Visualizing and injecting the tympanic membrane in guinea pigs using a rigid endoscope or an otoscope

ASR 2024 -- Guinea pigs are a commonly used research model for hearing studies. Hearing studies are aimed to determine the ototoxic potential of otic medications in guinea pigs by examining the effects of tympanic membrane injections on hearing function and cochlear histopathology. The normal function of the cochlea and auditory pathways are assessed for results after sustaining noise exposure damage, ototoxic drug treatment, etc. The biggest challenges of this procedure are visualizing the tympanic membrane, which can be done with a rigid endoscope or an otoscope with a small speculum attachment, and then visualizing the needle within the field of view of the camera or speculum. Both techniques are viable ways to visualize the tympanic membrane, but which is the most efficient when also inserting a needle and syringe to inject into the tympanic membrane?

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.