NEW DRUG DEVELOPMENT

AND APPROVAL PROCESS

 LEARNING OBJECTIVES
1. Give examples of the sources of new drugs
2. Differentiate between the various methods of drug discovery
3. Define pharmacology, drug metabolism, and toxicology
4. Differentiate between Phase 1, Phase 2, Phase 3, and Phase
4 clinical trials
5. Compare and contrast an Investigational New Drug (IND)
Application from a New Drug Application (NDA)
 SOURCES OF NEW DRUGS
• New drugs may be DRUGS SOURCES USES
discovered from a variety Reserpine Rauwolfia Hypotensive
of natural sources serpentina agent
Tranquilizer
Vinblastine, Vinca rosa Anti tumor
Vincristine
Taxol Taxus Treatment for
brevifolia Acute Leukemia,
Hodgkin disease,
Lymphocytic
lymphoma
 LEAD COMPOUND
• is a prototype chemical compound
that has a fundamental desired
biologic or pharmacologic activity.
• Although active, the lead compound
may not possess all of the features
desired, such as potency,
absorbability, solubility, low toxicity,
and so forth.
 PRODRUG
• is a term used to describe a compound that
requires metabolic biotransformation after
administration to produce the desired
pharmacologically active compound.
• The conversion of an inactive prodrug to an
active compound occurs primarily through
enzymatic biochemical cleavage.
• Example: enalapril maleate (Vasotec)
SOLUBILITY
• A prodrug may be designed to possess solubility advantages
over the active drug, enabling the use of specifically desired
dosage forms and routes of administration.
ABSORPTION
• A drug may be made more water or lipid soluble, as desired, to
facilitate absorption via the intended route of administration.
BIOSTABILITY
• If an active drug is prematurely destroyed by biochemical or
enzymatic processes, the design of a prodrug may protect the
drug during its transport in the body.
PROLONGED RELEASE
• Depending on a prodrug’s rate of metabolic conversion to an
active drug, it may provide prolonged drug release and
extended therapeutic activity
TOXICOLOGY
• Toxicology deals with the adverse or undesired effects of drugs.
Although the ability to predict the safe use of a new drug in
humans based on preclinical animal studies is desirable, it is not
entirely achievable
DRUG METABOLISM
(a) the extent and rate of drug absorption from various routes of
administration, including the one intended for human use;
(b) the rate of distribution of the drug through the body and the
site or sites and duration of the drug’s residence;
(c) the rate, primary and secondary sites, the mechanism of the
drug’s metabolism in the body, and the chemistry and
pharmacology of any metabolites; and
(d) the proportion of administered dose eliminated from the body
and its rate and route of elimination.
 CLINICAL RESEARCH
PHASE STUDIES
PHASE 1
• Study participants: 20-100 healthy volunteers or people with the
disease/condition
• Length of study: several months
• Purpose: safety and dosage
• Approximately 70% of drugs move to the next phase
 CLINICAL RESEARCH
PHASE STUDIES
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
• Approximately 33% of drugs move to the next phase
 CLINICAL RESEARCH
PHASE STUDIES
PHASE 3
• Study participants: 300 – 3,000 volunteers who have the
disease/condition
• Length of study: 1 – 4 years
• Purpose: efficacy and monitoring of adverse reactions
• Approximately 25-30% of drugs move to the next phase
 CLINICAL RESEARCH
PHASE STUDIES
PHASE 4
• Post-Marketing Surveillance
• Study participants: several thousand volunteers who have the
disease/condition
• Purpose: safety and efficacy
 DRUG DEVELOPMENT AND
APPROVAL PROCESS
INVESTIGATIONAL NEW DRUG (IND)
- to protect the rights and safety of the subjects
- to ensure that the investigational plan is sound and is designed
to achieve the stated objectives

NEW DRUG APPLICATION (NDA)

- to gain permission to market the drug product