The medications and drugs you see in your bathroom medicine cabinet and in your local pharmacy have taken a long journey to get there, from their initial origins in the laboratory to approval by the U.S. Food & Drug Administration (FDA), and finally, marketing to consumers. This article, the first in a series, will describe the processes of drug discovery, drug development and pre-clinical research.
How the Drug Development Process Begins
Out of 1,000 to 5,000 initially tested drugs, only five will make it to clinical trials in human patients. Researchers in the research and development sector of pharmaceutical companies tend to begin by casting a wide net, screening large libraries of molecular compounds to find potential candidates, which may have beneficial effects on various diseases.
New ideas for drug design may also come from studies of disease mechanisms or the development of new technologies, allowing improved drug delivery in the body.
Once promising compounds are identified, researchers work to characterize their various properties. These include how the drug is absorbed and excreted, its potential mechanism of action, the optimal dosage (which requires balancing the benefits and the toxicity — also known as side effects), and drug interactions and efficacy compared to other drugs.
At this step, the majority of candidate compounds will be eliminated while approximately 250 will go on to pre-clinical studies.
The main function of pre-clinical studies is to determine whether a drug is safe to give to human patients in the clinical trials. A series of experiments are conducted to determine drug efficacy and toxicity.
Pre-clinical studies are required to be done both in vitro (literally meaning “in glass,” or in a test tube) and in vivo (in a living organism, which could be in cell culture or in an animal model). Generally, animal studies required the drug to be tested in at least two different mammalian species.
The first of these studies are acute studies, where drug toxicity is determined for an acute treatment with the drug over a 24-hour period. These may be followed by repeated dose studies, where the dose determined in the acute toxicity studies is administered over a longer period.
Genetic toxicity studies are conducted to determine whether the drug will cause mutations. Reproductive toxicity studies are required for drugs that will be given to women of child-bearing age; here, researchers determine the effects the drug may have on fertility, embryo and post-natal development.
There are a plethora of other studies that may be called for, depending on the kind of drug being tested. These studies need to be designed to mimic the anticipated clinical trials.
Final Steps Before Taking a Drug to Trial
If favorable results are obtained in the pre-clinical studies, the researchers may move on to the final step before beginning clinical trials in patients — submitting an Investigational New Drug (IND) application to the FDA.
This application requires the investigators to submit data from the animal pharmacology and toxicology studies, information on how the drug is to be manufactured, and protocols on how the clinical trials are to be conducted, as well as how the investigators will follow regulations for working with human subjects.
Upon submission of this application, the investigators allow 30 days for the FDA to review the IND. After this, clinical trials can begin.
Despite the long path taken to get to this step, there is no guarantee that drugs even at this point will eventually make it to market.
As of this writing, Elena Shuvaeva did not hold a position in any of the aforementioned securities.