The problem of preclinical toxicity studies
Pharmaceutical development has always been a challenging and dynamic field, especially in the late twentieth and early twenty-first centuries. The process comes with its fair share of risks and expenses, mainly due to a high failure rate. Interestingly, successfully bringing a new chemical entity (NCE) through the entire drug discovery and development process to gain approval as a new therapeutic can cost over one billion dollars (U.S.).
Moreover, the journey from research initiation to marketing approval typically spans a lengthy period of 10 to 12 years. Despite advances in technology, such as early screening assays and in silico methodologies, our experience in the past decade hasn’t met the anticipated productivity improvements. Surprisingly, it’s becoming increasingly challenging to identify lead molecules that can effectively and safely contribute to the development of new therapeutics.
Taken from: Rupa, Gamarra. “Preclinical Pharmacology and Toxicology: an Important Aspect in Drug Discovery.” (2016).
After successfully passing through the discovery phase, candidate molecules enter preclinical development and progress through the various stages of clinical development: Clinical Phases I, II, and III.
Animal models play a crucial role in predictive toxicology by providing valuable insights into the potential toxicity of chemicals and substances. These models, which typically involve rodents or other animals, allow researchers to study how a substance affects biological systems, identify potential adverse effects, and assess the overall safety of a compound. By exposing animals to various doses of a substance and carefully monitoring their physiological and behavioral responses, researchers can gather data on potential toxicity, including acute and chronic effects, organ-specific impacts, and long-term consequences. Animal models also enable the study of dose-response relationships, helping to determine the safe dosage levels for human exposure. The data generated from animal models provide a basis for extrapolating potential risks to human health. While animal models are not a perfect reflection of human biology, they offer valuable insights into the potential effects of substances on various physiological systems and can help identify potential hazards early in the drug development process. This information is then used to guide further research, optimize safety profiles, and make informed decisions regarding human exposure to chemicals and pharmaceuticals.
Throughout this process, the NCE is carefully evaluated for safety and efficacy humans, using larger groups of volunteers and patients. Starting with small-scale studies involving normal subjects or patients, the research then expands to include hundreds and even thousands of patients in later stages.
If you’re fascinated by the challenges and complexities of pharmaceutical development, the field of predictive toxicology offers incredible opportunities. To this end, extensive knowledge and experience in in vitro and preclinical studies is essential to de-risk the path to the clinic. Let’s work together to make a difference in drug development and bring innovative therapies to those in need.