The Drug Development Process From Discovery to Market This workforce solution was funded by a grant awarded under the President’s Community-Based Job Training Grants as implemented by the U.S. Department of Labor’s Employment and Training Administration. The solution was created by the grantee and does not necessarily reflect the official position of the U.S. Department of Labor. The Department of Labor makes no guarantees, warranties, or assurances of any kind, express or implied, with respect to such information, including any information on linked sites and including, but not limited to, accuracy of the information or its completeness, timeliness, usefulness, adequacy, continued availability, or ownership. This solution is copyrighted by the institution that created it. Internal use by an organization and/or personal use by an individual for non-commercial purposes is permissible. All other uses require the prior authorization of the copyright owner.
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The Drug Development Process
From Discovery to Market
This workforce solution was funded by a grant awarded under the President’s Community-Based Job Training Grants as implemented by the U.S. Department of Labor’s Employment and Training Administration. The solution was created by the grantee and does not necessarily reflect the official position of the U.S. Department of Labor. The Department of Labor makes no guarantees, warranties, or assurances of any kind, express or implied, with respect to such information, including any information on linked sites and including, but not limited to, accuracy of the information or its completeness, timeliness, usefulness, adequacy, continued availability, or ownership. This solution is copyrighted by the institution that created it. Internal use by an organization and/or personal use by an individual for non-commercial purposes is permissible. All other uses require the prior authorization of the copyright owner.
Phase IPhase IPhase IPhase I Phase IVPhase IVPhase IVPhase IV
PreclinicalPreclinicalPreclinicalPreclinical
INDFiled
Phase IIIbPhase IIIbPhase IIIbPhase IIIb
NDAFiled
NDAApproved
• Laboratory and animal testing - Toxicology and pharmacokinetics• 1 - 3 years - Studies with various species and durations • 250 compounds
Drug Development: Preclinical
Safety PharmacologyIn vitro and in vivo studies conducted to determine whether this compound has any effects on:
• Brain –central nervous system
• Lungs –respiratory system
• Heart –cardiovascular system
Drug Development: Preclinical
Genetic ToxicologyIn vitro and in vivo studies conducted to determine whether this compound has the potential to induce mutations and chromosomal damage
• bacterial mutation
• cytogenetics
• mammalian gene mutation
Drug Development: Preclinical
Animal Toxicity Studies• Single- and multiple-dose toxicity studies• Developmental and reproductive
toxicology (DART)• Carcinogenicity• Special toxicity studies/evaluations
•Animals given a single dose by the intended route of exposure and monitored for 14 days
•Clinical signs•Information on overdose effects
•Minimum and median lethal dose
Repeat-Dose Toxicity Studies
•Study cumulative effects
•Extensive clinical
evaluation of test animals
–physical, neurologic,
and ophthalmic exams
–ECG evaluation
–Clinical and anatomic
pathology analyses
Drug Development: Preclinical
Developmental and Reproductive Toxicology (DART)
• Effects on male and female fertility• Teratogenic potential (embryo-fetal toxicity)• Effect on peri- and post-natal development of
offspring, including maternal development• Supports inclusion of women
in clinical trials
Drug Development: Preclinical
Carcinogenicity Studies• Test the potential to produce tumors in
animals• Lifetime exposure in rats and mice (2
years)• Large doses (MTD) are generally used • Effects may be due to exaggerated
pharmacodynamics• Not always needed in advance of safety
and efficacy trials
Drug Development: Preclinical
Exposure Assessment• A few different terms: toxicokinetics,
pharmacokinetics, ADME, bioanalytical• These all describe the science of
determining the levels of the drug that were absorbed into the blood stream or tissues and how long it stayed in the system.
• Key to determining dose levels and frequency the drug can be taken (e.g., two times/day, once/week, every 4 hours, etc.)
Drug Development: Preclinical
Definition “ADME”•Absorption – does the compound get into the body?
•Distribution – where does it go?
•Metabolism – what happens to it when in the body?
•Excretion – how does it get out?
0.1
1
10
100
1000
10000
0 4 8 12 16 20 24 28
Time (hr)
Plas
ma
Con
cent
rati
on (n
g/m
L) Male Rats
Female Rats
Filing an IND•Information filed with regulatory agency providing the results from the preclinical phase testing–Chemistry, manufacturing, and control information
–Pharmacology and toxicology information
–Clinical information/ proposed clinical studies to be conducted
• Purpose– Required prior to conducting
clinical studies in humans– Demonstrates the drug is safe
enough to administer to humans– Represents the initiation of the
first phase of clinical development
• i.e., Phase I or First in Human (FIH) studies
• Duration and Success Rates– 30 days for regulatory agency to