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

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)

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)

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

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)

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) SCHEDULING @ TIME BOTTLENECK - equipment/resource that limits the number or batches per year. Further classification: B) SIZE @ 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)

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)

A) SCHEDULING @ TIME BOTTLENECK Batch time = 11.49 hr PCT for P-1 = 10.52 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)

Throughput Analysis Chart B) SIZE @ 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)

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

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)

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

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

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

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)

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

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)

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

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 ERT 315/4 SIMULATION OF BIOPROCESS SEM 1 (2010/2011)

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

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

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. Save file as “Scheme 2” Execute the simulation & check answers. ERT 315/4 SIMULATION OF BIOPROCESS SEM 1 (2010/2011)

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

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

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. ERT 315/4 SIMULATION OF BIOPROCESS SEM 1 (2009/2010)

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

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

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)

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)

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. ERT 315/4 SIMULATION OF BIOPROCESS SEM 1 (2010/2011)

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

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

BASE CASE SIMULATION Annual Operating Time 8 hours 52 weeks 5 day x 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)

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

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

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

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

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

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

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

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

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

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

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

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

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)

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)

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)

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)

Thank You