The Importance of Toxicology Studies in Preclinical Research

Before a study enters the first phase of clinical trials, scientists need to spend several years on preclinical research. One of the most important parts includes toxicological research on specific drugs or drugs. Both the FDA and researchers attach great importance to the importance of preclinical safety assessment. According to the FDA's preclinical safety assessment industry guidelines, pharmacokinetic studies need to include experimental drugs or biopharmaceutical products that represent drugs used in toxicity tests. This route of administration should be similar to that used in clinical trials.

In vivo preclinical toxicology studies aim to assess the onset, severity, duration, dose dependence and irreversibility of toxic effects. At Creative Bioarray, in vivo toxicology services range from acute (single dose) to chronic (multi-dose) dosing regimens. Several exposure routes are available in various species such as rodents, rabbits and guinea pigs (for example, oral, intravenous, intraperitoneal, intramuscular, topical, etc.). A comprehensive toxicology assessment can be obtained through internal resources or through strategic partnerships with external suppliers. These assessments include hematology, urinalysis, clinical chemistry, histopathology, biological analysis and toxicokinetics.

Identifying potential toxicity in the early stages of drug development can save time and development costs, and most importantly, reduce the possibility of late failure. Before using animal models, in vitro procedures can be used to determine specific effects on cells and tissues. In vitro toxicity analysis includes applying new substances to mammalian cells that have been cultured in a single-layer 2D or biomimetic 3D structure, and monitoring their subsequent biochemical and phenotypic responses to identify cells that represent the results of toxicity.

During the toxicity test, systemic exposure and absorption patterns should be monitored. Before starting clinical trials, it is necessary to provide information about the absorption, clearance, and disposal of each compound in the animal model in order to predict the exposure safety of human subjects.

In addition, in animal and human models, methods for assessing absorption, removal, and disposal should be equivalent. It is very important to determine the metabolism of the tested drug and how it reacts in the human body. There are two main strategies used in toxicology research?

Single dose toxicity studyThrough single-dose studies, useful information about local toxicity or the link between dose and systemic response can be collected. In addition to single-dose testing, information about dose-response relationships can also be obtained from efficacy studies in animal models. When designing such studies, safety pharmacology parameters must be included.

Repeated dose toxicity studyThe dosing regimen in preclinical research needs to follow the regimen that will be used in clinical trials. Some researchers choose to repeat the dosing daily, while others use intermittent dosing. This choice will depend on the specific drug being developed and tested. Repeated dose studies will require monitoring of toxicokinetic effects.

Animal toxicity studies usually take 1 to 3 months before they can be used for biotechnology-derived drugs. For any drug intended for short-term use (usually less than 7 days), a two-week toxicity study is usually sufficient to meet federal regulations and market licensing requirements.

On the other hand, for drugs intended to treat chronic diseases, toxicity studies that last about six months are usually required. Various drugs may trigger or suppress immune response, in this case, may increase immunotoxicity research in preclinical trials. Many biological companies already have advanced facilities and rich preclinical research experience that can accelerate the development of drug candidates, from discovery to regulatory submission. For example, Creative Bioarray can provide complex and unique evaluation methods, including ultrasound, CT scan, digital radiography, MRI, laser Doppler, IVIS imaging and contour photography.

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