Final Review I

Question 1

Write the name in full and then define the role of each:

NF and USP

Answer 1

• the United States Pharmacopeia (USP) and the National Formulary (NF)

the USP lists monographs for active ingredients and formulations and the NF lists those for inactive ingredients

• Need for uniform standards to ensure quality
• Adopt standards for drugs, pharmaceutical ingredients and dosage forms
• Reflect the best current practices of medicine
• Provides information on tests and assay procedures for demonstrating compliance with these standards
• For individual components not combinations

Question 2

CDER

Answer 2

CDER- Center for Drug Evaluation and Research

• Assess benefit to risk relationship
• High priority drugs go through
• Safe and Effective drugs
• drugs available sooner
• clear standards for drug evaluation

Question 3

Difference between FDA of 1906 and FDA of 1938

Answer 3

1906 1938
Strength Safety
Purity NDA -(new drug application)
Quality Label- Directions
FDA has the right to inspect pharmacies

Question 4

Answer all parts of this question. What is the name of the agent that caused the Sulfanilamide Tragedy? Was the ingredient an excipient (i.e. used to solubilize),or was it the active agent? What was the finished preparation intended to treat? How could the tragedy have been prevented?

Answer 4

• Agent-Diethylene glycol
  • Excipient used as solvent to prepare the elixir
  • Liquid Antibiotic
  • Testing (1938) for safety and also using a different solvent such as propylene glycol

Question 5

Who is Frances Kelsey, and why was she awarded the Distinguished Federal Civilian Service Award?

Answer 5

Dr. Frances Kelsey was the FDA’s chief medical officer that refused Thalidomide into the US marketplace.

Question 6

In a few words define each of the following.

FDA act of 1938:

Answer 6

Required testing for safety; NDA (new drug application; drugs label with adequate directions; and FDA to conduct unannounced inspections

Question 7

A manufacturers’ claim of therapeutic benefit was not regulated until the passage of this Amendment.

A) FDA act of 1938
B) Sherley Amendment of 1912
C) Durham-Humphrey Amendment of 1952
D) Prescription Drug Marketing Act of 1987

Answer 7

B) Sherley Amendment of 1912

Question 8

In a few words define each of the following.

Kefauver Harris Amendment of 1962:

Answer 8

• Thalidomide Tragedy was the main reason
• required manufacturers to prove a drug to be both safe as well as efficacious

Exempted drugs that happened to enter the market between 1906 and 1938 aka ~ grandfather clause. Why? Drugs were never subjected to NDAs.

Question 9

In a few words define each of the following.

Durham-Humphrey Amendment of 1952:

Answer 9

• No refills without a valid prescription
• drugs that cannot be used safely without proper medical supervision
• Determined what drugs are OTC (over-the-counter) and what drugs are not available OTC
• Refilling necessary only if authorized in prescription
• Further supported by the drug abuse control amendments of 1965 and the Comprehensive drug abuse prevention and control Act of 1970.

Question 10

Can a Drug Product Recall ever be initiated by the manufacturer? If so, explain.

Answer 10

Yes, if the product causes threat to the public.

Question 11

Prescription Drug Marketing Act of 1987:

Answer 11

• Aka “Dingell Bill”
• This act prohibits reimportation of drugs, prohibits sales, trading and purchasing of drugs.

Functioned to protect the supply of prescription agents and prevent repackaged and mislabeled drugs from entering the legitimate market

Question 12

Name the natural plant source from which each of the following drugs was derived?
Morphine _______________________
Quinine _______________________
Digitalis _______________________
Belladonna _______________________

Answer 12

Morphine __Opium Poppy____________
Quinine __Cinchona Bark_____________
Digitalis __Foxglove_________________
Belladonna ———_deadly night shade

Question 13

What is the difference between the lead compound and the goal drug?

Answer 13

• Lead Compound- Closest to the goal drug possessing the fundamental desired biologic or pharmacologic activity
• Goal Drug- Can produce desired effect, administered by the best ROA (orally), minimal dosage and frequency, does it’s thing and then gets eliminated quickly with limited side effects

Question 14

Partition Coefficient and Ficks law of Diffusion

Answer 14

Partition Coefficient- Optimal balance between water/lipid solubility - Preference for lipid verses preference for aqueous phase

Ficks Law- Simple passive diffusion dQ/dt=(DA/h)(C1-C2)

Question 15

Crystal and Amorphous drug form

Answer 15

Crystal- less soluble; crystalline

Amorphous-More soluble; non crystalline

Question 16

How are Phase I, Phase IIand Phase III Clinical Trials different?

