The ultimate aim of pharmacological studies in animals is to find out a therapeutic agent suitable
for clinical evaluation in man. No doubt, animal studies provide analogies and serve as useful
models. The administration of biologically active agent to human beings is associated with an
element of risk, which cannot be predicted by even the most careful and exhaustive animal
experiments.
Scientists all over the world are in a continuous effort to develop new drugs although drug
development is an extremely technical and enormously expensive operation. Among thecontributors to new drug development, pharmacologists are more concerned in evaluating “new
chemical entities” (NCE). Synthesis and evaluation of thousands of NCEs are usually necessary
for new drugs to be introduced in the market. Research and development of new drugs have
been done under strict government regulations which have greatly increased over the past
couple of decades.
Drug development comprises of two steps.
a) Preclinical development and
b) Clinical development
A) Preclinical development: Synthesis of new chemical entities is done as per research policy
decision which is based on:
(i) Random synthesis
(ii) Structure activity relationship (SAR)
(iii) Biochemical and pharmacological insight and
(iv) Chance finding.
The aim of the preclinical developmeent phase for a potential new medicine is to explore the
drug’s efficacy and safety before it is administrated to patients. In this preclinical phase, varying
drug doses are tested on animals and/or in vitro systems.
If active compounds are found, then studies on animals are done which include
pharmacodynamics, pharmacokinetics, toxicology and special toxicological studies
(mutagenicity and carcinogenicity) have to be done. In this study single dose is used for acute
toxicity and repeated doses for sub chronic and chronic toxicity studies. Most of the preclinical
tests have to be conducted in accordance with the standards prescribed.
B) Clinical development: About one in 1000 NCEs reach this stage. The steps to be studied in
this stage include:
a) Pharmaceutical study
b) Pharmacological study
c) Clinical trial.
a) Pharmaceutical study covers stability of formulation and compatibility of the NCEs with other
tablet or infusion ingredients.
b) Pharmacological study includes further chronic toxicological study in animal, initially animal
metabolic and pharmacokinetic study. When studies in animals predict that a NCE may be
useful medicine i.e. effective and safe in relation to its benefits, then the time has come to
put it to the test in man i.e. clinical trial.
c) Studies on human or Clinical Trial:
Clinical trial is a means by which the efficacy of drug is tested on human being. It may also give
some idea about the risk involved. It is divided into 4 phases. With each phase, the safety and
efficacy of the compound are tested progressively.
Phase – I: This is the first exposure of the new drug on man which is usually conducted in
healthy volunteers and which is designed to test the tolerable dose, duration of action. This
phase is usually carried out in only one centre on 20 to 50 subjects.
Phase – II: This phase comprises small scale trials on patients used to determine dose level and
establish that the treatment offers some benefit. It usually involves 100-500 patients and is
usually conducted in several centres.
Phase – III: Full scale evaluation of treatment comparing it with standard treatment is done in
this phase. It involves randomised control trials on 250 to 2000 patients and is done in multiple
centres. Information from all studies are received by the “Committee of safety of medicines”
(CSM). If the drug is satisfied by the CSM, the product license is issued then the drug is
marketed.
Phase – IV: It is also called as phase of post marketing surveillance. Reports about efficacy and
toxicity are received from the medical practitioners and reviewed by the committee of review of
medicines. Renewal or cancellation of the product license depends on the comment of the
review committee
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