Drug approval

Question 1

What law Prohibited mislabeling and adulteration of drugs?

Answer 1

Pure Food & Drug Act: 1906

Question 2

What law Prohibited false or fraudulent advertising claims?

Question 3

What was Harrison Narcotic Act: 1914?

Question 4

What was the Food, Drug, & Cosmetic Act: 1938?

Answer 4

Required that new drugs be safe as well as pure (no proof of efficacy). Enforcement by FDA

Question 5

What law was Vested in the FDA the power to determine which products could be sold without prescription?

Answer 5

Durham-Humphrey Act: 1952

Question 6

What did the Kefauver-Harris Amendments (1962) to the Food, Drug, & Cosmetic Act cause?

Answer 6

Required proof of efficacy as well as safety for new drugs and for drugs released since 1938;

established guidelines for reporting of information about adverse reactions, clinical testing, and advertising of new drugs

Question 7

What was the effect of Comprehensive Drug Abuse Prevention & Control Act: 1970?

Answer 7

Outlined strict controls for habit-forming drugs; established drug schedules and programs to prevent and treat drug addiction

Question 8

What was the effect of Orphan Drug Amendments: 1983?

Answer 8

Provided incentives for development of drugs that treat rare diseases (<200,000 in USA)

Question 9

What was the effect of Drug Price Competition & Patent Restoration Act: 1984?

Answer 9

Abbreviated NDAs for generic drugs (bioequivalence data).

Patent life extended to account for FDA review process ( max ≤ 5 extra years or 14 years post-NDA approval

Question 10

What was the law that caused the effect of Manufacturers pay user fees for certain NDAs?

Question 11

Where was the effect Dietary Supplement Health and Education Act: 1994?

Answer 11

Established standards for dietary supplements; prohibited full FDA review as drugs.

Required specific ingredient and nutrition information labeling that defines dietary supplements and classifies them as part of the food supply but allows unregulated advertising

Question 12

What was the effect of Bioterrorism Act: 2002?

Answer 12

Enhanced controls on dangerous biologic agents and toxins.

Seeks to protect safety of food, water, and drug supply

Question 13

What was the effect of Food&DrugAdministration Amendments Act: 2007?

Answer 13

Grants FDA greater authority over drug marketing, labeling, and direct-to-consumer advertising;

• requires post-approval studies,
• establishes active surveillance systems,
• makes clinical trial operations
• results more visible to the public

Question 14

“Right” dose must balance what?

Answer 14

benefits and risks across all patients

Question 15

Describe how a drug makes it to the market place

Answer 15

1. year 0-2, in vitro studies, biologic products, chemical synthesis, optimization along which finds the lead compound
2. years 2-4, animal testing determines the efficacy selectivity mechanism
3. years 4-8, undergo drug metabolism and safety assessment with use of phase I, II and III testing
4. Phase I => 20-100 subjects (is it safe, pharmacokinetics)
5. Phase II => 100-200 patients (work in patients?)
6. Phase III=> 1000-6000 patients (work, double blind?)
7. years 8-9, NDA (new drug application)
8. years 9-20, marketing via phase 4 with postmarketing surveillance
9. year 20, generics become available

Question 16

Describe the experimental system of molecular eg adreno-receptor wrt to species/tissue, delivery, measurement

Answer 16

species/tissue => cell fraction; cultures; cloned receptors

delivery => in vitro

measurement => affinity & selectivity

Question 17

Describe the experimental system of isolated tissue wrt to species/tissue, delivery, measurement

Answer 17

species or tissue => blood vessels; heart; lung; ileum

delivery=> in vitro

measurement => Contraction or relaxation; receptor selectivity; effects on other smooth muscles

Question 18

Describe the experimental system of blood pressure wrt to species/tissue, delivery, measurement

Answer 18

1. species/tissue => dog/cat (anesthezed)
2. delivery => parenteral
3. measurement => systolic/diastolic changes
4. species/tissue => hypertensive rat
5. delivery => oral
6. measurement => antihypertensive effects

Question 19

Describe the experimental system of cholesterol; blood sugar wrt to species/tissue, delivery, measurement

Answer 19

species/tissue => rat, dog

delivery => parenteral, oral

measurement => serum measurement

Question 20

Describe the Cumulative distribution of new drugs by discovery strategy wrt first-in class drugs and follower drugs

Answer 20

First-in-class drugs =>A lag is not strongly apparent in a comparison of the cumulative number of small-molecule new molecular entities (NMEs) that were discovered from the different approaches during the period analysed.

Follower drugs => ratio of small-molecule NMEs discovered through target-based screening to those discovered through phenotypic screening appears to increase in the second half of the time period.

Question 21

Describe phase I clinical trials

Answer 21

Essentially a process to define the MTD

Starting from lower dose (mg/kg) than animal data

Only conducted in a small # (10-15) of adult volunteers

• Terminal cancer patients

Question 22

Describe phase II clinical trials

Answer 22

• Typically 100-300 patients are enrolled
• Begin with ~MTD from phase I trials
• Vary dosing regimen
• Length of study determined by enrollment
• Active, non toxic drugs proceed to phase III trials

Question 23

Describe phase III clinical trials

Answer 23

• crucial phase involving thousands of patients
• blinded fashion
• eliminate bias by pt or investigator
• multi-center trials simultaneously
• comparison studies
• lengthy trials

Question 24

What are the 5 types of clinical trials?

Answer 24

1. controlled/uncontrolled
2. open or blind
3. parallel
4. sequential
5. cross-over

Question 25

Describe the placebo wrt to clinical trials

Answer 25

placebo group patients often improve effect of drug \> than existing agent or placebo If neither drug "beats" placebo, trial is a bust