Fidelis Pharmaceuticals 36/37 Hilltop Lab Animals Inc

THURSDAY MORNING

SEMINARS

3Rs Improvements in Strategic Rodent Colony Management and Reproductive Techniques

8:00 AM - 10:15 AM Leaders: Bernard J Doerning, Barbara J Stone Moderator: Bernard J Doerning Facilitator: Sarah Srodulski Strategic vivarium management can be achieved using methods which provide 3Rs benefits for technique refinement and reduction in the number of animals used. Specifically for rodents, colony management is key to implementation of the 3Rs. This session will focus on colony management strategies and procedures which can be used to reduce animal numbers. First, mouse breeding will be discussed, including important practices and helpful tips for production. Reduction of wasted cage space and improved lab efficiency using colony management software will also be reviewed. Next, the benefits of assisted reproduction techniques (ARTs) including gamete cryopreservation, in vitro fertilization (IVF), artificial insemination, and embryo transfer will be considered. Cryopreservation is critical for disaster recovery, reducing genetic drift, and reducing the number of animals bred which are not actively used for research. How and when to cryopreserve rodent models as embryos or sperm will be discussed as will the advantages of sharing strains and stocks through mouse repositories. Age-matched cohorts can be produced using IVF, artificial insemination, or embryo transfer. Rederivation, or the removal of pathogens using embryo transfer techniques, will be outlined. Last, the use of nonsurgical alternatives for artificial insemination and embryo transfer (for mice and rats) will be presented. During this session, participants will learn about the 3Rs benefits and practical applications of ARTs in vivarium management. The target audience is personnel involved with rodent vivarium management and transgenic core facility management as well as researchers and technicians responsible for animal care and use.

Speakers/Topics: 8:00 Bernard J Doerning & Barbara Stone Welcome and Introductions 8:10 Carrie LeDuc Increasing Breeding Efficiency with Software 8:50 Robert Taft The Benefits of Cryopreservation and IVF for Rodent Colony Management 9:25 Barbara Stone 3Rs Applications for Rodent Embryo Transfer and Artificial Insemination 10:00 All Presenters Questions & Answers

ASAP: Assessment and Surveillance of Adverse Phenotypes in Genetically Engineered Models

8:00 AM - 10:15 AM Leader/Moderator: Megan M MacBride Facilitator: TBA Generation of genetically engineered models (GEMs) is associated with animal welfare challenges due to adverse phenotypes that may manifest because of the genetic modification, a change in genetic background, and/or a change in health status or microbiome. Depending on the phenotype, special husbandry or observations may be required and humane endpoints developed. The Guide states “determination of humane endpoints should involve the PI, the veterinarian, and the IACUC, and should be defined when possible before the start of the study.” To meet and exceed regulatory and industry standards, we sought to develop and implement a process to evaluate novel and established models for adverse phenotypes, including a communication plan to animal care staff on clinical observations and humane endpoints. Our panelists will discuss how we assembled a collaborative problem-solving method (Sprint Method) to quickly develop the best solution to our GEMs welfare concerns. We will discuss our novel questionnaire that requests essential details from researchers and allows us to categorize the line by organ system, examples of our global severity scoring system and assessments for models, plus how we conduct postapproval monitoring for such lines. Another important aspect of our program is when unforeseen adverse phenotypes or unexpected escalation of expected adverse phenotypes occur. In these circumstances, there is rapid formation of a response team with all stakeholders for an ASAP (assessment and surveillance of adverse phenotypes) meeting to quickly mitigate the issue and prevent further distress in our animals. At the end of the seminar, we welcome discussion and ideas from the audience on other ways to predict adverse phenotypes and communicate them to the staff and IACUC. This presentation should be of interest to veterinarians in clinical and regulatory roles, IACUC members, and researchers and animal care staff that work with GEMs.

Speakers/Topics: 8:00 Megan M MacBride Welcome and Introductions 8:05 Bart Smits Genetic Assessments for Potential Adverse Phenotypes in GEMs 8:45 Briony D Smith Using SPRINT Problem-solving to Develop ASAP 9:25 Mila C Kundu Establishing Humane Endpoints and Postapproval Monitoring for GEMs 10:05 All Presenters Questions & Answers

Corynebacterium bovis: New Insights, Extraordinary Challenges

8:00 AM - 10:15 AM Leader/Moderator: Neil S Lipman Facilitator: Morganne Campbell Since its initial discovery more than 4 decades ago, Corynebacterium bovis (Cb) has posed significant challenges to institutions using immunodeficient mouse models in oncology and other disciplines whose murine models require the engraftment of allografts and xenografts. As the use of these models increase, the problems associated with Cb infections are of even greater significance. Cb is highly infectious and once present in a vivarium it is extraordinarily challenging to eradicate. Introduction almost always leads to endemic infections that require intensive husbandry and clinical management. Despite the associated scourge and years of challenges, our understanding of the biology of the bacterium and the associated disease remains limited. The presenters in this seminar will share novel experimental findings and management tools that will shed new light on Cb, it's containment, and our eventual ability to eradicate the bacterium from infected colonies. The seminar will be of high interest to veterinarians, scientists, managers, and technicians supporting the use of immunodeficient mouse models.

