Drug Development Flashcards
What govt. organization is specifically charged with drug approval in Canada?
Health product and food branch
which one is NOT typical reason promising compounds might be abandoned:
a. safety/toxicity
b. poor absorption/ineffective
c. manufacturing difficulties.
d. generic erosin
e. limited marketing potential
d. generic erosion
drug has already been in market. when sold as generic drug, means it has been demonstrated to be safe for long time. but drug will still be sold unless generic is made better
clinical development represents a shift from ___ to ___
laboratory science TO
project management responsibility needed for human trials
what is major milestone of preclinical development
A. filing IND application with FDA or HPFB or CTA
B. identifying target population
c. aligning development process with aims of company
d. determine anticipated revenue
filing IND application with FDA or HPFB or CTA
when does company seek permission to market product in US/Canada:
a. Following completion of Phase 1
b. Following completion of Phase 2
c. Following completion of Phase 3
d. Following completion of Phase 4
c. following completion phase 3
Which phase of clinical development is largest investment of both time and money?
phase 3
On what does phase 3 clinical trials test?
large scale test in ppl with target disease
What is not true about phase 4 trials:
a. They are not randomized/placebo
b. When product is finalized nd submitted for patent protection
c. May include new population
d. May include new formulations and adjusted dose regiments
d. may include new formulations and adjusted dose regimens
adulterated
something change from what it initially should’ve been
misbranded
something sold as something else
Kefauver-Harris amendment
proof of efficacy requierd prior to marketing
adverse event reporting to FDA
(following Thalidomide disaster in Europe, sedative that caused fetal abnormalities)
Health Product & Food branch
part of Ministry of Health
• Legislates what can be sold, level of control, issue of drug abuse
• Provincial governments legislate drug distribution and payment for drugs
• Mandate: management of risks and benefits related to product
steps of drug development
- Discovery
- Pre-clinical (submit IND or CTA)- in canada its CTA: clinical trial application
- Phase 1
- Phase 2
- Phase 3 (submit NDA (new drug application) or NDS)
- Review
- Approval
- Post-market
routes of drug development
- new use for old drug
- natural source: exogenous/endogenous
- systemic drug design- in industry based on knowledge from academia
3a. molecular targeting
3b. disease targeting
molecular targeting
potential target for drug is known protein involved in disease process.
use high throughput screening, combination chemistry, molecular modelling
why are clinical success rates higher in certian infections than in diseases like AD/HD
for infection:
In vitro testing: well characterized methods
in vivo testing: well characterized modules
not true for AD/HD
pre-phase 1
toxicity
find lethal dose
genotoxic panel: damge to gene/chromosomes
after phase 1
reproductive and developmental toxicilty (fertility, DME, metabolites)
clinical human testing
in between pre-clinical and phase 1, submit CTA
phases 1-3
- safety in humans (small group)
- proof of concept- test efficacy in patients with target condition. identify common short term SE.
- pivotal trials. confirmatory proof- confirm efficacy in patient population. monitor SE. 100s to 1000s
standard for pivotal trial
- Controlled
- Ideally blinded design
- Randomized assignment of treatment
- Adequate size to ensure statistical power of at least p<0.05
phase 4
post approval
regulator specify post-marketing surveillance study requirements to obtain further info on safety
recall can happen
name the north american agencies involved in drug regulation
Canada: HPFB regulates, evaluates and monitors the safety, efficacy, and quality of therapeutic and diagnostic products available to Canadians
US: FDAurisdiction over all products (drugs, food, cosmetics, etc) in interstate commerce. The FDA reviews clinical research, ensures safety and efficacy, manages proper product labeling, inspects manufacturers and enforces regulatory compliance.
why might a drug not reach market
a. Safety/toxicity issues
b. Poor absorption or ineffectiveness
c. Manufacturing difficulties
d. Generic erosion- the drug has already been in market. When it gets sold as generic drug, that means its been demonstrated to be safe for a long time. Generic drugs often eat at the market. But the main drug will still be sold unless a generic is made better than Initial (usually not the case)
e. Limited marketing potential
