Throughout history, various methods have contributed to the advancement of public health and quality of life. Of these methods, Drug therapy (pharmacotherapy) has certainly been the major factor in extending our life expectancy. The history of drug research and development is a most important event in the story of man’s triumph over diseases. The arrests of epidemics of life-threatening and widespread infectious diseases, the control of intractable diseases and physiological disorders and genetic illnesses have come under the influence of powerful and relatively safe drug products. It is painful for us to imagine that a century back more than 15 million people in Asia were wiped out by the plague; that the same period every seventh German over age of 16 died of tuberculosis; 20 million people died worldwide from an influenza epidemic in 1918-19; and just six decades ago every second patient with pneumonia succumbed to this disease.
Today in advanced countries a person can, on the average, live twice as long as his great-grandparents, whose life expectancy at the end of the nineteenth century was barely 40 years! This is expected to touch 100 years by 2020. In India, a person born in 1920 could expect to live only 32 years. Today we can expect to live over 69 years and the life expectancy is estimated to cross 78 years by 2021 with improved sanitation and public health along with drug therapy. Public today best recognizes the great achievements of drug research who owe drugs and medicines their good health and frequently even their lives.
New drug development: Since the thalidomide disaster in the 1960’s and following Kefauver-Harris amendments to the FDC Act in 1962, the development of a new drug had to meet increasingly stringent requirements. Federal food and drug administration’s (FDA) approval is required for a new drug to be marketed in the USA and many other countries. Marketing approval in India and most countries depends on the status of the drug in other countries particularly in the USA, Great Britain, and Germany. United States FDA in this regard is considered to be the most thorough in the world. After the discovery of a new chemical entity (NCE) and only when the requisite series of pre-clinical studies (in animals) demonstrate adequate safety, the drug’s sponsor can file an Investigational New Drug application (IND) to the FDA. The total time of drug development from the period of discovery to final approval averages approximately 12 years (depicted in Fig. 1).
At pre-clinical testing stage animal pharmacology and toxicology data are obtained to determine some degree of safety and efficacy of the drug. The clinical testing takes place after submission of the IND application to the FDA. The post-marketing surveillance of drug usage is conducted to detect infrequent but significant adverse effects. The progressive sequence of clinical testing is given in Table 1.
When all the clinical trials are completed, an NDA is submitted to the FDA for review and approval. The resulting prolongation of development times through different steps leads to higher expenditure before a new drug goes to market. Today invention of a new drug and its development costs as high as US$ 1.1 billion at 2011 prices. This cost, however, does not include the cost of numerous failures.
The normal development time for a drug varies between eight and fourteen years (average 12 years). The rule of thumb in search for a new drug: only one out of approximately 10,000 compounds synthesized in the laboratory manages all the obstacles and become a drug. The road to a new drug is long. Even when a chemical entity close to being a marketable drug has cleared all the phases of test and development, there is another cumber- some procedure- the application to the registration authority. The application with thousands of pages of documentation carrying evidence of quality, safety, and efficacy is submitted to legal authority. All these efforts required to solve the equation: – optimal efficacy plus minimal side effects equals a safe drug.
Meanwhile, the question confronting today is one side society’s justified desire to reduce health problems with the use of the drug and the other side its escalating cost resulting from the development of a new drug. FDA approval certifies a drug as safe and efficacious for its labeled indication(s). It doesn’t address the key issue, whether the additional cost associated with possibly only marginal benefits can be justified.
A man has existed for million of years but has been assured of quality drug products and good drug therapy from about 1940’s. Notwithstanding the public, in general, pay more attention to the degree of potential risks and higher cost of a new drug than to its benefit. Drug research is still indispensable. Of roughly 30,000 diseases that we know today, only about 10,000 can be treated pharmacologically, many of them inadequately. In addition the possibility that a drug that is safe today may have to ban tomorrow as a result of new findings. The need of drug research and its development is greater today in face of many incurable diseases and of course the impending worldwide life-threatening catastrophe.