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the free encyclopedia
Drug Development or
Preclinical Development is
defined in many pharmaceutical
companies as the process of taking
a new chemical lead through the
stages necessary to allow it to be
tested in human
clinical trials, although a
broader definition would encompass
the entire process of drug
discovery and clinical testing of
novel drug candidates.
Novel chemical entities (NCEs)
are compounds which emerge from
the process of
drug discovery. These will
have promising activity against a
particular biological target
thought to be important in
disease, however little will be
known about the safety,
toxicity,
pharmacokinetics and
metabolism of this NCE in man.
It is the function of drug
development to assess all of these
parameters prior to human clinical
trials. A further major objective
of drug development is to make a
recommendation of the dose and
schedule to be used the first time
an NCE is used in a human clinical
trial ("First-in-Man", FIM).
In addition, drug development
is required to establish the
physicochemical properties of the
NCE: its chemical makeup,
stability, solubility. The process
by which the chemical is made will
be optimised so that from being
made at the bench on a
milligram scale by a
synthetic chemist, it can be
manufactured on the
kilogram and then on the
ton scale. It will be further
examined for its suitability to be
made into
capsules,
tablets or
intravenous
formulations. Together these
processes are known in preclinical
development as CMC:
Chemistry, Manufacturing and
Control.
Many aspects of drug
development are focussed on
satisfying the
regulatory requirements of
drug licensing authorities. These
generally constitute a number of
tests designed to determine the
major toxicities of a novel
compound prior to first use in
man. It is a legal requirement
that an assessment of major organ
toxicity be performed (effects on
the heart and lungs, brain,
kidney, liver and digestive
system), as well as effects on
other parts of the body that might
be affected by the drug (eg. the
skin if the new drug is to be
delivered through the skin).
While, increasingly, these tests
can be made using
in vitro methods (eg. with
isolated cells), many tests can
only be made by using experimental
animals, since it is only in an
intact organism that the complex
interplay of metabolism and drug
exposure on toxicity can be
examined.
The process of drug development
does not stop once an NCE begins
human clinical trials. In addition
to the tests required to move a
novel drug into the clinic for the
first time it is also important to
ensure that long-term or chronic
toxicities are determined, as well
as effects on systems not
previously monitored (fertility,
reproduction, immune system, etc).
The compound will also be tested
for its ability to cause cancer
(carcinogenicity testing).
If a compound emerges from
these tests with an acceptable
toxicity and safety profile, and
it can further be demonstrated to
have the desired effect in
clinical trials, then it can be
submitted for marketing approval
in the various countries where it
will be sold. In the US, this
process is called a
New Drug Application or
NDA. Most NCEs, however, will
fail during drug development,
either because they have some
unacceptable toxicity, or because
they simply do not work in
clinical trials.
