Bioanalysis in drug development is the process of quantitating a drug or its metabolites in biological fluids. Today, drug discovery and development have endured radical changes. We can divide a typical drug development process into the discovery of a new drug molecule, the preclinical development phase, and the clinical trial phase. Compared to earlier studies and guidelines, pharmacokinetics and toxicokinetics are now the pillars of a successful drug product and its transition from the drug discovery phase to the clinical trial phase.
A toxicological study (tox study or tk study) in drug development evaluates the efficacy and toxicity of new drug molecules. Toxicological studies are a fundamental component of the preclinical phase, as a majority of potential drug molecules fail in the clinical phase because they lack safety and efficacy parameters. Toxicological research forms the core of IND enabling studies as toxicokinetics data sharply defines the filing of an IND application and its subsequent success.
Experimental and pharmacological toxicology
Only after an extensive preclinical study, researchers test a potential drug molecule in humans. The primary goal of a preclinical study is to determine a drug molecule’s safety profile. A drug molecule may undergo a wide spectrum of nonclinical research that includes pharmacokinetics, pharmacodynamics, bioavailability studies, ADME studies, and toxicity research via animal testing. IND-enabling studies comprise pharmacology, efficacy, and experimental toxicology studies research that help us understand the ideal drug dose and route for subsequent clinical studies.
Initial toxicology studies in drug development follow single-dose and multi-dose drug administration protocols, observed at various timelines. These early toxicological studies help decide the maximum tolerated dose, apparent signs of toxicity, and dose levels for more complex subsequent definitive studies. Keeping in mind the regulatory guidelines, early toxicological studies and definitive studies both require investigations to be carried out in at least two animal species, a rodent species such as mouse or rat and another non-rodent species such as dog, rabbit, or nonhuman primates. The study group size for early studies generally comprises a few animals with a single animal per dose level. After researchers identify an ideal dose range, they increase the group size to at least three animals per sex per dose level. Unless the study comes up with a particular toxicity concern, early toxicological studies collect a few endpoints for the preclinical data.
Pivotal toxicokinetics and safety
Toxicokinetics is the study of PK parameters on the drug dose levels of toxicological studies. Toxicokinetics helps us understand the relationship between drug exposure and the administered dose, educate about the potential-dose levels and its correlation with time-dependencies kinetics, and explore sex and age-related differences observed in the study. Definitive animal studies establish the “no observable adverse effect level” of a drug candidate. These early animal studies are GLP-FDA-toxicology studies, following high standards in the documentation processes. The highest dose levels determined in definitive studies depend on maximum tolerated doses observed in the range-finding studies and not on the expected clinical dose levels or expected plasma levels.
Future of toxicological studies
Bioanalytical companies understand the importance of toxicological studies and bioanalysis in drug discovery and development. The primary aim of a drug development process is to provide an ideal drug candidate that is rugged and backed by enough PK/PD and toxicological studies.