Everyone seemed to know how a new drug is created a long time ago, especially after covid-19, when everyone was watching those very clinical trials of vaccines. However, it's not that simple. In a nutshell - in this publication, you will learn how long the process of creating a drug takes and how expensive it is. And maybe you can guess that if they say on TV that scientists have discovered a substance that can beat cancer or some other disease, it's too early to run to the pharmacy hoping to buy this new medicine.
Idea
Idea
- In order for scientists or a pharmaceutical firm to begin developing a drug, there must be a combination of several factors:
- The social significance of the disease;
- Known molecular mechanisms of disease development;
- Financial resources and the ability to create a specific drug.
In other words, there must be an idea.
What constitutes a "target" for the drug?
Together, a team of scientists chooses a target and a way to target it in order to treat or prevent the disease.
A drug target is a biological macromolecule associated with a specific function, the disruption of which leads to a disease. The most common targets for drugs are proteins - receptors and enzymes. The infographic shows which macromolecules are most often targeted by drugs. Looking ahead, it is worth noting that the substance - the drug - is then matched to the "target. The most common example is cyclooxygenase 1 (target) and acetylsalicylic acid (drug).
Searching for ligands
Once scientists have found a target for a drug, they need to figure out what to "aim" at it with. A ligand (potential drug) is a chemical compound (usually low molecular weight) that specifically interacts with its target and thereby affects processes inside the cell.
The study of all possible substances is, of course, unrealistic: there are at least 1,040 ligands. Therefore, a number of restrictions are imposed on the structure of potential ligands, which significantly narrows the search.
As a starting point, libraries of compounds are usually used that are created by specialized companies according to the conditions set by the developer, or are already available in the arsenal of a pharmaceutical company. Such libraries can contain millions of substances.
Initially, the screening assay helps to determine whether the selected ligands affect the target under study. The screening assay is either laboratory (in vitro) or computer (in silico).
Laboratory screening: On special slides, a robot digs test substances out of pipettes following a predetermined program.
The slides are plates containing wells with thousands of microliters of different target proteins or whole genetically modified cells.
Then a readout takes place, telling which well has the biological activity detected. The detector can detect it by radioactive signal, fluorescence, light polarization, and many other parameters.
Optimizing
Out of thousands of available substances with certain properties, hundreds of molecules should be selected that are capable, after further modification and testing on bacteria or cell cultures, of yielding dozens of "candidate" compounds intended for preclinical studies, including animal testing.
Optimization can consist in "cutting off" a part of the known ligand, or vice versa, adding new elements to it and new testing for interaction with the target. Going back to aspirin: it is derived from salicylic acid by adding an acetyl group.
What constitutes a "target" for the drug?
Together, a team of scientists chooses a target and a way to target it in order to treat or prevent the disease.
A drug target is a biological macromolecule associated with a specific function, the disruption of which leads to a disease. The most common targets for drugs are proteins - receptors and enzymes. The infographic shows which macromolecules are most often targeted by drugs. Looking ahead, it is worth noting that the substance - the drug - is then matched to the "target. The most common example is cyclooxygenase 1 (target) and acetylsalicylic acid (drug).
Searching for ligands
Once scientists have found a target for a drug, they need to figure out what to "aim" at it with. A ligand (potential drug) is a chemical compound (usually low molecular weight) that specifically interacts with its target and thereby affects processes inside the cell.
The study of all possible substances is, of course, unrealistic: there are at least 1,040 ligands. Therefore, a number of restrictions are imposed on the structure of potential ligands, which significantly narrows the search.
As a starting point, libraries of compounds are usually used that are created by specialized companies according to the conditions set by the developer, or are already available in the arsenal of a pharmaceutical company. Such libraries can contain millions of substances.
Initially, the screening assay helps to determine whether the selected ligands affect the target under study. The screening assay is either laboratory (in vitro) or computer (in silico).
Laboratory screening: On special slides, a robot digs test substances out of pipettes following a predetermined program.
The slides are plates containing wells with thousands of microliters of different target proteins or whole genetically modified cells.
Then a readout takes place, telling which well has the biological activity detected. The detector can detect it by radioactive signal, fluorescence, light polarization, and many other parameters.
Optimizing
Out of thousands of available substances with certain properties, hundreds of molecules should be selected that are capable, after further modification and testing on bacteria or cell cultures, of yielding dozens of "candidate" compounds intended for preclinical studies, including animal testing.
