The modern process of bringing a new drug to market can be broken down into two distinct components: drug discovery and drug development. Small molecule drug discovery is the process of inventing a novel compound, understanding the protein target/compound interaction, and how the compound is biologically processed; known as drug metabolism and pharmacokinetics (DMPK). Drug development is the process of testing the drug in human clinical trials. Preclinical testing is the final process of discovery, and can overlap somewhat with development, but generally the transition from discovery to development occurs when an initial new drug application (IND) is filed with the FDA and accepted. A precursor to human clinical trials.
Although research into existing drugs can turn up new targets or indications (e.g. Viagra), this is happening less frequent today. Drug discovery should be called drug invention, as drugs are seldom discovered serendipitously in a natural state anymore. Instead they are created and engineered in a painstaking process of first identifying a protein target to modulate. Then using high throughput screening, of up to millions compounds, to find those with activity against the target. Hits or leads are then screened further using techniques like cell based assays and protein x-ray crystallography, to gain a more full understanding of the mechanism of action and related pathways. Resulting compounds are optimized by medicinal chemists for enhanced modulation of the target; those not meeting standards are discarded throughout the processes. And finally, methods to understand DMPK are employed, and the compound goes through preclinical testing in animal models. At this stage, the drug is handed off to drug development, an IND is filed, and if accepted, human clinical trials commence; even as longer term animal studies continue and help guide the clinical trials. For large molecule or biologic therapies, some discovery process components differ, but the development process is essentially unchanged.
Drug development is generally composed of four parts: phases I-III clinical trials and post market surveillance, sometime referred to as a Phase IV trial. Phase I trials use tens of people and primarily test drug safety and some drug activity; pharmacokinetics and absorption. Phase II trials test for short term side effects, optimize dosing, and utilize up to hundreds of people. Phase III trials are long, large trials of thousands of people, looking for efficacy and adverse events; is the drug safe and effective? After a phase III trial a new drug application (NDA) can be filed with the FDA, which will then analyze the cumulative data, from target research through the phase III clinical trial, before approving the drug. After reaching the market, the FDA may request further, longer term trials, or trials for a specific population subset or demographic. At a very minimum the FDA will require continued safety monitoring be filed on the drugs behalf.
Hughes J.P., Rees S., Kalindjian S.B., Philpott K.L. (2011). Principles of Drug Discovery. Br J Pharmacol. 2011 Mar;162(6):1239-49. doi: 10.1111/j.1476-5381.2010.01127.x
Video:Drug Discovery | PhRMA. (n.d.). Retrieved October 24, 2016, from http://phrma.org/video/drug-discovery
New Medicines. New Hope. - JA Online. (n.d.). Retrieved October 24, 2016, from http://www.ja-online.com/industry/Module2Cost_of_Prescription_Drugs.pdf
Robert Fawcett September 1, 2020