The document outlines the drug discovery and clinical evaluation process, highlighting its complexity, high costs, and lengthy timeline, which can take 8-14 years and over $1 billion to develop a new drug. It details the collaborative efforts of various scientific disciplines, the rigorous preclinical and clinical testing phases required for drug approval, and the specific studies and testing methods used to ensure safety and efficacy. The document also describes the phases of clinical trials and the regulatory requirements necessary to obtain FDA approval for marketing a new pharmaceutical.

1. DRUG DISCOVERY & CLINICAL
EVALUATION OF NEW DRUGS
PRESENTED BY:
HEENA PARVEEN,
M.PHARMACOLOGY,
ASST.PROFESSOR.

2. DRUG DISCOVERY & CLINICAL
EVALUATION OF NEW DRUGS
Drug discovery & development is a challenging & expensive
activity of the pharmaceutical industry.
With the advent of technologies in biological screening
procedures of new chemical entities , the time involved in
drug discovery has gone down in recent years but,
the cost of drug discovery has touched a new high of
US $ 1 billion per molecule from conception to drug launch.

4. Aim :
 Develop clinically efficacious & safer drug .
 Economically Viable
 Discover entirely new class of drugs
 Explore the mechanism or Pharmacodynamic properties
It takes nearly 8-14 years for the development process.
For every 6200 compounds sythesized ,only 21 will reach testing stage
for Sub-acute toxicity.
Only 2-6 of these compounds will reach clinical trials & subsequent
evaluation. Ultimately, one of these compounds may become a drug.
To get approval for marketing a new drug it must be thoroughly tested
for safety & efficacy for its intented use.

6. DRUG DISCOVERY
The combined efforts of
Chemists,Biologists,Pharmacologists,Toxicologists,Statistcians,Clinici
ans,Pharmacists,Pharmaceutcal scientists, Engineers, & many others
are involved in the drug discovery & development process.
New Drugs SOURCE:
Natural sources – Plants, Animals, Minerals,Marine or chemically
synthesised in the laboratory.
Recently, the advent of Genetic engineering & sub-microscopic DNA
manipulation techniques, the development of pharmaceutical products
has witnessed a new era.

7. Methods of Drug Discovery
Most drugs nowadays are the result of carefully designed
 Research programmes of screening,
 Molecular modification &
 Mechanism based Drug design.
Biological Characterisation:
Prospective drug substances must undergo preclinical testing for biologic
activity n order to assess their potential as useful therapeutic agents.
These studies fall in to general areas of Pharmacology, Drug
Metabolism,& Toxicology & involves many types of biologic
scientists.

8. Pre-Clinical Testing
• In drug development, preclinical development, also
named preclinical studies and nonclinical studies, is a
stage of research that begins before clinical trials.
• During this important feasibility, iterative testing and
drug safety data are collected, typically in laboratory
animals.
• The main goals of preclinical studies are to determine a
starting, safe dose for first-in-human study and assess
potential toxicity of the product, which typically include
new medical devices, prescription drugs,
and diagnostics.

9. Each class of product may undergo different types of
preclinical research. For instance, drugs may undergo
Pharmacodynamics,
Pharmacokinetics,
ADME, and
Toxicology testing.
It allows researchers to estimate a safe starting dose of
the drug for clinical trials in humans.
Typically, both in vitro and in vivo tests will be performed.
Studies of drug toxicity include which organs are targeted
by that drug, as well as if there are any long-
term carcinogenic effects or toxic effects causing illness.

10. Pre-clinical Animal Models:
• Rabbits
• Rats
• Mice
• Guinea pigs
• Hamsters
• Dogs
• Swine
• Sheep
• Calves

11. Treatments may be administered via the following routes of
administration:
• Oral
Intravenous
Subcutaneous

12. • Intracutaneous
• Intraperitoneal
• Continuous infusion
• Intratracheal
• Intrathecal
• Dermal

13. Investigational Areas:
• Cardiovascular
• Endocrine
• Anti-infective
• Oncology
• Musculoskeletal
• Dermal
• Central Nervous System

14. Preclinical Tests Information
• Exploratory Studies such as ADME and PK studies.
• Regulatory Studies including toxicity, immunogenicity, and
safety pharmacology.
• Formulation Support
• Microdosing studies for ultralow dose clinical studies.
• Downloadable Test Timing Chart

16. The IND application must contain information in three broad
areas:
• Animal Pharmacology and Toxicology Studies - Preclinical data
to permit an assessment as to whether the product is
reasonably safe for initial testing in humans. Also included
are any previous experience with the drug in humans .
• Manufacturing Information - Information pertaining to the
composition, manufacturer, stability, and controls used for
manufacturing the drug substance and the drug product. This
information is assessed to ensure that the company can
adequately produce and supply consistent batches of the
drug.
• Clinical Protocols and Investigator Information - Detailed
protocols for proposed clinical studies to assess whether the
initial-phase trials will expose subjects to unnecessary risks.

17. Also, information on the qualifications of clinical investigators--
professionals (generally physicians) who oversee the
administration of the experimental compound--to assess
whether they are qualified to fulfill their clinical trial duties.
Finally, commitments to obtain informed consent from the
research subjects, to obtain review of the study by an
institutional review board (IRB), and to adhere to the
investigational new drug regulations.
Once the IND is submitted, the sponsor must wait 30 calendar
days before initiating any clinical trials.
During this time, FDA has an opportunity to review the IND for
safety to assure that research subjects will not be subjected
to unreasonable risk.

18. CLINICAL TRIAL PHASES

20. TRIALS NO.OF
PATIENTS
LENGTH PURPOSE SUCCE
SS
PHASE 0 10-15 - First in human trials
(MICRO DOSING
STUDIES)
-
PHASE 1 20-80
VOLUNTEERS
Several Months Mainly safety in
Volunteers
67%
PHASE 2 100-500 Months to Years Short –term safety,
mainly effectiveness
in patients.
45%
PHASE 3 1000-5000 1-4 years Safety ,effectiveness,
large number of
patient population.
5-10%
PHASE 4 - - Post-marketing
survilience to detect
ADR.
-

21. PHASE 0:
It is Explanatory, First in human trials .
Also called as Human Microdosing studies in small group of healthy
volunteers (10-15 numbered) to speed up the development of
promising drugs.
This Phase doesn’t give safety & efficacy but gives an idea on ranking
the promising drug candidates to take forward the drug development
studies.
PHASE 1:
In small number of normal human volunteers , it is conducted(20-30).
Here, the acute effects of the agents are studied over a broad range of
dosage, starting with one that produces no detectable effect
&progressing to one that produces either a major therapeutic response
or minor toxic effect.

22. PHASE 2:
To evaluate drugs in a moderate number of patients(100-500) with a
target disease.
A placebo or positive control drug s included in single blind / double
blind design.
The goal s to determine whether the agent has the desired therapeutic
effects at doses that are tolerable by patients.
PHASE 3:
It consists of large design involving may patients(1000-5000) & many
clinicians who are using the drug in manner proposed for its ultimate
general use.(OUTPATENTS).
The goal is to explore further the spectrum of beneficial actions of the
new drug, to compare it with older therapies & to discover toxicities.

23. PHASE 4:
It represents the Post-marketing survillance phase of evaluation, in
which it is hoped that toxicities occur very infrequently will be
detected & reported early enough to prevent major therapeutic
disasters.
NDA application is the vehicle through which the drug sponsors
formally
propose that the FDA approve a new pharmaceutical foe sale &
marketing in the U.S.
The data gathered during the animals study & human clinical trials of an
IND become an NDA.