What are Preclinical Trials?

Preclinical research refers to chemical synthesis or natural product purification research, drug analysis research, pharmacodynamics, pharmacokinetics and toxicology research, and pharmacy research conducted before the drug enters clinical research.

Preclinical Trials Content

Preclinical research of drugs for drug registration, including drug synthesis technology, extraction methods, physical and chemical properties and purity, dosage form selection, prescription screening, preparation technology, inspection methods, quality indicators, stability, pharmacology, toxicology, animal drugs Generation dynamics and so on. Traditional Chinese medicine preparations also include the source, processing and processing of raw medicinal materials, and biological products also include the source of starting materials, quality standards, storage conditions, biological characteristics, genetic stability, and immunology of bacteria, cell strains, biological tissues, etc. Research and so on.

According to the requirements of drug registration application materials, pre-clinical research can be summarized into three aspects:
(1) Literature research: including the name of the drug and the basis for naming, and the basis and basis of the title.
(2)Pharmaceutical research: raw material drug process research, preparation prescription and process research, test to confirm chemical structure or composition, drug quality test, drug standard drafting and description, sample inspection, excipients, stability test, packaging materials and container related Test etc.
(3) Pharmacological and toxicological research: general pharmacological test, main pharmacodynamic test, acute toxicity test, long-term toxicity test, allergy, hemolytic and local irritation test, mutagenicity test, reproductive toxicity test, carcinogenic toxicity test, dependent Sex test, animal pharmacokinetic test, etc.

Preclinical Drug Safety Evaluation (DSE) is the core content of preclinical drug research. Drug safety evaluation research must implement the “Non-clinical Drug Research Quality Management Practice” (GLP).

In the process of preclinical trials of a compound or biological agent into a drug, the compound involved must go through the trials phase. First, we need to identify potential targets that can treat the disease. Then, a variety of compounds or preparations are screened out. Any compound that has shown potential as a drug for the treatment of this disease needs to be tested for toxicity before clinical trials to reduce the possibility of injury.

Medicilon is a Preclinical Research Outsourcing (CRO) company. With our more than 10 years experience on preclinical research services, we dedicated to provide our clients with customized preclinical services program in drug metabolism, pharmacokinetics, efficacy studies, and toxicology. We provide our clients a high-quality data and rapid turnaround time to support their drug development, preclinical studies and clinical research and to help them to select the most valuable drug candidates into clinical trials stage. Our preclinical research services consist in three major parts: pharmacokinetics, disease transplantation models and drug safety evaluation. Our preclinical research services cover all of the aspects including design, in vivo studies, sample analysis, professional data analysis, IACUC review, and the preparation of application materials.

Medicilon is one of the first CRO in China to provide integrated services, including compound synthesis, biological activity screening, structural biology, pharmacodynamics, pharmacokinetics, toxicology, and IND filing. Our high quality services are well-recognized internationally.  

Overview of Preclinical Drug Development Process

• Drug Discovery

• Screening

• Pre-Clinical Testing

• IND Application

• Phase I Clinical Trials

• Phase II Clinical Trials

• Phase III Clinical Trials

• New Drug Application (NDA) / Biologics License Application (BLA)

• Phase IV and Beyond

What is the basis of preclinical trials?

According to US Food and Drug Administration (FDA) regulations, a series of tests are required before a new drug is approved for use. In the first stage, basic research determines a hypothetical target for the treatment of a certain disease, and then screens small molecules or biological compounds to discover any substance with the potential to treat the disease.

Then, a preclinical research phase followed, before which, as described above, the potential toxicity of the compound was determined. Factors such as dosage, method of administration, and frequency of administration are also studied to support the next phase of clinical trials, also known as clinical studies. Here, the compound was tested in humans to see if it can be used to treat the disease that triggered the search.

Identify potential targets

The main reason why the compound cannot be used as a medicine is that the compound cannot be used as a medicine or is toxic. Therefore, determining drug targets is one of the most important parts of preclinical trials. The latest advances in technology have increased the number of potential targets or targets that can be used. Bioinformatics tools can now be used to “mine” the available data to search for these potential targets. These may come from published studies or patents, gene expression and proteomics data sets, data on transgenic phenotypes, and compound analysis data.

Targets include a wide range of biomolecules, such as proteins, RNA and DNA. A key requirement for treating biomolecules as targets is whether they are “absorbable by the body.” This means that the compound to be tested needs to be able to approach the target and then induce a measurable response.

Certain classes of target compounds are more suitable for different classes of compounds. For example, G protein-coupled receptors are good potential targets for small molecules, and antibodies are more suitable for blocking protein-protein interactions.

How to find the “target”?

Once the treatment goal is determined, the next stage of preclinical trials will be to determine the “hit drug.” The effects of these compounds may be able to treat the disease. Here, different kinds of measurements need to be used.

In high-throughput screening, a large number of compounds are tested against target compounds to see if any compounds show the potential to enter the next stage. These rely on automated systems that can test a large number of compounds without making any assumptions about how these compounds might interact with the target. In contrast, centralized screening can only detect a smaller number of compounds, but compounds that are more likely to interact with the target. Other screening methods used in this stage of preclinical trials include: fragment screening (in which the protein structure of the compound-target interaction is determined) and physiological screening (in which only tissues are used instead of targets or cells).

What happens once the hit is confirmed?

Once the target is determined, it will be further studied to make the compound more selective and effective. This stage of preclinical trials studies the structure-activity relationship between the compound and the target, and then studies whether the compound interacts with the target of different species.

This indicates whether the compound can be tested in animal models of the disease, which is an important part of toxicity testing during preclinical trials. The compound is then refined to maintain the beneficial properties while reducing or eliminating the unfavorable aspects.

What other factors need to be considered for pre-clinical trials?

Other factors that should be considered during preclinical trials are the nature of the disease and the demographic characteristics of the patient suffering from it.

For example, neurodegenerative diseases (such as Alzheimer’s disease) are progressive diseases and therefore require long-term treatment. This means that in preclinical trials, it is crucial to test the compound in a way that mimics long-term treatment. This highlights any compounds that may cause toxicity after prolonged exposure.

Because neurodegenerative diseases have a greater impact on the elderly, potential reproductive toxicity can be investigated in the later stages of preclinical trials. However, since these patients may also be taking other drugs, it may be prudent to test the interaction between the compound and the approved drug as early as possible in preclinical trials.

The route and frequency of administration are also factors that need to be considered in patient demographics. For example, in neurodegenerative diseases, patients will benefit from more manageable treatments, such as small tablets or liquids taken once a day or less. Focusing on compounds that can be administered in this way may become the focus of preclinical trials.

Article Source:

1.fda.gov The Drug Development Process www.fda.gov/…/drug-development-process

2. Hughes, J. P., et al. (2011) Principles of early drug discovery. British Journal of Pharmacology doi: 10.1111/j.1476-5381.2010.01127.x

3. Steinmetz, K. L. and Spack, E. G. (2009) The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurology https://doi.org/10.1186/1471-2377-9-S1-S2

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