Explained: How Long Does Nonclinical Toxicology For IND Submission & Approval Take?

Developing a drug compound involves assessing safety and efficacy data in both animal and human studies.

Developing a drug compound involves assessing safety and efficacy data in both animal and human studies. The primary aim of nonclinical safety studies is to characterize toxic effects in regards to the dose-exposure relationship and target organs. The data obtained from nonclinical safety evaluations determine the initial dose range for human studies and identify factors that may help monitor drug toxicity.

Although nonclinical toxicology analysis (TK analysis) is performed in the initial stages of drug development, it should be adequate to provide reliable and robust data to characterize any potential adverse events in subsequent clinical trials. Sponsors submit Investigational New Drug (IND) applications to receive approval for conducting studies in human participants. Preclinical toxicology testing consists of repeated-dose and single-dose toxicity studies. ICH toxicology studies are an important aspect of IND studies and nonclinical toxicological findings can have a major impact on the approval of IND applications.

How Long Does Nonclinical Toxicology For IND Submission Approval Take?

If the FDA approves an IND, the study begins in 30 days of its receipt. If additional information is needed, FDA may place the IND on clinical hold until sponsors provide all the necessary data. The IND is active throughout the drug development program and should be updated as new information becomes available in Phase II and Phase III clinical trials.

Preclinical safety studies should be conducted in at least two animal species while assessing chronic, subchronic, and acute toxicity characteristics. Sponsors should conduct all toxicology studies in three dose levels and control samples, with the highest dose demonstrating frank toxicity and the lowest with little to no toxicity. Moreover, toxicological studies should be GLP-compliant.

During chronic and subchronic toxicity studies, sponsors should simultaneously conduct toxicokinetic and pharmacokinetic analyses to understand ADME properties and determine systemic absorption of the drug. Sponsors should develop appropriate study models early to ensure reliable, precise, and consistent PK data. Sponsors should assess human and animal PK data, along with primary PK endpoints including bioavailability, the area under the curve, and volume of distribution.

A drug should be tested for genotoxic effects. The results of genetic toxicity studies may increase the duration of preclinical toxicological assessments. Genotoxic tests involve conducting three tests; (a) testing gene mutation in bacteria, (b) studying chromosomal aberrations in in-vitro mammalian cell cytogenetic test or in vitro mouse lymphoma assays, and (c) assessing chromosomal damage through mouse micronucleus test or bone marrow cells in rodents. If all three tests are negative, no further studies are needed. However, if one or more tests are positive, sponsors will have to conduct additional genotoxicity tests.

Conclusion

Meeting regulatory requirements for IND submission is a crucial step in the drug development process. Submitting and maintaining an IND application throughout the life cycle of a novel drug development program may seem intimidating. However, FDA provides complete assistance for IND submissions. Officers handling IND can be easily contacted, and guiding documents are readily available on the FDA website. Thus, sponsors should not regard IND submissions as a hurdle in doing clinical research.