Today the development of newer and safer drug products has become challenging. There is increasing pressure to bring effective yet safe products to the patient population. Identifying toxic effects early in drug development projects can help expedite promising candidates to later stages of clinical trials. Hence, toxicology studies in drug development are a crucial aspect of any drug development project.
Nonclinical toxicology studies are conducted in animal models to identify safe doses for subsequent first-in-human studies. Besides in-vivo toxicological studies, researchers also conduct in-vitro studies to assess the safety and discover potential toxic substances. However, these in-vitro approaches are generally complementary to animal studies.
Despite the availability of several drug development protocols, the conduct of toxicology studies in a sequence can be advantageous for drug development projects. Hence, the current article highlights the steps you can follow to increase the approval chances of a drug candidate.
Steps to increase approval chances of a drug candidate
In the initial drug development phases, researchers conduct exploratory screening tests to evaluate any possible toxic effects. These safety studies are usually in vitro studies coupled with a reduced number of animal studies. As these studies do not require GLP compliance, they are relatively less expensive. Exploratory studies are vital for making informed decisions regarding the time and investment needed for the new drug candidate. Besides, they are crucial for the planning of subsequent toxicological studies.
Dose range finding studies are the first set of in vivo toxicity studies that are conducted in rodents. Generally, studies are explored first in rodent species before moving to non-rodent species. Such early rodent analysis helps researchers design studies for subsequent non-rodent species. The maximum tolerated dose study is the next test researchers conduct during in vivo toxicology studies. This study follows an escalation protocol for upto 30 days. It helps identify the organs with toxicity and study the impact of drugs on animal morbidity and mortality.
The next important step in toxicological studies is acute and repeated dose toxicity studies. Although the maximum tolerated dose study provides crucial toxicity data, repeated dose toxicity studies give a complete picture of histopathology, clinical and behavioral analysis, and biochemical and hematological tests, and evaluate any potential side effects after recovery. Acute toxicity studies are generally conducted at three different doses, and the test animals are watched for 14 days after drug administration.
Finally, toxicokinetic studies are another crucial aspect of toxicological analysis. These GLP studies measure systemic drug exposure in animals and help correlate the administered dose and the time course of drug movement. Indeed, comparing the toxicokinetic profile with pharmacokinetics data at different drug concentrations will be required for the interpretation of the study findings. Moreover, toxicokinetic assessments are vital for evaluating toxic accumulation in specific tissues or organs. Hence, toxicokinetic is a process of interpreting drug toxicity compared to clinical data and extrapolating the data to assess safety and risk in the human population. Generally, toxicokinetic tests are a part of nonclinical battery tests.