Lecture 2

Question 1

Bioprocess Design Flow

Answer 1

Target Molecule Development –> Bioprocess Development (Cell Cultivation -> Purification -> Formulation) –> Application

Question 2

Questions to be answered by Design

Answer 2

1. Requiered raw materials and ulitilies for single batch
2. size of equipment
3. total capital investment
4. optimum batch size
5. required time
   …

Question 3

DEFINITION Bioprozess design

Answer 3

conceptual work done prior to b uilding, expanding or retrofitting a prozess plant. TWO main activities
1. PROCESS SYTHESIS arrangement of unti operations (process steps) to produce desired product at accaptable costa nd quality
2. PROCESS ANALYSIS evaluation and comparison of different process synthesis solution

Question 4

Investment Cost in Industry?

Answer 4

3.3 - 6.2 Million$/m^3

Question 5

DEFINITION Process Synthesis

Answer 5

Development of a flow sheet for the recovery and purification of a biological product

Question 6

What does an optimal process control require?

Answer 6

orthologe techniques!

Question 7

Rule of Thumps

Answer 7

1. Remove the largest quantity first
2. exploit physical characteristics with the greatest difference between product and impurities
3. use different separation bases in successive steps
4. keep it as simple as possible

Question 8

General classification

Answer 8

1. Recovery and solid-liquid separation
2. capture, isolate, concentrate
3. Purification
4. Polishing

Question 9

What to keep in mind for the product classification

Answer 9

1. Scope of application (3 triangles, from no contact to living organism to intake into human bloodstream)
2. Side requirements (budget, location, space, time)
3. Production system (intra- extracellular, pretreatment, modification, …)
4. Product Class (molecular characteristics, …)

Question 10

Steps of recovery of intracellular products?

Answer 10

1. Cell harvesting
   a. removal of extracellular liquids (centrifuge, filtration)
2. Cell disruption (break open host cell and release intra product)
   a. high pressure homogenizis (large capacity)
   b. beat mill
3. Removal of cell debris (depents on size and solubility of product)
   a. soluble (centrifugal, microfiltration)
   b. in-soluble (1. seperate, 2. dissolve, 3. refold)

Question 11

Step for recovery of extracellular product

Answer 11

1. Removal of biomass (types: disk stack(light MO), rotary vacuum filtration(mycalial), membrane filtration(low weight), floatation(algea))

Question 12

intermediat Recovery for soluble and in-soluble

Answer 12

soluble –> concentrate –> purify
in-soluble –> dissolve and erfold –> concentrate –> purify

Question 13

Types of techniques to concentrate

Answer 13

1. Ultrafiltration (protein concentration)
2. reverse osmosis (low molecular weight
3. evaporation (low and high molecular weight)
4. precipitation (blodd protein, citric acid)
5. distillation (low molecuule weight and alkohle)

Question 14

Steps to renaturate inclusion bodies

Answer 14

1. dissolve by strong chaotrope (zB urea)
2. refold after diafiltration of chaotropes, dilution or chomatography, folding (thiol, high temp)
3. dilution to minimize molecule interaction

Question 15

Differance chaotrope and kosmotrope

Answer 15

chaotrope: lower hydrophobic effect (disrupes water water interaction)
kosmotrope: higher hydrophobic effect (stronger water water interaction)

Question 16

final purification for biopharma and bioindustry

Answer 16

biopharma:
- high purity
- combi chroatography anf filtration steps
bioindustrial:
- medium to low purity
solvent removal
general:
- cristilation and …
- dehydration or solvent removal

Question 17

pairing of unit operations

Answer 17

1. identify specifications for final product
2. apply rule of thumps
3. think about media conditions needed for process steps

Question 18

What is the process analysis based on?

Answer 18

1. capital investment
2. manufacturing cost
3. enviromental cost
4. time consumption
5. experiance

Question 19

what is used for capital investment and manufacturing cost

Answer 19

spreatsheet and process simulator based on material and energy balances, equipment sizing
–> allows chracterizing a prozess scanrio and change it quick and accuarte wehen different data etc.

Question 20

Manufactering flow

Answer 20

Idea Generation (project screening) –> Process developement (evaluation of alternatives and common language)–> from R&D to manufacturing (facility, tech) –> manufactering (ongoing optim)

Question 21

DEFINITION Process Economics

Answer 21

Estimation of working capital investment, estimation of operating cost, analysis of profitability)

Question 22

Avarage durh developent cost

Answer 22

500- 1 bio $/ successful drug

Question 23

DEFINITION of Capital Cost estimation

Answer 23

directes fixed capital, working capital, start-up & validation cost

Question 24

Direct fixed capital (DFC)

Answer 24

• estimated based opon total equipment purchase cost (prior projects etc)
• function of industrial application and plant location
• scaling law for equipment (das mit alpha 0.5-1)
• price equimpent changes over time: CE Index

Question 25

Working Capital

Answer 25

accounts for cash that must be available for investments in on-going expenses (material, labor, utility, waste, facility overhead)

Question 26

Profitablility analysis

Answer 26

3 gleichungen gross margin return of investment payback time (years)