The drug development process involves lengthy preclinical and clinical testing that can take over 12 years and cost $350 million. It begins with drug discovery followed by preclinical studies to test the drug's toxicity, pharmacokinetics, and efficacy in animals. If successful, an IND application is submitted to the FDA to begin human clinical trials. Clinical trials involve 4 phases to test the drug's safety and efficacy in humans. If phase 3 is successful, an NDA is submitted for FDA review and potential approval to market the new drug. Post-approval monitoring continues to ensure safety.

1. DRUG DEVELOPMENT AND
DISCOVERY
BY : GROUP FOUR

2. OBJECTIVES
Learn the processes involved in drug discovery and development
Define the phases involved in FDA drug approval
be aware of why/how new drugs are discovered
know the processes involved in drug discovery and development
see where pharmacologists/bioscientists may contribute
know about the difficulties and dangers inherent in the drug development
process.
WOLYITA UNIVERSITY DEPT. OF
PHARMACY

3. A substance used in the diagnosis, treatment, or prevention
of a disease or as a component of a medication recognized
or defined by the U.S. Food, Drug, and Cosmetic Act.
A drug is any chemical or biological substance, synthetic or
non-synthetic that can alter the structure and function of an
organism.
09/07/2007 DEPT. OF PHARMACEUTICS 3
drug
Introduction

4. The discovery and development of new medicines is along,
complicated process. Each success is built on many, many
prior failures.
Advances in understanding human biology and disease are
opening up exciting new possibilities for break through
medicines. At the same time, researchers face great
challenges in understanding and applying These advances
to the treatment of disease.
These possibilities will grow as our scientific knowledge
expands and becomes increasingly complex. Research-
based pharmaceutical companies are committed to
advancing science and bringing in new medicines to patients

5. THE CHANGED CONTEXT
OF DRUG DISCOVERY
AND DEVELOPMENT
The 1800s: natural sources; limited possibilities;
prepared by individuals; small scale; not purified,
standardized or tested; limited administration; no
controls; no idea of mechanisms.
The 1990s: synthetic source; unlimited possibilities;
prepared by companies; massive scale; highly
purified, standardized and tested; world-wide
administration; tight legislative control; mechanisms
partly understood.

6. SOURCES OF DRUGS
Animal insulin (pig, cow)
growth hormone (man)
Plant digitalis (digitalis purpurea - foxglove)
morphine (papaver somniferum)
Inorganic arsenic mercury
lithium
Synthetic chemical (propranolol)
biological (penicillin)
biotechnology (human insulin)

7. DRUG
DISCOVERY/DEVELOPME
NT PROCESS
discovery; refinement; chemical & biological
characterisation
safety & toxicity in animals; formulation development
volunteer studies; patient studies regulatory process
marketing
post registration
monitoring
lessons
&
development
Discovery=find new active structure : Development=convert it to a useful drug

8. RESEARCH AND
DEVELOPMENT
PROCESS (R&D)
Development of new drugs is a complex and costly process
It takes an average of 12 years and about $350 million to get a
new drug from the laboratory to the pharmacy shelf
R&D involves discovery (preclinical studies) and development
(clinical studies)
Only one in 1000 compounds which begin laboratory testing
will make it to human testing

9. ROLE OF FDA
The Food and Drug Administration (FDA) is required to review
and approve all new drugs in the United States
The FDA reviews and evaluates new drugs based on the
evidence presented from the clinical research studies
performed by the drug sponsor-typically a pharmaceutical
company

10. PRECLINICAL STUDIES
Synthesis and purification of the new drug
Pharmacology of the new drug:
 Pharmacokinetics: absorption, distribution, metabolism, excretion,
half-life
 Pharmacodynamics: mechanism of action and estimates of
therapeutic effects
 Toxicology including carcinogenicity, mutagenicity, and
teratogenicity
Efficacy studies on animals

11. IND
Investigational New Drug (IND): Application for permission to
administer a new drug to humans
Outlines the proposal to use the new drug for human testing in
clinical trials
Studies in humans can only begin after IND is reviewed and
approved by the FDA and an institutional review board (IRB)

12. CLINICAL STUDIES
Phase 1: Efficacy studies on healthy volunteers
Phase 2: Clinical studies on a limited scale
Phase 3: Comparative studies on large number of patients
Phase 4: Continued comparative studies. Registration and
market introduction

13. PHASE 1
Typically involves 20-80 healthy volunteers (no women of
childbearing potential)
Emphasis is on drug safety
Goal is to identify major side effects, metabolism and routes of
excretion
Lasts about 1 year
About 70% of drugs will pass this phase

14. PHASE 2
Typically involves 100-300 individuals who have the target
disease
Emphasis is on effectiveness
Patients receiving the drug are compared to similar patients
receiving a placebo or another drug
Lasts about 2 years
About 33% of drugs will pass this phase

15. PHASE 3
Typically involves 1000-3000 patients
Emphasis is on safety and effectiveness
Investigates through well-controlled studies different
populations and different dosages as well as uses new drug in
combination with other drugs
Lasts about 3 years
25-30% of drugs will pass this phase

16. NDA
Pre-NDA period: FDA and drug sponsors meet
Submission of NDA: Formal step asking the FDA to consider
approving a drug for marketing
FDA has 60 days to decide whether it will file it for approval
consideration
If filed, a review team is assigned to evaluate the new drug

17. FDA ROLE
The review team evaluates the research on the safety of the
drug and its effectiveness
The FDA reviews the information to go on the drug label
It inspects the facilities where the drug will be manufactured
The application will be classified as “approvable” or “not
approvable”

18. FDA ROLE
If approvable, the FDA requests additional information from the
sponsor
The NDA is again reviewed
Following drug approval, sponsors of the drug will be required
to continually assess the safety of the drug

19. PHASE 4
Post-market surveillance of the drug to continually assess the
safety of the drug
May include incidence and severity of rare adverse reactions,
cost-effectiveness analyses, comparative trials, and quality of
life studies

20. SUMMARY OF DRUG
DEVELOPMENT AND
EVALUATION

22. 22
QUESTIONS?