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Drug Design and Development

By

Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Last full review/revision Jul 2019| Content last modified Jul 2019
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Many of the drugs Overview of Drugs A drug is defined by U.S. law as any substance (other than a food or device) intended for use in the diagnosis, cure, relief, treatment, or prevention of disease or intended to affect the structure... read more in current use were discovered by experiments conducted in animals and humans. However, many drugs are now being designed with the specific disorder in view. Abnormal biochemical and cellular changes caused by disease are identified, and then compounds that may specifically prevent or correct these abnormalities (by interacting with specific sites in the body) can be designed. When a new compound shows promise, its structure is usually modified many times to

Ideally, a drug is

Stages of Drug Development

Early development

After a drug that may be useful in treating a disorder is identified or designed, it is studied in laboratory animals (a phase called early development). Early development gathers information about how the drug works, how effectively it works, and what toxic effects it produces, including possible effects on reproductive capacity and the health of offspring. Many drugs are rejected at this stage because they are shown to be not effective or too toxic.

If a drug seems promising after early development, a program describing the clinical study must be approved by an appropriate institutional review board (IRB) and an investigational new drug (IND) application is filed with the Food and Drug Administration (FDA). If the FDA approves the application, the drug is allowed to be tested in people (a phase called clinical studies).

Clinical studies

These studies occur in several phases and only in volunteers who have given their full consent.

  • Phase 1 evaluates the drug's safety and toxicity in people. Different amounts of the drug are given to a small number of healthy, young, usually male people to determine the dose at which toxicity first appears.

  • Phase 2 evaluates what effect the drug has on the target disorder and what the right dose might be. Different amounts of the drug are given to up to about 100 people who have the target disorder to see whether there is any benefit. Just because a drug is effective in animals in early development does not mean it is effective in people.

  • Phase 3 tests the drug in a much larger (often hundreds to thousands) group of people who have the target disorder. These people are selected to be as similar as possible to the people who might use the drug in the real world. The drug's effectiveness is studied further, and any new side effects are noted. Phase III tests usually compare the new drug against an established drug, a placebo, or both.

In addition to determining a drug's effectiveness, studies in people focus on the type and frequency of side effects and on factors that make people susceptible to these effects (such as age, sex, other disorders, and the use of other drugs).

Approval

If studies indicate that the drug is effective and safe, a new drug application (NDA)—including data from the animal and human tests, intended drug manufacturing procedures, prescribing information, and product labeling—is filed with the FDA, which reviews all the information and decides whether the drug is sufficiently effective and safe to be marketed. If the FDA approves, the drug becomes available for use. The whole process usually takes about 10 years. On average, only about 5 out of 4,000 drugs studied in the laboratory are studied in people, and only about 1 out of 5 drugs studied in people is approved and prescribed.

Each country has its own approval process, which may be different from the process in the United States. Just because a drug is approved for use in one country does not mean that it is available for use in another country.

Phase 4 (postmarketing)

After a new drug is approved, the manufacturer must monitor the use of the drug and promptly report any additional, previously undetected side effects to the FDA. Doctors and pharmacists are encouraged to participate in the ongoing monitoring of the drug. Such monitoring is important because before the drug is marketed, even comprehensive studies can detect only relatively common side effects (that occur about once in every 1,000 doses). Important side effects that occur once in every 10,000 (or more) doses can be detected only when a large number of people use the drug, that is, after it is on the market. The FDA may withdraw approval if new evidence indicates that a drug may cause severe side effects. For example, the diet aid fenfluramine was withdrawn from the market because some people who took it developed serious heart disorders.

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Genetic Makeup and Response to Drugs
Which of the following is described as the study of genetic differences in the response to drugs? 
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