Stages of drug development

Drug development is the process of bringing a new pharmaceutical drug to the market once a
lead compound has been identified through the process of drug discovery.

The process of drug discovery and development is very long and needs 10-12 years
which includes the close interaction of large number of scientific disciplines. Most
biotechnology and pharmaceutical companies employ teams to mentor the process of various
stages of drug development and making the drug candidate into therapeutic products.

Labeling
Synthesis NDA review
review

Site inspection
Optimized Phase III
by FDA

Tested on
Phase II NDA approved
animals

Post marketing
INDA filling Phase I
studies

Target identification:

Identification of the biological origin of disease. Drugs act on either cellular or genetic
chemicals is called as Target and are associated with disease

Example : G- proteins couple receptors, Enzymes, Hormones, Ion channel and Nuclear receptors

Target validation

Tests are conducted to confirm that interactions with the drug target are associated with a desired
change in the behavior of diseased cells. Research scientists can then identify compounds that
have an effect on the target selected.

Hit identification
Lot of screening Techniques can be used to identify a lead or hit compound. A “hit” can be
defined as a compound that interacts with the target of interest. There are several strategies that
can be used to discover “hits” including; high-throughput screening, phenotypic screening,
virtual screening, fragment-based screening and structure-based design.

Lead optimization

Lead compound is modified to improve the potency. It makes the drug less interact with other
chemical pathway in the body. In optimization Test are conducted to identify the absorption,
distribution, metabolism and elimination properties of hit compound.

pre-clinical research on microorganisms and animals,

Pre-clinical drug development it is begins before the clinical trials during this stage important
safety and pharmacology data are collected. Regulatory toxicity studies are conducted inorder to
in order to identify the possible hazards. Regulatory agencies are request to carryout studies in a
rodent (rat) and non rodent (dog). The choice of an animal depends on similarities of its
metabolism to humans

Preclinical research includes synthesis of new molecules, purification and animal testing
which is done to measure the biological activities and safety of an investigational new drug. A
preclinical study takes place in either part or whole animal to determine important information
including therapeutic effect side effect and metabolism. The main objective of preclinical study
is to determine a drug’s pharmacodynamic, kinetics and toxicity data

Types of preclinical studies:

In vitro studies:

In vitro studies are done for testing of drugs or chemical’s effect on a specific isolated tissue or
organ. The basic instruments used in the invitro studies are organ bath and recording devices

Examples:

1) Langen droffs heart preparations : the objective is to study the effect drugs like nor
adrenaline and acetylcholine on the coronary blood flow, heart rate and force of
contraction using rat isolated heart
2) Ileum preparation : the objective is to record effect of drug like histamine and
antihistamines by using ileum of guinea pig

In vivo studies

In vivo is the Latin term meaning “in the living” . Invivo experiments are carried out by using
whole living organism (animals). Here laboratory animal as model of humans to achieve the long
term objective such as developing new drug for particular disease and short term objective is to
find out how the animal responds to the treatments. If it is faithful model of human, then human
should respond in the same way. Animal models are used to define a new molecule’s therapeutic
potential, toxicity potential, pharmaceutical properties and metabolic pathway and mechanism

Examples for in vivo studies

1) Invasive method : BP recording in anesthetized dog or cat

Ex-vivo studies

Ex-vivo experiments performed n In vivo and then analyzed in –vitro, means the organs of the
animals detached from the body and replaced once an experiments is performed

Next is filing for regulatory status, for an investigational new drug to initiate clinical trials
on humans.

Clinical trial or clinical drug development

Phase I

(Human pharmacology trial – estimation of safety and tolerability)

Phase II

(Exploratory trial –estimation of effectiveness and short term adverse effect)

Phase III

(Confirmation trail – confirmation of therapeutical benefit)

Once we have completed preclinical and clinical studies. If results are positives then sponsor can
apply NDA to FDA. Once it is applied, initially reviewed and inspected by FDA and if
everything found to be acceptable then NDA will approved. Even after the approval drug product
post marketing studies has to be conducted