Citoxlab – Newsletter December 2017

Citoxlab Corporate Identity Evolution

Over seven years ago, (spring 2011), the Citoxlab Group was created after the acquisition of LAB by CiT. At that time, our Citoxlab logo was designed with Citox in blue and LAB in red. Since then, Citoxlab has acquired AccelLAB in Canada (2016) and more recently, Xenometrics in the USA (2017).
Following the successful integration of these acquisitions, we are now updating our brand identity with a new logo and colour.
The new logo is less complex, easier to read and remember. It aims to embody our overall corporate image, the Group being composed of companies that have joined us at different times.

Citoxlab  increases dog and minipig capacity at the French site

Soon after increasing our capacity in Canada, Citoxlab is now investing further in our Evreux, France site, expanding the non-Rodent unit, thereby increasing our global capacity to meet industry demands.

The facility will be fully compliant with European housing regulations (2010/63), with preconfigured add-ons, allowing for the complete performance of multiple readout studies whilst enhancing animal well-being. This building will be coupled to a new surgery room, resulting in improved processes and overall study performance.

As the number of programs supported has significantly increased since 2015, and particularly in 2017, this capacity adjustment was necessary to allow us to continue to meet the needs of our clients’ aggressive drug development programs. “With a projected demand for 2018 again on the increase, and Citoxlab entering into further strategic partnerships, it was necessary to adjust our production capacity. This is part of a much larger upscaling program to the benefit of our clients and partners.” said Jean-François Le Bigot, Chairman and CEO of the group.

With this expansion, Citoxlab-France will increase capacity by 40%. The new building will be opened in late Q3-2018.

Acquisition of the Siemens Acuson SC2000 ultrasound system at AccelLAB – a great tool for structural heart studies

AccelLAB, a company member of the Citoxlab Group, has solid expertise in structural heart research, working with multiple models such as aortic and tricuspid valve replacement and mitral valve repair. Classic two dimensional CT and echocardiography imaging, volume and flow measurements were always an important part of these procedures’ success.

With the recent acquisition of the Siemens Acuson SC2000 ultrasound system, AccelLAB can now offer live 3D imaging capabilities, both with ICE (Intra-Cardiac Echocardiography) and TEE (Transesophagial Echocardiography) modalities. The live 3D imaging provides the interventional team with a much better and clearer view of the structures, devices and dynamic blood flow during procedures, not to mention spectacular renditions of the implanted device for scientific communications and teaching purposes.

This system is equipped with all of the cardiac analysis modes and a color doppler.  It allows for more automated, precise and efficient calculation tools such as volume LV analysis, automated left ventricular and left atrial border detection, along with efficient exporting and reporting capacities. It is equipped with the velocity vector imaging technology (speckle tracking) which provides a reliable and detailed analysis of the regional myocardial muscle function and motion mechanics, with markers such as the velocity, strain and strain rate, ejection fraction and volume. While this system is mostly used for echocardiography, it is a complete and flexible system to cover most ultrasound imaging related needs with various probes.

Evaluating the use of minipigs as a model for preclinical CNS safety pharmacology 

The use of minipigs as a surrogate model for the human condition has long been considered in preclinical research, due in large part to the numerous similarities between human and porcine anatomy, physiology and biochemistry. The use of minipigs within the safety pharmacology arena has increased rapidly in recent decades, beyond traditional skin and dermal toxicity studies, to include cardiovascular and respiratory safety programs. Since minipigs share a high degree of similarity to the human brain anatomy, development and physiology, the interest in the use of minipigs as a model species has also been suggested for central nervous system (CNS) safety testing. Unfortunately, the incorporation of minipigs into CNS safety programs has been limited, in part by the absence of information on minipig CNS function. Accordingly, Citoxlab North America has begun to characterize the minipig CNS through numerous in vitro and in vivo tests in an attempt to highlight the utility of this model species for safety testing. In vitro electrophysiological assessment of seizure liability within the minipig hippocampus has uncovered the usefulness of minipig brain tissue in early drug safety assessments. Characterization of minipig sleep architecture (through electroencephalography, electromyography and electrooculography) has provided support for the use of the minipig as a non-clinical model for polysomnography and evaluation of drug-induced effects on sleep architecture. Intrathecal/epidural dosing as well as cerebrospinal fluid collection studies highlight that the anatomical characteristics of the minipig facilitate the use of the species for assessment of blood-brain barrier permeability and CNS distribution. Together, these studies help to elucidate the role and usefulness of the minipigs in CNS safety testing.

Bioanalysis of large molecule therapeutics by LC-MS/MS at atlanbio

The focus on development and advancement of large molecule therapeutics is changing the composition of pharmaceutical pipelines.  Such biologics or large molecules (LM’s) include polymers of amino acids (peptides, poly-peptides and proteins including antibodies), oligonucleotides and many endogenous biomarkers with molecular weights above 1000 Da.

Until recently, the primary bioanalytical approach was via classic “gold standard” ligand-binding immunoassay (LBA) techniques.  LBA’s have inherent challenges including the need to produce specific antibody reagents which can greatly increase the lead time and cost for assay development, and often reoccur during the lifecycle of the assay when these critical reagent lots change and require additional qualification.

