This document provides an overview of the drug development and approval process, including: 1) Drug discovery typically involves new disease insights, testing molecular compounds, existing treatments with unexpected effects, or new technologies. Thousands of candidates are narrowed down based on early testing. 2) Once a compound looks promising, development involves experiments to understand absorption, benefits, dosage, delivery method, side effects, and effectiveness compared to other drugs. 3) The FDA approval process includes multiple phases of clinical trials involving healthy volunteers and patients to evaluate safety, efficacy, and side effect management strategies before approval or accelerated approval in some cases.

1. PRODUCT DEVELOPMENT AND TECHNOLOGY TRANSFER (MQA – 104 T)
UNIT I
Principles of Drug Discovery and Development, Clinical Research Process
Presented By
V. Manikandan,
Roll No. 2061050003,
M. Pharm (Pharmaceutical Quality Assurance) – I Year,
Batch : 2020-2022,
Department of Pharmacy,
Annamalai University.
Submitted to
Dr. R. Murali, M. Pharm., Ph. D,
Assistant Professor,
Department of Pharmacy,
Annamalai University.

2. Drug Discovery and Development
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.

3. Development
• Once researchers identify a promising compound for development, they conduct experiments to gather
information on,
i. How it is absorbed, distributed, metabolized, and excreted.
ii. Its potential benefits and mechanisms of action.
iii. The best dosage.
iv. The best way to give the drug (such as by mouth or injection).
v. Side effects or adverse events that can often be referred to as toxicity.
vi. How it affects different groups of people (such as by gender, race, or ethnicity) differently.
vii. How it interacts with other drugs and treatments.
viii. Its effectiveness as compared with similar drugs.
Development & Approval Process of Drugs
i. Developing new drugs
ii. FDA approval: what it means

4. Developing New Drugs
• American consumers benefit from having access to the safest and most advanced pharmaceutical system in the
world. The main consumer watchdog in this system is FDA's Center for Drug Evaluation and Research (CDER).
• The center's best-known job is to evaluate new drugs before they can be sold. CDER's evaluation not only
prevents quackery, but also provides doctors and patients the information they need to use medicines wisely. The
center ensures that drugs, both brand-name and generic, work correctly and that their health benefits outweigh
their known risks.
• Drug companies seeking to sell a drug in the United States must first test it. The company then sends CDER the
evidence from these tests to prove the drug is safe and effective for its intended use. A team of CDER physicians,
statisticians, chemists, pharmacologists, and other scientists reviews the company's data and proposed labeling.
• If this independent and unbiased review establishes that a drug's health benefits outweigh its known risks, the
drug is approved for sale. The center doesn't actually test drugs itself, although it does conduct limited research
in the areas of drug quality, safety, and effectiveness standards.

5. FDAApproval: What it means
• FDA approval of a drug means that data on the drug’s effects have been reviewed by CDER, and the drug is
determined to provide benefits that outweigh its known and potential risks for the intended population. The
drug approval process takes place within a structured framework that includes:
• Analysis of the target condition and available treatments - FDA reviewers analyze the condition or illness
for which the drug is intended and evaluate the current treatment landscape, which provide the context for
weighing the drug’s risks and benefits. For example, a drug intended to treat patients with a life-threatening
disease for which no other therapy exists may be considered to have benefits that outweigh the risks even if
those risks would be considered unacceptable for a condition that is not life threatening.
• Assessment of benefits and risks from clinical data - FDA reviewers evaluate clinical benefit and risk
information submitted by the drug maker, taking into account any uncertainties that may result from imperfect
or incomplete data. Generally, the agency expects that the drug maker will submit results from two well-
designed clinical trials, to be sure that the findings from the first trial are not the result of chance or bias.

6. • In certain cases, especially if the disease is rare and multiple trials may not be feasible, convincing evidence from
one clinical trial may be enough. Evidence that the drug will benefit the target population should outweigh any
risks and uncertainties.
• Strategies for managing risks - All drugs have risks. Risk management strategies include an FDA-approved
drug label, which clearly describes the drug’s benefits and risks, and how the risks can be detected and managed.
Sometimes, more effort is needed to manage risks. In these cases, a drug maker may need to implement a Risk
Management and Mitigation Strategy (REMS).
Accelerated Approval
• In some cases, the approval of a new drug is expedited. Accelerated Approval can be applied to promising
therapies that treat a serious or life-threatening condition and provide therapeutic benefit over available therapies.
This approach allows for the approval of a drug that demonstrates an effect on a “surrogate endpoint” that is
reasonably likely to predict clinical benefit, or on a clinical endpoint that occurs earlier but may not be as robust
as the standard endpoint used for approval.

7. • This approval pathway is especially useful when the drug is meant to treat a disease whose course is long, and
an extended period of time is needed to measure its effect.
• After the drug enters the market, the drug maker is required to conduct post-marketing clinical trials to verify
and describe the drug’s benefit. If further trials fail to verify the predicted clinical benefit, FDA may withdraw
approval.
Drug Development Designations
• The agency also employs several approaches to encourage the development of certain drugs, especially drugs
that may represent the first available treatment for an illness, or ones that have a significant benefit over existing
drugs.
• These approaches, or designations, are meant to address specific needs, and a new drug application may receive
more than one designation, if applicable. Each designation helps ensure that therapies for serious conditions are
made available to patients as soon as reviewers can conclude that their benefits justify their risks.

