Charles River Laboratories, Inc., is an American corporation specializing in a variety of preclinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. According to its website, its customers include leading pharmaceutical, biotechnology, agrochemical, government, and academic organization around the globe.The chairman and chief executive officer is James C. Foster, the son of founder Henry Foster.
The coronavirus disease 2019 (COVID-19) pandemic, driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need for effective therapeutics, particularly as limitations of existing antiviral treatments persist. Establishing the proper strategy to set target concentrations for human dose projection is essential for any novel drug development project. In this study, we investigated the translatability of various preclinical models, specifically in vitro A549-hACE2 cells and air-liquid interface human nasal epithelial cultures, and in vivo Syrian golden hamsters and K18-hACE2 transgenic mice, using 3-chymotrypsin-like protease (3CLpro) inhibitors as model direct-acting antivirals. We assessed the minimal efficacious concentrations in these models of both ensitrelvir (ETV) and nirmatrelvir (NTV) co-dosed with ritonavir (Paxlovid) and compared this to clinical human data. Notably, in vitro models and the K18-hACE2 mice proved to be the most predictive for human efficacious exposures. Interestingly, lower efficacious exposures were needed in the more severe K18-hACE2 mouse model than in the Syrian golden hamster model for mild infection. Overall, we recommend applying a factor of 4-fold to the in vitro 90% effective concentration (EC90) for a conservative estimate of human efficacious exposure and recommend validation using K18-hACE2 mice. These insights are critical for guiding the development of effective SARS-CoV-2 therapeutics and optimizing clinical trial design.
BACKGROUND:Cryptosporidiosis is a leading cause of severe diarrhea and mortality in young children with no vaccine or effective treatment. Cryptosporidium controlled human infection model (CHIM) in healthy adults provides an opportunity to evaluate the safety and efficacy of novel chemical entities prior to testing in young pediatric patients. However, CHIM development has been hindered by the lack of current good manufacturing practice (cGMP)-compliant Cryptosporidium parvum oocysts, which are required for filing an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration. METHODS:To overcome this barrier, we developed a cGMP-compliant process for producing C. parvum oocysts. The approach involved sourcing well-characterized oocysts purified from neonatal calves under controlled non-GMP conditions, followed by cGMP processing that included peracetic acid-based surface sanitization, comprehensive microbial testing and release as a non-sterile oral product for human use. RESULTS:Peracetic acid (0.5% for 20 minutes) treated C. parvum oocysts demonstrated acceptable microbial safety and preserved viability. Viability was assessed through oocyst excystation, HCT-8 cell infection and mouse infectivity studies. The cGMP produced C. parvum oocysts with stringent batch-release test criteria for quantity, purity, identity, potency and bioburden was released as ABO809 for clinical use under an IND. ABO809 was successfully used in human challenge studies, producing reliable infection and characteristic clinical symptoms in healthy adult volunteers. CONCLUSIONS:We describe a robust cGMP-compliant and qualification process for C. parvum oocysts that enables CHIM studies in healthy adults. Thereby opening avenues to evaluate efficacy of novel therapeutics and vaccines to treat cryptosporidiosis.
Animal models are crucial in biomedical research, particularly in pharmaceutical discovery and safety testing. Recent legislative updates and regulatory shifts, such as the FDA Modernization Act 2.0 and European Parliament Resolution 2021/2784 (RSP), have opened new avenues for innovative nonclinical research. Among these innovations is the use of Virtual Control Groups (VCGs), a method which can significantly reduce animal usage and improve experimental designs. VCGs utilize historical control data and machine learning algorithms to replicate traditional control groups' statistical power and address preanalytical and analytical variations. We applied VCG data retrospectively to 20 pilot studies. The VCG and concurrent control group (CCG) data were compared to assess statistical alignment as well as biological relevance. The findings highlight the effectiveness of VCGs in maintaining toxicological study integrity and underscore the importance of specific selection criteria in ensuring accurate toxicological outcomes. This work supports the potential of VCGs in advancing the 3Rs and improving nonclinical research methodologies.
For more than 40 years, the Limulus Amebocyte Lysate (LAL) test has served as the standard method for bacterial endotoxin Testing (BET). The critical proteins required for endotoxin detection in LAL assays are sourced from amoebocytes-blood cells extracted from horseshoe crabs.Animal-free reagents have been developed to support conservation efforts and the 3Rs (Replacement, Reduction, and Refinement). One such alternative is the recombinant cascade reagent (rCR), which contains three recombinant proteins that replicate the natural enzymatic cascade found in horseshoe crab amoebocytes to detect bacterial endotoxins.This study assessed the equivalency of rCR to FDA-licensed LAL reagents using 563 pharmaceutically relevant samples. Of these, 134 samples were contaminated with natural environmental endotoxin (NEE), allowing for a direct statistical comparison.Results showed that the rCR assays were equivalent in performance to FDA-licensed LAL assays, detecting endotoxin at similar levels under real-world conditions. Equivalency was demonstrated using methods consistent with those outlined in compendial guidance for bacterial endotoxin testing.
Animal welfare assessment is a vital component of working with animals in a research environment and is a growing expectation. Rabbits are a common species worked with in biomedical research, but information on rabbit welfare and best practices are limited, making it difficult to assess welfare. To address this gap, a rabbit welfare assessment tool was developed within an international contract research organization and commercial breeder. The tool contained 134 descriptors including input- and output-based measures of welfare across six categories: physical, behavioral, environmental, training, procedural, and culture of care. Benchmarking assessments occurred in March and September 2025, assessing 13 facilities across seven countries. In March, overall scores were in the range of 70-92%, with high scores in the physical category (avg: 97%) and the most room for improvement in training (avg: 73%). In September, overall scores were in the range of 77-88%, with the highest score in the physical category (avg: 98%) and the most room for improvement in culture of care (avg: 74%). The results of the assessments identified strengths in rabbit management programs, as well as identified areas needing refinement. The results allow for development of facility and organizational level goals to improve rabbit welfare and create a culture of continuous improvement.