Optimization can consist in "cutting off" a part of the known ligand, or vice versa, adding new elements to it and new testing for interaction with the target. Going back to aspirin: it is derived from salicylic acid by adding an acetyl group.
Basic testing
Selected compounds are first tested in biochemical-pharmacological studies or experiments on cell cultures, isolated cells and isolated organs.
Since these models are not capable of fully replicating the full range of biological processes in a real organism, any potential drug is tested on animals. Only animal experiments can answer the question of whether the desired effects appear at non-toxic or low-toxic doses.
The toxicity study evaluates the following parameters:
Selected compounds are first tested in biochemical-pharmacological studies or experiments on cell cultures, isolated cells and isolated organs.
Since these models are not capable of fully replicating the full range of biological processes in a real organism, any potential drug is tested on animals. Only animal experiments can answer the question of whether the desired effects appear at non-toxic or low-toxic doses.
The toxicity study evaluates the following parameters:
- Toxicity during short-term and long-term use;
- The possibility of genetic damage (genotoxicity, mutagenicity);
- Possibility of tumor development (oncogenicity and carcinogenicity);
- Possibility of giving birth to a sick fetus (teratogenicity).
In animals, the compounds under study are also tested for absorption, distribution, metabolism, and excretion (pharmacokinetics).
After this stage of elimination to the stage of clinical trials in humans remains at best 1-3 drugs (recall that initially there were about 1000 potential drugs!).
After this stage of elimination to the stage of clinical trials in humans remains at best 1-3 drugs (recall that initially there were about 1000 potential drugs!).
Entering the market
Clinical testing involves several phases, which the infographic illustrates.
First, new drugs are tested on healthy individuals to determine if the effects found in animal tests are observed in humans and to identify dose-effect relationships.
Then a potential new drug is tested on selected patients to determine the therapeutic efficacy for the disease for which it is intended. Positive effects should be evident and undesirable effects acceptably small.
Next, large groups of patients are enrolled in the study, with which the drug under investigation is compared with standard treatment on therapeutic outcomes.
In the process of clinical trials, many new drugs are found to be unsuitable for use.
The decision to approve a new drug is made by the national regulatory agency (FDA). Applicants (pharmaceutical companies) submit to the regulatory body a complete set of preclinical and clinical trial documentation in which the efficacy and safety data obtained meet the established requirements and the intended form of the product (tablets, capsules, etc.)
After approval, the new drug can be sold under a brand name and thus becomes available for prescription by doctors and distribution in pharmacies. At the same time, the technological process of drug production, quality requirements, and methods of analysis are being developed.
The drug continues to be monitored as it is distributed. A final judgment on the benefit-risk ratio of a new drug can be made only on the basis of long-term experience of its use. This is how the therapeutic value of a new drug is determined.
In various cases, the process of developing a new drug from idea to implementation takes approximately 5 to 18 years. The total cost of development, including drugs that have not reached the market, often exceeds $1 billion (up to $2.5 billion on average).
Clinical testing involves several phases, which the infographic illustrates.
First, new drugs are tested on healthy individuals to determine if the effects found in animal tests are observed in humans and to identify dose-effect relationships.
Then a potential new drug is tested on selected patients to determine the therapeutic efficacy for the disease for which it is intended. Positive effects should be evident and undesirable effects acceptably small.
Next, large groups of patients are enrolled in the study, with which the drug under investigation is compared with standard treatment on therapeutic outcomes.
In the process of clinical trials, many new drugs are found to be unsuitable for use.
The decision to approve a new drug is made by the national regulatory agency (FDA). Applicants (pharmaceutical companies) submit to the regulatory body a complete set of preclinical and clinical trial documentation in which the efficacy and safety data obtained meet the established requirements and the intended form of the product (tablets, capsules, etc.)
After approval, the new drug can be sold under a brand name and thus becomes available for prescription by doctors and distribution in pharmacies. At the same time, the technological process of drug production, quality requirements, and methods of analysis are being developed.
The drug continues to be monitored as it is distributed. A final judgment on the benefit-risk ratio of a new drug can be made only on the basis of long-term experience of its use. This is how the therapeutic value of a new drug is determined.
In various cases, the process of developing a new drug from idea to implementation takes approximately 5 to 18 years. The total cost of development, including drugs that have not reached the market, often exceeds $1 billion (up to $2.5 billion on average).