Analytical Validation of the Labcorp® Plasma Complete™ Test, a Cell-Free DNA Comprehensive Genomic Profiling Tool for Precision Oncology

Key takeawaysThe Labcorp Plasma Complete test demonstrates high sensitivity, specificity, accuracy and robustnessThis liquid biopsy test enables tumor molecular profiling to inform treatment decisions

Does automation improve cell-based potency assay development?

Development and usage of virtual controls on nonclinical safety assessment studies

SOT 2025 -- In vivo studies are required for assessing nonclinical safety of products to which humans become exposed. Virtual control groups (VCGs) are one emerging strategy for the reduction of animal usage; VCGs are defined as the use of an on study representative dataset generated from historical control data to reduce or replace concurrent control animals. The purpose of this work was to determine the selection criteria required to generate a robust, consistent and representative virtual control dataset for a selected range of endpoints to support regulatory and industry movement towards the use of VCGs.

Historical control data of spontaneous tumors in transgenic CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mice

SOT 2025 -- Short-term (6-month) carcinogenicity studies using genetically engineered animals have been demonstrated to be a reliable alternative model to long-term conventional carcinogenicity studies. CByB6F1-Tg(HRAS)2Jic (rasH2) is a genetically engineered hemizygous transgenic mouse containing the human c-Ha-ras proto-oncogene (c-Ha-ras) and is approved by regulatory agencies for carcinogenicity assessment. Comparative data was collected from the historical data for mortality, body weights, and spontaneous tumor incidences in vehicle control article (vehicle) administered CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mice from 6-month carcinogenicity studies and were analysed from the data compiled from multiple Labcorp Safety Assessment facilities from 2014 to 2023.

The Morris water maze -- An assessment of learning and memory in regulatory developmental and reproductive toxicology (DART) studies

SOT 2025 -- There are many water maze tasks that have been developed to evaluate learning and memory in regulatory DART studies. EPA OPPTS 870.6300 and OECD 426 test guidelines require an assessment of learning and memory on developmental neurotoxicity (DNT) studies for the testing of chemicals that may cause adverse neurodevelopmental outcomes. ICH Harmonized Tripartite Guideline S5 (R3) for the testing of pharmaceuticals intended for human use also require an assessment of learning and memory to be evaluated in a complex learning task. Test guidelines such as the EPA OPPTS 870.6300 require evidence of positive control data to demonstrate the sensitivity of the procedures being used, ensuring  that the task is sensitive to detect learning impairments by using a chemical for which learning deficits have been established. This work was performed in order to validate and optimize the Morris water maze (MWM) to support preclinical safety studies utilizing the learning and memory assessment, thereby demonstrating that the learning and memory test procedure at Labcorp can detect chemically induced changes and therefore it’s suitability for use on regulatory DART studies.

Utilizing rodent ultrasonic vocalizations as a non-invasive technique

SOT 2025 -- Inhalation toxicology studies in rats are conducted to support development of therapeutics and risk assessment of chemicals. Respiratory tract toxicity is often not detected at a clinical level in rats, until histopathology is performed following the terminal euthanasia. Squamous cell metaplasia of the larynx is an adaptive response to local irritation and can be accompanied by adverse findings such as necrosis, ulceration and inflammation. Ultrasonic vocalizations (USVs) may be behavioral and are produced by a laryngeal neuromuscular mechanism that can be influenced by structural changes. “22-kHz calls” represent a negative, perilous response, and “50-kHz calls” represent a positive response or interacting with a complex environment. The objective of this study was to test whether USVs correlate with clinical observations and microscopic pathology in the larynx following inhalation of a toxicant.

