1. Modeling & Simulation of Bioprocess: ‘THROUGHPUT ANALYSIS &
ERT 315/4 SIMULATION IN
BIOPROCESS
SEM 1 (2010/2011)
Modeling & Simulation of Bioprocess: ‘THROUGHPUT ANALYSIS &
DEBOTTLENECKING STRATEGIES’
By; Mrs Hafiza Binti Shukor

2. Student should be able to;
ANALYZE the uncertainty problem that might be happen during the operations.
CLASIFY and ORGANIZE debottlenecking strategies to increase the annual production with low operation cost.
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

3. COURSE OUTLINE PART 1: Throughput Analysis Theory
PART 2 : Process Debottlenecking Strategies
PART 3 : Case Study & Discussion
Tongkat Ali extract production
Pharmaceutical cream production
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

4. PART 1 Throughput Analysis Theory
Types of bottleneck
Batch throughput
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

5. TYPES OF BOTTLENECKS Bottlenecks Equipment Resources Size Time Time
(utilities, labor, demand for raw materials)
Size
Time
Time
Size
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

6. BATCH THROUGHPUT ANALYSIS
Annual throughput of a batch process:
Annual
Throughput =
Batch x
Number of
Batches per Year
EQUIPMENT
To increase
annual throughput
Run
bottlenecks or
RESOURCE
(utilities, labor, demand for raw materials)
A) TIME BOTTLENECK
- equipment/resource that limits the number or batches per year.
Further
classification:
B) THROUHPUT BOTTLENECK
-equipment/resource that limits the batch throughput
(amount of material processed per batch).
Continuous process will only experience throughput bottlenecks.
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

7. THROUGHPUT /SIZE BOTTLENECK
Equipment
Capacity
Utilization
Liquid volume =
Max liquid volume OR
Operating throughput
Equipment
Capacity
Utilization =
Max throughput
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

8. A) SCHEDULING @ TIME BOTTLENECK
Batch time
= hr
PCT for P-1
= hr
PCT for P-1
=10.52 hr
Equipment
Uptime =
Total time equipment is utilized per batch
Batch Time (BT)
PCT = Procedure Cycle Time (duration spent to complete
an entire procedure including all operation in the procedure
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

9. Throughput Analysis Chart
B) THROUHPUT BOTTLENECK
Path: View/Throughput Analysis Charts/ Utilization
Remark: Throughput analysis will only carry out for equipment in rating mode (switch P-1 to rating mode)
Combined
Utilization =
Equipment
Capacity x
Uptime
Throughput Analysis Chart
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

10. PART 2 Process Debottlenecking Strategies
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

11. Debottlenecking strategies
Batch
Throughput
Annual
Throughput
Cycle Time or 8
Increase batch throughput until a size bottleneck is
reached.
Do the following:
Increase number of cycles of limiting procedure
Rearrange equipment, or;
Use new equipment
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

12. Debottlenecking Example 1
‘Tongkat Ali Extract Production’
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

13. Tongkat Ali extract production
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

14. Pilot Scale Production
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

15. Base Case Simulation
Spray drying time: 22 hrs
Annual production: 323 batches
Debottlenecking question: How to increase production?
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

16. Path: View/ Throughput Analysis Charts/ Utilization
Highest
combined
throughput
SPRAY DRYER
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

17. Operation Gantt chart Path: Tasks/ Gantt Charts/ Operation GC
Time bottleneck :
SPRAY DRYING
(22.44 hrs)
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

18. SCHEME 1 : ADD NEW SPRAY DRYER
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

19. SCHEME 1 - Instructions Delete outlet stream from storage tank
Add a mixer from Splitting/ Bulk Flow/ 2-way
Duplicate a new spray drier.
Select spray drier with its associated inlet & outlet streams
Press copy icon or Ctrl+C
Press copy icon or Ctrl+V
Reconnect stream between storage, splitter & dryers.
Unit procedure configuration:
Storage: increase transfer-out flowrate to 0.24 L/min
Splitter: 50% distribution to each stream; reschedule start time (start with transfer-out of storage) & duration (follow spray drying duration via Master-and-Slave)
Both spray dryers: reduce process time to hrs; reschedule start time of drying & CIP operations in new spray dryer
Save file as “Scheme 1”
Execute the simulation & check answers
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

20. AFTER ADD NEW SPRAY DRYER
Cycle time: hrs
Annual production: 591 batches
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

21. SCHEME 2 NEW EVAPORATOR ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

22. SCHEME 2- Instructions Use “Base Case” file for start
Delete outlet stream from storage tank.
Added a new evaporator from Phase Change/ Multi-Effect Evaporation
Reconnect streams between storage, evaporator & spray dryer; rearrange the procedures of needed
Unit procedures configuration:
Storage: increase transfer-out flow rate to 0.24 L/min
Evaporator: 50% water & 1% TA powder evaporated; schedule operation to start when transfer-out of storage starts; setup time: 20 min; process time: hrs.
Save file as “Scheme 2”
Execute the simulation & check answers.
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

23. AFTER ADD NEW EVAPORATOR
Cycle time: hrs
Annual production: 591 batches
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

