Class notes
Pharmaceutical Biotechnology - lectures
- Course
- Institution
Upstream processing (USP) Downstream processing (DSP) Quality by design
[Show more]
Seller
Follow
célinebrouwerswur
Content preview
UpstreamIntroduction lectures
Biopharmaceutical
- partly produced using a cell (yeast, E.coli, animal cell, animal)
- complex molecule
- injectable
- expensive
- used for life threatening disease
Defined Undefined
➢ Chemical structure / composition is ➢ Critical product attributes unknown
known ○ Extensive testing in clinical
➢ Critical product attributes known trials
○ Product failures
○ mechanism of action
➢ Process not understood
○ side effects ○ Process fixed early in
➢ Understanding of the process development
○ predict product quality ○ Process for trials =process
for market
○ Suboptimal process based
on old technology
○ Reject good batches/delay in
batch approval
Both make the biopharmaceutical very
expensive
Most are undefined, mainly due to Post translational modifications (PTMs)
Mainly glycosylation, effects:
- activity
- immunogenicity
- in-vivo half life (clearance from body)
- stability (storage)
Production platforms
➢ Bacteria → small proteins,
peptides, non glycosylated and
easily refolded proteins
➢ Yeast → more complex proteins
with limited glycosylation
➢ Animal cells → complex proteins
with extensive PTMs
,Approval path
Preclinical Cells, Basic safety: dosages
guinea Investigational new drug application
pigs
Phase 1 20-50 Pharmacological actions,
humans Product safety & side effects
Phase 2 50-200 Effectiveness: optimal dosage,
patients application scheme etc.
Phase 3 Hundreds Final safety and effectiveness
patients Very expensive
pharmaceuticals are very expensive:
- whole process costs 2 billion euros
- only 1 in 10 passes all the trials, 1 needs to make up for the other failures
fails in phase 3 → disaster for the company
Fast track
Orphan drugs
- smal patient group
- live threatening diseases
- clear therapeutic of public health advantage (e.g. COVID)
Biosimilars
= exact copies of originals that have gone off patent
,Animal cell culture
➢ In vitro studies
○ Basic cell physiology
○ Toxicity
○ Drug candidates
○ Food components
➢ Cell therapy
○ CAR-T cell cancer therapy
➢ Tissue engineering
○ cartilage (kraakbeen) repair
○ cultured meat
➢ Pharmaceutical proteins
○ EPO = hormone that will increase red blood cell production
normally made in kidney, EPO used for patients with kidney failure
➢ Viral vaccines
➢ Gene therapy (lecture 9 molecular virology)
○ gene delivery by AAV virus
➢ Sponge derived pharmaceuticals
○ sponge = animal
○ defense mechanism = production of complex chemical molecules
○ sponge cells in bioreactor for production
Cell line development
Some cells can escape this Hayflick limit like cancer cells → better cell line
- Infinite life span
- Acceptable growth rate
- Low growth factor dependence
- Suspension growth
- aneuploid = having an abnormal number of chromosomes in a haploid set
Transformed cells obtained by
- Mutagens
- Viruses
- Oncogens
- Spontaneous
- Tumors
Examples
- CHO (Chinese Hamster Ovary): epithelium
- SF-21/SF9 Spodoptera frugiperda: Ovary
, Growth
Media
animals cells need complex media, certain ingredients can only be added up until a certain
amount, because otherwise it will precipitate → limited growth
E. coli grows much faster → in case of contamination, E. coli will outgrow the animal cells
Serum
= fluid and solvent component of blood which does not play a role in clotting
Functions Problems
Growth factors ●Infectious agents
Transferrin (Fe) (viruses, prions)
Lipids ●Variable composition
Insulin ●Expensive
Shear protection ●High protein content
Detoxification problems in DSP
because of the problems, almost not used anymore
if really needed, serum from the patient themself is used
Shear sensitivity
Cause: lack cell wall, cel size
Reactor design: mixing, gas transfer
Comparison
mammalian insect yeast bacteria
nutritional complex complex simple simple
media cost 10-100 10-100 <1 <1
(€/dm3)
Secretion Yes yes/lytic variable No
PTMs ++ + +/- --
DSP simple simple complex complex
Scale-up difficult difficult simple simple
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller célinebrouwerswur. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $10.87. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
74735 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now