This SlideShare gives an overview on how a drug is discovered, researched, developed, tested and reviewed for approval. It follows the current standard of approval set by the Food and Drug Administration (FDA), a federal agency of the United States Department of Health and Human Services. The process is generally divided into 4 Stages: Pre-Clinical, Clinical, New Drug Application (NDA) Review & Post-Marketing.

1. From R&D & Clinical Trials to Review & Post-Marketing
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Clinical Trials &
Drug Approval Process
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2. Coronavirus Pandemic Series
The Drug Approval Process
• The FDA & centers of
evaluation
• Approval process pathway
• Pre-clinical
• Clinical
• NDA review
• Special designations
• Post-marketing
• Time & cost factors
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3. What is The FDA?
Source: https://www.drugwatch.com/fda/approval-process/
The U.S. Food and Drug
Administration (FDA) controls
the drug-approval process
and is tasked with reviewing
new drugs and medical
devices before companies
can sell them.
FDA is a government regulatory
agency within the U.S. Department
of Health and Human Services.
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The FDA has its headquarters in White Oak,
Maryland. The agency also has 223 field
offices and 13 laboratories.

4. Definition of a Drug (FDA)
Source: Drugs@FDA Glossary of Terms
A substance recognized
by an official
pharmacopoeia or
formulary.
A substance intended for
use in the diagnosis,
cure, mitigation,
treatment, or prevention
of disease.
A substance (other than
food) intended to affect
the structure or any
function of the body.
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5. Centers of Evaluation: CDER, CBER & CDRH
Source: US FDA
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CDER
• CENTER FOR DRUG
EVALUATION AND
RESEARCH
• Reviews new
compounds, generic
& over the counter
pharmaceuticals
• Also reviews
monoclonal
antibodies and
other therapeutic
proteins
CBER
• CENTER FOR
BIOLOGICS
EVALUATION AND
RESEARCH
• Reviews biologics
and related
products such as
vaccines, live
biotherapeutics
(probiotics), blood
products, and cell,
tissue, & gene
therapies
CDRH
• CENTER FOR
DEVICES AND
RADIOLOGICAL
HEALTH
• Reviews all medical
devices, as well as
overseeing the
manufacturing,
performance and
safety of these
devices.

6. General Stages of Drug Approval
Source: US FDA
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Phase 4
Detection of
serious
unexpected
adverse events
MedWatch
Postmarket
Studies
4: POST
MARKETING
Meeting
Application
Labeling
Facility
Inspection
Drug Approval
3: NDA REVIEW
Phase 1
20-80 subjects
Phase 2
>100 subjects
Phase 3
>1,000 subjects
NDA
2: CLINICAL
Drug
Development
Animal Testing
IND
Application
1: PRE-CLINICAL

7. Stage 1: Pre-Clinical
R&D, GLP, Animal Testing & IND Application
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8. Drug Discovery & Development
Source: https://www.fda.gov/patients/drug-development-process/step-1-discovery-and-development
The first step is for the ‘sponsor’
company to conduct research,
discover & develop new drugs.
Typically, new drugs are discovered
through:
• New insights into a disease process
• Tests of molecular compounds to find
possible beneficial effects against a
disease
• Existing treatments that have
unanticipated effects
• New technologies & pathways
After initial testing of thousands of potential
compounds, only a small number of
compounds would qualify.
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9. Screening of Promising Compounds
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Source: https://www.fda.gov/patients/drug-development-process/step-1-discovery-and-development
Absorption, metabolism & excretion
Potential benefits & mechanism of action
Dosage & delivery methods
Side effects or adverse events (toxicity)
How it affects different groups of people
How it interacts with other drugs

10. Pre-Clinical Research: GLP
Researchers must determine
whether a candidate has the
potential to cause serious harm,
also called ‘toxicity’.
FDA requires researchers to use
good laboratory practices (GLP).
The 2 types of preclinical research:
• In Vitro - in glass test tubes or plastic
vessels within a laboratory
• In Vivo - in a living organism, mainly
select species of animals
Source: https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research
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Facilities Equipment
SOPsPersonnel
Study
Reports
QA

