Preclinical Research: The Drug Discovery Process

Drug development is a highly complex, time-consuming, and expensive endeavor. Only a few of the
thousands of compounds synthesized end up being marketed for consumer use. Of the compounds that
do make it to market, development time averages 15 years and development costs can be hundreds of
millions of dollars.

Drug development proceeds in several stages:

y Discovery—New chemical compounds believed to have therapeutic promise are identified.
y Development—During preclinical research, compounds are tested in the laboratory and on animals.
Early development also includes preliminary testing in healthy humans, defined as Phase I and early
Phase II clinical research. Later development includes greater numbers of subjects and is typically
referred to as late Phase II and Phase III clinical research.
y Marketing—Post-marketing studies are conducted for the purpose of expanding the market for drug.
These studies may focus on safety, cost-effectiveness, new indications, and expanded target
populations.

Properties of an Ideal Drug

A drug is a compound or substance other than food that can affect the structure or function of living cells.
The therapeutic objective of a drug is to provide the maximum benefit with minimum harm. When
developing a drug, scientists focus on three primary properties:
y Safety—The drug does not produce harmful effects.
y Efficacy—The drug elicits the responses for which it is given.
y Selectivity—The drug elicits only the responses for which it is given.

Drug Discovery
Drug discovery is the first step in new drug development. It begins with identifying a mechanism of action
that could treat or prevent a disease or identify a new technology that enables the exploitation or control
of a known mechanism of action. The goal of drug discovery is to find and produce chemical compounds
that either arrest mechanisms of disease or achieve other effects identified in research objectives.

Some of the key elements issues that are considered during drug discovery include:
y Is the drug effective in the models that are being used?
y What is the cost of goods needed to produce the drug?
y Can a patent be obtained for the drug?

The discovery process typically involves:

y Identification and validation of a target
y Identification of molecule collections an/or compounds to be screened
y Development of assays for screening compounds
y Screening of compounds for hits
y Identification of lead compounds
y Optimization of lead compounds
y Filing of patent applications

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Summary of Preclinical Research
Preclinical Research

After a lead compound has been identified, its suitability as a drug therapy is evaluated in a series of tests
that focus on toxicology, pharmacokinetics, and metabolism. Preclinical testing focuses on demonstrating
a compound’s drug activity in vitro (test tube or culture media) and in vivo (animals) prior to administration
in man. Preclinical research includes laboratory work and studies to determine the feasibility of
manufacturing the compound in a form that can be administered to humans.

Pharmacology tests are conducted to measure a drug’s activity (pharmacodynamics) and to study the
time course of the drug in the body (pharmacokinetics). In addition, toxicology studies are performed to
evaluate the safety profile of the drug. Preclinical research often continues throughout the drug’s
development.

Research questions that are addressed during preclinical research include:

y How does the dose/concentration relate to the drug’s effect?
y Does the compound have the type of action desired for the intended medical use?
y How is the compound absorbed, distributed, metabolized, and excreted (ADME studies)?
y What are the undesirable effects of the compound?
y Can the compound be manufactured in a dosage form appropriate for humans?

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Summary of Preclinical Research