assignment 1

Question 1

list the following for phase i: goals, number of patients, type of patients, average time taken, drug failure

Answer 1

1. Safety, Find max safe dose
2. ~100
3. healthy volunteers
4. <1 year
5. 30%

Question 2

list the following for phase ii: goals, number of patients, type of patients, average time taken, drug failure

Answer 2

1. Safety, efficacy, Find max safe dose
2. 200-300
3. patients
4. ~1 year
5. 70%

Question 3

list the following for phase iivi: goals, number of patients, type of patients, average time taken, drug failure

Answer 3

1. Safety, efficacy, rare side effects
2. thousands
3. patients
4. ~1 year
5. 70%

Question 4

what are the two general types of large pharmaceutical companies? describe their main characteristics

Answer 4

• Ethical companies, discover and develop new molecular entities, very large
  companies that invest heavily in research
• Generic companies, market products no longer protected by patents, very
  large or medium companies that perform limited research focused on
  manufacturing

Question 5

what is the difference between drugs in terms of drug products and molecular entities? which is more common, and why is one much more common than the other?

Answer 5

• molecular entities are the active chemical substances used in
  pharmaceuticals. These produce the effects of the product. Drug products are
  different forms or combinations of molecular entities, they are the final form
  administered to the patient. These are much more common, because a drug
  can be sold in different doses, formulations or combinations

Question 6

list the following for the discovery phase: time, major goals, end product

Answer 6

1. 1-3 years
2. start with an idea and discover a new molecular entity (drug candidate)
3. drug candidate

Question 7

list the following for the development phase: time, major goals, end product

Answer 7

1. 1-2 years
2. turn drug candidate into a sellable product (investigational new drug)
3. investigational new drug

Question 8

list the following for the clinical trials phase: time, major goals, end product

Answer 8

1. 1-5 years
2. Test IND for safety. Establish safe limits for dosing. test for efficacy, establish dosing, test for rate side effects
3. new drug application

Question 9

list the following for the FDA approval phase: time, major goals, end product

Answer 9

1. 6 months to 1.5 years
2. review data from clinical trials to ensure testing was done properly, verify that data shows clear benefit which outweighs risk
3. market approval

Question 10

list the following for the market phase: time, major goals, end product

Answer 10

1. unlimited
2. make money, Continue safety testing, Identify very rare side effects, Find new indications
3. $$$

Question 11

what is meant by drug candidate

Answer 11

molecule identified as potential drug. Structure is kept secret by
company until development is complete

Question 12

what is meant by IND

Answer 12

Application filed with FDA asking permission to enter clinical trials.
Includes pharmacology and toxicity data from animal studies as well
as manufacturing information proving consistency of manufacture.
Plan for clinical trials and investigator info is part of this as well.

Question 13

what is meant by NDA

Answer 13

Application filed with FDA to enter the market. Includes full data
proving safety, efficacy, dosing information and drug labeling from
human clinical trials and animal experiments. Data proving sound
manufacturing methods and quality controls used are included.

Question 14

what is meant by ANDA

Answer 14

Application filed with FDA for permission to market a generic version
of a drug. Data showing that the drug identity, dose, formulation,
route of administration, performance and route of administration are
included

Question 15

why do drug companies prefer to treat chronic conditions rather than acute ones

Answer 15

-chronic conditions require long-term administration of the drug. This
provides a long-term market with assured customers. Company more likely
to make more profits over long periods of time

Question 16

what are the three most common methods of lead identification in the pharmaceutical industry

Answer 16

• high throughput screening
• rational drug design
• identification of natural products

Question 17

what characteristics makes a good lead compound

Answer 17

-proven biological activity, specificity, pattern of drug-like properties,
patentable, modifiable (chemistry is possible and practical)

Question 18

what are two key difficulties associated with natural products in terms of drug development

Answer 18

-complex structures make chemical modification difficult
-establishing supply of large amounts of drug (for complex chemical
structures)

Question 19

describe how drug companies perform safety testing during drug development

Answer 19

• initial tests done in vitro using as many biochemical and biological tests as
  possible
• if profile of results is consistent with a good safety profile in humans, tests
  are run on animals
• at least 2 species must be used, normally companies use 3 (including one
  primate)

Question 20

list 4 types of excipients and briefly explain their importance for formulation

Answer 20

• stabilizers (acid or base) protect drug from chemical degradation
• preservatives prevent mold or bacterial growth
• fillers ensure consistent dosing
• disintegrants help with water dissolution by forcing the components of pills
  apart
• binders hold solid components together in pills
• flavors mask the taste of active ingredients (many drugs are bitter)
• colors help to identify pills (important for prescription safety)
• lubricants help manufacturing by preventing pills from sticking to machinery

Question 21

list 4 different types of formulation and provide a key advantage and disadvantage of each

Answer 21

• pills or caplets – oral dosing, convenient for patient
• capsules – oral dosing, convenient for patient
• liquids – oral dosing, convenient for patient
• topical cream – avoid liver, deliver drug to a specific location
• patch - avoid liver, deliver drug to a specific location, provide steady dosing
  over a long time period
• injectable liquid - avoid liver, avoid digestive tract (stomach), deliver drug to
  a specific location, provide rapid entry into the body, provide steady dosing
  over a long time period
• nasal spray - avoid liver, deliver drug to a specific location, provide rapid
  entry into the body
• eye drops - avoid liver, deliver drug to a specific location
• suppositories - avoid liver, provide rapid entry into the body, provide steady
  dosing over a long time period

Question 22

what are the key parts of the Nuremburg code for research on humans

Answer 22

• voluntary participation
• informed consent
• prior animal studies
• benefits outweigh risks
• qualified researchers
• no suffering (minimal)
• stop experiments if they become dangerous
• prevent unnecessary or unethical experiments

Question 23

approximately when were the first government regulations for drugs created? why were these rules created, and what was the major focus of the legislation

Answer 23

• first rules in 1908
• rules created to ensure consumers knew what they were buying
• rules focused on labeling only, and only on listing the ingredients

Question 24

describe the event that lead to the creation of the FDA. what key ideas were introduced as part of the FDA’s creation

Answer 24

• formulation of sulfanilamide containing diethylene glycol poisoned children
  taking the drug
• company had not performed any safety testing at all
• drug was sold without instructions
• FDA introduced the idea of required safety testing in animals and humans
• Directions were now required on the label
• Companies would do the testing according to FDA guidelines
• FDA now started inspecting companies

Question 25

what are 4 key requirements for modern drug safety testing in animals? why is each of these requirements important?

Answer 25

• testing in at least 2 species
• at least one species must be a primate
• must take blood samples to show drug is bioavailable (gets into the body)
• must use dose that is relevant to future human use

Question 26

briefly describe how agencies such as the FDA and Health Canada operate

Answer 26

• safety testing done by companies
• provide full data to FDA
• FDA checks the data to ensure experiments done properly
• Approves marketing of drugs
• Companies are required to monitor the effects of their drugs in patients
• Companies required to report any difficulties to FDA
• FDA inspects drug manufacturing facilities