The need for new medicine arises with time as older available medicines lose desirable effect due to tolerance or origination of newer diseases that require advance cure through new medicines. In order to treat a particular disease, it is important to understand the cause behind it. Attributes of disease such as acquiring, transmission and progression needs to be studied. Type of cells that are affected, alteration in genetic factors of diseased cells and the presence or absence of proteins in the affected cells should also be taken into account. In the case of infectious diseases, the characteristics of microorganisms and its replication in the human body requires thorough knowledge and understanding.
In modern day laboratory set ups, sophisticated tools are used for shedding light on above concerns. The tools are designed to discover the molecular roots of disease and pinpoint critical differences between healthy cells and diseased cells. By determining the molecular defects behind a particular disease, scientists can identify the best targets for new medicines. In some cases, the best target for the disease may already be addressed by an existing medicine, and the aim would be to develop a new drug that offers other advantages. Although, drug discovery aims to provide an entirely new type of therapy by pursuing a novel target.
Gathering data on disease progression-
Amongst different models of studying a disease, cell cultures help studying diseased and healthy cells and differences in cellular processes and protein expression. Cross species studies are done in which genes and proteins that are found commonly between humans and other species. Function of these human genes are revealed to be parallel with other organisms. Bioinformatics is a field of biotechnology that is associated with biology and information technology. It aids in better assessment of disease. Biomarkers are protein substances used for measuring biological function, identifying disease processes or determining response to a therapy. They also have diagnostic applications. Proteomics is the study of protein activity within a given cell, tissue or organism. A change in protein activity can provide information on the disease process and the impact of medicines under study.
After crucial analysis of the disease in question, a target is selected or identified, which is supposed to have an effect by a novel intervention. For instance, cholesterol lowering drugs target enzymes that are involved in production of cholesterol. Antibiotics are designed to target specific proteins that are critical for survival of bacteria. Scientists and researchers estimate there are about 8,000 potential therapeutic targets that might provide a basis for developing new medicines. Most of them are proteins of various types, including enzymes, growth factors, cell receptors, and cell-signalling molecules. Some targets are present in excess during disease, so the goal is to block their activity which is achieved by developing a medicine that binds to the target and prevents it from interacting with other molecules in the body. On the other hand, the target protein is deficient or missing, and the goal is to enhance or replace it in order to restore healthy function. Advancements in the field of biotechnology have made it promising, to create therapies that are similar or identical to the complex molecules the body depends on to remain healthy. It is essential for researchers to prove the validity of a particular target through establishing its role in disease progression. The key is to demonstrate that the activity of the target is running the course of the disease.
Once the target has been selected, the next step is to identify a drug that impacts the target in the desired way. Multiple chemical compounds can be studied simultaneously with a technology called drug screening. With automated systems, scientists can rapidly test thousands of compounds to observe the ones that interfere with the target’s activity. Potential compounds can be put through added tests to find a lead compound with the best potential to become a drug.
Collecting preclinical data
Once a promising test drug has been identified, it must go through extensive testing before it can be studied in humans. This testing for analysing safety of a drug constitutes preclinical studies. Many drug safety studies are performed using cell lines engineered to express the genes that are often responsible for side effects. Cell line models have decreased the number of animals needed for testing and have helped accelerate the drug development process. Some animal tests are still required to ensure that the drug doesn’t interfere with the complex biological functions that are found in humans.
Clinical phases of drug testing
If a test drug has no serious safety issues in preclinical studies, researchers can seek permission from regulatory authority to perform clinical trials in humans. There are three phases of clinical studies which are executed in the form of clinical trials, and the new drug is required to meet certain criteria before moving on to the next phase.
Phase 1: Tests in 20 to 100 healthy volunteers and under special circumstances, patients. The main goals are to assess safety and tolerability and explore the behaviour of the drug in the body. Half-life of the drug is estimated.
Phase 2: Studies in about 100 to 300 patients. The goals are to evaluate the efficacy of the drug, calculate dosage based on data from preclinical studies and to explore the safety index of the drug.
Phase 3: Large studies involving 500 to 5,000 or more patients, depending on the disease and the study design. Large scale trials are often needed to determine if a drug can prevent negative outcomes on a patient’s health. The goal is to compare the effectiveness, safety, and tolerability of the test drug with standard drug or a placebo.
If the test drug shows clear benefits and acceptable risks in phase 3, the company can file an application requesting regulatory approval to market the drug. In India, the Central Drugs Standard Control Organisation, CDSCO, is governed by the Directorate General of Health Services, Ministry of Health & Family Welfare, MoHFW. Regulators review data from all studies conducted and make a decision whether the benefits of the medicine outweighs the risks it may have.
New drug launch in the market
Post approval for marketing of the new drug, routine monitoring is required up till 5 years which is called Pharmacovigilance or Post marketing surveillance. It is Phase 4 of clinical studies. A pharmaceutical company can also continue its clinical trials on an approved drug to spot its effects under other specific conditions (alternative use) or in other groups of patients, and additional trials may also be required by regulatory agencies.
The whole drug development process from drug discovery till marketing approval takes 10 to 18 years to complete on average with high expenses going up to 1.3 billion USD. Only a limited number of drugs are able to achieve success through each phase. Hence, developing a new drug is an extensive process and the time, money and effort that goes behind it stands high for superior quality drugs becoming available in the market.