Having a proactive approach in planning pivotal toxicology studies (tox studies) in drug development is crucial before engaging with any bioanalytical labs for IND enabling studies. A sound and robust clinical strategy ensures that the data generated is more than enough to support IND applications and will mitigate any risks associated with study delays.
All regulatory agencies require testing the safety and tolerability of potential new medicines in animals before initiating human trials. Such requirements include benefit/risk and dose setting assessments to support dosages in humans and longer-term studies, including for patients, healthy populations, or children and the elderly. However, the key is to come up with appropriate ways to optimize toxicology studies so that they are sufficient for IND submissions.
Optimization of GLP toxicology studies for IND submissions
Performing toxicological studies in a sequence is decisive in the discovery and development of novel medicines. Despite knowing this fact, there are no standard programs to perform the assays. A well-planned study design can help save time and money and avoid several study errors and unnecessary animal experiments. Toxicological studies involve both GLP and non-GLP studies. Non-GLP toxicology studies are preliminary tox studies that do not need to be compliant with good laboratory practices. Non-GLP tox studies are crucial factors in IND submissions as they provide early insights into the characteristics of how a drug might behave in subsequent GLP studies.
Regulatory toxicology studies help assess drug toxicity levels using protocols that are recommended by regulatory bodies. These studies are GLP-compliant and are conducted after preliminary toxicity studies. Except for mutagenicity tests, sponsors should conduct GLP studies in two animal species. Sponsors can plan regulatory toxicology studies based on efficacy and safety data obtained from exploratory studies.
In vivo/in vitro genotoxicity studies and repeated-dose toxicity and dose-selection studies can be deciding factors in the optimization of GLP-toxicity studies. Generally, these tests complemented with efficacy, pharmacokinetic, and safety pharmacology studies can help submit a dossier for permission to conduct tests in humans. Before moving on to IND submission, the test drug should be the same formulation compared to the one that will be used for clinical studies. Moreover, the same goes for route administration, where it is recommended to have the same route of administration in toxicological and human studies.
Reproductive toxicology studies are carried out during the clinical trial phase. A drug may influence reproductivity through implantation, teratogenicity, or during birth development. Hence, reproductive toxicology studies are the most rigorous studies and are necessary for the approval of a drug product. Toxicokinetic studies are usually a part of toxicology studies in drug development. Toxicokinetic studies estimate systemic drug exposure and establish a link between the administered dose and the time course in the body. Having toxicokinetic data can help optimize GLP toxicology studies by combining them with other toxicology data to interpret and compare risk and safety associated with a drug product.
A robust IND program requires efficient preparation and proactive planning. Since a lot depends on toxicological data, developing an integrated approach will streamline and ensure the success of IND enabling studies and help counter any unexpected hurdles during the drug development process.