TK assay

A Look Inside The Factors Affecting Tk Assay In Drug Development

Over the last couple of decades, the field of toxicology has undergone massive transformations. The toxicology experts are now turning their back to the traditional toxicity testing methods. They are now in search of novice methods. Moreover, these experts are embracing the advancements made to the fields of molecular biology, cell culture, and computer modelling for predicting the outcome of toxicological developments.

Here are four essential advancements of GLP toxicological studies FDA –

In vivo toxicology –

The pre-clinical tox study is performed for determining the dose-specific and organ-specific effects produced by an investigational compound. It was somewhere in the early 1920s that the animal models were introduced at the pre-clinical stage for toxicity evaluation of an investigational drug.

If you take a keen look at the past few decades, there has been a sharp shift from in vitro toxicity testing to an alternative form of in vivo testing. There are several factors which may affect the results obtained from the in vivo investigational product analysis. Different living systems possess different internal mechanisms. Any form of human contact, unnatural conditions, and stress – all can produce a change and sometimes an irreversible change in the way animal models respond to the studies being conducted.

In vitro toxicity –

In the past few years, both in vitro and in silico investigational product testing procedure has seen a considerable increase in its applicability. In vitro testing with two-dimensional cellular assays e routinely employed throughout the drug discovery pipeline. However, there are many limitations to the use of two-dimensional models. The three-dimensional model offers a better understanding of the physiological systems. Wide-scale applicability of the organ-on-a-chip model has increased the ability of the researchers in re-constructing the responses produced by human tissues.

In silico toxicity –

These tk assay involve computational techniques for analyzing, simulating, and predicting the toxic effects and ADME characterization of an investigational compound under analysis. Thus, they form the best alternative to both real-life (in vivo and in vitro) tox studies. These studies primarily rely on quantitative structure-activity relationships (QSARs). They also help in a complete evaluation of the chemical structure of a compound and its biological efficacy.

Toxicogenomics –

Here, you have a tox study which combines the mechanism of toxicology and the technology of omics. The omics technology employed here spans across all the four domains of genomics, proteomics, transcriptomics, and metabolomics. A combined mixture of all these computational techniques can be applied in the determination of a molecular mechanism responsible for controlling responses to toxic compounds.

What is the purpose behind conducting the GLP toxicology studies for FDA?

The non-clinical or pre-clinical toxicology studies are crucial for establishing the toxicology profiles of an investigational drug product. This is a pre-requisite of the Food & Drug Administration before administering the drug in humans. GLP toxicology studies are also crucial in extending the known profiles of marketed products such as – new indications, the newly commercialized formulations, and the new route of administrations. The length of the non-clinical studies varies greatly – acute, sub-acute, chronic, and sub-chronic studies.  

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