GLP Toxicology (tox) Studies Commonly Requested By FDA For IND Application

In vivo GLP toxicological studies are intended for assessing the onset, duration, and severity of the adverse effects or toxicity of a pharmaceutical product under analysis. Such in vivo toxicology studies also helps in the determination of both the dose dependency as well as degree of reversibility. Both GLP and non-GLP studies are required to assess the potency of the pharmaceutical drug candidate for assessment of its non-clinical toxicology. Such studies can encompass dosing regimens ranging from acute to chronic levels.

The GLP tox studies can help in the evaluation of several routes of drug exposure such as intravenous, intramuscular, oral, topical, etc. Some of the animal species that goes into the GLP toxicology studies are rabbits, mice, hamsters, rats, guinea pigs, etc.

What is the purpose of performing GLP tox studies?

Non-clinical or pre-clinical tox studies are essential for establishing the toxicological profiles of new pharmaceutical drug candidate prior to their human administration. These are also used for extending the known profiles of all the existing pharmaceutical drug candidates. Such profiles are inclusive of new formulations, new indications, new routes of administration, etc.

The non-clinical GLP studies may be performed in accordance with a non-GLP fashion under preliminary investigation. However, for direct extrapolation of the drug profiles to humans requires compliance with the GLP studies. Non-clinical studies vary widely in their length of performance such as acute toxicology studies, sub-chronic toxicological studies, chronic toxicological studies, etc. These study lengths vary in accordance with the dosing length under clinical trials which are supported and the pharmaceutical development stage of the test candidate i.e. NDA, IND, PMA, BLA, etc.

These studies help in establishing the characterization of the drug toxicity profile by identifying their impact on the organ structure and function. Such toxicological studies are inclusive of the assessment of both severity and reversibility of the toxicological studies, their dose ranges, and their exposure relationship. ICH M3 (R2) guidelines covers the necessary information related to the scope of performing the non-clinical toxicological studies which is important to be performed at diverse stages of drug discovery and development.

In vivo toxicology studies are important for establishing toxicological profiles of the pharmaceutical drug candidates possessing a severe risk to human health and well-being. Such studies ought to be performed in a non-GLP fashion for accomplishing preliminary characterisation.

Testing categories for in vivo toxicology evaluation –

The testing categories available for in vivo toxicology evaluation are as follows –

• Acute systemic toxicity studies

• Subacute toxicity studies

• Sub-chronic toxicity studies

• IND enabling studies

• Dose escalation studies

Species recommended –

• Rat

• Mouse

• Guinea pigs

• Rabbits

• Hamsters

Preferred routes of administration –

• Subcutaneous

• Oral

• Intraperitoneal

• Intravenous

• Intramuscular

• Topical

Through the evaluation of the injuries incurred to vital organs such as heart, kidneys, muscles, etc, non-clinical studies help in the determination of the drug safety levels for their expected clinical dose. This information is essentially critical for evaluating the guiding parameters of clinical trials for maximising their efficacy and minimizing their associated risks.