Presented at the World Batch Forum North American Conference Woodcliff Lake, NJ April 13-16, 2003

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Application of S88 Model in the Control of Continuous Distillation Facilities

Author Name Title Company Address City, State Postal Code Country Telephone Number Fax Number e-mail address

Franjo Kralj Process Specialist PLIVA, Pharmaceutical industry Jagieva 31 Zagreb 10000 Croatia +385 1 3782066 +385 1 3782059 Franjo.Kralj@pliva.hr

KEY WORDS
recipe control, continuous operation, distillation column, equipment phase, recipe structure, process validation

ABSTRACT
A recipe control of a continuous distillation plant was a challenge in its design, simulation, validation and successful exploitation. The plant was used for solvent recovery in an Active Pharmaceutical Ingredients Production Facility (API). Following S88 models, which were used as tools in structuring a specific process cell, which had several trains with batch operating units, it was decided to apply and extend the same approach on the continuous processes as well.

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This problem is solved by establishing specific equipment phases for particular process actions covering the complete process of solvent recovery which includes: dynamic transition from initial to steady state, continuous operation of distillation columns and dynamic transition from steady state to final quiescent state. All equipment phases were carried out by means of the typical control recipe, whose structure was carefully arranged to permit a repeated and smooth performance of the whole process, with continuously good product quality. The application of S88 model in the control of the continuous distillation facility was successful, the system remained stable, and it was validated. The measurable economic benefit achieved was a significant reduction in variability of product quality, which is very important for pharmaceutical manufacturers.

INTRODUCTION
A design of the solvent recovery plant as a part of a multiproduct API facility in Croatia included a consistent control philosophy for the complete process. Mostly this is a continuous process, but its main part, distillation process, begins with dynamic transition from initial to steady state and ends also with dynamic transition from steady state to final quiescent state. During start up of the continuously operating distillation columns, these dynamic transitions are usually performed manually until the column reaches stable steady state conditions after which the column is switched to fully automatic control. The same principle is usually applied during shut down of such columns. In both cases alarms generated during these dynamic transitions must be suppressed either by switching them off or by temporary changing their set values. In the application described in this work this was done in a different way i.e. by creating a master recipe which was typical for batch processes but in this situation it was applied and extended on continuous ones as well.

PROCESS DESCRIPTION
Downstream isolation units in API production, mother liquors were further treated in the adjacent solvent recovery plant. The purpose of the unit is to recover solvents (methanol, acetone and ethanol) from their water solutions in the mother liquors in order to recycle them back into process. Process model contains 3 parallel processes and it is shown in Figure 1. Each process consists of ordered set of dynamic or continuous operations and they are shown in Figure 2 for the first representative process part methanol recovery. A more detailed structure of process model up to the level of process actions is shown in Figure 3 for one of the representative continuous operation methanol rectification. Description of the process operations are given in Figure 2: Stripper preparation (dynamic) inertisation, initial feeding, vent condensation Stripper heating (dynamic) preheating to operating conditions

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Stripping (continuous) feeding, heating, primary and vent condensation, distillate and bottom outlets Stripping end (dynamic) shut-down of heating and closing of inlet and outlet streams, vent condensation Vessel preparation (dynamic) charging, vent condensation Acidification (dynamic) mixing at high speed, pH adjustment Vessel emptying (dynamic) mixing at low speed, transfer out Column preparation (dynamic) inertisation, initial feeding, vent condensation Column heating (dynamic) preheating to operating conditions, total reflux, bottom outlet Rectification (continuous) feeding, heating, reflux, primary and vent condensation, distillate and bottom outlets Rectification end (dynamic) shut-down of heating and closing of inlet and outlet streams, vent condensation The Physical Model on which all of the main process actions were carried out is a type with a single path structure. The juxtaposition of the procedural operations combined with the specific process units which provides the performance of the process operations in the representative process methanol recovery (Figure 2) shows the influence of the related physical model on the overall process functionality. A flexibility of the physical model is achieved by the construction of the special manifold, suitable for connections of a variety of the process combinations of the units. This flexibility is necessary to follow the different process demands of the designed multipurpose synthesis plant, in which the solvent recovery plant is an important part. The whole solvent recovery plant actually consists of 9 units: 5 continuously operating distillation columns (3 stripping and 2 rectification columns) and 4 agitated vessels. These units are further connected with 13 equipment modules i.e. feeding and receiving tanks. The Procedural Control Model on the level of the characteristic procedural operations for the above mentioned physical model is shown in the same picture (Figure 2). The finer structure of the procedural control model, containing the procedural phases of the procedural operations, describes how to carry out the specific process actions shown in Figure 3. It was done by creating the specific equipment phases which describe the manner in which the sequential functions for manipulating the pertinent equipment entities are executed. The characteristic sequences of a typical and the most representative equipment phase feeding with mother liquor at the constant feeding tray temperature - is shown in Figure 4.

