From Laboratory to Medicine Cabinet

Aniket Keshav Sharma

Man has made significant advances in medicine throughout the course of human history. The ancient Greek physician Hippocrates is known as the Father of Medicine, and doctors even today swear an oath known as the Hippocratic Oath, which requires them to save lives and heal the sick. However, modern medicine as we know it acquired its present form beginning in the nineteenth century. Have you ever wondered about the journey that a pill, tablet or injection takes before reaching the patient? You may be surprised to know that it is a long process that can take well over a decade! It all starts with a process known as drug discovery. In the past, medicines were discovered by the direct use of natural substances like plants and herbs, or by accident as in the case of the discovery of penicillin by Alexander Fleming in 1928. However, today scientists specifically test a variety of naturally occurring as well as chemically synthesized substances for their medicinal properties. This process is called drug discovery, and major pharmaceutical companies like Pfizer, Roche, Sanofi, Novartis, and GlaxiSmithKline spend billions of dollars each year on discovering new drugs. Despite the best efforts of the industry, the rate of identification of new drugs remains low, and it often takes years of screening to identify useful substances. An arduous task indeed! Once the medicinal activity of a new discovery, known as a new chemical entity (NCE), is established, its properties must be studied and analyzed further. Scientists study whether the NCE is stable, in what forms it is medicinally active, is it safe to use or does it

present any dangers, and many other issues. These investigations are collectively known as pre-clinical studies. One of the most important and also most debated aspects of pre-clinical studies is testing of NCEs on animals. Mice, dogs, pigs, as well as apes are used for testing of NCEs. Such testing is necessary to determine whether the drug will be safe within a living environment, and what the form of administration should be. However, in recent years, through the development of alternate methods like testing on cultured tissue, the amount of animal testing required has been reduced. Once pre-clinical studies are concluded, the pharmaceutical company developing the NCE must apply for permission to test the NCE on human beings. Since human lives are at stake, various governmental bodies control and supervise the testing process: y y y US: Food and Drug Administration (FDA) EU: European Medicines Agency (EMA) India: Drugs Controller General (DCGI)

The process of conducting tests of NCEs on human beings is known as a clinical trial. The government body will only grant permission for a clinical trial if it is convinced that the drug being tested is safe and non-toxic. In recent years, the DCGI has rightly adopted a strict stance while granting permissions for clinical trials. Once permission is received, the clinical trial is organized and conducted. The results help scientists understand the following: y y y Effectiveness of the drug in the disease or medical condition Ideal dosages Methods of administration (tablet, injection, capsule, or other method)

Whether the drug should be used on its own or in combination with other means of treatment Whether there are any side-effects of the drug (in medical terminology, these are known as adverse events)

Note that clinical trials are conducted using both healthy volunteers, as well as patients who are actually suffering from the disease or medical condition. A clinical trial is a complex event which takes place in multiple phases: y Phase I: The drug is tested on healthy volunteers to study how the human body reacts to the drug. Phase II: Low dosages of the drug are given to a small number of patients to study its effects. Phase III: Normal dosages are given to a large number of patients to see its effectiveness in treating the disease.

Marketed medicines are usually of two kinds: over the counter (OTC) or controlled. OTC drugs can be purchased from pharmacies without a doctors advice. Common medications for headache, fever, cough and cold, etc. are usually in this category. Controlled drugs can only be given to patients on the advice of a doctor. This advice is known as a prescription. Therefore, controlled drugs are also known as prescription drugs, and most medicines for serious ailments fall into this category. Now that you have understood the process of bringing a medicine into your medicine cabinet, I am sure you will appreciate the efforts of the scientists, chemists, doctors, nurses and other people involved in this process. But wait, the story does not end there. Even after the drug has been approved for sale, the process continues. This is known as Pharmacovigilance or Post-Marketing Surveillance, wherein the safety and effectiveness of the medicine is continuously assessed in real patients for a number of years. Therefore, it will be clear that the entire process from drug discovery to Pharmacovigilance is designed to ensure patient safety, good health, and the eradication of disease it is highly regulated and subject to the strictest controls by the government. It is humanitys fervent hope that this methodical approach to treating disease will ultimately lead to healthier, happier, and longer lives!

At all times, clinical trials are monitored by qualified and experienced doctors, who ensure that the primary aim is patient safety and health. Once the clinical trial is concluded, the results are written down and reports prepared in a particular format. These reports are submitted to the government body in-charge, which in India is the DCGI. The government body then studies the reports and decides whether to approve the drug for sale within the country or region of its authority. In case a drug is not shown to be greatly effective during the clinical trial or there are very serious side effects, the government body may refuse to grant approval to the drug. In this case, the pharmaceutical company which manufactures the drug cannot sell it in the market. However, in case the body gives its approval, the pharmaceutical company begins marketing the drug.