Drug Discovery and Development: industry academic regulatory axis

Question 1

new drug development is

Answer 1

complex and involves;
academic institutions
pharmaceutical industry
gov. agencies

Question 2

primary and clinical research funded by

Answer 2

National Institutes of Health

Question 3

Food and Drug Administration FDA provides

Answer 3

regulatory review and oversees drug development process

Question 4

investigational new drug (IND) application

Answer 4

used by FDA to regulate clinical testing in people

Question 5

new drug application submitted by drug company

Answer 5

summarizes all data to determine risk/benefit analysis of new drug is sent to FDA for review and approval after testing.

Question 6

investigators in clinical trials need

Answer 6

to understand regulatory development process and the national institutes of health funding process

Question 7

department of health and human services from Food and Drug administration

Answer 7

has different agencies to approve either drugs, devices, evaluation of research, and biological evaluation

Question 8

if product looks promising what happens?

Answer 8

preclinical development history and clinical development plan compiled in an investigational new drug application (IND) sumbmitted for FDA review and permission for human testing

Question 9

an active IND permits?

Answer 9

clinical testing on humans

Question 10

INDs are ?

Answer 10

dynamic documents residing with sponsor (company or individual) and updated annually for adverse events within clinical trial

Question 11

IND include info in 3 areas:

Answer 11

1) animal testing for safety in humans
2) manufacturing information to ensure sponsor can produce and supply drug
3) clinical protocol to ensure safety of subjects from unnecessary risks and investigator information to ensure they are qualified to conduct clinical trial

Question 12

letter code S or P assigned to each application by the FDA. Whats S and P?

Answer 12

S= standard review of a drug thats similar to those currently available (10 months)
P= priority review is a quicker review for drug with significant advance over existing therapy (6 months)

Question 13

NDA (new drug application)

Answer 13

submitted to FDA after phase III clinical trial in order to get approval and put out on market

Question 14

when is IND sumbitted to FDA?

Answer 14

After pre- clinical phase to request for human testing in phase I

Question 15

phase I key characteristics

Answer 15

first testing in humans
safe drug dose for phase II
few patients

Question 16

phase II key characteristics

Answer 16

well defined eligibility criteria with placebo or active control and historical control
weeks- months study
establishes effectiveness by tumor shrinkage but does not garuntee survival in phase 3
large number of subjects (100-300)

Question 17

phase III key characteristics

Answer 17

large study with hundreds-thousands of patients
confirm safety and efficacy
time: month-years
efficacy power greater than 80%, type 1 error rate alpha= 0.5 and P<0.05

Question 18

phase IV key characteristics

Answer 18

post marketing studies provide additional safety and efficacy data
must be conducted if FDA approves product on fast track (before all premarketing data are compiled)
evaluates adverse data

Question 19

drug development process

Answer 19

stage 1 - drug discovery
stage 2 - preclinical
stage 3 -clinical trials
stage 4= FDA review

Question 20

1938 Food. Drug, and cosmetics Act

Answer 20

safety

every new drug brought to market in US must be approved by FDA through NDA process

Question 21

1962 - amendments to food, drug, and cosmetics act required?

Answer 21

efficacy

drugs be shown scientfically be effective before being marketed and benefits of drug must outweigh known risks

Question 22

what made evidence in drug development programs limited?

Answer 22

• few women studied
• few minorities
• focused on white men
• poor dose response info
• lacking long term or chronically administered drugs
• data on drug-drug interaction not available

Question 23

1980-1990s as more drug therapies became available

Answer 23

FDA expanded requirements making modern development programs more extensive and have more clinical studies / patient exposures than usual

Question 24

1983 orphan drug act

Answer 24

provided incentives for research and development on products to treat rare disease

Question 25

1992 precription drug user fee act

Answer 25

established user fees for applications and expedited the drug approval process within FDA

Question 26

1997 FDA modernization act

Answer 26

further reduced review times and allowed for electronic submissions

Question 27

2001 best pharmaceutical for children act

Answer 27

established an office within FDA for pediatric therapeutics

Question 28

3 phases of regulatory development :

Answer 28

1) IND - evaluated within 30 days and may begin clinical trials if not rejected in this time period
2) NDA - FDA review is longer (months)
possible outcomes are approval, approvable (need further study) or not approved
key document from NDA is package insert
3) post marketing phase 4 studies - important function of FDA from office of drug safety

Question 29

whats the package insert in NDA?

Answer 29

includes summary of data and serves as guide for review of marketing, advertising, and communication regarding product

Question 30

FDA relies on voluntary reporting by?

Answer 30

clinicians with mandatory periodic reporting by manufacturers

Question 31

medwatch system is

Answer 31

form used by clinicians to report adverse events outside of clinical trial

Question 32

where is post marketing reporting of adverse events by health care professionals?

Answer 32

in drugs that get approved by fast track

Question 33

Improvements in FDA Regulation: FDA process Fast Track

Answer 33

to be eligible: medical need not adresses by a product or claim before
seeks FDA input into development plan
allows submission of NDA
substitue endpoints

Question 34

improvement in FDA regulation: priority review

Answer 34

drugs must address unmet medical needs

reduces drug review process from 10 months to 6

Question 35

improvement in FDA regulation : 1992 accelerated approval

Answer 35

for serious or life threatning illness and provide significant benefit over existing treatments

Question 36

biological therapies

Answer 36

endogenous compounds in body for defense mechanisms or as naturally occuring biochemical processes

• protein/peptide therapeutics
• monoclonal antibodies
• aptamers/antibody derivatives
• oligionucleotides
• rna
• gene therapy
• cell therapy
• immunotherapy

Question 37

new chemical entity (NCE)

Answer 37

are evaluated fro desired interaction with target

Question 38

only 10% of ADRs in wide clinical use are?

Answer 38

reported to regulators from spontaneous reporting

Question 39

ADR

Answer 39

may not occur in test animals
rare even go undetected in clinical trials as their incidence is inherently too small
clinical trials too short in duration to detect ADR
occur only in certain genetically susceptible individuals
occur only in presence of other drugs/special diets
only in patients suffering from other disease
FDA system of spontaneous ADR reports is not accurate because no active drug surveillance system in place

Question 40

there is a decrease in price change as ?

Answer 40

number of generic versions increase

Question 41

whats type of study has the greatest level of evidence?

Answer 41

randomized, dbl blind, placebo controlled, multicenter, phase III clinical trial

Question 42

types of studies: in order from greates level of evidence to lowest

Answer 42

randomizes trials, dbl blind, multicenter, phase III, placebo
meta analysis
randomized
controlled cohort
uncontrolled cohort
retrospective anectodal
expert opinion

Question 43

intellectual property (IP)

Answer 43

Tradmark
copyright
trade secret
patent
patent term restoration
data exclusivity
oprhan drug exclusivity

Question 44

external innovation

Answer 44

licensing deals
mergers
acquisitions
scientific collaborations

Question 45

the key is?

Answer 45

cooperation between the industry-academia-government axis