Before a study reaches Phase I clinical trials, scientists spend years conducting preclinical research. One vital part of this includes performing toxicology research on a particular medication or pharmaceutical product. The U.S. Food and Drug Administration (FDA) put great emphasis on the importance of preclinical safety evaluations.

According to the FDA’s guidance for industry on preclinical safety evaluation, pharmacokinetic research needs to include experimental medicines or biopharmaceutical products that represent drugs meant for toxicity testing. This administration route should be similar to the one which will be used in clinical trials.

During toxicity testing, systemic exposure should be monitored, along with patterns of absorption. Before beginning a clinical trial, it will be necessary to provide information on absorption, clearance, and disposition of each compound in animal models in order to anticipate safety of exposure in human subjects.

Additionally, the methods for evaluating absorption, clearance, and disposition should be equivalent in animal and human models. It is important to determine the metabolism of tested drugs and how they will react within the human body. There are two types of strategies to use in toxicology research. These are:

1. Single Dose Toxicity Study 

   With single dose studies, useful information may be gathered on local toxicity or the connection between dosage and systemic reaction. Along with single dose testing, information on the dose-response relationships can also be obtained from animal model efficacy studies. When designing this type of study, it is imperative to incorporate safety pharmacology parameters.

2. Repeated Dose Toxicity Study 

   The dosing regimen in preclinical studies needs to follow the regimen that will be used in clinical trials. Some researchers choose daily repeated dosing while others use intermittent dosing, the choice will depend upon the particular medications that are being developed and tested. Repeated dose studies will need to monitor toxicokinetic effects.

Animal toxicity studies usually take between one to three months for biotechnology-derived pharmaceutical products. For any medications that are intended for short-term use – less than seven days typically – a toxicity study lasting two weeks is generally adequate for federal regulations and marketing authorization.

On the other hand, for medication meant to treat chronic disease, toxicity studies lasting approximately six months are  typically required. Various pharmaceutical products may trigger or suppress an immune response, in which case, immunotoxicity studies may be added in preclinical trials.

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Categories: Toxicology and Pharmacology

Tags: animal models, preclinical research, toxicology research