Stages of Drug Development

Stages of drug
development

Stages of Drug Development

Introduction
Average time to develop new drug is
10 -12 years. On an average out of
10,000 30,000 potential substances
only 1 could make it to the market. As
per 2010 estimates, the cost of
bringing a new drug could vary from
500 million to 2,000 million USD.

Stages of Drug Development

Historical
Timelines
sulfanilamide disaster
1906
No Regulatory
control for Drug
safety
1937

Thalidomide crisis

1938

1961

Federal Food, Drug

and Cosmetic Act passed

Stages of Drug Development

Lessons Learned
As a result of the sulphanilamide and thalidomide
tragedy, the following lessons were learned:
Pharmaceutical products should be
systematically tested for developmental effects
prior to marketing.
There are differences in species sensitivity and
manifestations of developmental toxicity.
Use of a second species or more thoroughgoing
interpretation of results in a single species
(taking pharmacokinetics into consideration) are
important considerations in drug testing.

Stages of Drug Development

Stages in Drug Development

1.Drug Discovery
2.Pre-Clinical Testing
3.Phase I Clinical Trials
4.Phase II Clinical Trials
5.Phase III Clinical Trials
6.New Drug Application (NDA)
7.Phase IV and Beyond

Life Cycle for new drug :

Stages of Drug Development

Concepts of Drug Development

Pharmacokinetics (PK):
(Absorption,
Distribution, Metabolism
& Excretion - ADME)

Pharmacodynamics
(PD): (effects on
organs or systems)

-- Evaluation or quantification
of what the body does to a
drug substance over time

-- Evaluation or
quantification of what the
drug substance does to
the body over time, and
over drug concentrations

Drug Discovery

Determine the target disease

Determine each component of disease :

Search for the target drug :

Symptoms
Target organ
Biochemical pathways
Chemically synthesized compound
Biologically synthesized compound
Computer simulated compound

Isolate the compound

Proceed to next Stage

Drug Discovery

Pre CLINICAL TRIALS :

Evaluation of acute and short term
toxicity in animals. It Involves :
-Lethal dose determination
-Effect of dose at normal level for short/Long
term

Assess how the drug is

absorbed/distributed/metabolized and
excreted in animals.
Proceed to next Stage.

Drug Discovery

IND program
It is the means by which a pharmaceutical
company obtains permission to ship an
experimental drug across state lines
(usually to clinical investigators) before a
marketing application for the drug has been
approved.
The FDA reviews the IND application for
safety to assure that research subjects will
not be subjected to unreasonable risk.
If the application is approved, the candidate
drug usually enters a Phase 1 clinical trial.

Drug Discovery

Phase 1 CLINICAL TRIALS :

Begins after 30 days after IND acceptance.
Drug given to 20-100 healthy volunteers
Duration could vary from 1 month to 1 year.

Following is studied here :

Drug absorption/Metabolism in human.
Effect on organs and tissues. -Side affect of
different dosages.
Thus early evidences on effectiveness are
achieved.

Proceed to next Stage

Drug Discovery

Phase 2 CLINICAL TRIALS :

Drug given to 100 - 300 patient volunteers
Duration could vary from 1 year to 2 years
Cost could vary from $10 - $100 million.
Following is studied here : Drug effectiveness in treating the disease.
Short term side effects in patients
Less than 1/3rd of INDs survive phase 2

Proceed to next Stage.

Drug Discovery

Phase 3 CLINICAL TRIALS :

FDA consulted before beginning phase 3
Drug given to 1000-3000 patient volunteers
Duration could vary from 3 years to 4 years.
Cost could vary from $10 - $500 million

Following is studied here :

Safety of Drug [ Benefits v/s risk analysis ]
Long term side effects in patients

Proceed to next Stage.

Drug Discovery

NDA
NDA Refers to New Drug Application
Formal proposal for the FDA to approve a
new drug for sale in the U.S.
Sufficient evidences provided to FDA to
establish:
Drug is safe and effective.
Benefits outweigh the risks.
Proposed labeling is appropriate.

Drug Discovery

Market Launch/Phase 4 :
launched to the Market
Additional post marketing testing of
patients to
Support the use of the approved indication
Finding new therapeutic opportunities
Extending use of the drug to different classes
of patients like children