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Stages of drug development Stages of Drug Development
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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 2010 estimates, the cost of bringing a new drug
could vary from 500 million to 2,000 million USD. Stages of Drug
Development
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Historical Timelines19061937No Regulatory control for Drug
safetysulfanilamide disasterFederal Food, Drug and Cosmetic Act
passed19381961Thalidomide crisisStages of Drug Development
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Lessons LearnedAs a result of the sulphanilamide and thalidomide
tragedy, the following lessons were learned:Pharmaceutical products
should be systematically tested for developmental effects prior to
marketing.There are differences in species sensitivity and
manifestations of developmental toxicity.Use of a second species or
more thoroughgoing interpretation of results in a single species
(taking pharmacokinetics into consideration) are important
considerations in drug testing.
Stages of Drug Development
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Stages in Drug Development Drug Discovery Pre-Clinical Testing
Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical
Trials New Drug Application (NDA) Phase IV and Beyond Stages of
Drug Development
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Life Cycle for new drug :
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Concepts of Drug DevelopmentPharmacokinetics (PK): (Absorption,
Distribution, Metabolism & Excretion - ADME) Pharmacodynamics
(PD): (effects on organs or systems)-- Evaluation or quantification
of what the body does to a drug substance over time-- Evaluation or
quantification of what the drug substance does to the body over
time, and over drug concentrations
Stages of Drug Development
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Determine the target disease Determine each component of disease
: Symptoms Target organ Biochemical pathways Search for the target
drug : -Chemically synthesized compound Biologically synthesized
compound Computer simulated compound Isolate the compound Proceed
to next StageDrug Discovery
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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 termAssess how the drug is
absorbed/distributed/metabolized and excreted in animals. Proceed
to next Stage. Drug Discovery
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IND programIt 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.
Drug Discovery
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Phase 1 CLINICAL TRIALS :
Begins after 30 days after IND acceptance. 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
StageDrug Discovery
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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. Drug Discovery
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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. Drug Discovery
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NDANDA 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. Drug
Discovery
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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 Drug
Discovery
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