11. Pre-Clinical Research: Animal Testing
Source: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32001L0083:EN:HTML
Animals are sometimes used
in the testing of drugs &
equipment to determine the
safety of the medical
product.
Animal testing typically involves 2
species, one of which must be a
non-rodent.
Choice of species is based on
which will give the best correlation
to human trials.
Animal testing has been reduced in recent
years both for ethical and cost reasons. Most
research will still involve animal-based
testing for the need of similarity in anatomy
and physiology.
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12. Pre-Clinical Activities
Source: https://www.fda.gov/drugs/drug-information-consumers/fdas-drug-review-process-continued
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Discovery
IDENTIFY TARGET
Identify a target
of disease to
detect, remedy or
prevent
Testing of
thousands of
compounds to
identify potential
candidates
Screening
LAB TESTS
Potential
compounds are
screened to
determine
potential benefits,
effectiveness on
target, toxicity,
etc.
Pre-Clinical
ANIMAL TESTS
Screened
candidates are
tested in animals
to determine
mechanism of
action, safety,
metabolism, &
efficacy.
Pre-clinical activities from drug discovery & development to animal tests can take
4.5–7 years before an IND application is filed.

13. Investigational New Drug (IND) Application
After several years of lab testing,
the sponsor can file an
Investigational New Drug (IND)
Application.
It would contain specific details
such as results from initial testing,
the drug’s composition & chemistry,
manufacturing and initial plans for
human testing.
The IND is reviewed by the FDA to
ensure the safety of clinical trials.
Source: https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research
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SAFETY
• Sponsor must provide sufficient
pre-clinical data to ensure that
clinical trials will be safe for
humans.
CONSENT
• Adequate informed consent to
protect the human subjects
during clinical trials.

14. Stage 2: Clinical Trials
Clinical Studies & Human Trials
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15. Clinical Trials of Investigational Drugs
Source: https://www.fda.gov/drugs/drug-information-consumers/fdas-drug-review-process-continued
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Phase1
SAFETY
20-80 healthy
volunteers
Determine safety,
side-effects,
metabolism &
excretion
*1 year Phase2
EFFECTIVENESS
>100’s patient
volunteers
Obtain preliminary
data on whether the
drug works or not
Compare with
similar patients
undergoing different
treatment
*2-3 years
Phase3
LARGE SAMPLE
>1,000’s (up to
3,000) in clinics &
hospitals
Gather more
information about
safety &
effectiveness,
dosage and combo
treatments with
other drugs
*3 years
Upon FDA's approval (of an IND), the investigational drug will enter 3 phases of clinical trials.
This process can take up to 6-8.5 years.

16. Clinical Studies: Human Trials
Source: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32001L0083:EN:HTML
At the end of Phase 2, the
sponsor would meet with FDA
officials to discuss how
large-scale studies in Phase 3
will be done.
Phase 3 studies begin if evidence
of effectiveness is shown in Phase
2. The number of subjects usually
ranges from several hundred to
about 3,000 people.
Sponsors often compile and present
promising Phase 2 data to encourage
participation from clinics & hospitals.
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17. Stage 3: NDA Review
New Drug Application Review & Approval
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18. After successful completion of
clinical trials, FDA officials
would meet with the sponsor
prior to submission of a New
Drug Application (NDA).
The sponsor must agree to
conduct post-market requirements
and commitment studies after the
FDA has approved a drug or
medical device.
Pre-NDA Review Meeting
The FDA uses post-market requirement and
commitment studies to gather additional
information about a product's safety,
efficacy, or optimal use.
Source: https://www.fda.gov/drugs/drug-information-consumers/fdas-drug-review-process-ensuring-drugs-are-safe-and-effective
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19. Source: https://www.drugs.com/fda-approval-process.html
New Drug Application (NDA)
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The NDA is the official
request for FDA
approval of a drug.
It contains thousands of
pages for the FDA to
review. The NDA includes
all data obtained from
both animal testing &
human trials, plus side
effects, dosing, and
effectiveness.
Credit: FDA History

