m A number of different strategies are adopted by

the pharmaceutical industries in their efforts to

identify new drug products.
m These approaches ranges from random screening
of a wide range of biological materials to
knowledge- based drug identification.
m Once a potential new drug has been identified, it is
then subjected to a range of tests(both in vitro and
in animals) in order to characterize it in terms of its
likely safety and effectiveness in treating its target
disease
 DRUG DEVELOPMENT PROCESS

Years 1 2 ` 4 5 6 7 8 9 10 11 12 1` 14 15 16
Start Approval
Clinical Trials

Phase 1 Phase 2 Phase ` Phase 4

50-100 100-200 500-5000
people people people
nitial Drug Clinical Full Scale
research discovery Development Manufacture

Toxicology and Pharmacokinetics

Chemical development

Pharmaceutical development
Sales and Marketing

$2M $150M $`00M

Cost
10,000 compounds 1 new medicine

`
 Drug Discovery

Initial Characterization

Pre-Clinical trials

Regulatory approval sought to commence trials in humans

Clinical trials (Phase I,II,III)

Submission of marketing/ manufacturing authorization

applications to regulatory authorities

Regulatory authorities review information and grant ( or

refuse) marketing/ manufacturing licenses

Product goes on sale

Post marketing surveillance

m The developer will also undertake manufacturing
related work, as well as investigating suitable
potential routes of product administration
m After completing pre-clinical trials;
m The developing company apply to the appropriate
government- appointed agency like FDA for
approval to commence clinical trials
m Upon completion of clinical trials, the developing
company collates all the preclinical and clinical
data have generated.
m They submit this information to regulatory
authorities
m Regulatory scientific officers then access the
information provided and decide whether the
drug should be approved for general medical
use.
m This is largely dependent on the criteria of
drug safety and efficacy.
m f marketing approval is granted, the company
can sell the product from there on.
m As the drug has patented, they will have no
competition for a no of years
m n order to sell the product, a manufacturing
facility is required
m For this the company will also have to gain
manufacturing approval from the regulatory
authorities
m The regulatory authorities will review it and
will only grant the license if they are satisfied
with the every aspects
m Post marketing surveillance is generally
undertaken, with the company being obliged to
report any subsequent drug- induced side
effects
m The regulatory authority will also inspect
regularly to ensure that satisfactory
manufacturing standards are maintained.
m n order to gain approval for general medical
use, the quality, safety and efficacy of any
product must be demonstrated.
m Such pre-clinical studies can take upto ` years
to complete, and at a cost of anywhere between
$10 - $ `0million
m On an average, approximately 10% of potential
new drugs survive pre clinical trials
m Major tests undertaken on a potential drug during
preclinical trials are
[ Pharmacokinetics profile
[ Pharmacodynamic profile
[ Bioequivalence and bioavailability
[ Acute toxicity
[ Chronic toxicity
[ Mutagenicity
[ Carcinogenicity
[ Immunotoxicity
[ Local tolerance
m Pharmacology may be described as the study
of the properties of the drugs and how they
interact with / affect the body.
m PK relates to the fate of a drug in the boby,
particularly its ADME properties
[ Absorption into the body
[ Distribution with in the body
[ Metabolism by the body
[ Excretion from the body
m t will point out the most appropriate method
of drug administration and most likely
effective dosage regime.
m PD studies deal more specifically with how
drug bring about its characteristic effects
m i·e., how drug interacts with a cell/ organ type,
the effects and side effects it induces and dose-
response curves are also observed.
m ‰ioavailability relate to the proportion of a drug that actually
reaches its site of action after administration

m f they are delivered parentally ( by injection) , their bioavailability

is virtually 100%

m Where as, in case if administered through mouth, then

bioavailability will be 0%- 10%

m ‰ioequivalence studies come into play if any change in the

product production/ delivery systems is being contemplated

m These studies would seek to identify if such modifications still

yield a product equivalent to the original one in terms of safety
and efficacy.
m Toxicity studies are carried out by animal
testing to ascertain whether the product
exhibits any short term or long term toxicity
m Acute toxicity is usually assessed by the
administration of a single high dose of the test
drug to rodents
m The animal is then monitored for 7-14 days
with all fatalities undergoing extensive
analysis.
m Calculation of the approximate lethal dose.
m Chronic studies require large no. of animals
and can last up to 2 years
m t demands daily administration of the test
drug
m t will assess drug levels required to induce an
observable toxic effect.
m All animals are subjected to routine clinical
examination and periodic analyses are
undertaken
m Extensive pathological examination of all
animals is undertaken at the end of the studies
m Mutagenicity tests aim to determine whether
the drug is capable of inducing DNA damage
by inducing alterations
m Carcinogenicity tests are undertaken if the
product·s likely therapeutic indication will
necessitate its administration for prolonged
periods.
m mmunotoxicity tests are undertaken to find
out its ability to induce an allergic or
hypersensitive response