Stages of drug development

Pharmacology lab MSc.Ikhlas Jarrar

Introduction
Average time to develop new drug is 10 -12 years. On an average out of 10,000 30,000 potential substances only 1 could make it to the market. As per 2006 estimates, the cost of bringing a new drug could vary from 500 million to 2,000 million USD.

Life Cycle for new drug :

Historical Timelines :
Historical Timelines Elixir

sulfanilamide disaster

Thalidomide crisis

1906 No Regulatory control for Drug safety

1938

1937

1961

Federal Food and Drug Act passed

Stages in Drug Development :

Stages in Drug Development 1. Drug Discovery 2. Pre-Clinical Testing 3. Phase I Clinical Trials 4. Phase II Clinical Trials 5. Phase III Clinical Trials 6. New Drug Application (NDA) / Biologics License Application (BLA) 7. Phase IV and Beyond

Drug Discovery :
Determine the target disease Determine each component of disease :
Symptoms Target organ Biochemical pathways Chemically synthesized compound Biologically synthesized compound Computer simulated compound

Search for the target drug :

Isolate the compound Proceed to next Stage

Pre CLINICAL TRIALS :

Evaluation of acute and short term toxicity in animals. It Involves :
-Lethal dose determination -Effect of dose at normal level for short/Long term

Assess how the drug is absorbed/distributed/metabolized and excreted in animals. Proceed to next Stage.

IND program
It is the means by which a pharmaceutical company obtains permission to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. The FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk. If the application is approved, the candidate drug usually enters a Phase 1 clinical trial.

Phase 1 CLINICAL TRIALS :

Begins after 30 days of filing IND. Drug given to 20-100 healthy volunteers
Duration could vary from 1 month to 1 year.

Following is studied here :

Drug absorption/Metabolism in human. Effect on organs and tissues. -Side affect of different dosages. Thus early evidences on effectiveness are achieved.

Proceed to next Stage

Phase 2 CLINICAL TRIALS :

Drug given to 100 - 300 patient volunteers Duration could vary from 1 year to 2 years
Cost could vary from $10 - $100 million. Following is studied here : Drug effectiveness in treating the disease. Short term side effects in patients Less than 1/3rd of INDs survive phase 2

Proceed to next Stage.

Phase 3 CLINICAL TRIALS :

FDA consulted before beginning phase 3
Drug given to 1000-3000 patient volunteers Duration could vary from 3 years to 4 years. Cost could vary from $10 - $500 million

Following is studied here :

Safety of Drug [ Benefits v/s risk analysis ] Long term side effects in patients

Proceed to next Stage.

NDA
NDA Refers to New Drug Application Formal proposal for the FDA to approve a new drug for sale in the U.S. Sufficient evidences provided to FDA to establish:
Drug is safe and effective. Benefits outweigh the risks. Proposed labeling is appropriate.

Market Launch/Phase 4 :
launched to the Market Additional post marketing testing of patients to
Support the use of the approved indication Finding new therapeutic opportunities Extending use of the drug to different classes of patients like children