Toxicology studies are crucial for the success of drug discovery and development processes. Similar to bio availability and bio equivalence (BA/BE) studies, toxicology studies have benefited from recent advancements in biology and biotechnology. The current clinical toxicological analysis uses a system based on expanding protocols without evaluating these experimental systems. Such an approach has relatively increased the testing costs, time, and use of laboratory animals for toxicity data. Besides, many regulatory requirements for toxicology analysis overlook the testing of several chemicals, which may have potential risks to humans.
Some of the generated toxicology data often need to address crucial questions concerning the risk to humans. Accordingly, the US Environmental Protection Agency approached the National Research Council to undertake a long-term approach to effective toxicology testing. In response to this request, the National Research Council developed a comprehensive report for toxicology studies. The current article highlights the advancements in in-vivo toxicology studies mentioned in this report.
Recent advancements in in-vivo toxicology studies
Clinical and nonclinical toxicology aims at developing study data that protects the safety of the patient population. Current toxicity approaches rely on observing the adverse effects of high drug doses in study animals. However, these studies may often lack demonstrating relevance in terms of risks associated with lower concentrations of drugs to the patient population. These toxicity studies are time-consuming and expensive. Besides, several animals are needed for toxicity testing. Hence, only a short fraction of chemicals are tested through these methods.
Moreover, adequate coverage of life stages and inadequate study endpoints, such as developmental neurotoxicity and environmental agents, are certain issues related to toxicological analysis. Current tests may need more data regarding the mechanism and mode of action and variability observed within the human population.
The report released by the US National Academy of Sciences changed the conduct of toxicity testing. This report was significant, particularly for in vivo and nonclinical toxicology testing. The report recommends increased efforts in toxicity testing while decreasing the number of animal models used in in-vivo toxicology studies. Today many lengthy and expensive in vivo studies are replaced by in vitro toxicity studies using cell lines and robotic screening with quantitative parameters. Toxicokinetic analysis has also become a crucial aspect of toxicological studies. Toxicokinetic studies involve assessing drug toxicity in terms of dose and time.
Moreover, assessing risk factors in study subjects must focus on avoiding differences in toxicity pathways. Computational biology models are increasingly used to determine the dose-response of pathway functions. Besides, in vitro data must be extrapolated to in vivo human blood concentrations using PK models for that specific experimental exposure. Such approaches will ensure all relevant data points are covered, which may not necessarily comply with traditional toxicological strategies.
Today all necessary interventions are available for replacing in vivo toxicological studies at different phases of drug discovery and development. However, all relevant stakeholders must commit to accepting these changes and broadly discuss the shortcoming while implementing this vision. Scientists must also focus on acquiring knowledge about pathways in humans and complement this data with computational biology systems. Executing these strategies will ensure that newer approaches are implemented smoothly across the scientific community.