The use of LC-MS/MS to quantify these complex molecules eliminates the need to generate specific antibodies while yielding similar levels of detection (especially with immunocapture; hybrid LBA/LC-MS/MS) along with additional advantages of a larger dynamic range without significant cross-reaction interference.  Further, the LC-MS/MS approach allows for a multiplex assay with simultaneous analysis of several molecules and an increase in throughput.

To meet the needs of our clients and the proliferation of large molecule therapeutic portfolios, atlanbio is pleased to welcome Dr. Jordane Biarc who will lead our LM LC-MS/MS team  and drive the expansion of these services.

Jordane obtained her Ph.D (Cellular and Molecular Pharmacology) at Louis Pasteur University in Strasbourg, France and has considerable industry experience in biomarker and drug quantitation, and the analysis of proteins/peptide by mass spectrometry.

Avian toxicology and reproduction studies

Avian toxicity and reproduction studies are required for registration of agrochemical products where avian exposure is a potential risk. They are also required for environmental biocides, biopesticides and pharmaceutical/veterinary products where environmental persistence is considered to be a potential risk. These studies provide data on acute toxicity and/or reproductive effects in birds, for substances and mixtures administered orally via gavage, drinking water or in diet.

Citoxlab Hungary is a leader in the field of laboratory avian toxicology. Expert staff with over 14 years of avian experience provide advice and assure high quality study design and performance for our clients. We conduct screening studies, preliminary studies and full GLP studies to meet the needs of our clients, with expert analytical support.

The test species generally used is the Japanese quail (Coturnix coturnix japonica). This standard species for avian ecotoxicological studies is available all-year round (non-seasonal egg-laying) so studies can be planned and performed rapidly. For the US EPA, the Northern Bobwhite quail (Colinus virginianus) is often the species of choice. For other regulatory objectives, the Mallard Duck (Anas platyrhynchos) is sometimes required, and we have reliable suppliers for these seasonal species.

In our state-of-the-art avian facility, our pens exceed the latest EU animal welfare standards of 1m2 for each pair of quail. We are one of the most experienced EU facilities for quail reproductive toxicology studies.

The avian reproduction study is the only routinely performed regulatory study which is a specific test for reproductive performance of non-mammalian terrestrial vertebrates. The study is a standard part of testing packages for agrochemical products and can also be a testing requirement for biocides, REACH, chemicals and pharmaceuticals.

Avian reproduction studies are performed at our facility according to recommendations in the OECD Guidelines for testing of chemicals (Section 2: Effects on Biotic Systems. No.206; Avian Reproduction Test (1984) Avian reproduction toxicity test Draft Guideline October 1998) in compliance with Good Laboratory Practices.

Our reference data can be valuable for the interpretation of study results. They compare well with published data and also demonstrate the general health and good reproductive performance of Japanese quail in our facility.

Krisztina Sipos, M.Sc. – Principal Scientist, Ecotoxicology, Krisztina graduated in chemistry and ecology at the University of Veszprém and her thesis was on acute toxicity to honey bees.

She started work at Citoxlab Hungary in May 2003 as a technician in the Ecotoxicology department. In 2005, she became an assistant scientist, and in 2007 was promoted to Study Director.  In 2012, she was promoted to Senior Study Director, and since 2015 has been a Principal Scientist.

Krisztina has conducted more than 900 ecotoxicology studies (aquatic toxicology, ready biodegradability, activated sludge, avian acute and reproductive toxicology, acute and chronic earthworm, non-target anthropods and honey bees). She was involved in five collaborative poster presentations at annual meetings and has been a member of the Society of Hungarian Toxicologists since 2004. Her current responsibility is to lead our Ecotoxicology service, coordinating and mentoring the Ecotoxicology Group.

Citoxlab now offering services in drug metabolizing enzymes and transporters genotyping

One third of the pharmacogenomics biomarkers used in drug development in the US are related to genetic polymorphism of enzymes involved in drug metabolism. Indeed, many of these enzymes are genetically polymorphic. Consequently, the metabolic capacity of individuals may differ depending on an individual’s genotype. For example, drugs may be metabolized more slowly in individuals who are carriers of a genetic polymorphism that results in decreased activity of a given enzyme, which can lead to adverse drug reactions and therapeutic failure. This is why investigating the polymorphisms in genes’ encoding for Drug Metabolism Enzymes and drug Transporters (DMET) is used to provide significant information during clinical research, by predicting the impact of an individual’s genetic variations on metabolic capacity, pharmacokinetics and pharmacodynamics. This brings us one step closer to the vision of pharmacogenetics, by helping to avoid adverse drug responses and increasing treatment efficacy.

Using Affymetrix DMET arrays to genotype healthy donors and patients, Citoxlab genomics laboratory now offers the analysis of drug metabolizing and transporter genetic variations analysis. These arrays permit the analysis of a comprehensive and relevant genetic content, including 1,936  Single Nucleotide Polymorphisms (SNPs), copy number and indel markers across the 231 genes involved in drug transport and metabolism. The performance of our analyses on a set of reference samples provided by Affymetrix, showed an extremely high concordance with the reference genotypes (higher than 99.95%).

This new service, offered in compliance with Good Clinical Practices, completes our comprehensive bioanalytical, biomarker and immunogenicity services as our clients  transition from preclinical to clinical programs.