Steps and stages of new drug development

New drug discovery research starts with the discovery and confirmation of drug targets, followed by screening using various screening libraries like activity-based libraries, fragment libraries and design, optimization of lead compounds, and finally confirmation of candidate compounds for preclinical research. New drug development research is to verify whether the candidate compounds for preclinical research are safe, effective, and stable, which can be further divided into two parts: preclinical research and clinical trials. Preclinical research starts with study of drug quality and evaluation of pharmacodynamics, drug metabolism, and drug safety, so as to screen clinical candidate new drugs with safe, effective and controllable quality for clinical trials. The clinical trial is divided into four phases. Once all finished, the new drug development is finally completed and approved for marketing. 

The first pharmaceutical companies originated in Europe. But in recent decades, American pharmaceutical companies have surpassed their counterparts in Europe to become the industry leader owing to the discovery of potent chemical drugs and their leading role in innovative drug development. 

New drugs can be sourced from natural products, semi-synthesis and total-synthesis of natural products, semi-synthetic and fully synthetic chemicals. In the past, the main method of drug selection relied much on practical experience. Now it is possible to find close relatives for screening based on the plant taxonomy of effective drugs or to infer from the relationship between the chemical structure of effective drugs and pharmacological activity, and then synthesize these targeted products, and finally to perform pharmacological screening. In recent years, DNA genetic recombination technology has been used to obtain disease-resistant substances. By this technology, the specific gene segments of DNA are separated and implanted into rapidly growing bacteria or yeast cells, and at last, a large number of required protein drugs are obtained. In addition, chemical structures can be modified (semi-synthesized) or the dosage forms of existing drugs can be changed to obtain drugs with better curative effect or less toxicity.

As mentioned above, the research process of new drugs can be roughly divided into three steps, namely preclinical research, clinical research and after-sales research. Preclinical studies include systematic pharmacological studies with animals and observation of acute and chronic toxicity. For drugs with selective pharmacological effects, it is necessary to determine the absorption, distribution, and elimination process of the drug in animals before conducting clinical trials. Pre-clinical research is to find out the spectrum of action and possible toxicity of new drugs. Clinical trials can only be conducted after preliminary approval by the drug regulatory authority. The purpose is to ensure medication safety.

In clinical research, researchers first observe the tolerance of the new drug among 10 to 30 normal adult volunteers and found a safe dose, then select patients with specific indications by random grouping, setting up double-controls with known effective drugs and placebos. Double-blind method observation is needed, and finally researchers can perform statistical analysis of treatment results to objectively judge the efficacy of the new drug. At the same time, blood concentration monitoring and calculation of pharmacokinetic data are required. The number of tested cases should generally not be less than 300, and it can be expanded to more than three medical units for multi-center cooperative research in a hospital. For those new drugs that require long-term medication, there should be an observation record of 50 to 100 patients accumulating medication for six months to one year. Based on this, indications, contraindications, dosage courses, and possible adverse reactions are formulated, and then subjected to the pharmaceutical administration department’s approval before production and marketing.

It takes an average of 12 years for a drug to go from initial laboratory research to final sales in a medicine cabinet. Only 5 of the 5,000 compounds undergoing preclinical trials can enter subsequent clinical trials, and of these 5 compounds, only 1 of these compounds can be finally approved for marketing. All proved that new drug development is a time-consuming and costly process with extremely low success rate.