers working in cardiovascular safety science or a related field for the 2023 Early Career Seminar Award Series. This award offers an opportunity to share your research, learn from and network with experts in the toxicology and safety pharmacology fields from academia, regulatory agencies and pharmaceutical companies.

Award: Selected candidates will receive a $500.00 USD award and be invited to present their research on a public webinar with HESI Cardiac Safety Committee scientists and other invited guests. Webinar dates will be scheduled with the awardees in Q1 2023.

Qualifications and Requirements: Eligible candidates must have a PhD or equivalent degree in biology or related field (cell biology, biochemistry, pathology, biomechanical engineering, or similar); have current post-doc position/appointment or consider themselves an early career scientist (~1-5 years post-academic training) and may not have previously received an award under this program.

Application: To apply, please send along the following: 1) completed application form, 2) CV, and 3) one reference letter to Jennifer Pierson or E’Lissa Flores at cardiacsafety@hesiglobal.org.

Deadline to Apply: 21 November 2022

Click here to download the Application Form

The HESI GTTC seeks graduate students or postdoctoral fellows working in genetic-toxicology or genomics field for a new HESI GTTC Professional Development Award. This award offers an opportunity to attend scientific conferences, workshops, or courses, etc. to build core competencies and transferrable skills, and/or share your research. Awardees will also be welcomed to attend GTTC’s Annual Meeting in May 2023 to learn about the emerging projects and science at HESI and to network with experts in the genetic toxicology field.

Award: Selected candidates will receive up to $1000.00 USD award to support attendance at relevant scientific conferences, workshops, training courses, or another related opportunity during the 2023 calendar year that contributes to professional development (e.g., laboratory visit for specialized training or another venture – please describe in the application form). Proof of attendance 30 days after such event is required to be submitted to GTTC committee.

Qualifications and Requirements: Eligible candidates must be currently enrolled in a graduate program (MS or PhD candidates) in genetic toxicology, genomics, or related field (cell biology, biochemistry, or similar) OR hold a current postdoc position/appointment (no longer than 5yrs) AND have not previously received a professional development award from the GTTC.

Application: To apply, please send along the following: 1) completed application form 2) CV or bioksketch, and 3) one reference letter from a mentor to gttc@hesiglobal.org

Deadline to Apply: 28 November 2022

Click to learn more about the HESI Genetic Toxicology Technical Committee

The 2022-2023 HESI Innovation Prize will recognize public sector scientists who have helped to reduce disproportionate health burdens in underserved populations and/or to promote greater health equity. Both Mid-career ($75,000 USD) and Lifetime Achievement ($25,000 USD) awards will be offered.

Interested in applying? Click here!

Applicants must submit a short letter (maximum 5 pages) that includes examples of the impact of the nominee’s work in creating novel, cross-disciplinary collaborations in relation the year’s thematic focus. Applications must also include a CV (5-10 pages maximum) for the nominee, as well as 1-2 letters of support.

Applications are being accepted from October 1 – December 15, 2022

The HESI ITC seeks graduate students working in immuno-safety or immunotoxicology fields for a new HESI ITC Professional Development Award. This award offers an opportunity to attend scientific conferences, workshops, or courses, etc. to build core competencies and transferrable skills, and/or share your research. Awardees will also be welcomed to attend ITC’s Business meetings to learn about the emerging projects and science at HESI and to network with experts in the immuno-safety field.

• Award: Selected candidates will receive up to $2000.00 USD award to support attendance at relevant scientific conferences, workshops, training courses, or another related opportunity that contributes to professional development (e.g., laboratory visit for specialized training or another venture – please described in the application form). Proof of attendance 30 days after such event is required to be submitted to ITC committee.
• Qualifications and Requirements: Eligible candidates must be currently enrolled in a graduate program (MS or PhD candidates) in immunology, toxicology, pathology, or related field (cell biology, biochemistry, or similar).
• Application: To apply, please send along the following: 1) completed application form, 2) CV or bioksketch, and 3) one reference letter from your mentor to itc@hesiglobal.org
• Deadline for submission: Friday, January 6th, 2023. However, applications will be reviewed on a rolling basis for approval.

