Exploratory IND enabling studies are those wherein you have a limited exposure of the pharmaceutical drug products to humans. This IND application or the Investigational New Drug (IND) application is a pre-requisite of the USFDA regulatory norms before the start of actual toxicology studies in drug development. IND enabling studies helps in predicting potential safety concerns of the pharmaceutical drug under evaluation, estimation of their safety doses, and identifying their key monitoring parameters.
What do you mean by IND enabling studies?
IND enabling studies helps in the in vitro clinical toxicological analysis of the pharmaceutical drug candidate under evaluation. These studies help in the determination of both the toxicological and pharmacological profile of the drug under analysis. It includes the assessment of both the dose and exposure dependencies as well as the reversibility of the toxicogenic effects of the pharmaceutical drugs.
Nonclinical safety studies for the conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals along with Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals are both relevant regulatory guidelines to be religiously followed for performing GLP toxicology studies.
Such IND enabling studies helps in the assessment of the following –
Safety pharmacology as well as the pharmacodynamics profile
Pharmacokinetic parameters including ADMET characterization of the pharmaceutical candidate under evaluation.
Toxicology study findings including single dose, repeated dose, developmental and reproductive toxicity studies, genotoxicity studies, etc.
The IND enabling clinical toxicology analysis and the preclinical toxicity studies is inclusive of both the single dose study as well as repeated dose toxicity studies. Acute toxicity studies are usually performed in two different mammalian species using a common clinical administration route and a parenteral route. The dosing levels should be shortlisted in such a way that such studies will allow the determination of MTD or maximum tolerated dose as well as a NOAEL or no-observed-adverse-effect level. Both these parameters play a critical role in evaluating the human safety profiling as well as selection of the clinical dose levels.
Acute toxicity studies can function as your preliminary IND-enabling studies; however, they are often combined with other repeated dose toxicity studies. These repeated dose toxicity studies are defined by a similar duration and administration route as they are proposed in the process of clinical evaluation.
Such studies should look forward towards matching or exceeding the overall treatment duration for the proposed clinical trials. It is therefore imperative to select both the dose levels and dose regimens in such a way that the observed exposures of Cmax and AUC within the non-clinical species adequately covers the expected range of clinical exposures.
The determination of the mutagenic potential of the investigational pharmaceutical drug may be conducted for supporting the findings of the single dose clinical evaluations. Additionally, assessments should be worked out for chromosomal damage tracing which in turn, supports the data retrieved from the repeated-dose clinical evaluations. It is also important that the complete genotoxicity studies are accomplished prior to the start of the Phase 2 clinical trials.
On a concluding note, it can be said that the IND enabling studies plays a crucial role in the evaluation of a potential risk possessed by the pharmaceutical drug candidate to humans. Nevertheless, it also helps in the estimation of the starting doses to initiate your clinical evaluation.