20. Source: https://www.drugwatch.com/fda/approval-process/
Key Contents of NDA
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Manufacturing
Information
Animal Test
Results
Human Trials
(Clinical Data)
Proposed
Labeling

21. The FDA team has 60 days to
decide whether the NDA is to
be filed.
If the FDA files the NDA, a review
team is assigned to evaluate the
sponsor’s research on the drug’s
safety & effectiveness.
NDA reviews can take up to a
year and a half (6-8 months if
under priority review).
NDA Review Process
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Source: https://www.drugs.com/fda-approval-process.html
Credit: Policy & Medicine

22. NDA Review Activities
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Source: https://www.drugs.com/fda-approval-process.html
DRUG LABELING
Assure appropriate
information is communicated
to healthcare professionals &
consumers.
STATISTICS, TOXICOLOGY &
PHARMACOLOGY
Consistent data in all trial
results. Ensure safety &
effectiveness.
FACILITY INSPECTION
Ensure sponsor’s capacity to
manufacture drug according
to cGMP.
NDA reviews typically take 1–1.5 years.
Specially designated drugs can take as little as 6–8 months to review.

23. Special Designations Towards Rapid Availability
Source: https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research
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Facilitate development &
expedite review of drugs to
treat serious conditions & fill
an unmet medical need.
Regulations that allow drugs
for serious conditions that
filled an unmet medical need
to be approved based on a
surrogate endpoint (SE)*.
Expedite development &
review of drugs with
substantial improvement
over available therapy.
FDA’s goal is to act on an
application within 6
months.
Fast Track
Breakthrough
Therapy
Accelerated
Approval
Priority
Review
*Marker to ‘predict’ clinical benefit based on initial findings, allows faster approval.
Approval can be withdrawn if clinical trials fail to verify the said benefit(s).

24. Potential Accelerated Pathway: COVID-19 Vaccines
Source: BCG Analysis
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Start Phase 2 with
interim Phase 1 data
Phase 1 Phase 3
Phase 2
Commercial
Launch
Commercial scale-up
Small-scale clinical trials
Startup at financial risk
Scale to meet global
demand (billions of doses)
0
Years
1 2
Limited pre-
clinical testing
Data on SE for
protection*
Emergency use authorization for small-
volume release (millions of doses)
Discovery
*There are currently no clear markers on long-term protection against COVID-19 to
support a surrogate of protection endpoint. Marker would have to be defined.
Given the global pandemic situation, companies are moving
aggressively to accelerate COVID-19 vaccine development.

25. Source: BioCentury Inc. - End of the beginning for COVID-19 vaccines
Accelerated Timeline of COVID-19 Vaccines
Credit: BioCentury

26. Source: BioCentury Inc. - End of the beginning for COVID-19 vaccines
Accelerated Timeline of COVID-19 Vaccines
Credit: BioCentury

27. Source: https://www.news-medical.net/news/20200421/PiCoVacc-vaccine-candidate-for-COVID-19-effective-in-animal-trials.aspx
FDA Advisory committee
A group comprising
independent physicians and
other clinicians, meets to
discuss with the review team
and manufacturer of the
product.
After the meeting (often take 1-2
days), the Advisory Committee will
vote to recommend for approval,
or not, to the FDA.
The FDA often follows the advice of the
committee but is not obligated to do so.
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28. Upon final approval, the drug
becomes available for
physicians to prescribe.
Market availability depends on
patent disputes, manufacturing &
distribution issues, etc.
Pricing is usually revealed after
approval, although the FDA does
not consider pricing & economics
as part of the approval process.
Final Approval
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Source: https://www.drugs.com/fda-approval-process.html

