Preclinical models are developed to test lead compounds for toxicity and efficacy. This report 1) explores novel preclinical models (in vivo, in vitro, in silico, and systems biology) that show promise to expedite and improve the target validation, lead optimization, and toxicity screening timelines, and 2) discusses the various advantages and disadvantages of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) screening techniques. In addition, the report provides an outlook for preclinical testing over the next decade. It focuses on more than 60 companies that are involved in using or developing ADMET technologies to advance preclinical research and provides an update on how new models and systems have been employed to accelerate the discovery and development process.
Scope of this report
• Understand the basis of ADMET testing and why it is a necessary and important component of preclinical research
• Up-to-date information on the preclinical models and systems currently used in drug discovery and development.
• Evaluation of the key recent developments and activities of companies who are developing and licensing new ADMET technologies.
• Identification of existing models and how new ones are being developed to improve productivity and knowledge.
Source: Business Insights
Despite greater emphasis on safety as a result of attrition, the application of toxicology (~6% of the total R&D budget) to the preclinical drug development process has remained largely unchanged for over 30 years! For this reason, the impetus to reduce safety risks early has been slow to evolve, with limited resources specifically dedicated to this endeavor. Revolutionizing the way that toxicology is applied, such as moving from a hazard identification and risk assessment preclinical paradigm to one that reduces or eliminates risk prior to major expenditures, may provide a means of narrowing the productivity gap within the biopharmaceutical industry. This paper suggests a strategy for the integration of toxicology into early drug development (discovery phase) through identification of potential safety issues related to therapeutic use, target selection, and compound selection, with a primary emphasis on new chemical entities. Information gained may also guide the appropriate selection of the toxicological species used to support clinical trials. Assays predictive of target organ effects (insufficiently discussed, in my opinion, in the present article) vs. assays designed to look at specific mechanisms of drug-induced toxicities at the intracellular level are presented relative to the need for development of high throughput safety screens.
In conclusion, the preclinical toxicology strategy needs to accommodate the unique attributes of the target, the compound, and the therapeutic application, along with assays that are “fit-for-purpose” for that specific project. This paper provides an overview of safety issues for initial exploration and cites possible techniques available to address them in the preclinical space.
Source: Pharmaceutical Outsourcing
The dream of tailor-made medication is not a new one, but the prospective cost of such treatments has always been a barrier to growth. Simply put, the return on compounds that only treat small populations cannot justify the investment. With life expectancy increasing and the cost of health care rising, however, an economic imperative is driving the change from managing sickness to managing wellness. A wellness-management approach detects conditions early, and hence the level of reversibility is high; the current reactive model has lower reversibility. With drugs targeted toward specific populations, the importance and acceptance of in silico modeling would increase. The author presumes that drug development programs will run more quickly, and that regulatory bodies would be able to approve drugs much earlier once a response in the target population has been proven. This is anticipated to reduce the clinical development time line and lead to cheaper drugs and prolonged exclusivity.
With the trend towards a lower acceptance of risk and thus bigger and more expensive clinical trials, do you agree with the author’s assumptions, especially given a smaller target population?
Source: Drug Discovery and Development