FDA Drug Development

Process
Course Leader
Dr. Sharon Furtado

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Learning Objectives

At the end of this session, student will be able to

• Outline the major steps in drug development process
• Summarize each phase of drug development
• Appraise the importance of each stage

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The Drug Development Process

Post
FDA review Market
Safety
Clinical Monitoring
Research
Preclinical
Research
Discovery &
Devpt

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Step 1: Discovery and
Development
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

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Step 1: Discovery and
Development

….Contd
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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Step 2: 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:
In Vitro

In Vivo

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Step 2: Preclinical Research

• FDA requires researchers to use good laboratory practices (GLP), defined in

medical product development regulations, for preclinical laboratory studies

• The GLP regulations are found in 21 CFR Part 58.1: Good Laboratory Practice for
Nonclinical Laboratory Studies

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Step 2: Preclinical Research

GLP guidelines 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

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Step 3: Clinical Research

• “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)

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Designing Clinical Trials

Researchers review prior information about the drug to develop research questions and
objectives and decide
• Who qualifies to participate (selection criteria)?
• How many people will be part of the study?
• How long the study will last?
• Whether there will be a control group and other ways to limit research bias
• How the drug will be given to patients and at what dosage?
• What assessments will be conducted, when, and what data will be collected?
• How the data will be reviewed and analyzed?

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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:
• Animal study data and toxicity (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

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Clinical Trial Phases

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Clinical Trial Phases

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Clinical Trial Phases

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Clinical Trial Phases

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FDA IND Review Team

1. Project Manager: Coordinates the team’s activities throughout the review process,
and is the primary contact for the sponsor.

2. Medical Officer: Reviews all clinical study information and data before, during, and
after the trial is complete.

3. Statistician: Interprets clinical trial designs and data, and works closely with the
medical officer to evaluate protocols and safety and efficacy data

4. Pharmacologist: Reviews preclinical studies

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FDA IND Review Team

5. Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism, and

excretion processes. Interprets blood-level data at different time intervals from clinical
trials, as a way to assess drug dosages and administration schedules.

6. Chemist: Evaluates a drug’s chemical compounds. Analyzes how a drug was made and
its stability, quality control, continuity, the presence of impurities, etc.

7. Microbiologist: Reviews the data submitted, if the product is an antimicrobial product,

to assess response across different classes of microbes

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IND 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:

Approval to begin clinical trials.

Clinical hold to delay or stop the investigation

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IND Approval

FDA can place a clinical hold for specific reasons, including:

Participants are exposed to unreasonable or significant risk
Investigators are not qualified
Materials for the volunteer participants are misleading
The IND application does not include enough information about the trial’s risks

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Clinical Research

• The developer is responsible for informing the review team about new protocols,
as well as serious side effects seen during the trial

• This information ensures that the team can monitor the trials carefully for signs
of any problems

• After the trial ends, researchers must submit study reports

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Step 4: FDA Drug Review

• If a drug developer has evidence from its early tests and preclinical and clinical
research that a drug is safe and effective for its intended use, the company can
file an application to market the drug

NEW DRUG APPLICATION

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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

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New Drug Application (NDA)

Along with clinical results, developers must include:

• Proposed labeling
• Safety updates
• Drug abuse information
• Patent information
• Any data from studies that may have been conducted outside the United States
• Institutional review board compliance information
• Directions for use

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NDA 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

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NDA Review

• Each member of the review team conducts a full review of his or her section of
the application

• 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

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Step 5: FDA Post-Market Drug
Safety Monitoring

• 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

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Supplemental Applications

• Developers must file a supplemental application if they wish to make any

significant changes from the original NDA

• Generally, any changes in formulation, labeling, or dosage strength must be

approved by FDA before they can be made

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INDs for Marketed Drugs

• If sponsors want to further develop an approved drug for a new use, dosage
strength, new form, or different form (such as an injectable or oral liquid, as
opposed to tablet form), or if they want to conduct other clinical research or a
post-market safety study, they would do so under an IND

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Manufacturer Inspections

• FDA officials conduct routine inspections of drug manufacturing facilities across the
United States, and abroad if approved products are manufactured overseas

• Manufacturers may be informed of inspections in advance, or the inspections may be

unannounced

• Inspections may be routine or caused by a particular problem or concern

• The purpose of these inspections is to make sure that developers are following good
manufacturer practice. FDA can shut down a facility if minimum standards are not met

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Generic Drugs

• New drugs are patent protected when they are approved for marketing

• This means that only the sponsor has the right to market the drug exclusively

• Once the patent expires, other drug manufacturers can develop the drug, which
will be known as a generic version of the drug

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Generic Drugs

Generic drugs are comparable to brand name drugs and must have the same:

• Dosage form

• Strength

• Safety

• Quality

• Performance characteristics

• Intended use
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Abbreviated New Drug Application
(ANDA)

• Because generic drugs are comparable to drugs already on the market, generic
drug manufacturers do not have to conduct clinical trials to demonstrate that
their product is safe and effective

• Instead, they conduct bio-equivalence studies and file an Abbreviated New Drug
Application

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