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53 Cards in this Set
- Front
- Back
Bioprocessing |
process that uses complete living cells or their components to obtain desired products |
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Bioprocess engineering |
the engineering discipline involved in designing/developing/optimizing the equipment/processes to manufacture bioprocessing products |
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Example Products |
Biopharmaceuticals Vaccines Antibiotics Fermentedproducts: beer/wine/kombucha Bioethanol |
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Current biopharmaceuticals |
Predominantly monoclonal antibodies andother recombinant protein products |
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Next Generation biopharmaceuticals |
Proteins
Antibodies Gene therapy Stem cell therapy Cellular immunotherapeutics Regenerative medicine |
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what do next generation biopharmaceuticals target? |
they target more difficult to treat and rarer diseases |
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Car T-cell Therapy |
-example of a next generation biopharmaceutical - t cells are taken out of body. modified, and put back into the body to target cancer |
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How long is the development pathway of a biopharmaceutical's bioprocessing development and manufacturing? |
10-15 years it is from pharmaceutical discovery to market |
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when does the bioprocessing development part actually start? |
after the discovery of the drug |
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Molecular specific processes |
process that caters specifically to the molecule you are working with |
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platform processes |
- the universal or standard processes - process that can be done the same from one company to another |
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upstream processes |
- bioreactor - harvesting (sometimes considered upstream) - involves making the molecule, things that involve the cells |
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Downstream processes |
- harvesting - capture -purification - polishing - concentration/buffer exchange -freeze/ storage |
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Harvesting |
getting what you care about via centrifugation and filtration. getting the target product from the cell |
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capture |
for mAb, use protein A - affinity chromatography - considered first step of purification |
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purification and polishing |
purification via ion exchange (including cation and anion), or chromatography |
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concentration/buffer exchange |
done via further filtration (TFF) |
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TFF |
tangential flow filtration |
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API |
Active pharmaceutical ingredient |
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what is TFF used for? |
1. primary recovery (harvest, cell separation) 2. to get a more concentrated volume 3. for buffer exchange (diafiltration) |
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TFF's role in API process |
TFF helps get the active ingredient |
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Production time and cost using e.coli --> yeast--> plant--> animal |
e.coli doubles every 30 min mammalian cells double every day THEY INCREASE FROM LEFT TO RIGHT due to rate of growth |
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Post transitional modifications using e.coli --> yeast--> plant--> animal) |
e.coli don't require any mammalian cells highly require them to change certain fxns DONT NEED IT --> HIGHLY NEED IT |
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explain Glycosylation |
depending on where and what glycosylations done, the function of the antibody is changed |
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list glycosylation modifications |
stability, solubility, half life, protein folding |
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cell line development process |
ex: transfecting host cell with protein of interest, then attach the protein of interest with selection marker. selects successfully transfected cells with high copy number. engineer cells to produce protien product/ of interest |
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media selection |
sugars, amino acids, fatty acids, lipids, vitamin, ph buffers, salt needed for cell growth/survival |
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bioreactor design |
1. put in media at appropriate temperature (cooling water or heating jacket system to control ) 2.put in cells 3. sparge in air so cells have O2 4. air is towards agitator, therefore it spins 5. spins and breaks down bubbles -- baffles = make the flow turbulent -- inlet/outlet ports: where you can put things in/out --outlet gas goes out |
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medium supplements |
serum, hydrolysate, phospholipids, growth factors |
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Batch mode of bioreactor operation |
simple. media put into bioreactor to grow cells |
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fed- batch of bioreactor operation |
media and food (glucose) put into bioreactor * feeding it while the process of growth |
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Continous (chemostat) mode of bioreactor operation |
media put into the bioreactor, then take out media and send to harvest |
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fermentation |
has to do with bacteria and yeast growth |
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bioreactor is for? |
growing mammalian cells |
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continuous ( perfusion) mode of bioreactor operation |
media put into the bioreactor, then take out media but ALSO separating out cells and putting the cells back in -- to achieve high cell densities and more product out |
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which mode of bioreactor operation an industry standard for Monoclonal Ab production? |
fed-batch |
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scale up of bioreactors |
to make lots of bioreactors. from lab/small scale to a commercial scale - need to preserve geometric, dynamic, and kinematic similarity in order to preserve optimal physiological conditions (growth, cell density, productivity) |
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scale up criteria |
1. constant kLa (related to O2 transfer) 2. constant impeller tip speed 3. constant P/V (power/unit volume) 4. constant mixing time * the apporach chosen depends on variables important to particular process |
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pH for cell growth and metabolism |
most cells require pH conditions in the range: 7.2 - 7.4 |
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temperature for cell growth and metabolism |
temp for most mammalian cells: 37 C |
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Oxygen transfer for cell growth and metabolism |
need O2 to go from air bubbles put into bioreactor --> to the media so that it can then go to the cells |
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metabolites |
through cell culture process, the cells release metabolites and they often become toxic - remove these wastes and metabolites out to remove the toxicity |
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why is O2 continuously supplied? |
O2 solubility in cell media is super low. which is bad bc need it to diffuse through media to get to cell |
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O2 into media |
O2 in air bubble. bubble has a boundary layer. hard for it to get out and into the media. need enough O2 for cells kLa coefficient= how well O2 goes from air bubbles to media |
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Viral clearance/inactivation operations ( in purified protein products ) |
solvent/detergent mix and low pH hold causes damages to the envelope part of the virus |
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viral clearance / inactivation for non-envelope viruses from protein prdts |
Nano- filtration |
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CQAs |
critical quality attributes - physical, chemical, biological or microbiological properties that should be within an appropriate limit, range, or distribution to ensure the desired product quality |
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protein drug CQAs |
pH, DNA, sterility, high and low molecular weight spaces, acidic and basic species, protein concentration |
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QbD |
quality by design - scientific, risk-based, holistic and proactive approach to pharmaceutical development. - design effort from pdt conception to commercialization - understanding of how pdt attributes and process relates to pdt performance |
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six sigma |
measure process performance quality in terms of variability expects 3.4 defective features per million opportunities |
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the higher the sigma value |
the lower the defects |
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biosimilars |
- not true generics - not bioequivalents - not biobetter - not biologics (not small molecule equivalent to a biologic pdt) -not better nor worse BUT SIMILAR |
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freeze/storage |
has bulk drug substance. Liquid and protein. It has API. stored in buffer |