A new drug, also called innovative or original drug is studied on average between 10 and 15 years from the preparation of active substances, generally called “active pharmaceutical ingredients.” The drug discovery begins with the identification of a mechanism or a series of biological mechanisms that lead to illness or disability. To modulate this deficiency in whole or in part, scientists synthesize chemical molecules or biological substances to be tested to confirm their activity on the identified mechanism. From an active pharmaceutical ingredient synthesis, a patent is filed in various national and international organizations around the world, especially in developed countries, to protect the invention of a new drug. In most countries, the duration of the period of exclusivity of these patents is 20 years. For synthetic drugs, tens of thousands of molecules are created and tested in the laboratory. Finally only the few most promising compounds will be retained. A single molecule become the commercial drug. On average, one molecule out of 10,000 molecules tested, becomes a drug. Each active pharmaceutical ingredient is first tested in the laboratory. Then it is tested on animals. Finally, the metabolism, the exposure dose, the safety and efficacy of the new drug is assessed and tested on humans. The tests on animals determine the safety profile and benefits versus the risks of future drug before giving it to human beings. Once the profile of the benefits versus the risks of a new drug is considered favorable by the pharmaceutical company that developed the drug and by regulatory agencies worldwide, the drug can be studied in humans following well-defined clinical phases. Three clinical phases are needed to test the drug in humans. During the clinical phase I, the drug is studied in a battery of clinical studies on groups of 20-100 people, usually on healthy volunteers to determine its absorption, distribution, metabolism and excretion. This allows to know the effect of drug in the body and body effect on the drug. Some drugs known to be toxic by nature, such as anticancer drugs, are not studied in healthy volunteers and can be tested directly on patients. The clinical phase II is to ensure that the drug has the desired effect in sick humans. At this stage of development, scientists determine the optimal dose of the drug and its possible adverse events on a population of fewer than 500 patients on average. Phase II clinical trials are divided into 2 phases IIa and IIb. Phase IIa considers the effectiveness of the molecule on a limited number of 100 to 200 similar patients to avoid that too much diversity makes too much variability to measure the effectiveness of the new drug. Phase IIb determine the therapeutic dose of the molecule on a larger scale of at least 100 to more than 300 patients. The true test to determine if the drug will be approved by regulatory agencies are studies Phase III or “pivotal studies” which are the comparative effectiveness studies themselves. Clinical Phase III comparing the new treatment with either a placebo or a standard treatment. Comparison to a standard treatment, when it exists, is increasingly preferred by regulatory agencies. In Clinical Phase III studies as well as in Clinical Phase II studies, patients and physicians usually ignore whether the patient receives the experimental drug, a dose it receives, or if it receives a placebo or a standard treatment. These clinical studies are called double-blinded studies. Patient cohorts are large, often several thousands, even tens of thousands of patients. Unlike Phase II, Phase III studies are in cohorts of patients who are more similar to patients in the general population. However, strict criteria applies for the inclusion of participants or not in the studies. The costs associated with this phase are very high. Given the financial interests and risks, pharmaceutical companies, regulatory agencies and ethics committees must pay greater attention to avoid ethical drifts that have been sometimes observed in certain programs. These Clinical Phase III studies will determine the usage of the new product, which is also called the indication of a drug product listed on the label of the product. Clinical Phase IV or post-marketing studies are the long-term monitoring of a new treatment after the new drug is authorized and marketed. This is a true test under “real life” of the drug. Clinical Phase IV studies can be used to detect rare adverse events or late complications related to the use of a product. Clinical Phase IV is also used to validate the prescriber patterns and patient’s compliance in the use of the product. Therefore, the development of a new drug not only requires the collaboration of a multidisciplinary team but also a lengthy regulatory approval process by Regulatory Agencies around the world as well as approval of independent research and ethical committees for clinical studies. During each clinical or non-clinical phase, the future drug must meet strict criteria. It is estimated on average between 6 and 7 years the time required to develop a new drug in clinical trials. When a new drug is finally on the market, it remains on average 10 years of a patent life for the pharmaceutical firm that has developed, to market it exclusively. Throughout the development of the drug, formulation, or simply, the recipe of the new drug is refined as to reach a final recipe at the time of a new drug submission, which is reviewed and approved by regulatory agencies. The product to be marketed is the same as the one that was used in Clinical Phase III. All parameters that influence the quality of the drug must be studied. These include the source and quality of the active pharmaceutical ingredient, its stability, the source and the quality of the excipients, primary packaging containers, the effect of temperature and humidity on the drug, including temperatures extreme temperature and humidity that may prevail during transit and during transportation, the effect of light on the drug, etc. The final result is a scientific and technical dossier prepared by the pharmaceutical company developing the new drug. This dossier is submitted to regulatory authorities around the world for registration. It takes between 1 and 2 years for regulators to make the final decision to either approve or to deny the approval of the new drug. A formal process of interaction by face to face meetings and written communications between regulatory agencies and the pharmaceutical company is required before regulatory agencies such as Health Canada make a final decision. After this process, the drug is either approved or denied. In some cases, regulatory agencies may require additional clinical studies before approving the drug. Once approved, the drug should be not only used but also manufactured, stored and distributed within the parameters, for which the drug was approved. Any changes that may affect these parameters must be approved by regulatory agencies before being implemented. This article was prepared and edited by Dr. Jean-Pierre Metabanzoulou, Ph.D., MBA. He holds a Ph.D. in Chemistry from the University Louis Pasteur of Strasbourg in France, and a Master of Applied Chemistry from the same University. He also obtained a Master in Business Administration at Queen’s School of Business in Kingston, in Canada. He did his postdoctoral studies at the Institute of Inorganic Chemistry and Analytical, ICMA, of the University of Lausanne in Switzerland. After a short academic career, Dr. Metabanzoulou works for over 20 years now in the pharmaceutical industry in the private sector both for the innovative pharmaceutical industry and generic in Canada, in Switzerland, in France as well as in Africa.
How does a drug discover and what are the different stages leading to its commercialization?
By Jean-Pierre Metabanzoulou|2020-05-23T09:34:51-05:00May 13th, 2015|Health & Wellness|Comments Off on How does a drug discover and what are the different stages leading to its commercialization?