1. ERT 323/2 SIMULATION FOR BIOPROCESS ENGINEERING SEM 2 (2012/2013) Modeling & Simulation of Bioprocess: ‘THROUGHPUT ANALYSIS & DEBOTTLENECKING STRATEGIES’

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.

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

4. PART 1 Throughput Analysis Theory  Types of bottleneck  Batch throughput

5. TYPES OF BOTTLENECKS Bottlenecks Equipment Resources SizeTime Size Time (utilities, labor, demand for raw materials)

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

7. THROUGHPUT /SIZE BOTTLENECK Equipment Capacity Utilization = Liquid volume Max liquid volume Equipment Capacity Utilization = Operating throughput Max throughput OR

8. Batch time = 11.49 hr Equipment Uptime = Total time equipment is utilized per batch Batch Time (BT) A) SCHEDULING @ TIME BOTTLENECK PCT for P-1 = 10.52 hr PCT = Procedure Cycle Time (duration spent to complete an entire procedure including all operation in the procedure

9.  Path: View/Throughput Analysis Charts/ Utilization  Remark: Throughput analysis will only carry out for equipment in rating mode (switch P-1 to rating mode) Throughput Analysis Chart B) SIZE @ THROUGHPUT BOTTLENECK Combined Utilization = Equipment Capacity Utilization x Equipment Uptime

10. PART 2 Process Debottlenecking Strategies

11. Debottlenecking strategies  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 Annual Throughput Cycle Time Batch Throughput or 8

12. Debottlenecking Example 1 ‘Tongkat Ali Extract Production’

13. Tongkat Ali extract production

14. Pilot Scale Production

15. Base Case Simulation Debottlenecking question: How to increase production? Spray drying time: 22 hrs Annual production: 323 batches

16. Throughput analysis Path: View/ Throughput Analysis Charts/ Utilization Highest combined throughput SPRAY DRYER

17. Operation Gantt chart Path: Tasks/ Gantt Charts/ Operation GC Time bottleneck : SPRAY DRYING (22.44 hrs)

18. SCHEME 1 : ADD NEW SPRAY DRYER New SPRAY DRYER

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 11.05 hrs; reschedule start time of drying & CIP operations in new spray dryer  Save file as “Scheme 1”  Execute the simulation & check answers

20. AFTER ADD NEW SPRAY DRYER Cycle time: 13.39 hrs Annual production: 591 batches ERT 315/4 SIMULATION OF BIOPROCESS SEM 1 (2010/2011)

21. SCHEME 2 NEW EVAPORATOR

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: 11.05 hrs. Spray dryer:reduce process time to 11.05 hrs  Save file as “Scheme 2”  Execute the simulation & check answers.

23. AFTER ADD NEW EVAPORATOR Cycle time: 13.39 hrs Annual production: 591 batches

24. SCHEME 3 – SCHEME 1 + SCHEME 2

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 0.465 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.

26. AFTER SCHEME 1 + SCHEME 2 Cycle times: 8 hrs Annual production: 984 batches

27. SCHEME 4- PACKAGING LINE

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)

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

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: 7.984 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. Continue………

31. ASSIGNMENT Throughput & economic analysis Process parametersBase 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’

33. BASE CASE SIMULATION dayyear Annual Operating Time = 8 hours x 52 weeks x 5 day week = 2080 hours year Challenge: How to increase additional 150% of current production rate?

34. Throughput Analysis Chart Highest combined throughput

35. Operation Gantt Chart The longest operation

36. SCHEME 1- Intermediate Tank

37. Scheme 1: Throughput analysis Slight increase Slight decrease

38. Scheme 2- New Blending Tank

39. Scheme 2- Throughput analysis Further increase Further decrease

40. SCHEME 3- New Multifunctional Tank + New Filter

41. Scheme 3 - Throughput analysis Further increase Further decrease Slight decrease

42. Scheme 4- Schemes 1 + 2

43. Scheme 4- Throughput analysis Huge increase New bottleneck

44. Scheme 5- Future expansion

45. Scheme 5- Throughput analysis Further increase Further decrease

46. Combined utilisation Equipment Tag Procedure Name Base case Scheme 1 Scheme 2 Scheme 3 Scheme 4 Scheme 5 V-102P-2Jacketed Heater 2 V-101P-1Jacketed Heater 1 V-103P-4Main Blending Tank FL-101P-5Filler BC101P-6Belt Conveyor BX- 101 P-7Manual Cartoning GBX- 101 P-8Shrink Wrapping BX- 102 P-9Manual Pallet Packaging

47. Process Throughput Economic parametersBase case Scheme 1Scheme 2Scheme 3Scheme 4Scheme 5 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 alternative - Revenue of current operation Investment cost of alternative + Operating cost of alternative - Operating cost of current operations

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)