If you have any questions about the HESI ITC or this award, please contact Dr. E’Lissa Flores or Dr. Shermaine Mitchell-Ryan.

Download Application Form HERE

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 (NIH) and/or other major institutions. This year, we have expanded this opportunity to accept international applications, broadening our reach and heightening the visibility of this important research area. For details on eligibility, funding, the application process, and key deadlines, please click here.

THRIVE will accept letters of intent starting 18 October 2022, and the letters of intent deadline is 10 January 2023. For more information, contact research@hesithrive.org.

HESI is seeking your suggestions for new scientific projects (human or environmental health) for consideration as an emerging issue in 2023. Proposals will be reviewed in early 2023, and one or more may be selected to form a new scientific collaborative program within HESI. Although this is not a grant, the selected program will receive support from HESI for scientific program design, coordination, and staffing.

Learn more about the HESI Emerging Issues Process on our website or download the proposal form here. The deadline to submit proposals is 12 January 2023. Don’t miss out!

HESI’s Developmental and Reproductive Toxicology (DART) committee hosted a hybrid workshop in Washington, DC, titled “Interpretation of developmental and reproductive toxicity in regulatory contexts and frameworks”. The workshop was HESI’s first in-person workshop since the start of the pandemic and was aimed at providing training to bolster the ability for scientists to interpret DART data in the context of regulatory frameworks and processes. We were pleased to welcome more than 40 participants in-person and 90+ virtually for the two-day meeting from around the globe. On Day 1, participants heard foundational presentations from key DART-leaders and then spend the remainder of the day in breakout groups discussing case studies focused on interpretation of in vivo test data. Day 2 was focused on incorporating in vitro/NAMs into decision making. Organizers will be publishing the key learnings from the workshop.

This year the HESI Emerging Systems Toxicology for the Assessment of Risk Committee’s Annual Meeting took place virtually on 3 and 4 November! This open meeting had over 180 participants over the two days. The event provided updates from the Committee’s multiple research programs covering topics including miRNAs, error corrected sequencing, transcriptomic-based biomarkers, and the use of Cell Painting for toxicological assessment, and more. The recorded talks can be found on the website (https://hesiglobal.org/estar-webinar-video-library/). Want to get involved in the projects? Please fill out this survey (https://forms.office.com/r/HeAeke6UvP) or email Connie Mitchell (cmitchell@hesiglobal.org)

HESI Executive Director Dr. Syril Pettit led a session on Communicating Risk in Emergent Health Crises at the APHA 2022 Annual Meeting & Expo on November 8th.

The panel discussion engaged perspectives from experienced public health practitioners on the challenges of effectively communicating evolving science to the community during an emergent public health crisis. In these situations, public health is challenged by rapidly changing scientific data, evolving resource availability and priorities, uncertain epidemiology, and quickly modulating interventional recommendations. The panelists shared their own experiences in responding to emergent public health crises in their communities. Panelists and participants exchanged best practices for conveying uncertainty in the available information on an emergent crisis, for characterizing unknowns around emergent disease pathology or interventions, and for handling the frequent absence of data relevant to underserved populations. While these issues are relevant for all communities, the session focused on the impact of these challenges on communication and health protection within underserved communities.

HESI Executive Director Dr. Syril Pettit gave a seminar titled ‘Cross-Sector Collaboration in Toxicology: Scientific Consortia as a Critical Resource for Applied Safety Science‘ as part of the Ottawa-Carleton Chemical and Environmental Toxicology Seminar Series on November 9th.

The HESI CT-TRACS and GTTC committees gave presentations at the ACT 2022 Annul Meeting in Denver, Colorado on November 14th.

CT-TRACS committee co-chair Dr. Mick Fellows gave an overview of the CT-TRACS’ Advanced Sequencing project in a talk titled “Assessment of CRISPR-Cas9 Induced Off-Target Mutagenesis in Gene-Edited Cellular Therapeutics (Induce-Seq + DS): A HESI CT-TRACS Supported Project”. The talk was part of a symposium titled  “Applications for Duplex Sequencing of DNA in Genetic Toxicology: A Sneak Peek into the Future of Hazard Identification and Risk Assessment”. Abstract available HERE; see abstract #3-4

For more information about the  Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee contact Dr. Lucilia Mouriès (lmouries@hesiglobal.org)

GTTC committee members Drs. Anthony Lynch (GSK) and Andres Czich (Sanofi) gave a talk titled “The HESI Nitrosamine Subgroup: Overview and update on activities” during Workshop 4 “Addressing the Global Challenge of Nitrosamine Impurities in Pharmaceutical Products”.

