Exam 3 Byrn Flashcards
Patents
Find ingredients of each marketed version of dosage form.
Find recalls of drug dosage form.
Use google scholar and US patent office for patents.
Patent search
search for patent examples that contain all the excipients in package insert.
Make sure dose is correct.
EX – interest in tablets
Syrup
drug containing sugar/sugar substitute
sometimes contains an antimicrobial preservative
Elixir
clear sweetened solutions containing a drug and alcohol
antihistamine elixir
Non aqueous solutions
liniment, minimum water
alcoholic or other types of solutions
Solution dosage form vs solid
solution is faster because drug is already in solution and it takes longer for solid to dissolve
Quality of solutions
ethylene glycol contamination killed 100s people, 1937 sulfonamide elixir scandal, numerous incididents in Africa, 2022 dozens died in gambia due to contaminated ethylene glycol
Solution formulations of biologics
drug, buffers for pH, stabilizer, solubilizer, tonicity modifier, insulin ingredients
Forms of biological dosage forms
solution in vials, freeze dried vials w/ powder
Stability
increase stability when drying solution to solid form due to decrease degradation rate. Solid has 100x less degradation rate.
Freeze drying
more quality control, advantage for bulk crystallization, we freeze fry parenterals historically.
Surfactants are stabilizers
using surfactants can increase particle counts. Using polysorbate w/ surfactants can keep stability similar from 3 to 5 freeze dries.
Biologics
the process is the product, biotech is tech based on biology that harnesses cell and biomolecular processes to develop medicines
Drug substance manufacturing
expression system like gene expression/protein production and cell culture.
Harvesting
protein purification
Drug substance characterization
positive for identity and have specific criteria for purity, potency, and microbial contamination
acceptance criteria for release and stability attributes established
results from release should be provided in IND
data supporting drug substance characters provided in IND
safety, purity and characterization, identity, potency, strength, stability
drug substance cont (methodolgy)
safety - bacterial endo/exotoxins
purity + charactization - peptide mapping, and pure assays
identity - unique protein of interest
Drug product manufacturing
formulation, fill/finish
stability program
drug substance + product have real time stability data
stress studies to show product degradation
limited time stability studies are acceptable for short-term trial
stability data from engineering lots also acceptable
failure to demonstrate product stability is hold issue
gene cloning
monoclonal antibodies are major product
putting plasma into a bacterial cell. Bacterial cell will replicate the plasma and make proteins.
master cell bank
cell bank that contains genome that make the drug. they make the monoclonal.
preserve these by freezing them.
working cell bank
derived from vials from MCB
cell lines
advantages: produce human like proteins, secrete proteins, proteins are biologically active
disadvantages: slow growth rate, low cell densities and productivities, sensitive to fermentation conditions
fermentation process
upstream
cell bank put into spinner cultures
then put into multiple bioreactors
then harvest it
upstream process
clear definition of product -> selection of producing organism -> strain screening -> medium optimization -> small scale bioreactor culture -> process control requirements -> scale-up
downstream process
biomass/product seperation -> product purification -> concentration, crystalization, drying -> fill-finish -> storage, stability -> clinical trials -> marketing
