Lecture 2 Review Flashcards
What are the challenges of new drug development?
Short timeline, broad dose range, minimal amounts of API, API with different attributes
What is the strategy for new drug development?
Knowledge-based decision making, prepare in small scale, determine performance often (assess stability, dissolution, animal PK) and plan for manufacturing
What was the first commercial beta blocker and histamine H2 receptor blocking agent?
Propranolol and Cimetidine
What is required for and investigational new drug application?
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
What does a new drug application consist of?
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
What are supplemental, abbreviated and other applications?
Supplemental NDA, abbreviated NDA, biologics license application, animal drug applications, medical devices
In biological characterization, what does drug metabolism cover?
ADME studies, rate primary and and secondary sites, and the mechanism of the drugs metabolism in the body, biochemical transformation
What are the preformulation studies that are conducted?
Drug solubility, partition coefficient, dissolution rate, physical form and stability
What is drug solubility?
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.
What is the partition coefficient?
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.
What is the dissolution rate?
The speed or rate at which a substance dissolves. Related to solubility, dissolution constant, partition coefficient, particle size
What do they look at for the physical form?
Crystalline vs amorphous and particle size
What is important to stability?
Physical and chemical, formulation, absorption, hydrolysis (moisture in packaging) and heat
What are the initial product formulation and clinical trial materials?
Dosage form, dosage strength, initial formulations, clinical suppliers (manufacturing and compounding pharmacies)
What happens in phase 1 of clinical investigation?
Determining the human pharmacology of the drug, structure-activity relationships, side effects with increasing doses and possible early evidence of effectiveness
What happens in phase 2 of clinical investigation?
Controlled clinical studies for effectiveness in patients with conditions
What happens in phase 3 of clinical investigation?
Several hundred to several thousand patients in a controlled and uncontrolled trials
What are the stats of phase 1 of clinical investigation?
20-100 patients, last several months, mainly safety purpose and 67% of successful completion
What are the stats of phase 2 of clinical investigation?
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
What are the stats of phase 3 of clinical investigation?
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%
What are the two types of clinical trial study designs
Parallel and crossover
What are the 4 different types of parallel clinical trial study designs ?
Common, two-part, introduction of placebo and multiple doses
What are the 3 types of crossover clinical trial study designs?
Single crossover with no intervening baseline, single crossover with intervening baseline and extra period crossover
What does the abbreviated new drug application consist of?
Nonclinical laboratory studies and clinical investigations may be omitted. Studies pertaining to drug bioavailability stay. Potentially generic drug products too based off innovators NDA.