For more information about the Genetic Toxicology Technical Committee (GTTC) contact Dr. Connie Chen (cchen@hesiglobal.org)

HESI staff will attend SETAC North America this week. The following talks and posters will be presented by the Next Generation Ecological Risk Assessment Committee.

Oral Presentations

• Control Performance of Amphibian Metamorphosis Assays with Xenopus laevis. Presented by Raechel Puglisi.
• Quantifying Conservatism in ecoTTC and CTD: Case Study of Benzene-Like Chemicals with Regulatory Water Quality Criteria Values. Presented by Connie Mitchell.
• A Retrospective Look at Regulatory Whole Effluent Toxicity Data: Can we learn more from the data? Presented by Michelle Embry.

Posters

• Predicting Fish Acute Toxicity Using a Bayesian Weight of Evidence Approach. Presented by Michelle Embry.

The Health and Environmental Sciences Institute (HESI) & Safety Pharmacology Society (SPS) present a new, on-demand training opportunity: A closer look at the new ICH E14/S7b Q&A’s and Training Materials. The target audience includes all sponsors (small and large; other stakeholders in pharma), safety pharmacologists and toxicologists participating in the delivery of the nonclinical data, clinicians, and regulators.

This training is being provided complimentary for SPS and HESI members, and offered to nonmembers for $49.00 USD until 31 December 2022.

Click to link to training course

Contact Jennifer Pierson at jpierson@hesiglobal.org for details.

Register now for the Immuno-Safety Technical Committee’s “Introduction to Immuno-safety Science” on-demand training course module.

This module features a collection of 16 lightening talks (~10-20mins) designed to introduce you to key concepts and tools that are essential to mastering fundamental knowledge within this discipline. All together this course will provide a comprehensive overview of the field in “bite size” digestible pieces suitable for professionals who need refresher or quick snapshot of the immuno-safety landscape to ground them in human risk and safety assessment as it pertains to agents that may modify the immune system. Register now and begin taking the course today at https://elearning.hesiglobal.org/ . Tiered pricing is available for graduate and post-doctoral trainees. Groups of 5 or more are eligible for a 20% discount, please contact Dr. Shermaine Mitchell-Ryan (smitchell-ryan@hesiglobal.org) for more information regarding the group discount rate. An Advanced course in Cancer Immunotherapies will be released in November!

As the summer draws to a close, it’s good to reflect on the great science we have delivered so far this year, and the great opportunities the next few years will bring. It’s remarkable that there are so many calls for applications in this newsletter, all of which will catalyze outstanding collaborations and initiatives. We have the call for Emerging Issues, the GTTC professional development award, the Innovation Prize and the Cardiac Safety Early Career Seminar Award Series. We also have the excellent THRIVE program, that invests in translational work to improve quality of life after cancer. Notable this year is that this is open to international applicants – we look forward to seeing the exciting ideas we receive!

In addition to calls for proposals, I would also like to highlight the call for case studies to help us address how we can minimize the use of primates in DART. Please share ideas for this as well as encouraging your networks and communities to propose ideas for all our initiatives.

As I am writing this ‘From the Leadership’ column, I am at the Society for Neuroscience meeting in San Diego. There are some great new ideas being shared here on everything from memory engrams (the neural substrate for storing memories) through to the role of sleep in recovery from trauma. I also just heard a talk on brain patterns in seizure; I see lots of opportunities for collaboration and dissemination of the work of the HESI Biomarkers of Neurotoxicology Committee to our colleagues here at SfN! We are working on putting something a proposal for SfN 2023, so fingers crossed!

Finally, may I wish you all a lovely autumn/fall and a great holiday season.

With best regards,

Ruth Roberts, PhD, FRSB, FRCPath, HESI Chair of Board