Biosimilars Flashcards
What are biological drugs?
are complex products that are derived from biologic sources (human, animal, microorganisms, or yeast).
include
- viruses, genes, antibodies, toxins or antitoxins, vaccines and blood/body tissues
What are biosimilars?
a new biological product that has been developed to be similar to an existing biological product
- no significant clinical differences from the originator in terms of safety, efficacy and quality
are not identical to the original
What are examples of biosimilars?
reference product - biosimilar product
genotropin (somatotropin) - omnitropin
eprex (epoetin alpha) - binocrit (epoetin alpha)
eprex (epoetin alpha) - retacrit (epoetin zeta)
What is the process of recombinant DNA technology?
Foreign DNA; characterised, isolated & purified.
Vector DNA: isolated, purified & cut with restriction enzymes to allow insertion of DNA.
DNA is joined & closed via ligase enzyme.
Ligated DNA introduced into host cell.
Protein is expressed and harvested
What is sonication?
process of cell lysis using sound waves
- created heat which causes degradation
What is the purpose of a Histidine tag?
enables further purification of proteins
all proteins bind to a chromatography column containing Ni2+ (nickel)
- less specific proteins are washed off the column with low concentration imidazole
- our protein is then washed off the column with high concentration imidazole
What are the different recombinant polypeptide expression systems? What are the advantages and disdvantages?
prokaryotes
eukaryotes
What are the advantages and disadvantages of prokaryote recombinant polypeptide expression systems?
advantages
- rapid growth
- high cell density
- cheap media is needed
disadvantages
- no machinery for glycosylation
- may not perform post translational modifications
- little ability to correctly fold
- no membrane transport
What are the advantages and disadvantages of eukaryote recombinant polypeptide expression systems?
advantages
- able to glycosylate proteins
- may perform other post translational modifications
- more easily fold multidomain polypeptides
- have membrane transporters
disadvantages
- slow growth
- low cell density
- often need expensive media
What is PEGylation? What is its purpose?
the covalent attachment of polyethylene glycol to a therapeutic active
purpose
- improve protein solubility
- extend circulating life
- reduces dosage frequency (potentially reduces toxicity)
- increased drug stability (reduces aggregation)
- enhanced protection from proteolytic degradation
What are the issues with PEGylation?
stable linkages can reduce activity.
presence at active or binding site can block substrate access.
may be steric hindrance.
breakable linkages include
- thiol groups and ester bonds
