The discovery of new medically active compounds historically began with the identification of substances found in traditional remedies that were known to produce noticeable health benefits. An example is the use of willow for pain relief. This remedy was used in Egypt as long ago as the second millennium BC. The medically active compound, acetylsalicylic acid, was first isolated in 1853. Modern research has led to a deeper understanding of the mechanisms that make plants such a rich source of beneficial compounds. These include the chemical response of plants to interaction with animals or to environmental stress.
Once a potential source of medically active compounds is found, a process referred to as “bioassay” is undertaken. This pharmacological evaluation identifies substances likely to be responsible for health benefits and measures the quantity in which they are found in the test material. Bioassay determines whether the medically active compounds can be used as they occur naturally, perhaps increasing their potency by concentration, or if further chemical manipulation is needed to separate out potentially beneficial molecules. It also aims to elucidate the way in which these compounds work both chemically and biologically, in order to establish exactly how the substance creates the observed medicinal effect.
Having identified candidate substances and assessed their modes of action, the next stage in the development of a new treatment is to test the active substances in the laboratory. Both potentially harmful and potentially beneficial effects must be measured, as well as the concentrations at which these effects are observed. Typical laboratory tests might include an assessment of the rate at which substances are absorbed by the blood, how they are broken down within cells or how long they persist within the body. This process must be comprehensive and thorough, laboratory testing is a lengthy process typically taking more than three years to complete.
Approximately one in every thousand compounds will pass the laboratory testing process and be considered suitable for the next stage known as clinical trials. At this stage, substances identified in the laboratory as potentially safe and effective treatments are tested on human subjects. In order to be tested on humans, approval must first be sought from the US Food and Drug Administration (FDA). Depending on the drug being tested and the stage of development, testing usually begins on a small pilot group of volunteers or patients. Once the substance has been judged to be safe for this small group, the trial is expanded to include larger numbers of individuals. The two aims of clinical trials are to test the safety of the new compound and to test its efficacy. The drug must be deemed safe to use, with minimal unwanted effects on patient health and it must be effective against the condition it aims to treat. Clinical trials will also establish the ideal frequency and dose to maximise health benefits for patients. The trials usually include a follow-up period of out patient visits, to monitor how the new drug is metabolized and how long it stays in the system.
Having undergone many years of rigorous testing and assessment, all the relevant data is submitted go the FDA for final approval. A team of specialist scientist, including statisticians, pharmacologists, chemists and doctors carefully assess all the available information on the new compound. When the team are satisfied that the drug is safe and effective, it is approved and released to the global market for sale.
About the Author: This article was written by Nick Davison for Covance, a global leader in clinical research and medical trials.