Citoxlab Newsletter – June 2018

In vitro ProArrhythmia Assays at the forefront of drug safety testing

While cardiac safety remains the most important reason for drug attrition when developing new chemical entities, the U.S. Food and Drug Administration Initiative on Comprehensive in vitro Proarrhythmia Assay (CiPA) continues to progress with broader implementation confirmed in recent months including upcoming additions to proarrhythmia testing guidelines from the International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH). These regulatory guideline updates are expected to expand on proarrhythmia assays in the context of CiPA. Driven by this new regulatory landscape, the portfolio of in vitro proarrhythmia assays at Citoxlab has significantly progressed in recent years to cover the scope of CiPA and also emerging needs in drug discovery or late stage follow-up studies. As scientific considerations remain our priority, the Citoxlab team was also involved in the preparation of the 3rd most downloaded publication in the Journal of Pharmacological and Toxicological Methods this month which addresses the landscape leading to CiPA (link). Non-clinical proarrhythmia testing is undergoing transformation as the industry aligns with CiPA. After two decades during which QTc stood as the pillar of proarrhythmia testing, this new chapter in cardiac safety testing will be supported by science, technology and innovation in our industry where translational value and timeline are essential decision making factors.

Ellegaard Göttingen Minipigs Research Foundation grant awarded

The Scientific Board of Ellegaard Göttingen Minipigs Research Foundation granted €35,000 to the project “Speedgene targeted knock out of the PCSK-9 gene in Göttingen Minipigs” and the research teams behind the project, led by Dr. Jaya Krishnan and Dr. Jonathan Ward, Genome Biologics, together with Dr. Roy Forster, Citoxlab. The grant was announced by CEO Lars Friis Mikkelsen at the 12th annual Minipig Research Forum in Barcelona during the month of May and was accepted by Dr. Pramila Singh, Director of Toxicology, Citoxlab. The project is based on the knock down of the PCSK-9 gene using an adeno associated viral vector containing a short hairpin sequence to produce the knockdown effect. PCSK-9 is involved in the processing and control of blood levels of LDL. The in vivo minipig studies will be performed at Citoxlab in Denmark this year.

The Ellegaard Göttingen Minipigs Research Foundation granted up to  €50,000 in 2018 to support scientific research aimed at the characterization of the Göttingen minipig and the promotion of the development of Göttingen minipig disease models. Projects that are oriented toward improving animal welfare, optimizing handling or research techniques and enhancing educational activities related to the use of minipigs in scientific research are eligible to receive funding.

The general requirements for research funding grants from the Ellegaard Göttingen Minipigs Research Foundation include to be of high-level scientific content, excellent international qualifications of the applicants and well-established academic environment of the host institution. The project should also ensure that significant background data will be generated and will promote the use of the Göttingen Minipigs in scientific research.

AccelLAB acquired the Olympus Exera III Endoscopy Tower, a key tool for gastroenterology studies

AccelLAB has been increasingly involved in recent years with gastroenterology studies that utilize medical devices such as colonic stents, biodegradable clips and ablation technologies with successful testing in large animal models.
With the recent acquisition of the Olympus Exera III Endoscopy System, AccelLAB can now offer superior imaging support for a wide variety of endoscopic and laparoscopic interventions (GI, ENT, Thoracic, Abdominal, etc.).
Among its many features, the EVIS EXERA III , with its Full HD 3CCD camera head, delivers exceptional images in high definition to enable observation of the utmost detail. More specifically, Olympus has developed narrow band imaging technology that enhances the observation of mucosal tissue. Also, similar to a magnifying glass, Dual Focus provides the ability to closely examine tissue as needed throughout a procedure. Finally, the EVIS EXERA III dramatically increases the sharpness and clarity of still-image captures, due to a new still-image capture algorithm.
With this new imaging tool, in combination with other existing technologies such as computed tomography and magnetic resonance imaging, AccelLAB provides high quality in vivo images of the implanted device to its clients.

Infusion studies with group housed NHPs

Many new drugs, in particular biologics and in the oncology field, are administered by intravenous infusion and require studies in non-human primates (NHPs) as a relevant model. As there is an increasing awareness of the groups housing benefits in NHP study as well as European regulations phasing out single housing, Citoxlab has implemented state-of-the-art procedures for intravenous infusion for group-housed and freely moving animals.

The revision of European Directive 2010/63/EU on the protection of animals used for scientific purposes presents challenges for fulfilling scientific and regulatory requirements for these studies in combination with ethical guidelines. For continuous IV administration in NHPs, the use of tethered single-house animals has been the gold standard. Although this model provides excellent scientific data, it does not comply with the revised Directive, which specifies that single-housing is not appropriate or accepted for long-term duration.

