Lecture 2 Review

Question 1

What are the challenges of new drug development?

Answer 1

Short timeline, broad dose range, minimal amounts of API, API with different attributes

Question 2

What is the strategy for new drug development?

Answer 2

Knowledge-based decision making, prepare in small scale, determine performance often (assess stability, dissolution, animal PK) and plan for manufacturing

Question 3

What was the first commercial beta blocker and histamine H2 receptor blocking agent?

Answer 3

Propranolol and Cimetidine

Question 4

What is required for and investigational new drug application?

Answer 4

Content of the IND, the clinical protocol, Pre-IND meetings, FDA review of IND application, the FDA drug classification system, phases of clinical investigation, clinical study controls and designs, drug dosage and terminology, treatment IND, IND for an orphan drug, withdrawal or termination of an IND

Question 5

What does a new drug application consist of?

Answer 5

General content of the NDA submission, drug product labeling, FDA review and action letters, Phase 4 studies and post marketing surveillance, post marketing reporting of adverse drug experiences, annual reports

Question 6

What are supplemental, abbreviated and other applications?

Answer 6

Supplemental NDA, abbreviated NDA, biologics license application, animal drug applications, medical devices

Question 7

In biological characterization, what does drug metabolism cover?

Answer 7

ADME studies, rate primary and and secondary sites, and the mechanism of the drugs metabolism in the body, biochemical transformation

Question 8

What are the preformulation studies that are conducted?

Answer 8

Drug solubility, partition coefficient, dissolution rate, physical form and stability

Question 9

What is drug solubility?

Answer 9

Necessary for absorption and transport, can be increased by modifying the structure, form, complexation or particle size reduction. Less that 10mg/ml you can experience incomplete or erratic absorption and produce a minimal response.

Question 10

What is the partition coefficient?

Answer 10

It is the preference of the drug for lipid:water. The drug must pass the biological membrane of protein/lipid, which acts as a lipophilic barrier to many drugs. This value is indicative of the ability to penetrate biological multiphase systems.

Question 11

What is the dissolution rate?

Answer 11

The speed or rate at which a substance dissolves. Related to solubility, dissolution constant, partition coefficient, particle size

Question 12

What do they look at for the physical form?

Answer 12

Crystalline vs amorphous and particle size

Question 13

What is important to stability?

Answer 13

Physical and chemical, formulation, absorption, hydrolysis (moisture in packaging) and heat

Question 14

What are the initial product formulation and clinical trial materials?

Answer 14

Dosage form, dosage strength, initial formulations, clinical suppliers (manufacturing and compounding pharmacies)

Question 15

What happens in phase 1 of clinical investigation?

Answer 15

Determining the human pharmacology of the drug, structure-activity relationships, side effects with increasing doses and possible early evidence of effectiveness

Question 16

What happens in phase 2 of clinical investigation?

Answer 16

Controlled clinical studies for effectiveness in patients with conditions

Question 17

What happens in phase 3 of clinical investigation?

Answer 17

Several hundred to several thousand patients in a controlled and uncontrolled trials

Question 18

What are the stats of phase 1 of clinical investigation?

Answer 18

20-100 patients, last several months, mainly safety purpose and 67% of successful completion

Question 19

What are the stats of phase 2 of clinical investigation?

Answer 19

Up to several hundred people, last several months to 2 years, purpose is for short term safety and mainly effectiveness. Has a 45% for successful completion

Question 20

What are the stats of phase 3 of clinical investigation?

Answer 20

Several hundred to several thousand people, last 1-4 years, purpose is to establish safety, effectiveness and dosage. The percent to successfully complete is 5-10%

Question 21

What are the two types of clinical trial study designs

Answer 21

Parallel and crossover

Question 22

What are the 4 different types of parallel clinical trial study designs ?

Answer 22

Common, two-part, introduction of placebo and multiple doses

Question 23

What are the 3 types of crossover clinical trial study designs?

Answer 23

Single crossover with no intervening baseline, single crossover with intervening baseline and extra period crossover

Question 24

What does the abbreviated new drug application consist of?

Answer 24

Nonclinical laboratory studies and clinical investigations may be omitted. Studies pertaining to drug bioavailability stay. Potentially generic drug products too based off innovators NDA.