The document discusses the process of drug development from discovery through clinical trials and regulatory approval. It begins with an overview of the iterative process involving biology, animal testing, and medicinal chemistry. It then outlines the typical 5 steps in drug development according to the FDA: discovery/screening, pre-clinical research including in vitro and in vivo testing, clinical research consisting of Phase I-III trials, FDA review, and post-marketing monitoring. The document provides details on each stage of development including pre-clinical and clinical research requirements and processes.

1. Trainer: Md. Zakaria Faruki
Orion Pharma Limited
Dhaka, Bangladesh
Training on
Drug Development &
Clinical Studies
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2. Overview
Drug discovery is an iterative process. It goes back and forth between
theoretical biology; the necessary, appropriate, and humane use of
animal assays to determine a compound’s biological activity in the
body; and medicinal chemistry to optimize the compound. Then in
human studies, clinical observations test hypotheses about how a
candidate drug may target cancer cells; determine its safety and
effective doses; and compare its ability to shrink tumors or stop cancer
progression relative to standard therapy. The NIH generally helps fund
all stages of research up through phase II clinical trials, as indicated by
the red borders of some panels of the flowchart. While NIH also
supports some phase III clinical trials, this portion of the drug
development process is usually funded by industry and other private
organizations and is distinguished by blue borders. Because this process
is so rigorous, only four to seven percent of candidate drugs receive
approval from the Food and Drug Administration (FDA).
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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3. Drug Development Lifecycle
According to FDA 5 steps are involved in the drug
development which are-
 Discovery / Screening
 Pre-clinical Research
 In-vivo,
 in-vitro
 Clinical Research
 Phase I
 Phase II
 Phase III
 Phase IV*
 FDA Review
 Post Marketing Monitoring*
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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4. Discovery/Screening
Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
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5. Drug Discovery
Typically, researchers discover new drugs through:
 New insights into a disease process that allow researchers to
design a product to stop or reverse the effects of the disease.
 Many tests of molecular compounds to find possible beneficial
effects against any of a large number of diseases.
 Existing treatments that have unanticipated effects.
 New technologies, such as those that provide new ways to target
medical products to specific sites within the body or to
manipulate genetic material.
 At this stage in the process, thousands of compounds may be
potential candidates for development as a medical treatment.
After early testing, however, only a small number of compounds
look promising and call for further study.
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6. Development
Once researchers identify a promising compound for
development, they conduct experiments to gather
information on:
 How it is absorbed, distributed, metabolized, and excreted.
 Its potential benefits and mechanisms of action.
 The best dosage.
 The best way to give the drug (such as by mouth or
injection).
 Side effects or adverse events that can often be referred to
as toxicity.
 How it affects different groups of people (such as by
gender, race, or ethnicity) differently.
 How it interacts with other drugs and treatments.
 Its effectiveness as compared with similar drugs.
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7. Pre-Clinical Research
 In-Vitro  In-Vivo
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8. Pre-Clinical Research Contd..
Before testing a drug in people, researchers must find out whether it has the
potential to cause serious harm, also called toxicity. The two types of preclinical
research are In Vitro & In Vivo tests. FDA requires researchers to use good
laboratory practices (GLP), defined in medical product development
regulations, for preclinical laboratory studies. These regulations set the
minimum basic requirements for:
 study conduct
 personnel
 facilities
 equipment
 written protocols
 operating procedures
 study reports and
 a system of quality assurance oversight for each study to help assure the safety
of FDA-regulated product
Usually, preclinical studies are not very large. However, these studies must provide
detailed information on dosing and toxicity levels. After preclinical testing,
researchers review their findings and decide whether the drug should be tested
in people.
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9. Investigational New Drug
(IND)
Drug developers, or sponsors, must submit an Investigational New Drug (IND)
application to FDA before beginning clinical research. In the IND
application, developers must include:
 Animal Pharmacology and Toxicology Studies (side effects that cause great
harm) data
 Manufacturing information
 Clinical protocols (study plans) for studies to be conducted
 Data from any prior human research
 Information about the investigator
Then developers need to-
 Asking for FDAAssistance
 FDA IND Review Team: Project Manager, Medical Officer, Statistician,
Pharmacologist, Pharmakineticist, Chemist, Microbiologist
 FDA Approval: The FDA review team has 30 days to review the original
IND submission. The process protects volunteers who participate in clinical
trials from unreasonable and significant risk in clinical trials.
