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An S88 based analysis of a Pharmaceutical plant

 

Authors :

Andy Rayner - Project Management Ltd

Francis Lovering - ControlDraw Ltd

Last update 02/10/14

Table of Contents

Introduction and Background

Pharmaceutical Plant Process Description

  • Solids/Liquids/Gas Bottle Deliveries
  • Warehouse
  • Dispensary
  • Tank Farm
  • Liquid Nitrogen Deliveries
  • Natural Gas Supply/Steam Boiler and Condensate Recovery
  • Power Supply
  • Packaging Warehouse
  • Bulk Pharmaceutical Chemical Production Facility - Building 1
  • Intermediate Product Warehouse
  • Finished Pharmaceutical Facility - Building 2
  • Quarantine Store
  • Final Product Store
  • Heat Transfer Oil Generation System
  • Solvent Recovery Plant
  • Waste Water Treatment Plant
  • Air Emissions Treatment Plant
  • Waste Solvent Tanks
  • Quality Control (QC) Laboratory
  • Maintenance Workshop and Stores
  • Offices
  • Customers

    Rework

    Products

    S88 Analysis

  • Plant Area
  • Process Cells
  • Plant Level Common Resources
  • Table of Figures

  • Figure 1 - Dispensary
  • Figure 2 - Typical Dispensary Operation
  • Figure 3 - Dispensary to Production Transition
  • Figure 4 - Bulk Primary Pharmaceutical Production Building Process Cell
  • Figure 5 - Finished Pharmaceutical Production Building Process Cell
  • Figure 6 - Tabletting Process Cell
  • Figure 7 - Packaging
  • Figure 8 - Typical Bulk Storage Tank
  • Introduction and Background

    At the April 1995 meeting of the European Batch Forum in Dublin, a number of participants expressed the view that while the S88 Part 1 standard seeks to cover only batch processes, there was a necessity to cater for certain non-batch processes and other activities found in typical "batch" industries.

    During the concluding discussions of the meeting, it was decided to form a new work group, to be known as Work Group 3, to explore these issues and if necessary to propose additions to the standard.

    The Pharmaceutical plant was devised as a means of illustrating the many issues which concern the working group. To this end and a fairly detailed P&ID has been produced for the plant along with a basic process description.

    Subsequently an ‘S88 Analysis’ of the plant and processes has been carried out, and this document has been produced to summarise the progress so far.

    A Process Description is provided first to give an indication of the general process requirements.

    Subsequent sections illustrate the analysis of the plant and discuss some of the issues that arise.

    The analysis is not complete, but it does illustrate many of the concepts.

    Back to Table of Contents 

    Pharmaceutical Plant Process Description

     

    Solids (such as pharmaceutical active powders, catalysts, filter aids, etc…), Liquids (such as solvents in drums) and gas bottles (such as nitrogen, hydrogen, argon, etc…) arrive at the warehouse. On arrival of a lorry at the warehouse reception bay the deliveries are unloaded by fork lift truck and taken to the Warehouse.

    A procedure is required to register the arrival, which should match an expected delivery as scheduled in the Manufacturing Execution System (MES).

    Warehouse

    The Warehouse stores the deliveries on pallets. A system to control the location of materials and to ensure that they are used in an appropriate order, such as first-in first out or according to use by dates will be required. This document does not explore these areas of functionality.

    Dispensary

    Solid powders or liquids from the warehouse are depalletised and sieved (if necessary), weighed, sampled, subdivided (if necessary) into smaller quantities and placed into containers (such as IBC’s or drums),labelled and shipped to the production plant for use in the production process.

    This process is driven by the production campaign requirements so that the right raw materials in the right quantities are processed.

    Tank Farm

    In addition to delivering to the warehouse, tankers can also offload bulk solvents (such as toluene, MIBK, Methylene Chloride, Acetone and Methanol) and/or reagents (such as bromine, caustic and hydrochloric acid) directly into bulk storage tanks (typically 20,000Litres to contain a full tanker load). On arrival of a tanker at the reception bay the tanker is connected up to one of the tank farm tanks. Tanks can be reallocated providing they are cleaned after the last solvent has been discharged.

    Liquid Nitrogen Deliveries

    Liquid nitrogen is delivered to a bulk storage tank from where nitrogen can be evaporated and distributed to different areas of the site for the purpose of nitrogen inertion of vessels to minimise the risk of an explosion as many of the solvents in use on the plant are flammable.

    A procedure is required to register the arrival, which should match an expected delivery as scheduled in the MES

    Natural Gas Supply/Steam Boiler and Condensate Recovery

    A natural gas supply is provided to the site to feed a steam boiler which in turn raises steam for use in heating processes (such as the heat transfer oil system and the Heating Ventilation and Air Conditioning (HVAC) system).

    Power Supply

    A power supply through a local substation is provided to the site through the national power grid.

     

    Packaging Warehouse

    A warehouse store is provided for the purpose of receiving empty packaging (such as glass bottles, stoppers, caps, labels, blisterpacks, boxes, cartons, sachets, etc…).