RECIPE CONTROL OF A CONTINUOUS DISTILLATION PROCESS

In this particular case the control recipe procedure included recipe unit procedures, recipe operations and recipe phases. Linkage between the control recipe procedure and equipment control was achieved by associating recipe phases with equipment phases.

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The sequences of equipment phases (typical representative is given in Figure 4) were the basis for generating the computer control program. The execution of this program was subordinated to a control recipe which was specially developed for this purpose. The structure of the recipe was adjusted in such a way that it strictly follows the process model shown in Figure 1-3. Actually, the recipe structure for the process units is a combination of dynamic and continuous operations according to the scheme shown on Figure 2. Here two units with generally continuous processes have also some dynamic operations included. Typically, these are distillation units, i.e. in this case, the stripper and the rectification column. The operation regime of these units begins with dynamic transition from initial to steady state, has the main steady state (continuous) part and ends also with dynamic transition from steady state to final quiescent state. The adequate selection of small process steps performing the specific process action enable a smooth transition between dynamic and continuous part of operation, and ensure the right performance of the typically continuous operations as well. Typically a continuous process action like continuous column feeding (Figure 4) was broken down in small pieces demonstrating how the same control philosophy, valuable for batch process, could also be applicable for the continuous ones.

BENEFITS ACHIEVED
Trends of process parameters (temperatures, flows, pressures) which were controlled and and/or monitored during recipe control execution confirmed smooth transitions between dynamic and continuous operations and stable control during whole process. The quality of products, monitored during process of solvent recovery, was consistently good and according to the specifications. In this way the whole system achieved the measurable economic benefits in the overall API production. The whole process, recipe controlled, was validated which is very important for pharmaceutical manufacturers.

CONCLUSION
S88.01 process model, physical model and procedural control model were used for consistent definition of application software development, FAT, commissioning and qualification scope, while S88 modularity power was used for strengthening the effectiveness of the Guide (ref. 1). The application of S88 model in the control of the continuous distillation facility was successful. The original thinking in this application was to define equipment phases properly i.e. in such forms that they could be combined effectively. Together with the adequately selected transitions in the recipe structure so that they could cover all the demands of both, dynamic and continuous, type of process could be met.

REFERENCE
1. ANSI/ISA-88.01 1995 Batch Control Part 1: Models and Terminology, ISA, 1995

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SOLVENT RECOVERY

Processes

METHANOL RECOVERY

ACETONE RECOVERY

ETHANOL RECOVERY

Figure 1 Process model of the solvent recovery plant

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Procedural Control Model Procedures RECIPE FOR METHANOL RECOVERY

Physical Model

Process Model

TRAIN FOR METHANOL RECOVERY

Process Equipment

METHANOL RECOVERY

Process

STRIPPER PREPARATION

Dynamic Dynamic

STRIPPER PREPARATION

O P E R

STRIPPER HEATING

STRIPPER HEATING

STRIPPER
STRIPPING

P R O C E S

Continuous

STRIPPING

STRIPPING END

Dynamic

STRIPPING END

U N I T S O N S
RECTIFICATION END COLUMN PREPARATION

VESSEL PREPARATION

Dynamic

VESSEL PREPARATION

S O P E R A

A
ACIDIFICATION

T
VESSEL EMPTYING

MIXING VESSEL

Dynamic Dynamic

ACIDIFICATION

VESSEL EMPTYING

I
Dynamic Dynamic
COLUMN PREPARATION

T I O N S

COLUMN HEATING

RECTIFICATION

RECTIFIC ATION COLUMN

COLUMN HEATING

Continuous

RECTIFICATION

Dynamic

RECTIFICATION END

Figure 2 Procedural control/equipment mapping (up to the operations level) for the process methanol recovery
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Process Model Process Operation METHANOL RECTIFICATION

INERTIZATION

HEATING AT CONST. STEAM FLOW

PRIMARY &VENT CONDENSATION

DISTILLATE SUBCOOLING

P R O C E S S

FEEDING WITH MOTHER LIQUOR AT CONSTANT LOW FLOW

BOTTOM OUTLET

DISTILLATE OUTLET AT CONSTANT FLOW INTO FEEDING TANK

FEEDING WITH MOTHER LIQUOR AT CONSTANT HIGH FLOW

DISTILLATE OUTLET AT CONSTANT FLOW INTO DISTILLATE RECEIVER

FEEDING WITH MOTHER LIQUOR AT CONSTANT FEEDING TRAY TEMPERATURE

A C T I O N S

CONTINUOUS FEEDING WITH MOTHER LIQUOR AT CONSTANT FEEDING TRAY TEMPERATURE

CONTINUOUS BOTTOM OUTLET

CONTINUOUS DISTILLATE OUTLET AT CONSTANT FLOW INTO DISTILLATE RECEIVER

AVAILABILITY CHECK OF SOURCE & DESTINATION TANKS

Yes

No
STAND BY OF FEEDING STAND BY OF BOTTOM OUTLET STAND BY OF DISTILLATE OUTLET

No Yes Figure 3 Process model for the process operation methanol rectification (up to the level of process actions) Copyright 2003 World Batch Forum. All rights reserved. Page 7

