Als 312 Midterm

Front 1

Bioprocessing

Back 1

process that uses complete living cells or their components to obtain desired products

Front 2

Bioprocess engineering

Back 2

the engineering discipline involved in designing/developing/optimizing the equipment/processes to manufacture bioprocessing products

Front 3

Example Products

Back 3

Biopharmaceuticals

Vaccines

Antibiotics

Fermentedproducts: beer/wine/kombucha Bioethanol

Front 4

Current biopharmaceuticals

Back 4

Predominantly monoclonal antibodies andother recombinant protein products

Front 5

Next Generation biopharmaceuticals

Back 5

Proteins

Antibodies

Gene therapy

Stem cell therapy

Cellular immunotherapeutics

Regenerative medicine

Front 6

what do next generation biopharmaceuticals target?

Back 6

they target more difficult to treat and rarer diseases

Front 7

Car T-cell Therapy

Back 7

-example of a next generation biopharmaceutical

- t cells are taken out of body. modified, and put back into the body to target cancer

Front 8

How long is the development pathway of a biopharmaceutical's bioprocessing development and manufacturing?

Back 8

10-15 years

it is from pharmaceutical discovery to market

Front 9

when does the bioprocessing development part actually start?

Back 9

after the discovery of the drug

Front 10

Molecular specific processes

Back 10

process that caters specifically to the molecule you are working with

Front 11

platform processes

Back 11

- the universal or standard processes

- process that can be done the same from one company to another

Front 12

upstream processes

Back 12

- bioreactor

- harvesting (sometimes considered upstream)

- involves making the molecule, things that involve the cells

Front 13

Downstream processes

Back 13

- harvesting

- capture

-purification

- polishing

- concentration/buffer exchange

-freeze/ storage

Front 14

Harvesting

Back 14

getting what you care about via centrifugation and filtration.

getting the target product from the cell

Front 15

capture

Back 15

for mAb, use protein A

- affinity chromatography

- considered first step of purification

Front 16

purification and polishing

Back 16

purification via ion exchange (including cation and anion), or chromatography

Front 17

concentration/buffer exchange

Back 17

done via further filtration (TFF)

Front 18

TFF

Back 18

tangential flow filtration

Front 19

API

Back 19

Active pharmaceutical ingredient

Front 20

what is TFF used for?

Back 20

1. primary recovery (harvest, cell separation)

2. to get a more concentrated volume

3. for buffer exchange (diafiltration)

Front 21

TFF's role in API process

Back 21

TFF helps get the active ingredient

Front 22

Production time and cost using

e.coli --> yeast--> plant--> animal

Back 22

e.coli doubles every 30 min

mammalian cells double every day

THEY INCREASE FROM LEFT TO RIGHT due to rate of growth

Front 23

Post transitional modifications using

e.coli --> yeast--> plant--> animal)

Back 23

e.coli don't require any

mammalian cells highly require them to change certain fxns

DONT NEED IT --> HIGHLY NEED IT

Front 24

explain Glycosylation

Back 24

depending on where and what glycosylations done, the function of the antibody is changed

Front 25

list glycosylation modifications

Back 25

stability, solubility, half life, protein folding

Front 26

cell line development process

Back 26

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

Front 27

media selection

Back 27

sugars, amino acids, fatty acids, lipids, vitamin, ph buffers, salt

needed for cell growth/survival

Front 28

bioreactor design

Back 28

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

Front 29

medium supplements

Back 29

serum, hydrolysate, phospholipids, growth factors

Front 30

Batch mode of bioreactor operation

Back 30

simple.

media put into bioreactor to grow cells

Front 31

fed- batch of bioreactor operation

Back 31

media and food (glucose) put into bioreactor

* feeding it while the process of growth

Front 32

Continous (chemostat) mode of bioreactor operation

Back 32

media put into the bioreactor, then take out media and send to harvest

Front 33

fermentation

Back 33

has to do with bacteria and yeast growth

Front 34

bioreactor is for?

Back 34

growing mammalian cells

Front 35

continuous ( perfusion) mode of bioreactor operation

Back 35

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

Front 36

which mode of bioreactor operation an industry standard for Monoclonal Ab production?

Back 36

fed-batch

Front 37

scale up of bioreactors

Back 37

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)

Front 38

scale up criteria

Back 38

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

Front 39

pH

for cell growth and metabolism

Back 39

most cells require pH conditions in the range: 7.2 - 7.4

Front 40

temperature

for cell growth and metabolism

Back 40

temp for most mammalian cells: 37 C

Front 41

Oxygen transfer

for cell growth and metabolism

Back 41

need O2 to go from air bubbles put into bioreactor --> to the media so that it can then go to the cells

Front 42

metabolites

Back 42

through cell culture process, the cells release metabolites and they often become toxic

- remove these wastes and metabolites out to remove the toxicity

Front 43

why is O2 continuously supplied?

Back 43

O2 solubility in cell media is super low. which is bad bc need it to diffuse through media to get to cell

Front 44

O2 into media

Back 44

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

Front 45

Viral clearance/inactivation operations

( in purified protein products )

Back 45

solvent/detergent mix and low pH hold

causes damages to the envelope part of the virus

Front 46

viral clearance / inactivation for non-envelope viruses from protein prdts

Back 46

Nano- filtration

Front 47

CQAs

Back 47

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

Front 48

protein drug CQAs

Back 48

pH, DNA, sterility, high and low molecular weight spaces, acidic and basic species, protein concentration

Front 49

QbD

Back 49

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

Front 50

six sigma

Back 50

measure process performance quality in terms of variability

expects 3.4 defective features per million opportunities

Front 51

the higher the sigma value

Back 51

the lower the defects

Front 52

biosimilars

Back 52

- not true generics

- not bioequivalents

- not biobetter

- not biologics (not small molecule equivalent to a biologic pdt)

-not better nor worse BUT SIMILAR

Front 53

freeze/storage

Back 53

has bulk drug substance. Liquid and protein. It has API. stored in buffer