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10. Clinical Research
 Human Testing: But unlike with animals; the sponsor cannot just go
ahead and run testing in humans without supervision
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11. Clinical Research Contd…
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Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
While preclinical research answers basic questions about a drug’s safety, it is not
a substitute for studies of ways the drug will interact with the human body.
“Clinical research” refers to studies, or trials, that are done in people. As the
developers design the clinical study, they will consider what they want to
accomplish for each of the different Clinical Research Phases and begin the
Investigational New Drug Process (IND), a process they must go through before
clinical research begins. It is involved with following terms-
Designing Clinical Trials
Clinical Research Phase Studies
The Investigational New Drug Process
Asking for FDAAssistance
FDA IND Review Team
Approval
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12. Clinical Trials
Researchers design clinical trials to answer specific research questions
related to a medical product. These trials follow a specific study
plan, called a protocol that is developed by the researcher or
manufacturer. Before a clinical trial begins, researchers review prior
information about the drug to develop research questions and
objectives. The clinical trails are-
 Highly regulated
 A panel of scientists, ethicists, and non scientists oversees each
clinical medical center
 A protocol document must be presented and approved by the FDA,
the protocol is very detailed specifies everything about the study…
There are mainly four Clinical trails which are- Phase I, Phase II,
Phase III & Phase IV Studies.
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13. Case Report Form (CRF)
 The collection of forms where all the clinical data is going
to be collected for a patient
 Designed according to the protocol
 A blank CRF is always submitted to the FDA for approval
before the trial must be run
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14. Phase I Clinical Trials
Phase I studies are primarily concerned with the drug's safety. These studies
are typically done in a small number of healthy volunteers (20-100), usually
in a hospital setting where they can be closely watched and treated should
there be any side effects. These volunteers are usually paid for their
participation and for the most part tend to be men (approximately 30 years
of age on average). The purpose of these studies is to determine how the
experimental drug is absorbed, metabolized, and excreted in humans.
Additionally, they seek to determine what types of side effects occur as the
dosage of the drug is increased. Any beneficial effects of the drug are also
noted.
 Small number of healthy volunteers or patients
 Assess the most common acute adverse effects
 Examine the size of doses that patients can take safely without a
high incidence of side effects.
 Begin to clarify what happens to a drug in the human body
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15. Phase II Clinical Trials
 If phase I studies do no reveal any major problems, such as unacceptable toxicity, the next step is
to conduct a clinical study in which the drug is given to patients who have the condition it’s
intended to treat. Researchers then assess whether the drug has a favorable effect on the condition.
 Once an experimental drug has been proven to be safe and well tolerated in healthy volunteers, it
must be tested in the patients that have the disease or condition that the experimental drug is
expected to improve/cure.
 In addition to ensuring that the experimental drug is safe and effective in the patient population of
interest, Phase II studies are also designed to evaluate the effectiveness of the drug. The second
phase of testing may last from several months to a few years and may involve up to several
hundred patients. Most Phase II studies are well controlled, randomized trials.
 In general, the purpose of Phase II studies is to provide the pharmaceutical company and the FDA
with comparative information about the relative safety of the experimental drug, the proper
dosage needed to treat the condition, and the drug's effectiveness. Only about one-third of
experimental drugs successfully complete both Phase I and Phase II testing.