Answer 16

Phase 1 Clinical Trial- Determines the safe dose. 20-100 healthy patients, study is less than 1 year. Determines toxicology, metabolism, and toxicological actions

Phase 2 Clinical Trial- Determines effectiveness, 100-300 patients who have the disease. Determines extensive pharmacologic, toxicological, and pharmacological testing

Phase 3 Clinical Trial- To demonstrate long-term safety & efficacy of drug product; to discover drug’s efficacy standards; (~1000-3000 people) Carried out over several years

Question 17

Can new clinical trial material(CTM) be introduced at a phase other than Phase I? If so, with all of our concerns regarding drug regulation and control, why do you think this is allowed?Weigh the benefit and the risk.

Answer 17

• Yes, a new formulation closer to the desired commercial dosage form can be introduced during phase II.
• If the requested dosage strength is not supported in phase I
• When the med to large scale is not feasible
• If allows you to maximize the result
• Changes are NOT allowed in Phase III

Question 18

Define MEC and MTC? What is the major implication of dosing below the MEC? What is the major drawback of maintaining MEC over an extended period of time?

Answer 18

MEC-Minimum Effective Concentration- min dosage required to get desired effect
MTC-Minimum Toxic Concentration- above this point is toxic

Low MEC-would not need to take as much drug but will accumulate in body over time. Drugs levels should be about the MEC and below the MTC. If the drug levels are below the MEC then there would be no therapeutic effect.

Question 19

What is the difference between the Prophylactic Dose and the Therapeutic Dose?

Answer 19

Prophylactic Dosage-taken before for prevention of disease

Therepeutic Dosage- taken once you have the disease/infection to rid body of issue

Question 20

What is the difference between Batch and Batchwise control?

Answer 20

Batch- Specific quantity of a drug of uniform specified quality produced according to single order during same cycle

Batchwise Control- The use of validated in-process sampling and testing methods that proves the process has done what it purports to do

Question 21

What is the difference between Lot and Lot number?

Answer 21

Lot- A batch or any portion of a batch having uniform specified quality and a distinctive identifying lot number

Lot Number- Any distinctive combination of letters, numbers, or symbols from which the complete history of the manufacture, processing, packaging, holding, and distribution of a batch of lot of a drug product may be determined.

Question 22

What is the name of the regulatory process through which industry measures quality performance, and compares to standards?

A) Quality control
B) Quality Unit
C) Quality assurance
D) Quality control unit

Answer 22

A) Quality control

Question 23

During the Production and Process Control written documentation is required to make sure that each drug product has the correct,
_________________, Strength, __________________ and Purity

Answer 23

_identity__, Strength, _____quality___ and Purity

Question 24

What are the major problems associated with the use of Plastic versus Glass containers for the packaging of finished pharmaceutical preparations? Be specific.

Answer 24

Some benefits of plastic containers are they are lighter, greater flexibility in terms of design and appearance, and can use a squeeze bottle.

Some major problems for plastics are permeability of containers, leaching of constituents of container, absorption of drug to container, transmission of light, change in container material over time

Question 25

What is required for OTC labeling?

Answer 25

• Product Name
• Net quantity of contents
• All ingredients
• Pharmacologic category
• Cautions/Warnings
• Sodium content (5mg of more per single dose, 140mg max dose)
• Storage conditions
• Must include “keep out of reach of children”
• Lot number
• Expiration date

Question 26

What are the storage temperatures as defined by USP?

Answer 26

___Cold__________ = 8 ºC
Cool = ___8-15____________
_____Room Temp_______ = 20- 25 ºC
Warm = __30-40_____________
____Excessive Heat________ = Above 40 ºC

Question 27

Biologics are stored at what temperature range?

Answer 27

2-8 C_________(usually 4C )

Question 28

Why are dosage forms necessary in Pharmacy?

Answer 28

1) Improve Drug Action
2) Improve target specificity
3) Provide protection from destructive influences (chemical and gastric PH)
4) Address taste and odor

=======

• To provide liquid preparations
• To control the rate of drug release
• To provide for insertion into body’s orifices

Question 29

How is the melting temperature of a drug product typically determined? What influence (if any) can the contamination of a drug agent have on the melting temperature?

Answer 29

MP is determined by DSC, contamination can cause MP to be lower (melt faster than it should)

Question 30

What is the influence of Particle size on drug absorption (Be sure to include the word dissolution in your discussion)?

Answer 30

Smaller size better absorption. Absorption will increase with decrease in particle size, more soluble it is better dissolution rate. Micronization of particles can increase the rate of drug dissolution and its bioavailability.