Exam 3 Byrn

Question 1

Patents

Answer 1

Find ingredients of each marketed version of dosage form.
Find recalls of drug dosage form.
Use google scholar and US patent office for patents.

Question 2

Patent search

Answer 2

search for patent examples that contain all the excipients in package insert.
Make sure dose is correct.
EX – interest in tablets

Question 3

Syrup

Answer 3

drug containing sugar/sugar substitute
sometimes contains an antimicrobial preservative

Question 4

Elixir

Answer 4

clear sweetened solutions containing a drug and alcohol
antihistamine elixir
Non aqueous solutions
liniment, minimum water
alcoholic or other types of solutions

Question 5

Solution dosage form vs solid

Answer 5

solution is faster because drug is already in solution and it takes longer for solid to dissolve

Question 6

Quality of solutions

Answer 6

ethylene glycol contamination killed 100s people, 1937 sulfonamide elixir scandal, numerous incididents in Africa, 2022 dozens died in gambia due to contaminated ethylene glycol

Question 7

Solution formulations of biologics

Answer 7

drug, buffers for pH, stabilizer, solubilizer, tonicity modifier, insulin ingredients

Question 8

Forms of biological dosage forms

Answer 8

solution in vials, freeze dried vials w/ powder

Question 9

Stability

Answer 9

increase stability when drying solution to solid form due to decrease degradation rate. Solid has 100x less degradation rate.

Question 10

Freeze drying

Answer 10

more quality control, advantage for bulk crystallization, we freeze fry parenterals historically.

Question 11

Surfactants are stabilizers

Answer 11

using surfactants can increase particle counts. Using polysorbate w/ surfactants can keep stability similar from 3 to 5 freeze dries.

Question 12

Biologics

Answer 12

the process is the product, biotech is tech based on biology that harnesses cell and biomolecular processes to develop medicines

Question 13

Drug substance manufacturing

Answer 13

expression system like gene expression/protein production and cell culture.
Harvesting
protein purification

Question 14

Drug substance characterization

Answer 14

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

Question 15

drug substance cont (methodolgy)

Answer 15

safety - bacterial endo/exotoxins
purity + charactization - peptide mapping, and pure assays
identity - unique protein of interest

Question 16

Drug product manufacturing

Answer 16

formulation, fill/finish

Question 17

stability program

Answer 17

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

Question 18

gene cloning

Answer 18

monoclonal antibodies are major product
putting plasma into a bacterial cell. Bacterial cell will replicate the plasma and make proteins.

Question 19

master cell bank

Answer 19

cell bank that contains genome that make the drug. they make the monoclonal.
preserve these by freezing them.

Question 20

working cell bank

Answer 20

derived from vials from MCB

Question 21

cell lines

Answer 21

advantages: produce human like proteins, secrete proteins, proteins are biologically active
disadvantages: slow growth rate, low cell densities and productivities, sensitive to fermentation conditions

Question 22

fermentation process

Answer 22

upstream
cell bank put into spinner cultures
then put into multiple bioreactors
then harvest it

Question 23

upstream process

Answer 23

clear definition of product -> selection of producing organism -> strain screening -> medium optimization -> small scale bioreactor culture -> process control requirements -> scale-up

Question 24

downstream process

Answer 24

biomass/product seperation -> product purification -> concentration, crystalization, drying -> fill-finish -> storage, stability -> clinical trials -> marketing

Question 25

Synthetic post translational modification

Answer 25

PEGylation - polyethylene glycol (PEG) is attached to a protein to: prolong half-life, increase solubility, reduce immunogenicity, increase resistance to proteolysis

Question 26

typical biotech manufacturing process

Answer 26

genetic development: wild vector + gene of interest to expression vector to expression system
cell banks: master cell bank to working cell bank
Drug substance production: culture/fermentation to purification to drug substance
drug product production: sterile filtration/aseptic filling to drug product

Question 27

analytical procedure lifecycle

Answer 27

change managment
analytical procedure development
analytical procedure validation

Question 28

polio vaccine

Answer 28

1955 more than half of vaccines were made by lilly. In 1968 vaccine was not produced anymore.

Question 29

4 main types of COVID vaccines

Answer 29

mRNA: uses mRNA to instruct cells to make piece of COVID for immune system
vector: use another virus to carry genetic instruction
protein subunit: small piece of virus circulates in the system
whole killed: whole inactivated virus

Question 30

novavax

Answer 30

begins early-stage trial for flu, COVID combo vaccine

Question 31

stability of RNA

Answer 31

liquid storage -20C is best, room temperature it begins to degrade faster

Question 32

RNA vaccine manufacturing

Answer 32

mix lipids in ethanol solution 1, mix nucleic acid in buffer solution 2
- two channels, mix syringe pump or flow system
forms lipid nanoparticles
-densely packed lipids, contains nucleic acid