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Background Research and drug development industries have multiphase drug screening procedures, which can be debated. As a result, harmful products may still reach for public health service delivery due to vulnerabilities in the process. Main body A wide range of test compounds have delayed manifestation of undesired effect on the study subject, with the time to undesired effects after acute exposure being weeks and months. Acute toxicology in a preclinical trial also has limited clinical value as its lethal dose is the endpoint for a conclusion, and death sometimes occurs after a scheduled period of acute toxicology. Countless resources are wasted, and numerous new drugs are introduced into the pharmaceutical market with assumed safety analysis every year due to vulnerable multi-procedures in preclinical trials. The principal use of collected data from a preclinical trial is to support regulatory categorization and harmful labelling decisions. However, the data can also be used to derive safe use threshold levels, which may lead to the use of unsafe material. The criteria for classification and labelling also differ among countries, sometimes among authorities within the same country. The fundamental concept of toxicology states that ‘all chemical substances are potential poisons depending on the amount and duration of exposure. However, the toxic property of a test compound cannot be created or eliminated by simply the amount administered to study animals. Conclusion All xenobiotics are poisons at any amount with different severity that can be calculated using biological parameters.
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.