The development of a new drug is a long, complex, and costly process taking at least 10 years and $500-1000 million. It involves pre-clinical studies in animals, followed by clinical trials in four phases with humans. Phase I establishes safety, Phase II establishes efficacy and side effects, Phase III tests efficacy in larger groups, and Phase IV monitors long-term safety after approval. After successful clinical trials, approval is sought from regulatory authorities like the FDA by submitting a New Drug Application before marketing.

1. Process of New Drug
Development & Approval
Dr. Marya Ahsan (MBBS, MD)

2. Introduction
• Drug development is a highly complex, tedious, competitive and
costly process
From the synthesis/identification of a candidate molecule, a new drug
development takes at least 10 years and costs 500-1000 million US$

3. Phases in the development of new drug
Synthesis/Isolation
of new compound
Pre-clinical studies
in animals: screening,
evaluation,
pharmacokinetic and
short-term toxicity testing
Scrutiny and grant
of permission for
clinical trials
Pharmaceutical
formulation,
standardization of
the compound
Clinical studies:
Phase I, Phase II,
Phase III
Review and grant
of marketing
permission
Post marketing
surveillance (Phase
IV studies)
(1 – 2 yrs) (2 – 4 yrs) (3 – 6 months) (0.5 – 1 year)
(3 – 10 years)(0.5 – 2 yrs)

4. Time line of invention of new drug

5. Approach to drug discovery
The usual approach to drug discovery is to screen a collection of
chemicals (library) for compounds with desired features or to
synthesize new compounds
Computer analysis is used for identifying ‘hits’ and ‘leads’

6. Discovery of potential drug molecule
• Exploration of natural sources (plants, animals, minerals, micro-organisms)
• Chemical synthesis of congeners of compounds with known
pharmacological property
• New classes of drugs can be developed after identification of novel
target of drug
• Molecular modelling
• Computational chemistry
• Recombinant DNA technology

7. Pre-clinical studies
• Before being administered to people, potential drugs are tested in
two species of animals:
One rodent (usually, mouse)
One non-rodent (often rabbit)

8. Pre-clinical studies
• Screening tests
• Tests on isolated organs, bacterial cultures
• Tests on animal models of human disease
• Confirmatory tests and analogous activity
• Systemic pharmacology
• Quantitative tests
• Pharmacokinetics
• Toxicity tests
Toxicity test include:
 Acute toxicity
 Subacute toxicity
 Chronic toxicity
 Reproduction &
teratogenicity
 Mutagenicity
 Carcinogenicity

9. IND license
• Before the drug candidate is administered in human subjects in a
clinical trial, the sponsor must file an “Investigational New Drug” or
IND application with the drug regulatory authority
IND describes in detail the following:
Preliminary evidence for efficacy in experiments
Complete pharmacology and toxicology of drug
Plan for investigating the drug in human subjects

10. Drug Regulatory Authority
• FDA (Food & Drug Authority) is the drug regulatory authority in the
US.
• It is established under the Food, Drug & Cosmetics Act
• It ensures the safety and efficacy of human and veterinary drugs,
biological products, medical devices, food supply, cosmetics and
products that emit radiation
Saudi Food & Drug Authority (SFDA) is
the government agency that
regulates drugs and medical devices
in Saudi Arabia.

11. Clinical trials
• Clinical trials of drugs are designed to acquire information about the
pharmacokinetic and pharmacodynamic properties of a candidate
drug IN HUMANS
A drug must be proven to be ‘efficacious’ and ‘safe’ before it can be marketed

12. Clinical trials
• Clinical trials are conducted in four phases:
• Phase I
• Phase II Establish safety and efficacy
• Phase III
• Phase IV Gives additional information
‘NDA’ application

13. Phase I clinical trials
• Drug is administered to ‘healthy volunteers’
• Small number of subjects are involved (usually < 100)
• Emphasis is on safety, tolerability and to detect any potentially
dangerous effects on vital functions
• Human pharmacokinetic parameters of the drug are measured for the
1st time

14. Phase II clinical trials
• Drug is administered to ‘patients’
• Usually 100-500 patients are selected (based on inclusion and exclusion
criteria)
Aim is to establish therapeutic efficacy, dose range and ceiling effect
Pharmacokinetic data is also collected

15. Phase III clinical trials
• Randomized double blind comparative trials are conducted in larger
number of patients (500 – 3000)
Safety and tolerability are assessed on a wider scale
Pharmacokinetic data is collected
Indications are finalized
Guidelines for therapeutic use are formulated

16. NDA application
• After completion of Phase III clinical trials, a ‘New Drug Application’ is
submitted to the licensing authority
• If the licensing authority is convinced, permission is granted for
marketing the drug

17. Phase IV clinical trials
• After the drug is marketed, data is collected about efficacy,
acceptability and adverse effects of the drug in the real field situation
• Very large number of patients are involved including special
populations (children, elderly, pregnant/lactating women and disease
conditions)
Also called Post-marketing surveillance
Uncommon/idiosyncratic adverse effects and adverse events on
long-term use are identified
Unsuspected drug-interactions are detected
Patterns of drug-utilization and additional indications may emerge

18. Typical characteristics of various phases of clinical
trials required for marketing of new drugs

19. Summary

20. Any Question??

21. References
• Goodman & Gillman’s: The Pharmacological Basis of Therapeutics,
13th edition. New York: McGraw-Hill, 2018