Toxicological studies in drug development are crucial in characterizing the extent of injury a drug product may have at varying drug doses. Such data help predict potential outcomes and better understand the risk/benefit ratio as to efficacy and safety. Depending on the development phase and individual research needs, sponsors perform both GLP and non-GLP toxicology studies in drug development.
Clinical and nonclinical toxicology analysis: Critical for a successful drug product
The primary aim of toxicological studies is to characterize the toxicity profile of a drug product and interpret its effects on organ structure and functionality. These assessments include in vivo and in vitro toxicology studies, reversibility and severity of toxic effects, and dose-dependent drug exposure. Ultimately, toxicology studies help determine the extent to which toxic effects can depend on the doses, species, mechanism, and method of administration.
What is a Toxicokinetic (TK) study?
TK study is similar to a pharmacokinetic study, where the toxic effects are studied with respect to time and how a particular drug product moves through the body. Hence, TK studies are a crucial aspect of toxicological studies in drug development. Besides, by understanding drug effects on kidneys, muscles, heart, and other vital organs, toxicological studies help determine safe doses for subsequent clinical toxicology analysis. These safe doses are necessary for designing clinical trials with maximum safety and minimum risk. Nevertheless, toxicology studies not only help set up different aspects of administration route, duration, and dose escalation, but they also help identify the primary organs for clinical monitoring.
Toxicological studies: From drug discovery to development
During the early drug development process, acquiring potential toxicity data is crucial before significant amounts of time and money are invested in screening novel therapeutic compounds. Such timely interventions can help sponsors anticipate toxicological-related challenges early in the drug development process and prioritize promising therapeutics for subsequent studies accordingly.
As a potential therapeutic compound enters the preclinical stage, researchers conduct acute toxicity studies to identify toxic effects at smaller doses and generate an acute toxicity profile. This data is complemented with repeated toxicity studies and dose range finding studies to analyze and characterize the toxic effects of escalating drug doses. By evaluating the compound at low, intermediate, and higher drug doses, researchers can identify the no observed adverse effect level (NOAEL). NOAEL is the highest dose at which no adverse effects are seen in test subjects. Hence, NOAEL is one of the most crucial parameters for determining safe drug dose regimes.
As mentioned earlier, toxicological studies can be conducted through GLP and non-GLP manners. However, GLP compliance is mandatory when requesting permission for human trials. Therefore, sponsors must have a bioanalytical laboratory that is completely ready and adhering to GLP standards, processes, and principles.
Conclusion
Toxicological studies can be performed in different matrices, including plasma, serum, and urine. Hence, sponsors must have a team of researchers experienced in conducting GLP and non-GLP toxicology studies in several biological matrices. Besides, toxicologicalstudies toxicological studies are necessary to characterize adverse effects and estimate the starting doses for in-human clinical trials. Hence, sponsors must conduct customized and standard toxicological studies to assess safety profiles and meet all regulatory requirements.
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