29. Stage 4: Post-Marketing
Continuous Monitoring, Phase 4 Studies & Safety Updates
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30. Purpose of Post-Marketing
Source: https://www.fda.gov/patients/drug-development-process/step-5-fda-post-market-drug-safety-monitoring
It is not possible to
predict all of a drug’s
side effects during
clinical trials.
The role of post-
marketing safety
system is to detect
serious unexpected
adverse events in a
larger market.
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31. Source: https://www.fda.gov/patients/drug-development-process/step-5-fda-post-market-drug-safety-monitoring
Phase 4 Studies & MedWatch
At this stage, the sponsor will
provide periodic safety
updates, clinical data on
long-term effectiveness and
report cases of adverse
reactions to the FDA.
The MedWatch voluntary system
(run by the FDA) allows patients
and healthcare providers to report
side effects or other concerns.
Rare side effects are more likely to be found
when large numbers of patients use a drug
after it has been approved and marketed.
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32. Time & Cost Factors
Overall Timeline & Key Points of Consideration
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33. Time From Drug Discovery to Approval
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10,000
compounds
250
compounds
5 compounds
1
FDA
Approved
Drug
Stage 1
Drug Discovery Pre-clinical
Stage 2
Clinical Trials
Stage 3
NDA Review
4.5 – 7 years 6 – 8.5 years 1 – 1.5 years
Submit IND Submit NDA
Source: Pharmaceutical Research & Manufacture of America

34. Source: https://www.drugs.com/fda-approval-process.html
Factors That Affect Approval Times
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Special Designation
• Innovative & novel
• Fulfills an unmet need (i.e.,
diseases currently without
treatment options)
• Breakthrough therapies
• Potential to treat serious
conditions (i.e., during an
outbreak)
Approval Issues
• Incomplete or inconsistent
data, affecting NDA
• Unexpected safety issues
• Failure to show
effectiveness
• Unexpected
manufacturing problems &
arising issues

35. Source: https://www.drugs.com/fda-approval-process.html
Est. $2.6 Billion
For a sponsor to get
a new drug from the
laboratory onto the
pharmacy shelf.
Post-approval R&D costs
increases the estimate to
$2.87 billion.
- Tufts Center for the
Study of Drug
Development
May 2016
4,500 Drugs &
Medical Devices
Recalled Annually
There is no guarantee
for safety, despite
approval from FDA.
Average of 12 to 15
Years
Time taken to
conduct R&D, clinical
trials & approval
process.
Only 1 out of 1,000
0.1% of compounds
that enter laboratory
testing will ever make
it to human trials.
Cost Factors in Drug Development & Approval
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36. Critical Milestones vs. Company valuation
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Source: Xeraya Strategic Research
Pre-
Clinical
Phase 1
Clinical
Phase 2
Clinical
Phase 3
Clinical
Post-
Marketing
• More data on
safety &
effectiveness
• Dosage
• Drug combos
• Effectiveness
• Compare with
current drugs• Human trials
• Safety
• Lab tests
• Safety
• Efficacy
• Phase 4 post-
market studies
IND
NDA
Company’s valuation increases over time

37. Source: PwC, Market Realist, The Pharma Letter
Est. $1.6 Trillion
Projected market
value for 2020.
• Demand for medicines
increasing rapidly
• New forms of medicine
in R&D pipelines
• Expanding middle
class populations
- PwC Pharma
Vision 2020
$1.3 Trillion in 2019
Revenue generated
for global pharma,
$1.2 tn in 2019 and
$980.1 bn in 2013.
Majority Profits by
Big Pharma (2019)
Pfizer – $51.75 bn
Roche – $50 bn
Novartis – $47.45 bn
Merck – $46.84 bn
Biggest Spender:
The US
Americans spend
$457 billion on
prescription drugs in
2015.
Key Market Figures in Pharmaceutical Industry
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38. • The FDA’s drug approval process is divided into 4 key stages:
pre-clinical, clinical, NDA review & post-marketing.
• The sponsor must successfully complete 3 Phases of clinical
trials in order to submit a New Drug Application for approval.
• On average, it costs $2.6 billion and takes 12-15 years from
development to approval. Given the demand for new
therapeutics & vaccines, the benefits far outweighs the cost.
• Company valuation increases over time, particularly when a
sponsor achieves critical milestones during clinical trials.
Conclusion
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