“PH.
REGULATROY SCIENCE”
TOPIC OF DISCUSSION
NEW DRUG DISCOVERY &
DEVELOPMENT
Presented by
Mr. Santosh Ganguly
Assistant Professor
Department of Pharmaceutics
Bharat Pharmaceutical Technology
Agartala, Tripura, INDIA
WHAT IS DRUG DISCOVERY?
Drug discovery is a programmed process by which drugs are
discovered and/or designed.
It is an intense, lengthy & an interdisciplinary endeavour.
A drug molecule may be either as in case of natural drugs or
synthesized through a process in a laboratory.
The molecule is then screened for its activity in animals. This stage
is called Pre-clinical trials/phase. (Approval from Committee
for Control & Supervision of Experiments on Animals)
If the molecule shows promising therapeutic activity and its
benefits overweighs the risk associated, then it is formulated into a
suitable dosage form for further experimentation on humans. This
stage is called Clinical trials/phase.
NOTE: Clinical trials require FDA consent & in this regard an
Investigational New Drug Application (IND) is submitted to
FDA.
STAGES INVOLVED IN CLINICAL TRIALS
Phases of Purpose Performed on Duration
Clinical Trial
Phase - I To determine safety Normal Volunteers Several
(20-80 volunteers) Months
To determine the
Phase - II therapeutic efficacy, Selected Patients Months to
dosage range, Years
kinetics of the drug.
Phase - III To determine safety Large number of 1-4 years
& efficacy of the new selected patients
drug
To determine the
Phase - IV ADRs of the newly Patients NA
marketed drug
Identification of a drug molecule
Pre-clinical trials (3-6 years)
High therapeutic efficiency
IND Submission
IND approved, Drug product formulated
Clinical Trials (Phase I - III)
Benefit of drug product overweighs the risk
NDA Submission
NDA approved (Patent)
Marketing of the drug product
Patent Expired
Patent Renewed
Fig: Schematic representation of the stages involved in
Drug Development Process
DRUG DEVELOPMENT PROCESS
Pre-Clinical Studies: Testing of lead compounds on animals to
determine their pharmacological profile is Pre-Clinical Studies.
Aspects of Pre-Clinical Studies:
Pharmacology: Screening of the drug compound is done on
animals to determine its pharmacological activities.
Types of Screening:
Simple Screening
Blind Screening
Programmed Screening
TYPE OF SCREENING
• Here, one or two simple tests are performed to identify if
the molecule is having that specific pharmacological
activity.
Simple
Screening • Ex: Hypoglycaemic Acitivity
• It involves detection of various pharmacological
activities of the new substance.
Blind
Screening • Ex: Anti-hypertensive, Anti-inflammatory activities
• It involves testing of new molecule for specific category
of pharmacological effects.
• Here the molecules are quantitatively assayed and
Programmed compared with standard.
Screening
• Ex: Test for CVS, CNS, Renal System etc
TYPE OF SCREENING MODELS
• These studies are carried out on isolated specific tissue in a
controlled environment.
In-Vitro
• Ex: Guinea pig Ileum (Ileal Portion) can be used to study the
Model effect of anti-histaminics. (Anti-histaminics binds to H1 receptor
which is responsible for causing itching, allergy etc).
• These studies are conducted on whole living organism.
• Ex:
In-vivo
• 1. Tail Flick Method: To detect analgesic effect of the drug.
Model • 2. Elevated Plus Maze Method: To analyze the anti-anxiety effect
of the drug
• In these studies, the experiment is performed in vivo and then
Ex-vivo analyzed in vitro
Model • Ex: Passive cutaneous anaphylaxis in rats.
BIOASSAY
Bioassay:
A bioassay (biological assay) is an analytical method that
determines the potency or effect of a substance by observing its
impact on living organisms, tissues or cells.
It is done by estimating the concentration of the active constituent
present in a unit preparation.
General Procedure:
Stimulus Application: A stimulus (e.g., a drug, chemical, or
toxin) is applied to a biological system (e.g., cells, tissues, or
organisms).
Response Measurement: The biological response to the stimulus
is then measured, which can be anything from growth, survival, or
a specific biochemical reaction.
Comparison and Analysis: The response is compared to a known
standard or reference substance to determine the potency or
concentration of the unknown substance.
BIOASSAY
There are several disadvantages of Bioassay:
Errors due to variation in techniques and interpretation by
different operators.
Time consuming.
Expensive.
Importance of Bioassay: To determine the LD50 & ED50 of the
drug.
Types of Bioassay:
Direct Bioassay determines the concentration of a substance
needed to elicit a specific response.
Indirect Bioassay determine the relationship between dose and
response, then extrapolate to find the dose required for a specific
response.
BIOASSAY
How direct bioassay works?
The stimulus is applied and its effect is measured.
The variable of interest is the dose required to produce a specific
biological effect (e.g., death of an animal, cessation of heartbeat).
This is also known as the "individual effect dose" (IED).
How indirect bioassay works?
Doses of both a standard and a test preparation are applied, and
the responses produced are observed.
The relationship between the dose and response is determined for
each preparation.
The relative potency of the test preparation is estimated by
comparing the dose-response curves of the standard and test
preparations.
METHODS OF BIOASSAY
Three Point Assay:
2 standard concentrations and one test concentration is taken into
consideration.
The 2 doses of standard whose response lies within a linear portion
of the curve is selected.
The conc. should be in simple ratio.
The dose of the test sample should be as such that the response lies
in between S1 & S2.
Now, these 3 doses are bioassayed.
S1 S2 T
T S1 S2
S2 S1 T
T S2 S1
DRUG DEVELOPMENT PROCESS
Drug Metabolism: Metabolism or Biotransformation is a process
of transformation of a chemical entity to entirely different
chemically active/inactive entity inside the living body by a series
of enzymes.
Sites for drug metabolism: Liver, Intestinal Mucosa (Extra-
hepatic site)
Toxicology: Potentiality of the drug molecule to produce toxic
effects.
Helps in determining the proper dose, dosage form, frequency of
dosing, route of administration etc.
DRUG DEVELOPMENT PROCESS
Toxicological Studies:
Acute Toxicity Studies:
THANK YOU
