Human insulin, created using recombinant DNA
Interferon alfa and muromonab-CD3 approved
CBER's Office of Therapeutics Research and
Review (OTRR) formed
First whole chimeric antibody, rituximab, and
first humanized antibody, daclizumab, approved
$30 billion share of biotechnological drugs of
$400 billion in yearly worldwide pharmaceutical
An inhaled form of insulin (Exubera) approved
Process of Drug Production
Cells and plasmid
Cell line manufacture Bioreactor process
Medium developmentdevelopment & scale-up
Therapeutic proteins will form the
back-born of future medicinal
• simple physiology
• short generation times, as bacteria grow and
• large yields of product - up to 10 % of mass (low cost)
• The expressed proteins often do not fold properly
and so are biologically inactive.
• The synthesised protein is often toxic to bacteria
preventing the cell cultures from reaching high
• Yeast is a simple eukaryote and performs many of
the post-translational modifications required for
• Presence of active proteases that degrade foreign
(expressed) proteins, thereby reducing their yield
• (a solution to this problem is the construction of
yeast strains from which the protease genes have
• High level of expression
• Correct folding
• More difficult to work with
• Slow generation time
• Not suitable for proteins with repetitive sequences
• competitive cost
the availability of established practices for their
efficient harvesting, transporting,
• sorting and processing
• cheap method
• produce the desired proteins in vast quantities when
using larger animals like cows.
• long lead time to generate a herd of transgenic
• concerns about the health of the animal.
• cause serious negative health effects
In vitro systems
• E. coli extract; plant wheatgerm extract; and
mammalian sources, rabbit reticulocyte lysate.
• lack both the genomic material and the cellular
• contain the cellular components required for
transcription and/or translation of genes.
proteins approved for
Eli Lilly, Novo Nordisk
Eli Lilly, Genetech, Upjohn,
GH deficiency in
Amgen, Ortho Biotech
Schering, Biogen, Chiron,
Hepatitis B and C,
Drugs in transgenic animals
(currently in the
drug is produced
in the chickens
from the breast
milk and modifies
it in the cow which
gives a more
Roslin Institute in
Hermitech, Inc. in
Sioux Falls, South
Schematic representation of the process used to
purify ATryn from the milk of transgenic goats.
Recombinant Hepatitis vaccine
• The hepatitis B virus (HBV) vaccine
– surface antigen purified from the
blood of infected individuals.
– Due to safety concerns, the HBV
vaccine became the first to be
produced using recombinant DNA
Vaccine Production at industry level
to respond to a human influenza pandemic.
• to respond to a human influenza pandemic.
• single vector containing the coding sequences for both
• After transfection, a genetically stable transformant
producing biologically active recombinant FSH was
• 150–450 gene copies were present in mammalian cells.
• FSH products from cell culture supernatants.
• collected from a perfusion-type bioreactor
• downstream purification
Bio therapeutics are delicate drugs
• Much larger and more
complex than traditional
proteins with a precise
history during storage