Investigative safety strategies to improve success in drug development
Journal Title: Journal of Medicines Development Sciences - Year 2016, Vol 2, Issue 1
Abstract
Understanding and reducing attrition rate remains a key challenge in drug development. Preclinical and clinical safety issues still represent about 40% of drug discontinuation, of which cardiac and liver toxicities are the leading reasons. Reducing attrition rate can be achieved by various means, starting with a comprehensive evaluation of the potential safety issues associated to the primary target followed by an evaluation of undesirable secondary targets. To address these risks, a risk mitigation plan should be built at very early development stages, using a panel of in silico, in vitro, and in vivo models. While most pharmaceutical companies have developed robust safety strategies to de-risk genotoxicity and cardiotoxicity issues, partly driven by regulatory requirements; safety issues affecting other organs or systems, such as the central nervous system, liver, kidney, or gastro-intestinal system are less commonly addressed during early drug development. This paper proposes some de-risking strategies that can be applied to these target organ systems, including the use of novel biomarkers that can be easily integrated in both preclinical and clinical studies. Experiments to understand the mechanisms’ underlying toxicity are also important. Two examples are provided to demonstrate how such mechanistic studies can impact drug development. Novel trends in investigative safety are reviewed, such as computational modeling, mitochondrial toxicity assessment, and imaging technologies. Ultimately, understanding the predictive value of non-clinical safety testing and its translatability to humans will enable to optimize assays in order to address the key objectives of the drug discovery process, i.e., hazard identification, risk assessment, and mitigation.
Authors and Affiliations
Franck Atienzar, Annie Delaunois, Frédéric Brouta, Miranda Cornet, Renaud Fleurance ,Helga Gerets, Stéphanie Glineur, Catrin Hasselgren, Andrea Kiessling, Andre Nogueira da Costa, Marie-Luce Rosseels, Karen Tilmant1 and Jean-Pierre Valentin
Keywords
Related Articles
- EP ID EP679243
- DOI -
- Views 183
- Downloads 0
Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue
Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory propertie...
The Association for the Accreditation of Human Research Protection Programs: 15 years of emphasizing research safety, ethics, and quality
This year marks the 15th anniversary of the founding of the Association for the Accreditation of Human Research Protection Programs (AAHRPP), an organization that has been instrumental in strengthening protections for re...
Japanese initiative for education in pharmaceutical medicine and clinical research training
Development of new medicines has become increasingly difficult with less possibility of success in seeds-finding and ever rising operational costs. Failure to comply with ethical standards for human research protection a...
The launch of the European Institute for innovation through health data
The European Institute for Innovation through Health Data (i~HD) has been formed as one of the sustainable entities arising from the Electronic Health Records for Clinical Research (EHR4CR) and SemanticHealthNet projects...
EUPATI: Collaboration between patients, academia and industry to champion the informed patient in the research and development of medicines
The value of collaborations and partnerships between different stakeholders to achieve optimum outcomes in the medicines research and development process is being recognised. Historically, there has been a lack of collab...