Speakers/Topics: 8:00 Neil S Lipman Welcome and Introductions 8:05 Neil S Lipman Current State of Knowledge

8:25 Gerardo Mendoza Dissecting the Relationship between Bacterial Isolate, Mouse Strain, and Disease. 9:05 Chris A Manuel The Environmental Stability of C. bovis 9:20 Anthony Mourino Designing and Implementing a Program to Effectively Detect C. bovis in Production Colonies 9:50 Rodolfo Ricart Approaches to Managing C. bovis in an Endemically Infected Vivarium 10:10 All Presenters Where Do We Go from Here? Questions & Answers

PLATFORM SESSIONS

8:00 AM - 10:45 AM Platform Session abstracts will be available on www.aalas.org in July. They will also be included in both the mobile app and the National Meeting Final Program.

SPECIAL TOPIC LECTURES

An Overview of the AVMA Working Group on the Psychological Impacts of Humane Endings and Related Guideance Documents

11:00 AM - 12:00 PM Speaker: Nathaniel S Kollias Moderator: Sally Thompson-Iritani Facilitator: Lisa M Kelly The psychological impacts of humane endings on veterinarians, animal health and production personnel, and support staff are a growing concern within the veterinary community. The COVID-19 pandemic has further highlighted the need for resources, understanding, and compassion for our colleagues involved in the care and wellbeing of animals. Whether humane endings activities are related to humane endings of animals, the veterinarian plays an important role in these determinations. The AVMA has led and continues to lead in providing guidance on humane endings, including their three documents: AVMA Guidelines for the Euthanasia of Animals, AVMA Guidelines for the Humane Slaughter of Animals, and AVMA Guidelines for the Depopulation of Animals. Recently, the AVMA formed a working group on the psychological impacts of humane endings to address the needs of veterinarians and other animal health professionals. They reviewed the existing literature to lay the foundation and rationale for improved preparation and development of mental health resources and to offer recommendations on pragmatic ways to support and prepare veterinary professionals impacted by depopulation events. While there are mental health challenges shared by those involved in euthanasia, slaughter, and depopulation, there are some stressors specific to depopulation, which is those that this group is addressing first. This lecture will have participants develop an understanding of the historical role the AVMA has played in humane endings, including the development of the three documents. Participants will also learn about the formation of the working group on the psychological impacts of humane endings and the resources under development by the group. The target audience for this lecture includes veterinarians, veterinary technicians, and all other animal support staff involved in the research community.

Evaluation of Pharmacokinetic Profiles and Safety of Immediate- and Extended-Release Buprenorphine

11:00 AM - 12:00 PM Speaker: Niora Fabian Moderator: Steven L Leary Facilitator: TBN The common marmoset (Callithrix jacchus), a New World nonhuman primate (NHP), is an important animal model used in neuroscience, transgenesis, and other research areas. Pain control is essential to all animal species' clinical management and welfare, including marmosets. Buprenorphine is the most used analgesic in marmosets and is available in immediate release and several long-lasting formulations. There is limited information in the literature supporting current dosing regimens for buprenorphine in marmosets. In addition, the metabolism of buprenorphine in marmosets and the effects on activity and behavior are not well understood. This lecture will showcase recent research to define evidence-based recommendations for various formulations of buprenorphine in marmosets for a target audience of veterinarians, veterinary technicians, NHP researchers, neurobehaviorists, and pharmaceutical developers. In addition to highlighting recent studies evaluating buprenorphine use in marmosets and other NHPs, I will present research studying immediate- and extended-release buprenorphine in marmosets at MIT, which includes 1) pharmacokinetic analysis of buprenorphine and its metabolite, 2) in vitro hepatic models for defining species-specific buprenorphine metabolism, 3) safety information, including histopathological characterization of injection site reactions, and 4) machine learning models of video-recorded marmoset activity and behavior as a non-invasive refinement to study drug-induced effects. The findings presented in this lecture will expand the current knowledge base of pain management options for marmosets and provide novel insights into buprenorphine metabolism, potential adverse effects, and drug effects on marmoset activity and behavior. This information will enable veterinarians and researchers to refine analgesic strategies, which will optimize research outcomes and the welfare of laboratory marmosets. This Special Topic Lecture is sponsored in part by Fidelis Pharmaceuticals.