Social interaction assessment in rodents: Positive control validation of automated three-chambered social interaction test in rats

SOT 2025 -- Social interactions are fundamental and adaptive components of the biology of numerous species. The integrity of social interaction behavior is critical in maintaining social skills, interpersonal functioning and effective social relationships that define societies. Deficits in social behavior and social recognition are well-recognized in several neuropsychiatric disorders, such as autism spectrum disorders, bipolar disorders, depression, obsessive-compulsive disorders and schizophrenia. Valproic acid, used for bipolar disorders and epilepsy, can increase autism spectrum disorder risk in children when mothers are exposed during pregnancy. Anesthetics like propofol can also heighten neuropsychiatric disorder risk due to N-methyl-D-aspartic acid (NMDA) antagonism and gamma-aminobutyric acid (GABA) activity during early brain development. Complex behavioral tests, like social interaction tests, can vary based on testing conditions and laboratory proficiency. OECD guidelines emphasize that laboratories must demonstrate their capability and the sensitivity of procedures for neurotoxicity and reproductive toxicity assessments. This study aims to validate social interaction assessments using positive controls to demonstrate the reliability and reproducibility of behavior assays in preclinical safety evaluation studies.

Evaluation of non-classical analytes in nonhuman primate cytokine release assays

SOT 2025 -- The various formats of cytokine release assays (CRAs) are in vitro assays utilizing nonhuman primate (NHP) immune cells representing a novel, inexpensive and rapid means of evaluating the safety profile of potential therapeutics prior to preclinical animal studies. Classically, CRA design across all formats focused almost exclusively on the evaluation of analytes such as IFNγ, IL-2, IL-6 and TNFα to assess the risk of eliciting cytokine release syndrome (CRS) in vivo. However, when considering an in vitro assay to evaluate potential immunomodulation of a therapeutic on NHP immune cells, the inclusion of a wider array of analytes can generate not only important safety data but provide key mechanistic insights as well. In the current study, we evaluated several prevalent positive control compounds used in CRAs in a commonly utilized CRA format – liquid phase stimulation of NHP peripheral blood mononuclear cells (PBMCs). These positive controls were chosen for their ability to stimulate production of cytokines and chemokines outside those traditionally included in CRAs.

Using computational fluid dynamics to estimate the efficiency of delivery by changing the position of the rat snout and airflow received using an inhalation directed flow chamber

SOT 2025 -- Inhalation administration is a common dose route used in nonclinical development for delivering drugs to the lungs. The standard approach is to evaluate drug safety in both a rodent and non-rodent species. With the continued use of both New Chemical Entities (NCEs) and biopharmaceuticals, rats continue to be the rodent species of choice. The standard method for delivering the aerosol to rats is using a snout-only inhalation chamber called a direct flow chamber. During the exposure period, the rats are restrained in plastic clear restraint tubes. Consistent dosing is pivotal in ensuring effective study conduct and data interpretation to draw accurate conclusions about the safety of the test article; however, it is commonly observed that the animal and animal snout frequently move during the dosing period and require adjustment where possible. Furthermore, there is anecdotal evidence that the animal-to-animal variation with the dose received is greater for the inhalation route of administration compared to other routes such as oral and intravenous. In this study, Labcorp wanted to establish whether the position of the snout relative to the end of the aerosol chamber delivery tube contributed towards this perceived animal-to-animal dose variability.

Development of a mouse bile-duct cannulated model for use in DMPK studies

SOT 2025 -- The use of surgical models can provide valuable information on the absorption and metabolism of new drug candidates over a continual time course. The mouse (Mus musculus), including genetically modified models, is a commonly used laboratory animal. In preclinical safety assessment studies (toxicology, metabolism, pharmacology and pharmacokinetic studies), the mouse is the most common alternative rodent species to the rat. The mouse can offer physiological or metabolic characteristics that are more relevant to the human condition than the rat. The objectives of this initiative were to: Further develop a mouse bile duct-cannulated (BDC) model and characterise the routes and rates of excretion of total radioactivity in urine, faeces and bile, following oral administration of a radiolabelled test article (5 mL/kg) to intact and biliary cannulated mice.