Drug Approvals - From Invention to Market ... A
In the United States, it takes an average of 12 years for an
experimental drug to travel from the laboratory to your medicine
cabinet. That is, if it makes it.
Only 5 in 5,000 drugs that enter preclinical testing progress to
human testing. One of these 5 drugs that are tested in people is
The chance for a new drug to actually make it to market is thus only
1 in 5,000. Not very good odds.
The process of drug approval is controlled in most countries by a
governmental regulatory agency. In the U.S., the Food and Drug
Administration (FDA) governs this process. The FDA requires the
following sequence of events before approving a drug.
- Preclinical Testing: A pharmaceutical company conducts
studies before the future drug is ever given to a human being.
Laboratory and animal studies must be done to demonstrate the
biological activity of the drug against the targeted disease. The
drug must also be evaluated for safety. These tests take on the
average 3 1/2 years.
- Investigational New Drug Application (IND): The
pharmaceutical company files an IND with the FDA to begin testing the
drug in people. The IND becomes effective if the FDA does not
it within 30 days. The IND must include the following information:
the results of previous experiments; how, where and by whom the new
studies will be conducted; the chemical structure of the compound;
how it is thought to work in the body; any toxic effects found in the
animal studies; and how the compound is manufactured. The IND must
also be reviewed and approved by the Institutional Review Board where
the studies will be conducted.
- Phase I Clinical Trials: Phase I studies are usually the
first tests of a drug under development in
healthy volunteers. These studies involve about 20 to 80 volunteers.
The tests determine a drug's safety profile, including the safe
dosage range, plus how the drug is absorbed, distributed, metabolized
and excreted, and the duration of its action. Phase I trials take on
average 1 year.
- Phase II Clinical Trials: These are slightly larger
studies that are done in patients with the disease for which the drug
intended. This phase is usually designed to identify what are the
minimum and maximum
dosages. The trials generally involve 100 to 300 volunteer patients
and are controlled in design. They are done to assess the drug's
effectiveness. Phase II typically takes about 2 years.
- Phase III Clinical Trials: These are the definitive, large
randomized trials that are submitted
to the FDA in order to obtain approval of a drug. This phase examines
effectiveness as well as the safety (adverse events) of the new drug.
Phase III trials usually
involve 1,000 to 3,000 patients in clinics and hospitals. Patients
are usually asked a list of possible side
effects, often derived from what was observed in phase II studies.
Patients are also free to report any other side effects that occur
while they are on the new drug or the placebo (the "sugar pill" that
is given to a percentage of patients in a trial study). Phase III
takes on the average 3 years.
- New Drug Application (NDA): Following the Phase III
Clinical Trials, the drug manufacturer analyzes all the data from the
studies and files an NDA
with the FDA (provided the data appear to demonstrate the safety and
effectiveness of the drug). The NDA contains all of the data gathered
to date about the drug. (An NDA typically consists of at least
pages.) The average NDA review time for new drugs approved in 1992
was close to 30 months (2 1/2 years).
- Phase IV Studies: Phase IV is any organized collection of
data from patients who are taking a drug that has already received
approval from the FDA. In Phase IV studies, patients may check boxes
on a list (as in phase III
studies) or they may just report other symptoms. Phase IV studies are
commonly called "post-marketing studies."
Although there are other routes that can expedite the process
(referred to as fast-tracking), this is the usual journey for a drug
from invention to market in the U.S.
Last Editorial Review: 7/14/1999 6:57:00 AM