Validation of in-vivo QT ICH E14/S7B Q&A guidance in minipig

SPS 2024 -- The E14/S7B Q&A guidelines introduce the concept of “double negative” (negative hERG and negative in vivo QTc) nonclinical data, which can be used along with negative Phase I clinical QTc data to substitute for a clinical thorough QT study in specific cases (Q&As 5.1 and 6.1). For the in vivo QT assay, best practice recommendations require characterization of individual study sensitivity, verification of independence QTc from heart rate, demonstration of test facility sensitivity and pharmacological translation to human using a positive control. We have previously validated E14/S7B Q&A compliant in vivo QT assays in dog and nonhuman primate (NHP). The objective of this work was to perform the validation in the minipig as the third non-rodent species commonly used for cardiovascular safety assessment. 

Sensitivity of Latin square and ascending dose designs for in vivo QT moxifloxacin positive control to support ICH E14/S7B studies

SPS 2024 -- The Latin square crossover is recommended as best practice for in vivo QT studies. However, an escalating design may instead be required due to long compound half-life, insufficient toxicity data to inform dose level selection, a need to build up tolerance to the test article to enable safe dosing or logistics (e.g., avoiding use of multiple simultaneous inhalation dose generation systems thereby reducing risk of contamination). We have performed ICH E14/S7B Q&A compliant in vivo QT validation studies with oral moxifloxacin using both a Latin square and an ascending dose design in nonhuman primate (NHP), dog and minipig. The objective of this work was to compare the sensitivity of the dosing designs and to generate positive control moxifloxacin QTc data in support of ICH E14/S7B studies when using an ascending dose design. 

Rodent models of anxiety and compulsion: When multiple endpoints add value

SPS 2024 -- Anxiety disorders are the most diagnosed mental illnesses and exist independently or as comorbidity with conditions such as autism spectrum disorder, major depressive disorder and/or substance use disorder. The acute treatment of moderate to severe anxiety includes medications, such as benzodiazepines, whereas for long-term treatment and compulsive disorders, selective serotonin reuptake inhibitors (SSRIs) are often prescribed. The objective of this investigation was to demonstrate the advantages of conducting a battery of behavioral tests to characterize the anxiolytic, anxiogenic and/or anti-compulsive properties of drugs.

Improving the safety pharmacology standard: CNS behavioural investigations using anticholinergics as a comparator against the standard Irwin test

SPS 2024 -- The ICH S7A safety pharmacology guidelines require a novel test article to be assessed for central nervous system (CNS) effects as a part of the core battery. Although follow-up behavioral studies are advised, these are rarely seen as part of the GLP safety pharmacology package of work, with an Irwin screen alone conducted to address this requirement. Anticholinergics are a type of drug that block acetylcholine (Ach), a neurotransmitter at synapses in the central and peripheral nervous system.

Labcorp to Announce Third Quarter Financial Results on October 24, 2024

BURLINGTON, N.C. , Sept. 24, 2024 /PRNewswire/ -- Labcorp  (NYSE: LH), a global leader of innovative and comprehensive laboratory services, will release its financial results for the third quarter of 2024 before the market opens on Thursday, October 24, 2024 .

Labcorp Biopharaceutical CMC Services: Antibody drug-conjugates (ADCs) Analytical considerations for QC release, stability testing, characterization and comparability

The importance of the cynomolgus macaque’s origin in drug safety assessment

Cynomolgus macaques are the most commonly used non-human primate species for drug safety assessment. However, recent supply shortages  have brought increased attention to the genetic differences between cynomolgus macaques of varying geographic origins. It is important to examine the relevance of geographic origin for cynomolgus macaques used in regulatory toxicology studies.

Key learnings from ECHA's review of the EOGRTS (OECD Test Guideline 443)

The extended one-generation reproductive toxicity study (EOGRTS) per OECD Test Guideline 443 is a crucial test for evaluating potential reproductive and developmental effects of chemicals. Recently, the European Chemicals Agency (ECHA) conducted an extensive review of EOGRTS  studies to assess the effectiveness of this test guideline and provide recommendations for improvement. This blog post summarizes  key learnings from ECHA's review and the impacts on current and future EOGRTS study design.

The three lab stewardship utilization rights: Underutilization in focus

Laboratory testing is critically important to a person’s healthcare journey. In fact, lab test results inform 70% of medical decisions despite only accounting for less than 3% of healthcare spending.However, with the great power of the lab, comes great fiscal responsibility. In this article, Todd Berman, payor solutions director of stewardship strategies at Labcorp, outlines the three lab stewardship rights, with an in-depth look at underutilization.

Nonclinical study in juvenile cynomolgus monkeys for a postmarketing requirement from FDA for gadolinium-based contrast agents

ETS 2024 -- In December 2017, the U.S. Food and Drug Administration (FDA) requested the four gadolinium-based contrast agent (GBCA) NDA holders to further investigate the effects of gadolinium (Gd) retention on fetal and neonatal development in mice and juvenile nonhuman primates (NHP) to evaluate the potential effect of GBCAs on behavioral, neurological and histopathological changes. The studies performed in mice have been previously presented and the results of the NHP study are presented here.