Block 4 -- History, FDA, Regulation

Question 1

What are the two solid forms?

Answer 1

1) Mixture

2) Pure forms

Question 2

Cause for 1938 FD&C Act

Answer 2

Sulfinilamide (normally tablets & powder)
Formulated into elixir sulfanilamide
– diethylene glycol
– killed > 100 people

Question 3

What went wrong in the 2012 NECC meningitis outbreak?

Answer 3

Methylprednisolone acetate (epidural steroid injection)
Vials contaminated with mold
Compounding labs not regulated by FDA (state)
NECC became a manufacturer

Question 4

How is particle size analyzed?

Answer 4

Sieve
Light Scattering
Microscopy

Question 5

Particle size reduction is also known as…

Answer 5

Comminution

Question 6

Which form of granulation is more common?

Answer 6

Wet

Question 7

What are the 2 types of capsules?

Answer 7

Hard Gelatin

Soft Gelatin

Question 8

Most common form of capsule?

Answer 8

Hard gelatin

Question 9

Hard Gelatin vs. Soft Gelatin capsules:

Answer 9

Hard: collagen, snap together
Soft: 
-- collagen + added softening agent
-- Two ribbons 
-- Used for liquids, suspensions, pastes, and solids

Question 10

What are the range of capsule sizes?

Answer 10

000 - 5 (smallest)

Question 11

What are types of tablets?

Answer 11

• • Compressed
• • Multiple compressed
• • Sugar coated
• • Film coated (delayed release)
• • Gelatin-coated (swallowing)

Question 12

What is hydroscopity?

Answer 12

Amount of water taken up by a solid

Question 13

What are the 3 types of deformation?

Answer 13

1) elastic
2) plastic
3) brittle

Question 14

What are the axes of the BPC system?

Answer 14

Permeability & Solubility

Question 15

Permeability limited BPC classifications?

Answer 15

3 & 4

Question 16

Solubility limited BPC classifications?

Answer 16

1 & 2

Question 17

Describe the history of ASA?

Answer 17

• • Hippocrates: willow bark (salicin)
• • 1839: oxidation yields salicylic acid
    
    • • GI upset
• • 1853: neutralize with NaOH = ASA

Question 18

Approximate number of NCE’s per year?

Answer 18

30

Question 19

Reasons for drug reforumulation?

Answer 19

1) $
2) Fewer ADRs
3) XR technology
4) Different routes of administration

Question 20

What is a counterfeit medicine?

Answer 20

drug sold under product name without prior authorization

– no drug, impure, or different

Question 21

Where are IND, NDA, ANDA, other reports submitted? What are they used for?

Answer 21

FDA–Center for Drug Evaluation & Research

• • id, strength, quality, purity of drug
• • support of US Pharmacopoeia monograph

Question 22

What must be contained in an NDA?

Answer 22

1) evidence of safety & efficacy
2) list of components
3) statement of composition
4) facilities, methods, and controls in manufacturing, processing, packing
5) samples of drug & labeling

Question 23

What must be contained in the IND?

Answer 23

1) detailed info regarding id, strength, quality, purity

- - final specs no required until end of IND (dosages, CMC)

Question 24

What are key CMC objectives for manufacturer?

Answer 24

1) characterize: API & product
2) quality: evidence for API & product
3) establish: manufacturing guidelines
4) control: make sure guidelines don’t change
test, test, test at all unit processes

Question 25

What is adulteration?

Answer 25

If the container is composed of poisonous or injurious substances.

Question 26

What is characterized as a class I recall?

Answer 26

Reasonable probability of serious health consequences or death.

Question 27

What is characterized as a class II recall

Answer 27

- - temporary or medically reversible consequences | - -remote probability of serious consequences

Question 28

What is characterized as a class III recall?

Answer 28

not likely to cause serious adverse effects

Question 29

What was the overall result of the poison squad?

Answer 29

Passage of the Pure Food and Drug (Wiley) Act of 1906.

Question 30

Who led the poison squad experiment?

Answer 30

Wiley.

Question 31

What did the Pure F&D Act do?

Answer 31

1) addressed interstate commerce 2) misbranding & adulteration are defined --aka Truth Labeling Law

Question 32

What did the FD&C Act do?

Answer 32

1) required safety & NDA 2) set safe tolerances on poisonous substances 3) later amendment = Rx only

Question 33

What brought about the Kefauver-Harris Amendment?

Answer 33

Thalidomide

Question 34

When was the K-H amendment passed?

Answer 34

'62

Question 35

When was the Pure Food & Drug Act passed?

Answer 35

1906

Question 36

When was the FD&C Act passed?

Answer 36

1938

Question 37

What were the results of the Kefauver-Harris Amendments?

Answer 37

1) effectiveness 2) FDA had to approve NDA 3) established rules of investigation 4) formalized GMP 5) required reporting of adverse events

Question 38

When was the Prescription Drug User Fee Act passed?

Answer 38

1992

Question 39

What did PDUFA do?

Answer 39

1) required fees for drug approval process | 2) mutually agreed upon target review completion dates

Question 40

What brought about PDUFA?

Answer 40

'80s AIDS crisis

Question 41

How much $ is required to bring a drug to market?

Answer 41

2.5 billion dollars

Question 42

What is achieved in Phase I clinical trials?

Answer 42

Safety | --tested in healthy volunteers

Question 43

What is achieved in Phase II clinical trials?

Answer 43

Effectiveness - -target population - -placebo/comparator controlled

Question 44

What is achieved in Phase III trials?

Answer 44

Safety & Effectiveness | --different populations, dosages, combinations

Question 45

What are the target completion dates for NDA?

Answer 45

10 months | 6 months if priority

Question 46

What is a BLA?

Answer 46

biologic license application

Question 47

What application is required for medical devices?

Answer 47

510k

Question 48

What is demonstrated in an ANDA?

Answer 48

bioequivalence