Preclinical Research

In this phase, chosen compounds are studied to determine their bioavailability, absorption, distribution, metabolism, and elimination. The necessary tests are carried out in cells and in animals to establish preclinical parameters for safety and efficacy.

Under FDA requirements, a sponsor must first submit data showing that the drug is reasonably safe for use in initial, small-scale clinical studies. Depending on whether the compound has been studied or marketed previously, the sponsor may have several options for fulfilling this requirement:

Compiling existing nonclinical data from past in vitro laboratory or animal studies on the compound.

Compiling data from previous clinical testing or marketing of the drug in the United States or another country whose population is relevant to the U.S. population.

Undertaking new preclinical studies designed to provide the evidence necessary to support the safety of administering the compound to humans.

During preclinical drug development, a sponsor evaluates the drug's toxic and pharmacological effects through in vitro and in vivo laboratory animal testing. Genotoxicity screening is performed, as well as investigations on drug absorption and metabolism, the toxicity of the drug's metabolites, and the speed with which the drug and its metabolites are excreted from the body. At the preclinical stage, the FDA generally asks, at a minimum, that sponsors: (1) develop a pharmacological profile of the drug; (2) determine the acute toxicity of the drug in at least two species of animals; and (3) conduct short-term toxicity studies ranging from two weeks to three months, depending on the proposed duration of use of the substance in the following proposed clinical studies:

Synthesis and purification. The research process is complicated, time-consuming, and costly; and the end result is never guaranteed. Hundreds and sometimes thousands of chemical compounds must be made and tested in an effort to find one that can achieve a desirable result.

The FDA estimates that it takes approximately eight and a half years to study and test a new drug before it can be approved for the general public. This estimate includes early laboratory and animal testing, as well as later clinical trials using human subjects.

There is no standard route through which drugs are developed. A pharmaceutical company may decide to develop a new drug aimed at a specific disease or medical condition. Sometimes, scientists choose to pursue an interesting or promising line of research. In other cases, new findings from university, government, or other laboratories may point the way for drug companies to follow with their own research.

New drug research starts with an understanding of how the body functions, both normally and abnormally, at its most basic levels. The questions raised by this research help determine a concept of how a drug might be used to prevent, cure, or treat a disease or medical condition. This provides the researcher with a target. Sometimes, scientists find the right compound quickly, but usually hundreds or thousands must be screened. In a series of test tube experiments called assays, compounds are added one at a time to enzymes, cell cultures, or cellular substances grown in a laboratory. The goal is to find which additions show some effect. This process may require testing hundreds of compounds as some may not work, but will indicate ways of changing the compound's chemical structure to improve its performance.

Computers can be used to simulate a chemical compound and design chemical structures that might work against it. Enzymes attach to the correct site on a cell's membrane, which causes the disease. A computer can show scientists what the receptor site looks like and how one might tailor a compound to block an enzyme from attaching there. But even though computers give chemists clues as to which compounds to make, a substance must still be tested in a living being.

Another approach involves testing compounds made naturally by microscopic organisms. Candidates include fungi, viruses, and molds, such as those that led to penicillin and other antibiotics. Scientists grow the microorganisms in what is known as a fermentation broth, with one type of organism per broth. Sometimes, 100,000 or more broths are tested to see whether any compound made by a microorganism has a desirable effect.

Animal testing. In animal testing, drug companies make every effort to use as few animals as possible and to ensure their humane and proper care. Generally, two or more species (one rodent, one nonrodent) are tested because a drug may affect one species differently from another. Animal testing is used to measure how much of a drug is absorbed into the blood, how it is broken down chemically in the body, the toxicity of the drug and its breakdown products (metabolites), and how quickly the drug and its metabolites are excreted from the body.

Project Management Made Easy

Project Management Made Easy

What you need to know about… Project Management Made Easy! Project management consists of more than just a large building project and can encompass small projects as well. No matter what the size of your project, you need to have some sort of project management. How you manage your project has everything to do with its outcome.

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