Drug Development

Question 1

What govt. organization is specifically charged with drug approval in Canada?

Answer 1

Health product and food branch

Question 2

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

Answer 2

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

Question 3

clinical development represents a shift from ___ to ___

Answer 3

laboratory science TO

project management responsibility needed for human trials

Question 4

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

Answer 4

filing IND application with FDA or HPFB or CTA

Question 5

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

Answer 5

c. following completion phase 3

Question 6

Which phase of clinical development is largest investment of both time and money?

Answer 6

phase 3

Question 7

On what does phase 3 clinical trials test?

Answer 7

large scale test in ppl with target disease

Question 8

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

Answer 8

d. may include new formulations and adjusted dose regimens

Question 9

adulterated

Answer 9

something change from what it initially should’ve been

Question 10

misbranded

Answer 10

something sold as something else

Question 11

Kefauver-Harris amendment

Answer 11

proof of efficacy requierd prior to marketing
adverse event reporting to FDA

(following Thalidomide disaster in Europe, sedative that caused fetal abnormalities)

Question 12

Health Product & Food branch

Answer 12

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

Question 13

steps of drug development

Answer 13

1. Discovery
2. Pre-clinical (submit IND or CTA)- in canada its CTA: clinical trial application
3. Phase 1
4. Phase 2
5. Phase 3 (submit NDA (new drug application) or NDS)
6. Review
7. Approval
8. Post-market

Question 14

routes of drug development

Answer 14

1. new use for old drug
2. natural source: exogenous/endogenous
3. systemic drug design- in industry based on knowledge from academia
   3a. molecular targeting
   3b. disease targeting

Question 15

molecular targeting

Answer 15

potential target for drug is known protein involved in disease process.
use high throughput screening, combination chemistry, molecular modelling

Question 16

why are clinical success rates higher in certian infections than in diseases like AD/HD

Answer 16

for infection:
In vitro testing: well characterized methods
in vivo testing: well characterized modules

not true for AD/HD

Question 17

pre-phase 1

Answer 17

toxicity
find lethal dose
genotoxic panel: damge to gene/chromosomes

Question 18

after phase 1

Answer 18

reproductive and developmental toxicilty (fertility, DME, metabolites)

Question 19

clinical human testing

Answer 19

in between pre-clinical and phase 1, submit CTA

phases 1-3

1. safety in humans (small group)
2. proof of concept- test efficacy in patients with target condition. identify common short term SE.
3. pivotal trials. confirmatory proof- confirm efficacy in patient population. monitor SE. 100s to 1000s

Question 20

standard for pivotal trial

Answer 20

1. Controlled
2. Ideally blinded design
3. Randomized assignment of treatment
4. Adequate size to ensure statistical power of at least p<0.05

Question 21

phase 4

Answer 21

post approval
regulator specify post-marketing surveillance study requirements to obtain further info on safety

recall can happen

Question 22

name the north american agencies involved in drug regulation

Answer 22

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.

Question 23

why might a drug not reach market

Answer 23

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