New Medicines: In Development for Children

DRUG DEVELOPMENT AND APPROVAL PROCESS
It takes 12 years on average for an experimental drug to travel from lab to medicine chest.
Only five in 4,000 compounds screened in preclinical testing make it to human testing.
One of these five tested in people is approved.

YEARS

Preclinical
Testing
3.5

Phase

Phase
II

Phase
III

Test j Laboratory and
Population Animal Studies

O
% of all
new drugs
that pass

Assess safety
and biological
activity

1 2 3
20 to 80 100 to 300 1,000 to 3,000
Healthy Volunteers Patient Volunteers Patient Volunteers
Evaluate erify effectiveness,
Determine effectiveness, monitor adverse
safety and Look for side reactions from
dosage effects. long-term use.
Expedited Review: Phases II
and III combined to shorten
approval process on new medicines
for serious & life-threatening diseases.
70% of 33% of 27% of
INDs INDs INDs

FDA
2.5
Review
Process
20% of
INDs

Approval
Total= 12
Post-marketing
safety monitoring
Large-scale
manufacturing

Distribution
Education

The Drug Approval Proce,

The U.S. system of new drug approvals
is perhaps the most rigorous in the
world. On average, it takes 12 years
and $231 million to get one new medicine from the laboratory to the pharmacist's shelf, according to a 1990
study conducted by the Center for the
Study of Drug Development at Tufts
University. Here is how a drug is tested
and approved.
Preclinical Testing. The promising
agent is first subjected to extensive
laboratory and animal testing to determine answers to two key questions: Is
the compound biologically active? Is it
safe? If the answers to both appear to
be affirmative, the drug sponsor is
ready to test in humans. This stage
generally lasts approximately three and
one-half years.
Investigational New Drug. Before
human tests can start, the drug sponsor
must file an Investigational New Drug
(IND) application with the Food and
Drug Administration (FDA), showing
the results of all animal testing and
how the drug is made. The IND
becomes effective if FDA does not disapprove the application in 30 days.
Human Testing (Clinical). There
are three phases of human testing, each
involving larger numbers of people
than the one before.
Phase I. Safety Studies and Pharmacological Profiling: This phase determines

the drug's pharmacological actions, its
safe dosage range, how it is absorbed,
distributed, metabolized and excreted,
and the duration of its action. These
tests involve a small number of normal
healthy subjects (not patients). Phase I
clinical testing can usually be conducted
in one year.
Phase II. Pilot Efficacy Studies: This
phase consists of controlled studies in
approximately 100 to 300 volunteer
patients to assess the drug's effectiveness. Simultaneous animal and human
studies continue to determine the drug's
safety. Phase II clinical testing may
require about two years to complete.
Phase III. Extensive Clinical Trials:
Here the testing moves to larger numbers of volunteer patients, usually
1,000 to 3,000, in clinics and hospitals.
The drug is administered by practicing
physicians to those suffering from the
condition the drug is intended to treat.
These studies must confirm earlier
efficacy studies and identify lowincidence adverse reactions. Phase III
clinical trials last about three years.
New Drug Application (NDA).
Following completion of Phase III, the
drug sponsor must file an NDA with
the FDA, containing all the information
the sponsor has gathered. NDAs typically run into thousands of pages. The
information submitted must include the
chemical structure of the drug, scientific

rationale and purpose, animal and laboratory studies, results of all tests in
humans, formulation and production
details, and proposed labeling. On average, the NDA review and approval
process by FDA takes two and one-half
years.
Approval. Once an NDA is
approved, the company is required to
periodically submit reports to FDA,
including adverse reaction data and
production, quality control and distribution records. For some drugs, FDA
requires affirmative post-marketing
monitoring, or additional studies to
evaluate the long-term effects.
NOTE: Early in 1989, the FDA implemented an Expedited Drug Approval
plan to speed the approval of drugs for
life-threatening and severely debilitating
diseases. Under the plan, FDA will
work more closely with pharmaceutical
companies during development and in
evaluating clinical trials. The goal is to
reduce the 12 years it now takes to
move a drug from the test tube to the
pharmacy. If a drug shows sufficient
promise after Phase I, Phases II and III
could be combined to save two to
three years from the five-year clinical
trial process. President Bush's Cancer
Panel has undertaken a review of the
FDA approval process for cancer and
AIDS drugs. A final report was submitted to President Bush in August 1990.