8. • Fast Track is a process designed to facilitate the development and advance the review of drugs that treat serious
conditions, and fill an unmet medical need, based on promising animal or human data. Fast tracking can get
important new drugs to the patient earlier. The drug company must request the Fast Track process.
• Breakthrough Therapy designation expedites the development and review of drugs that are intended to treat a
serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial
improvement over available therapy. A drug with Breakthrough Therapy designation is also eligible for the Fast
Track process. The drug company must request a Breakthrough Therapy designation.
• Priority Review means that FDA aims to take action on an application within six months, compared to 10
months under standard review. A Priority Review designation directs attention and resources to evaluate drugs
that would significantly improve the treatment, diagnosis, or prevention of serious conditions.

9. Clinical Research Process
Preclinical Research
• 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:
i. In Vitro
ii. In Vivo
• 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:
i. Study conduct
ii. Personnel
iii. Facilities
iv. Equipment
v. Written protocols

10. vi. Operating procedures
vii. Study reports
viii. 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.
Clinical Research
• 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.
i. Designing Clinical Trials
ii. Clinical Research Phase Studies

11. iii. The Investigational New Drug Process
iv. Asking for FDAAssistance
v. FDA IND Review Team
vi. Approval
Designing 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. Then, they decide:
i. Who qualifies to participate (selection criteria)
ii. How many people will be part of the study
iii. How long the study will last
iv. Whether there will be a control group and other ways to limit research bias
v. How the drug will be given to patients and at what dosage

12. vi. What assessments will be conducted, when, and what data will be collected
vii. How the data will be reviewed and analyzed
Clinical Research Phase Studies
Phase 1
Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.
Length of Study: Several months
Purpose: Safety and dosage
• During phase 1 studies, researchers test a new drug in normal volunteers (healthy people). In most cases, 20 to
80 healthy volunteers or people with disease/condition participate in Phase 1. However, if a new drug is
intended for use in cancer patients, researchers conduct Phase 1 studies in patients with that type of cancer.
• Phase 1 studies are closely monitored and gathered information about how a drug interacts with the human body.
Researchers adjust dosing schemes based on animal data to find out how much of a drug the body
• Can tolerate and what its acute side effects are.

13. • As a Phase 1 trial continues, researchers answer research questions related to how its work in the body, the side
effects associated with increased dosage, and early information about how effective it is to maximize possible
benefits. This is important to the design of Phase 2 studies.
• Approximately 70% of drugs move to the next phase
Phase 2
Study Participants: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years
Purpose: Efficacy and side effects
• In Phase 2 studies, researchers administer the drug to a group of patients with the disease or condition for which
the drug is being developed. Typically involving to show whether the drug will be beneficial.
• Instead, Phase 2 studies provide researchers with additional safety data. Researchers use these data to refine
research question, develop research method, and design new phase 3 research protocols.
• Approximately 33% of drugs move to the next phase

14. Phase 3
Study Participants: 300 to 3,000 volunteers who have the disease or condition
Length of Study: 1 to 4 years
Purpose: Efficacy and monitoring of adverse reactions
• Researchers design Phase 3 studies to demonstrate whether or not a product offers a treatment benefits to a
specific population. Sometimes known as pivotal studies, these studies involve 300 to 3000 participants.
• Phase 3 studies provide most of the safety data. In previous studies, it is possible that less common side effects
might have gone undetected.
• Because these studies are larger and longer in duration, the results are more likely to show long term or rare side
effects.
• Approximately 25-30% of drugs move to the next phase
Phase 4
Study Participants: Several thousand volunteers who have the disease/condition
Purpose: Safety and efficacy

15. • Phase 4 trials are carried out once the drug or device has been approved by FDA during the Post-Market Safety
Monitoring.
The Investigational New Drug Process
• 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:
i. Animal study data and toxicity (side effects that cause great harm) data
ii. Manufacturing information
iii. Clinical protocols (study plans) for studies to be conducted
iv. Data from any prior human research
v. Information about the investigator
Asking for FDAAssistance
• Drug developers are free to ask for help from FDA at any point in the drug development process, including:

16. i. Pre-IND application, to review FDA guidance documents and get answers to questions that may help
enhance their research
ii. After Phase 2, to obtain guidance on the design of large Phase 3 studies
iii. Any time during the process, to obtain an assessment of the IND application
FDA IND Review Team
• The review team consists of a group of specialists in different scientific fields. Each member has different
responsibilities.
i. Project Manager
ii. Medical Officer
iii. Statistician
iv. Pharmacologist
v. Pharma kineticist
vi. Chemist
vii. Microbiologist

17. 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. FDA responds to IND
applications in one of two ways:
i. Approval to begin clinical trials.
ii. Clinical hold to delay or stop the investigation. FDA can place a clinical hold for specific reasons,
including:
a. Participants are exposed to unreasonable or significant risk.
b. Investigators are not qualified.
c. Materials for the volunteer participants are misleading.
d. The IND application does not include enough information about the trial’s risks.
This process continues until the developer decides to end clinical trials or files a marketing application. Before filing
a marketing application, a developer must have adequate data from two large, controlled clinical trials.

18. References
 https://www.fda.gov
 The Pharmaceutical Sciences ; The Pharma Path Way ‘Pure and Applied Pharmacy’ By D. A Sawant, Pragathi
Books Pvt .Ltd.

19. THANK YOU