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Topic+5+-+The+Discovery+Process

The document outlines the drug discovery and development process, detailing stages from pre-discovery to clinical trials and FDA approval. It emphasizes the importance of understanding diseases, target validation, early safety tests, and the rigorous testing required before a drug can be marketed. Key phases include preclinical testing, Investigational New Drug application, and the three phases of clinical trials leading to a New Drug Application submission to the FDA.

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13 views25 pages

Topic+5+-+The+Discovery+Process

The document outlines the drug discovery and development process, detailing stages from pre-discovery to clinical trials and FDA approval. It emphasizes the importance of understanding diseases, target validation, early safety tests, and the rigorous testing required before a drug can be marketed. Key phases include preclinical testing, Investigational New Drug application, and the three phases of clinical trials leading to a New Drug Application submission to the FDA.

Uploaded by

lilianengo70
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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OUR LADY OF FATIMA UNIVERSITY

College of Pharmacy
Drug Discovery and Development (PDDD311)

The
Discovery
Process
UNIT OUTCOMES:

▷ Discuss strategies for


premarketing activities
▷ Discuss the principle, purpose and
process of drug safety monitoring
in the market
▷ Discuss the basic principles
underlying the protection of
intellectual property
REQUIRED READINGS
▷ The clinical trial of the future.
PharmaTimes magazine- October 2016.
http://www.pharmatimes.com/magazine/
2016/october/the_clinical_trial_of_the_fu
ture
▷ A precision medicine approach to clinical
trials.
http://scipol.duke.edu/content/precision-
medicine-approach-clinical-trials
▷ Doogue, M. P., & Polasek, T. M. The
ABCD of clinical pharmacokinetics 3
The Discovery Process
Topic 5

4
A. Pre-discovery:
Understand the disease

Ø Before any potential new medicine can be


discovered, scientists work to understand
the disease to be treated as well as possible,
and to unravel the underlying cause of the
condition.

5
Scientists try to understand..

How the genes are altered


↓
How that affects the proteins they encode and how those
proteins interact with each other in living cells
↓
How those affected cells change the specific tissue they are
in
↓
How the disease affects the entire patient.

This knowledge is the basis for treating the problem.


6
B. Target Validation

Ø Test the target and confirm its role in the


disease
Ø After choosing a potential target,
scientists must show that it actually is
involved in the disease and can be acted
upon by a drug (Lead Compound).

7
B. Target Validation

There are a few ways to find a lead


compound:
Ø Nature
Ø Bacteria
Ø De novo

8
B. Target Validation

HTS (HIGH-THROUGHPUT SCREENING)


Ø This process is the most common way that
leads are usually found.
Ø Advances in robotics and computational
power allow researchers to test hundreds
of thousands of compounds against the
target to identify any that might be
promising.

9
C. Early Safety Tests

Ø Perform initial tests on promising compounds


Lead compounds go through a series of tests
to provide an early assessment of the safety
of the lead compound.
Ø ADME/Toxicology

10
C. Early Safety Tests

SUCCESSFUL DRUGS MUST BE:


i. Absorbed into the bloodstream
ii. Distributed to the proper site of action in
the body
iii. Metabolized efficiently and effectively
iv. Successfully excreted from the body and
v. Demonstrated to be not toxic.

11
C. Early Safety Tests

LEAD OPTIMIZATION
Ø Alter the structure of lead candidates to
improve properties
Ø Lead compounds that survive the initial
screening are then “optimized,” or altered
to make them more effective and safer.

12
C. Early Safety Tests

TEAMS OF BIOLOGISTS AND


CHEMISTS WORK TOGETHER CLOSELY:
○ The biologists test the effects of
analogues on biological systems while
the chemists take this information to
make additional alterations that are
then retested by the biologists.
○ The resulting compound is the
candidate drug.

13
D. Preclinical Testing Lab
and Animal testing
▷ To determine if the drug is safe enough
for human testing
▷ With one or more optimized compounds
in hand, researchers turn their attention
to testing them extensively to determine
if they should move on to testing in
humans.
▷ Scientists carry out in vitro and in vivo
tests.

14
D. Preclinical Testing Lab
and animal testing
▷ Scientists try to understand how the
drug works and what its safety profile
looks like.
▷ The U.S. Food and Drug Administration
(FDA) requires extremely thorough
testing before the candidate drug can be
studied in humans.

15
D. Preclinical Testing Lab
and animal testing
▷ At the end of several years of intensive
work, the discovery phase concludes.
After starting with approximately 5,000
to 10,000 compounds, scientists now
have winnowed the group down to
between one and five molecules,
“candidate drugs,” which will be studied
in clinical trials

16
E. Investigational New Drug
(IND) Application and Safety
File
▷ Before any clinical trial can begin, the
researchers must file an Investigational
New Drug (IND) application with the
FDA.

17
E. Investigational New Drug
(IND) Application and Safety
File
▷ The application includes the results of
the preclinical work, the candidate
drug’s chemical structure and how it is
thought to work in the body, a listing of
any side effects and manufacturing
information.
▷ The IND also provides a detailed clinical
trial plan that outlines how, where and
by whom the studies will be performed.
18
F. Clinical Trials

▷ PHASE 1: CLINICAL TRIAL PERFORM


INITIAL HUMAN TESTING IN A SMALL
GROUP OF HEALTHY VOLUNTEERS
○ The candidate drug is tested in people for
the first time.
○ These studies are usually conducted with
about 20 to 100 healthy volunteers.
○ The main goal of a Phase 1 trial is to
discover if the drug is safe in humans.

19
F. Clinical Trials

▷ PHASE 2: CLINICAL TRIAL TEST IN A


SMALL GROUP OF PATIENTS IN
PHASE
▷ Phase 2 trials researchers evaluate the
candidate drug’s effectiveness in about 100 to
500 patients with the disease or condition
under study, and examine the possible short-
term side effects (adverse events) and risks
associated with the drug.
20
F. Clinical Trials

▷ PHASE 3: CLINICAL TRIAL TEST IN A


LARGE GROUP OF PATIENTS TO
SHOW SAFETY AND EFFICACY
▷ Researchers study the drug candidate in a
larger number (about 1,000-5,000) of patients
to generate statistically significant data about
safety, efficacy and the overall benefit-risk
relationship of the drug.

21
F. Clinical Trials

▷ PHASE 3: CLINICAL TRIAL TEST IN A


LARGE GROUP OF PATIENTS TO
SHOW SAFETY AND EFFICACY
▷ This phase of research is key in determining
whether the drug is safe and effective. It also
provides the basis for labeling instructions to
help ensure proper use of the drug
▷ Phase 3 trials are both the costliest and longest
trials.
22
G. New Drug Application
(NDA) and Approval

▷ Submit application for approval to FDA


▷ Once all three phases of the clinical trials are
complete, the sponsoring company
analyzes all of the data. If the findings
demonstrate that the experimental
medicine is both safe and effective, the
company files a New Drug Application
(NDA) — which can run 100,000 pages or
more — with the FDA requesting approval
to market the drug. 23
G. New Drug Application
(NDA) and Approval

▷ The NDA includes all of the information


from the previous years of work, as well as
the proposals for manufacturing and
labeling of the new medicine.
▷ FDA experts review all the information
included in the NDA to determine if it
demonstrates that the medicine is safe and
effective enough to be approved

24
FOLLOWING RIGOROUS
REVIEW, THE FDA CAN
EITHER:
Ø APPROVE the medicine
Ø send the company an “approvable” letter
requesting more information or studies
before approval can be given
Ø DENY approval

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