 Drug is given to Designed to test effectiveness patients who have the condition it’s intended
to treat/cure
 Often dose-ranging
 Control, randomized trials
 It’s Blinded
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16. Phase III Clinical Trials
In a Phase III study, an experimental drug is tested in several hundred to
several thousand patients with the disease/condition of interest. Most
Phase III studies continue to be randomized and blinded. The large-scale
testing provides the pharmaceutical company as well as the FDA with a
more thorough understanding of the drug's effectiveness, benefits/risks,
and range/severity of possible adverse side effects. Phase III studies
typically last several years. Seventy to 90 percent of drugs that enter
Phase III studies successfully complete this phase of testing. There are-
 Large-scale testing
 Several hundred to several thousand patients
 Typically last several years
 Most continue to be randomized and it is double-blinded
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17. Pre-approval Clinical Trials OPL
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18. New Drug Application
(NDA)
A New Drug Application (NDA) tells the full story of a drug. Its purpose is to
demonstrate that a drug is safe and effective for its intended use in the
population studied. A drug developer must include everything about a drug from
preclinical data to Phase 3 trial data in an NDA. Developers must include
reports on all studies, data, and analyses. Along with clinical results, developers
must include:
 Proposed labeling
 Safety updates
 Drug abuse information
 Any data from studies that may have been conducted outside the United States
 Patent information
 Institutional review board compliance information
 Directions for use
 An IND is filed with the FDA to begin human trials
 An NDA is filed with the FDA to obtain approval to market drug
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19. FDA Review
Once FDA receives an NDA, the review team decides if it is complete. If it is
not complete, the review team can refuse to file the NDA. If it is complete,
the review team has 6 to 10 months to make a decision on whether to
approve the drug. The process includes the following:
 FDA inspectors travel to clinical study sites to conduct a routine inspection.
The Agency looks for evidence of fabrication, manipulation, or withholding
of data.
 The project manager assembles all individual reviews and other documents,
such as the inspection report, into an “action package.” This document
becomes the record for FDA review. The review team issues a
recommendation, and a senior FDA official makes a decision.
 Each member of the review team conducts a full
review of his or her section of the application. For
example, the medical officer and the statistician
review clinical data, while a pharmacologist reviews
the data from animal studies. Within each technical
discipline represented on the team, there is also a
supervisory review.
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20. FDA Approval
In cases where FDA determines that a drug has been shown to be safe
and effective for its intended use, it is then necessary to work with
the applicant to develop and refine prescribing information. This is
referred to as “labeling.” Labeling accurately and objectively
describes the basis for approval and how best to use the drug. Often,
though, remaining issues need to be resolved before the drug can be
approved for marketing. Sometimes FDA requires the developer to
address questions based on existing data. In other cases, FDA
requires additional studies. At this point, the developer can decide
whether or not to continue further development. If a developer
disagrees with an FDA decision, there are mechanisms for formal
appeal.
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21. Timeline 3
Regulatory Operations Training 21
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22. Post Approval Clinical Research
 Phase IV Trials
 compare a drug with other drugs already in the market
 monitor a drug's long-term effectiveness and impact on a
patient's quality of life
 designed to determine the cost-effectiveness of a drug therapy
relative to other traditional and new therapies
 Marketing
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Regulatory Training on Drug Development Conducted by Md. Zakaria Faruki
Key Points of Phase 4:
Study Participants: Several thousand volunteers who have the
disease/condition
Purpose: Safety and efficacy
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23. FDA Post-Market Safety
Monitoring
Even though clinical trials provide important information on a drug’s efficacy and
safety, it is impossible to have complete information about the safety of a drug at
the time of approval. Despite the rigorous steps in the process of drug
development, limitations exist. Therefore, the true picture of a product’s safety
actually evolves over the months and even years that make up a product’s
lifetime in the marketplace. FDA reviews reports of problems with prescription
and over-the-counter drugs, and can decide to add cautions to the dosage or usage
information, as well as other measures for more serious issues. It is involved with
following terms-
 Supplemental Applications
 INDs for Marketed Drugs
 Manufacturer Inspections
 Drug Advertising
 Generic Drugs
 Reporting Problems
 Active Surveillance
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24. Summary of Drug Dev. Phases
Phase
I
Phase
II
Phase
III
Why?
Assess
safety,
toxicity, and
efficacy
Determine
safety and
dosage
Evaluate
efficacy,
assess
side
effects
Evaluate
efficacy,
monitor
adverse
reactions
from long
term use
Who /
What is
Tested?
Laboratory
and animal
studies
20-80
healthy
volunteers
100 to 300
patient
volunteers
w/ disease
1000 to
3000
patient
volunteers
w/ disease
How
long?
6-7 years ~1 year ~2 years ~3 years .5 - 2 years
Results
5,000
compounds
evaluated
1 drug
approved
Preclinical
Phase
FDA
Review
Phase
IV
File
IND
with
FDA
30d
5
evaluated in trials
File
NDA
at
FDA
Review NDA
for drug
approval or
disapproval
Annual
reporting
on
product
Additional
long term
testing
required
by FDA
Clinical Trials
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