Prepared By Pawan Dhamala RR College Of Pharmacy Bangalore

1. PAWAN DHAMALA
B.PHARMACY
RR COLLEGE OF PHARAMCY

2.  Not every compound that is tested in laboratory is
marketed ; it has to undergo several stages of
development called drug development.
 In this process new drug candidate get high standard for
its regulatory approval.
 Drug development is an uncertain pharmaceutical activity
with risks.
 In the drug development process, an innovator first has to
screen through many compounds that show hopeful
results.

3.  This is costly process as many compounds that are tested
are thrown away at the preliminary stage only.
 To innovate a new drugs a company needs to begin with
many thousands of compounds.
 The development of new drugs is a complex and costly
process.
 Cost of biopharmaceuticals are higher.
 R & D task involves discovery(preclinical studies) and
development (clinical studies) of New Chemical
Entities(NCEs)/(NMES).

4.  About 10,000 NCEs investigated to potentially treat disease ,
only 250 make it to animal testing stage, and approximately
5-10 would qualify for testing in humans.
 Only 1-2 products of the original 10,000 NCEs result in a
marketable product.
STAGES OF DEVELOPMENT OF A NEW DRUG
1) Preclinical stage:
 The preclinical stage involve on animals to find out various
parameters for a potential drug candidate under the process
of development.

5.  In this stage, innovator evaluates the drug’s toxic and
pharmacological testing through in vivo & in vitro laboratory
animal testing.
 In this stage USFDA minimum requirement is to develop
pharmacological profile of the drug; determine toxicity and
conduct short term toxicity studies.
2) Clinical stage
It is commonly conducted in 4 phases:
1. Phase 0 (Microdosing)
2. Phase 1
3. Phase 2

6. 4. Phase 3
5. Phase 4 (Post Marketing surveillance)

7. Phase 0 =
 This is an exploratory phase of a clinical trial.
 Phase 0 trail is done with very small number of people, usually
fewer than 15.
 Investigators use a very small dose of medication to make sure
it isn’t harmful to humans before they start using it in higher
doses for later phase.
Phase 1 =
 Phase 1 are carried out in a small number of healthy
volunteers usually 20 to 100.

8.  The purpose of Phase 1 is to identify the metabolic and
pharmacological effects of the drug in human and side effects
associated with increasing doses.
 The purpose of Phase 1 studies is to determine the safety
profile.
 During Phase 1, sufficient information about the drug’s
pharmacokinetics and pharmacological effects is required.
 Approximately 70% of drugs tested in this stage move to the
next phase.

9. Phase 2 =
 Phase 2 clinical trials conducted to obtain some preliminary
data on the effectiveness (efficacy) of the potential drug to
treat disease or condition.
 In this phase it helps to determine the common short-term
side effects and risks associated with the drug under testing.
 These studies are typically well-controlled, closely monitored,
and performed on larger groups of patients , usually 20-300.
 Duration of this phase ranges from several months to 2 years.
 Approximately 33% of drugs tested at this phase move to next
phase.

10. Phase 3=
 Phase 3 are expanded, controlled and uncontrolled trials.
 The purpose of this study is to gather information about the
effectiveness and monitoring of adverse reaction.
 Phase 3 includes 300 to 3,000 volunteers who have disease
or condition.
 To obtain approval from USFDA there must be at least 2
successful phase 3 clinical trials.
 The length of the study is about 1 to 4 years where
approximately 25-30% of drugs move to the next phase.

11. Phase 4 =
 It is also known as Post Marketing Surveillance(PMS).
 It is carried out once a candidate drug is approved as a drug and
marketed as a medicinal product.
 This phase aims is to find out the drug safety profile in a large
patient pool across the world and to establish its safety profile.
 It helps to detect rare or long-term adverse effect of the drug
over a large patient population.
 Several thousand volunteers who have the disease or condtion
are involved in this phase of the trial.

13. Time Required for Developing a New Drugs:
Drug development process is very slow process.
A candidate drug is examined at every stages of development by
regulatory authorities before it is launched in market.
According to PhRMA (Pharmaceutical Research and Manufacturers
of America, A pharma industry trade group of America ), it may
range between 12 to 15 years to develop a new drug.
It may take about six and half years of discovery ; preclinical testing
and toxicity testing; 1.5 years of Phase 1; about 2 years in Phase 2;
about 3.5 years in Phase 3 and about 1.5 years of regulatory
authority review and approval.
Once a drug get approval it may undergo Phase 4 to collect more
safety and efficacy data.

16. Cost of Developing New Drug:
• Drug development requires a huge investment from
pharmaceutical companies.
• According to various sources that the cost of developing a single
new drug varies from US$ 800 million to US$ 1.7 billion.
• The money invested by the pharmaceutical company for such
unsuccessful molecules in sunk cost and cannot be recovered.
3) Regulatory approval:
A) IND:
 Once the candiate drug is tested in animals (preclinical testing
), a sponsor files IND with the regulatory authorities for testing
it in humans.

17.  The IND application includes information such as: result of
previous experiment i.e: how ,where , and by whom the new
studies will be conducted; the chemical structure of the candidate
drug ; how it works on the body ( mechanism of action); toxic
effects found in the animal studies; and how it is manufactured.
 IND must be reviewed by Institutional Review Board (IRB).
 IND application contain information such as :
a) Animal pharmacology and toxicology studies.
b) Manufacturing information of candidate drug
c) Clinical protocols and investigator information.

18. B) NDA
 NDA application is the medium through which the new drug
sponsors purpose regulatory authority to approve this drug for
sale and marketing in the country of approval.
 The goal of NDA are to provide enough information to permit
regulatory reviewer for following key decisions:
a. Whether the drug is safe or effective
b. Whether the labelling of new drug is appropriate
c. Whether the methods used in manufacturing the new drugs
and control used to maintain its quality are adequate to
preserve its identity, strength, quality, and purity.
 The document submitted in NDA describes the whole picture of
new drugs.

19.  After completion of all phases of clinical trials , sponsor files
NDA with regulatory authority to show safety and efficacy of the
compound.
 NDA describes all relevant scientific information related to the
new drug that is gathered during the investigations.
 As NDA is a huge information submitted, regulatory authorities
requires enough time to review every details of information
submitted.