During the last two years, we designed in partnership with the company Ludomed, who manufactured an infusion jacket in which an infusion pump (Instech OrchesTA™) was inserted for a prolonged period of time without it being damaged. Although the surgical procedure is the same than the standard cannulation procedure, the new model adds an acclimation period to the weight of the jacket, along with socialization. It also allows the technical team to detect any issue with the catheter or the infusion procedures prior to the first day of the treatment period. During the infusion period, our specialized team monitors daily the animals for health condition, but also checks the integrity of the administration system which is key to insure proper delivery of the test item.

Today, Citoxlab runs studies of 40+ animals. We continue to refine the jackets so as to improve the animals’ comfort and provide adequate protection to the infusion pump ensuring appropriate delivery of the drug.

This technique has been presented at 2018 SOT annual meeting and the poster can be downloaded following this link.

SOLVO Biotechnology 8th Meet the Experts Transporter conference in Budapest

On April 26th and 27th, SOLVO Biotechnology organized its 8th Meet the Experts Transporter conference in Budapest. SOLVO has been organizing the Meet the Expert conferences since 2014 responding to a clear need for a scientific conference on Transporter Proteins at a reasonable cost in Europe. After its initial success in 2014 in Budapest, the company quickly decide to expand the scope of the meetings and organized meetings in San Francisco, Boston and Tokyo as well.

In contrast to many other user meetings organized by CROs and product providers, The Meet the Expert Transporter conferences are purely scientific meetings. Speakers include academics and scientists from industry, regardless of whether they are customers. The agenda is put together by Peter Krajcsi, SOLVO’s CSO.

This year’s meeting in Budapest was organized around 6 main topics: Drug disposition and drug-drug interactions, Biomarkers, Disease and Therapy, Organ impairment/toxicity, Xenobiotics and endobiotics and included keynote presentations from well known transporter scientists Prof. Yuichi Sugiyama, Dietmar Weitz (Sanofi), Yan Zhang (Incyte) and Prof. Roos Masereeuw (Utrecht University). In addition to the main program, the conference hosted a poster reception in the evening where over 25 posters were presented.

The presentations can be downloaded from SOLVO’s website (link)

Appointment of Dr. Adriana Looszova, DVM, PhD, ERT as Senior Toxicologist / Project Management Group Leader in France

Citoxlab is happy to announce that Dr. Adriana Looszova has joined our global team of scientific experts in drug safety after gaining extensive drug development experience in a large pharmaceutical company (17 years at Janssen Pharmaceutical Research & Development). As a PhD in Veterinary Science (Veterinary Pathology/ Immunology), Adriana has held a wide range of scientific positions in pharmaceutical drug development (Study Director/ Study Monitor/ Discovery Toxicologist and Toxicology Project Leader) with an overview of regulatory submissions for small molecules in many therapeutic areas including oncology, CNS, metabolic and infectious diseases. Adriana is a multilingual communicator with experience in research & development and in coordination of cross-functional research teams in a global environment.

In her role, she will be responsible for the Project Management Service. As a Project Manager herself, she will ensure the scientific quality of the study plans and study reports for study packages and will manage the tasks associated with the overall coordination of the project on behalf of the client.

One of her missions will be to support the training of new Study Directors in the field of regulatory and investigational toxicology, accompanying the change and the process of continuous improvement. As a leading scientist in our global team of scientific experts, she will assist Citoxlab clients in achieving their goals through scientific advice on the design and conduct of critical non-clinical studies.

Webinar invitation: Considerations in Non-clinical Inhalation Toxicology: Understanding the Complexities and Potential Problems with Inspired Tox – June 28th – 4 pm (CEST)

With 30 years’ personal experience and over 260 GLP inhalation studies performed in the past 5 years, Citoxlab has proven to be a leader in inhalation toxicology for our clients in the pharmaceutical, agrochemical and chemical industries.

We offer three pillars of insight-driven, customizable support:

  • Regulatory advice: our experience and a wide-ranging portfolio of study designs to answer your specific needs
  • Expertise: an expert team dedicated to providing high-quality data from your studies
  • Technical: state-of-the-art equipment and new facilities, to help you reach your objectives

Christopher Banks, Global Head of inhalation for the Citoxlab Group and Balazs Toth, Senior Study Director specialized in inhalation toxicology and Associate Director of Scientific Operations will be giving the presentation.

Join us for this experience-based review, exploring the best approach in handling the complexities of inhalation testing in a regulated environment. Critical aspects such as test article behaviour, exposure system characteristics and dosimetry considerations for the testing of both industrial and pharmaceutical products will be presented.

In parallel, a case study will be used to give an insight into how these unique challenges of inhalation testing were tackled at Citoxlab.

This information is presented to encourage proactivity when performing inhalation toxicology studies and to help the understanding of inhalation specific aspects.

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