TIME EXPIRED

Figure 4 The characteristic sequences of the equipment phase for the most representative process action column feeding with mother liquor at the constant feeding tray temperature (pages 7 8) Equipment Phase CONTINUOUS FEEDING WITH MOTHER LIQUOR AT CONSTANT FEEDING TRAY TEMPERATURE

1. STEP: INITIALIZATION SEND SOURCE ADRESS FROM LEADING PARAMETER TO ESTABLISH CONNECTIONS RESET PARTIAL AND TOTAL FLOW VALUES 2. STEP: LEVEL CHECK TAKE SLAVE EQUIPMENT PHASE TRANSFER OUT IF SOURCE DOES NOT HAVE ENOUGH INVENTORY GO TO HOLD GO TO STEP 3 OPEN INLET IF o COLUMN BOTTOM LEVEL IS LESS THAN A PREDEFINED VALUE GO TO STEP 5 CLOSE LINE IF U E N C E S o FEEDING TANK IS EMPTY 3. STEP: OPEN INLET OPEN VALVE FOR MOTHER LIQUOR INLET START FLOW INTEGRATION SET SLAVE FLOW CONTROLLER TO ACTUATE INTERNAL MODE START FLOW MONITORING SEND SLAVE EQUIPMENT PHASE TRANSFER OUT TO BE ACTIVE GO TO STEP 4 FEEDING CONTROL IF o MOTHER LIQUOR FLOW REACHED A MINIMUM PREDEFINED FLOW GO TO STEP 5 CLOSE LINE IF o FEEDING TANK IS NOT AVAILABLE OR SLAVE EQUIPMENT PHASE TRANSFER OUT IS IN FINAL STEP OR COLUMN BOTTOM LEVEL IS GREATER THAN A PREDEFINED VALUE

S E Q

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4. STEP: FEEDING CONTROL SET MASTER TEMEPERATURE CONTROLLER TO CONTROL INTERNAL MODE WITH A SETPOINT FROM A LEADING PARAMETER GO TO STEP 5 CLOSE LINE IF o COLUMN BOTTOM LEVEL IS GREATER THAN A PREDEFINED VALUE OR FEEDING TANK IS NOT AVAILABLE OR SLAVE EQUIPMENT PHASE TRANSFER OUT IS IN FINAL STEP 5. STEP: CLOSE LINE E Q 1.1 U E N C E 6. STEP: TANK EMPTY S SEND SLAVE EQUIPMENT PHASE TRANSFER OUT TO BASIC STATE GO TO STEP 2 LEVEL CHECK IF o FEEDING TANK IS AVAILABLE (FILLED) AGAIN AND IF QUANTITY IN FEEDING TANK IS GREATER THAN A PREDEFINED VALUE OR SLAVE EQUIPMENT PHASE TRANSFER OUT IS NOT IN FINAL STEP 7. STEP: CYCLIC STEP CHANGE SETPOINTS IF o ONE OR MORE LEADING PARAMETERS WERE CHANGED o PREPARE TEMPERATURE SETPOINT FOR CONTROLLER FROM THE LEADING PARAMETER Copyright 2003 World Batch Forum. All rights reserved. Page 9 CLOSE VALVE FOR MOTHER LIQUOR INLET SET MASTER TEMEPERATURE CONTROLLER IN INTERNAL ACTUATE MODE (CLOSE) SEND SLAVE EQUIPMENT PHASE TRANSFER OUT TO BASIC STATE GO TO STEP 2 LEVEL CHECK IF o FEEDING TANK IS AVAILABLE (FILLED) AGAIN AND IF QUANTITY IN FEEDING TANK IS GREATER THAN A PREDEFINED VALUE OR SLAVE EQUIPMENT PHASE TRANSFER OUT IS NOT IN FINAL STEP GO TO STEP 6 TANK EMPTY IF o FEEDING TANK IS NOT AVAILABLE FOR TRANSFER OR SLAVE EQUIPMENT PHASE TRANSFER OUT IS IN FINAL STEP