24. SCHEME 3 – SCHEME 1 + SCHEME 2
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

25. SCHEME 3- Instructions Use “Scheme 1” file for a start
Delete outlet stream from storage tank
Add a new evaporator from Phase Change/ Multi-Effect Evaporation
Reconnect streams between storage, evaporator & mixer; rearrange the procedures if needed
Unit procedures configuration:
Storage: increase transfer-out flowrate to L/min
Evaporator: 50% water & 1% TA powder evaporated; schedule operation to start when transfer-out of storage starts; set-up time: 20 min; process time: 5.71 hrs
Splitter: reduce process time to 5.71 hrs
Both spray dryers: reduce process time to 5.71 hrs
Save file as “Scheme 3”
Execute the simulation & check answers.
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2009/2010)

26. AFTER SCHEME 1 + SCHEME 2 Cycle times: 8 hrs
Annual production: 984 batches
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

27. SCHEME 4- PACKAGING LINE
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

28. SCHEME 4- Instructions Use “Scheme 3” file for a start
Delete outlet streams from both spray dryer
Add the following unit procedures:
Mixer: Mixing/ Bulk Flow/ 2-stream
Capsule mixing: Mixing/ Bulk Flow/ Custom
Capsuling: Formulation & Packaging/ Tableting (General)
Bottling: Formulation & Packaging/ Boxing
Boxing: Formulation & Packaging/ Boxing
Flip the equipment to reverse direction, reconnect the streams & rename the unit procedures
New component registration:
Maltodextrin (refer component: soybean flour)
Boxes (refer component: water)
Bottles (refer component: water)
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

29. SCHEME 4- Instructions
Set rating mode for the following (right click & select “Equipment Data”):
Capsuling: 50 entities/min for rated throughput
Bottling: 2 entities/min for rated throughput
Boxing: 1 entities/min for rated throughput
Unit procedures configuration:
Mixer: set-up time: 20 min; process time: 6.63 hours; start operation when either of the dryer starts
Capsule mixing: mix-in stream: maltodextrin; Set outlet composition for maltodextrin: 88.89% mass; start operation when mixing starts
Capsuling: Tablet name: TA capsules; Amount per tablet: 0.45 g: Operating throughput: 50 tablets/min; setup time: 10 min; process time: calculated based on throughput; start operation when capsule mixing ends
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

30. Unit procedure configuration (continue):
Bottling: boxing capacity: 60 items/box; container line-bottom [bottles (name); bulk amount per entity: 1g; purchase price: $ 0.10]; setup time: 20 min; process time: h; start operation when capsuling starts
Boxing: boxing capacity: 12 items/box; container line-bottom [bottles (name); bulk amount per entity: 1g; purchase price: $ 0.13]; setup time: 10 min; process time: 1h; start operation when capsuling starts
Save files as “Scheme 4”
Execute the simulation & check answers.
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

31. ASSIGNMENT 6 Throughput & economic analysis
Process parameters
Base case
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Overall product yield (%)
Batch production (kg/batch)
Minimum cycle time (hr)
Plant batch time (hr)
Number of batches per year
Annual production (kg/yr)
Capital cost ($)
Operating cost ($/yr)
Total revenues ($/yr)
Gross margin (%)
Return on investment, ROI (%)
Throughput
Economics

32. Debottlenecking Example 2
‘Pharmaceutical Cream Production’
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

33. BASE CASE SIMULATION Annual Operating Time 8 hours 52 weeks 5 dayx x = =
day
year
week
year
Challenge: How to increase additional 150% of current
production rate?
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

34. Throughput Analysis Chart
Highest
combined
throughput
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

35. Operation Gantt Chart The longest operation
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

36. SCHEME 1- Intermediate Tank
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

37. Scheme 1: Throughput analysis
Slight
decrease
Slight
increase
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

38. Scheme 2- New Blending Tank
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

39. Scheme 2- Throughput analysis
Further
decrease
Further
increase
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

40. SCHEME 3- New Multifunctional Tank + New Filter
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

41. Scheme 3 - Throughput analysis
Further
decrease
Further
increase
Slight
decrease
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

42. Scheme 4- Schemes 1 + 2 ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

43. Scheme 4- Throughput analysis
New
bottleneck
Huge
increase
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

44. Scheme 5- Future expansion
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

45. Scheme 5- Throughput analysis
Further
decrease
Further
increase
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

46. Manual Pallet Packaging
Assignment 7
Combined utilisation
Equipment Tag
Procedure Name
Base case
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme5
V-102
P-2
Jacketed Heater 2
V-101
P-1
Jacketed Heater 1
V-103
P-4
Main Blending Tank
FL-101
P-5
Filler
BC101
P-6
Belt Conveyor
BX-101
P-7
Manual Cartoning
GBX-101
P-8
Shrink Wrapping
BX-102
P-9
Manual Pallet Packaging
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

47. Process Throughput Assignment 8 Economic parameters Base case Scheme 1
Batch production (tube/batch)
Plant batch time (hour)
Minimum cycle time (hour)
Number of batches/ year
Annual production (tube/year)
Cost of investment ($)
Annual operating cost ($)
Unit production cost ($/tube)
Annual revenue ($)
Gross margin
Cost benefit ratio (CBR)

48. CBR = - + - Revenue of current Revenue of operation alternative
Investment
cost of
alternative
Operating
cost of
alternative
Operating
cost of
current
operations + -
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

49. Conclusions
Debottlenecking can never ending, it should be stopped when the debottlenecking objective has been meet.
Remember to check the economic
performance:
Payback time (PBT)
Return on investment (ROI)
Cost benefit ratio (CBR)
ERT 315/4 SIMULATION OF BIOPROCESS
SEM 1 (2010/2011)

50. Thank You