Kasuni Illeperume
Throughout history, people have used different medicines, mostly made from plants. Scientists now use advanced methods to study these plant-based remedies and find out how they can help treat diseases. They also discover new chemicals that can be used for medicine. Before doctors recommend or people take new medicines, they go through tests to make sure they are safe and work well. Once this testing is done, we have a lot of information about the medicine. Understanding this process helps people make smart choices about taking medicine.
The process of finding a drug chemical that can be used therapeutically to treat and manage a medical condition is known as drug discovery. The drug discovery process can categorize the identification of drug molecules, synthesis, characterization, screening, and assays for therapeutic efficacy. Following clinical trials, a molecule will begin the drug development process if it yields satisfactory results from these investigations. The process of finding and developing new drugs is costly because research and development (R&D) and clinical trial costs are high. A single new drug molecule is developed for approximately 12 to 15 years, from the time of discovery to the point of commercial availability for patient treatment.
Stages of drug discovery and development include:
- Target identification
The initial phase of drug discovery involves determining the biological cause of a disease and possible targets for treatment. The first step in target identification is determining the function and contribution to the disease of a potential therapeutic target, such as a gene, protein, or nucleic acid. The molecular mechanisms that the target addresses are characterized after the target has been identified. A perfect target would be safe, effective, able to satisfy commercial and clinical needs, and able to be “druggable.” Target identification methods can be grounded in the principles of molecular biology, biochemistry, genetics, biophysics, or other related fields.
- Target validation
The process of certifying the expected molecular target, such as a small molecule’s gene, protein, or nucleic acid, is known as target validation. Target validation includes: determining the structure-activity relationship (SAR) of analogs of the small molecule; generating a drug-resistant mutant of the presumed target; knock down or over-expression the presumed target; and monitoring the known signaling systems downstream of the presumed target.
- Lead identification
A chemical lead is characterized as a drug-like, synthetically stable, and feasible molecule that exhibits acceptable specificity, affinity, and selectivity for the target receptor in primary and secondary assays. Determining the synthetic feasibility, defining the structure-activity relationship, obtaining some preliminary data on in vivo efficacy, and engaging the target are all necessary for this.
- Lead optimization
The process of designing a drug candidate after the identification of an initial lead compound is known as lead optimization. To create a picture of how chemical structure and activity are related in terms of interactions with targets and metabolism, a prospective drug is synthesized and characterized iteratively.
- Product characterization
Any novel drug molecule that exhibits therapeutic potential is identified by its size, shape, strength, weakness, application, toxicity, and biological activity. The earliest phases of pharmacological research are useful for defining the compound’s mode of action.
- Formulation and development
To create a bioavailable, stable, and ideal dosage form for a particular administration route, the physicochemical properties of active pharmaceutical ingredients (APIs) are characterized during the pharmaceutical formulation stage of drug development.
- Preclinical research
In the pre-clinical stage of the drug development process, the safety and effectiveness of the drug are assessed in animal models with the ultimate goal of predicting human outcomes. The corresponding regulatory bodies must also approve the preclinical trials. The regulatory bodies are responsible for making sure that trials are carried out in a morally and safely manner and for only approving medications that have been proven to be both safe and effective. Pre-clinical trials are conducted in two ways. Such as General Pharmacology and Toxicology.
- Investigation new drug
Before starting clinical research, drug developers must submit an Investigational New Drug (IND) application to the Food and Drug Administration (FDA).
- Clinical trials
Volunteers participate in clinical trials aimed at providing targeted answers regarding the efficacy and safety of medications, vaccines, other therapies, or novel approaches to administering existing treatments. Clinical trials adhere to a particular study protocol that the manufacturer, investigator, or researcher designs.
When designing a clinical study, developers take into account the requirements of each of the Clinical Research Phases and initiate the Investigational New Drug Process (IND), which is a prerequisite to starting clinical research. In order to formulate research questions and objectives before the start of a clinical trial, researchers evaluate available data regarding the medication. Clinical trial includes main three phases:
Phase 1 – Studies the safety of medication and treatment on people.
Phase 2 – Studies the safety and effectiveness of people.
Phase 3 – Studies the safety, effectiveness, and dosing on people.
- New drug application
A drug’s complete story is expressed in its New Drug Application (NDA). Its goal is to confirm that a medication is both safe and effective in the subjects it is intended for. A drug developer must include all relevant information in the NDA, from preclinical data to Phase 3 trial data. Reports on every study, piece of data, and analysis must be included by developers.
- Approval
After receiving a fully completed NDA, the FDA team of review may need six to ten months to decide whether to approve the NDA. When the FDA receives an incomplete NDA, the FDA review team will reject the document.
Working with the developer to update prescribing information is crucial if the FDA decides that a drug is safe and effective for the intended use. It’s said that this is labeling. The basis for approval and instructions on how to use the medication are clearly defined on the label. Nevertheless, there are still problems that need to be resolved before the medication is authorized for sale.
In other situations, the FDA requires more research. The developer now has the option of moving forward with development or not. Developers can use official appeal procedures if they are unhappy with an FDA decision.
Phase 4 – Trials are carried out following FDA approval of the medication or device. These studies are also acknowledged as post-marketing surveillance, which includes ongoing technical support and pharmacovigilance following approval. Phase 4 trials employ a variety of observational techniques and assessment patterns to gauge the safety, cost-effectiveness, and effectiveness of participation in real-world contexts.
Reference – https://www.researchgate.net/publication/341097009_The_Stages_of_Drug_Discovery_and_Development_Process
Diagram resource – https://scialert.net/fulltext/?doi=ijp.2017.773.784
