BYRN Exam 1 Flashcards
Drug discovery
10,000 candidates, 1 drug molecule
Cardinal rules
- know what you have
- make the same thing every time ( controlled by specifications that are binding quality standards like methods and numbers)
United States Pharmacopeia (USP)
1820 established by physicians
1830 Rph join
National Formulary (NF) - published by APha, 1975 USP purchased NF
USP-NF is revised annually in hardcopy and online
Assay
Procedure used to test for potency
Monograph chart
tests for impurities
API
active pharmaceutical ingredient / active ingredient
IND
Investigational new drug, document to allow first in human trial
Ex - pure drug AB1234
needs component, quality, function, reference to standard
Ex - capsules: description, identification, content, degradation, dissolution
Excipients
substances in dosage form that may not have therapeutic use
wrong excipients can lead to death
excipients are controlled by USP
Universal tests for new drugs
description: state, color, identification, assay, impurities
specific tests for new drugs
physicochemical properties, particle size, polymorphic forms, tests for chirality, impurities, assay, identity, dissolution, disintegration, hardness, microbiol, water
New drug challenges
short time, broad dose range, minimal amounts of API, API w/ different attributes
New drug strategy
knowledge based decision making, prepare in small scale, determine performance often(assessing stability, animal pK, pKa for manufacturing.
Beta blockers
dischloroisoprotenol –> promethalol –> propanol
H2 antagonist
burimamide –> metiamide –> cimetidine
IND application
content, clinical protocol meetings, FDA review
clinical studies and control, dosage & terminology, treatment IND, withdrawal/termination drug
applying: content of NDA submission, product labeling, FDA review, phase 4 studies, adverse drug experience, annual reports
SNDA
supplemental new drug application
ANDA
abbreviated new drug application, nonclinical lab studies may be omited, generic drug products, requires study about bioavailability
other drug applications
animal drug application and medical devices
Biologics license application (BLA)
vaccines and monoclonal antibodies
ADME
absorption, distribution, metabolism, excretion
preformulation
drug solubility, partition coefficient, drug must pass bio membrane (be lipophilic enough to be able to penetrate bio membrane)
dissolution rate
speed at which substance dissolves related to size, partition coefficient, etc
physical form
crystalline vs amorphous, particle size
drug stability
physical + chemical, formulation, absorption, hydrolysis, heat
product formulation + trial materials
dosage forms, dosage strength, initial formulations, clinical supplies
clinical trials
phase 1: determine human pharmacology
- 20-100 people, months, 67% completion rate
phase 2: controlled chemical studies for effectiveness
- up to several hundred, months-2 years, 45% completion rate
phase 3: several hundred to thousands of patients in controlled and uncontrolled trials
- 100s-1000s, 5-10% completion rate
crossover study design
giving subjects both drug and placebo and seeing the effects
Personal Requirements
Responsibility of quality control unit, employees, consultants
Building and facilities
structure, space, equipment will have thorough cleaning for safe and effective use
equipment
appropriate, suitably located, standard operating procedure
control of components
use written procedures
production and process control
written procedures, correct quality and quantity, any deviation must be recorded and justified
package labeling
expiration date, tamper evident packaging
holding and distribution
written procedures, stored and shipped w/ appropriate conditions
lab control
conformance to standards and specifications
reports and records
complete production, control, distribution records for at least 1 year
NECC FDA inspection
example - observed 83/321 vials w/ black matter, tarnished surfaces, used to handle mattresses.
results - API were nonsterile, steam autoclave was not effective for cleaning surfaces, contaminated air.
ICH10 objectives
Achieve product realization, establishes state of control, gives us control, facilitates continuous improvements, cost, quality, strength.
monograph info
assay, definition, chart, impurities, solubility requirements
