College aantekeningen
Pharmaceutical Biotechnology - lectures
Upstream processing (USP) Downstream processing (DSP) Quality by design
[Meer zien]Voorbeeld 4 van de 50 pagina's
Voorbeeld 4 van de 50 pagina's
In winkelwagengesponsord bericht van onze partner
Verkoper
Volgen
Voorbeeld van de inhoud
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
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper célinebrouwerswur. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €9,50. Je zit daarna nergens aan vast.
Is Stuvia te vertrouwen?
4,6 sterren op Google & Trustpilot (+1000 reviews)
Afgelopen 30 dagen zijn er 52510 samenvattingen verkocht
Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen