Pharm: Drug Discovery Flashcards
What is a generic drug?
equivalent of drug that has been FDA approved but is being marketed after patent protection for initial drug has expired
What is a lead compound?
chemical entity that can be used as a starting point for development
signs of a good one: reasonably potent, obtained synthetically or produced biosynthetically if a protein, potential to make easy chemical modifications, “drug like”
Where does drug development begin?
knowledge of biology
clinical observation
screening libraries of chemical compounds
good luck/chance favors prepared mind
repurposing existing drugs (modification requires retesting)
What do you do when you have a lead?
optimize properties in convenient experimental system
test best candidate molecules in animals
evaluate results, do more optimization, test again
repeat cycle until compound that justifies testing in humans
Why is animal testing important?
reveal potential for side effects test whether compound potent in animal model of dz insights into max tolerated dose biodistribution pharmoacokinetic properties
What is the total time typically spent in drug discovery?
1-5 yrs or longer
What are the ethical considerations for clinical testing?
social value scientific validity fair subject selection informed consent favorable risk/benefit ratio IRB evaluation respect for human subjects
What are the different phases of clinical trials?
Phase 1: normal volunteers or pts w specific problems, small numbers, start low dose and go up
Phase 2: selected patients, moderate numbers
Phase 3: selected patients, large numbers, double blind placebo controlled, non-inferiority trials if standard of care
phase 4: post approval, post marketing surveillance of large population of treated patients
What is the total time spent in clinical testing typically?
2-10 yrs
Why is it difficult to find new drugs? Why is drug development so expensive and risky?
already existing drugs
need to establish efficacy against other treatments
many of easy targets already successfully dealt with
for every drug that succeeds, dozens fail
clinical trials are expensive
identifying new compound meriting clinical trials is expensive
few successful drugs pay the way for research and dev of all the unsuccessful drugs
How does drug regulation through the FDA work?
if drug seems promising in phase III - company files new drug application (NDA)
FDA will review (goal is less than one year)
committee will review
outcomes either: not approved (revisit data or give up), approvable (need minor changes), approved
What is the balance between safety and efficacy?
ideal drug is safe and effective BUT,
drug intended to provide minor benefit should be extremely safe
drug that is best choice for life threatening condition may be approved even though side effects severe
What happens after a drug is approved?
physicians can prescribe for off label use but drug companies cannot advertise for it
unanticipated side effects may occur with more patients using it - need long-term monitoring
What is a patent?
recognition from government that invention is novel and useful
lasts 20 yrs in USA in theory, but protection starts before drug is approved and can last as little as 7-12 yrs
no need to test generic drugs - just need to show FDA they contain same substance as approved drug and show similar bioavailability in the body
What can big companies do to make more money from their drugs?
invest in new versions - resets patent clock
investment in treating dzs already well treated because market well known and can be tapped by new agents