     

    Bulk Pharmaceutical Chemical Production Facility - Building 1

    The bulk pharmaceutical chemical production facility is where the reactions take place to form the active pharmaceutical ingredient. Whilst the reactions take many forms (such as grignard reactions, redox reactions, etc…) the basic process functions are similar at each vessel type, namely:

    Reactors:

    • Solid addition
    • Solvent Addition
    • Feed Tank addition
    • Gas addition
    • Heating/Cooling/Holding/Refluxing/Distillation temperature control,
    • Agitation
    • Inertion
    • pH control
    • Sampling
    • Discharge
    • Cleaning
    • etc…

    Centrifugation:

    • Feeding
    • Spinning
    • Washing
    • Discharging
    • Cleaning
    • Pressure Filtration/Drying:
    • Feeding
    • Washing
    • Reslurrying
    • Cake Smoothing
    • Drying
    • Discharging,
    • Cleaning

    Drying:

    • Feeding
    • Drying
    • Discharging (including milling),
    • Cleaning

     

    Back to Table of Contents  

    Intermediate Product Warehouse

    In between building 1 and building 2 (or in between process steps taking place in any building) products can be stored in an intermediate product warehouse.

    Finished Pharmaceutical Facility - Building 2

    The finished pharmaceutical chemical production facility is where the formulation of the active pharmaceutical ingredient into the final dosage form and the packaging of the doses takes place. The basic functions which can typically take place in such a facility include:

    Powder Preparation:

    • Milling
    • Sieving
    • Blending

    Solution Preparation:

    • Suspension Suspension of bulk active ingredient in water or solvent,

    Tabletting:

    • Granulation (size enlargement)
    • drying
    • compression
    • coating
    • inspection
    • printing
    • packaging

    Vial Filling:

    • Glassware washing
    • glassware sterilisation
    • stopper wash and sterilise
    • vial filling
    • lyophilisation (freeze drying)
    • capping
    • labelling
    • inspection and packaging.

    Other dosage forms:

    Other dosage forms not shown in this example but which have similar operations include capsules (beads, solid powders or liquid filled), syringe filling, sachet filling, transdermal patches, topicals (creams and ointments) and aerosols).

    Quarantine Store

    Product is held in the quarantine store until they have been cleared by QA, this depending on texts carried out on samples taken from the tabletting and vial filling lines along with a QA review of the batch records form the production of the batches

    Final Product Store

    Product is held in the product store until it is requested by a delivery work order

    Heat Transfer Oil Generation System

    In order to provide a heating and cooling system for vessels which is highly controllable a heat transfer oil generation system has been provided. This utilises a proprietary oil (such as syltherm, dowtherm or marlotherm) with a temperature range of -70°C to +225°C. A hot stream and a cold stream are generated (the hot by use of steam, the cold by use of chillers and a cooling tower) and these are fed to the various vessels where they can be blended to give the required temperature.

    Solvent Recovery Plant

    In order to reduce the quantity fresh solvent being purchased and the quantity of waste solvent being shipped offsite the Miracle Cure Company has a solvent recovery facility.

    Here, the solvents can be washed to remove salts (using liquid/liquid extraction), stripped from the salty organic wastes (using distillation) and waste water can be stripped to remove organic loading on the effluent treatment plant. Treated solvents are stored in the recovered solvent tanks pending clearance from QC after sampling to permit re-use.

    This facility consists of a liquid/liquid extraction tower to wash the waste solvents with acid or caustic to remove salts, followed by a distillation tower where steam is used to strip off the solvent which is then condensed and collected for re-use.

    The waste liquors remaining in the distillation column bottoms are distilled further in a second distillation column to remove remaining solvents from the aqueous stream down to an acceptable level so that the waste water can be sent to the waste water treatment plant. The solvents which are "stripped off" in this "waste water stripper" are collected by condensation and are shipped offsite for incineration.

    Waste Water Treatment Plant

    In order to comply with the effluent discharge licence under the IPC (Integrated Pollution Control) requirements all aqueous effluents which are being discharged to a local river are required to meet licensed emission limits. In order to achieve this limits all aqueous effluent is treated in the waste water treatment plant.

    Air Emissions Treatment Plant

    In order to comply with the air emissions discharge licence under the IPC (Integrated Pollution Control) requirements all airborne emissions are treated prior to discharge. The method of treatment can vary depending upon the source and content of the emission, typical treatment methods include incineration, thermal oxidation, carbon adsorption, liquid absorption/desorption, cryogenic or low temperature condensation, scrubbing and dust collection.

    Waste Solvent Tanks

    Waste solvents which cannot be recovered in the solvent recovery plant, and cannot be passed through the waste water treatment plant are stored in the waste solvent tanks awaiting collection for disposal offsite (by for example liquid incineration).

    Quality Control (QC) Laboratory

    Laboratory facilities are provided onsite for in process control testing. The QC laboratory is integrated with the manufacturing through the use of a Laboratory Information Management System (LIMS) which is integrated into MES.

    Maintenance Workshop and Stores

    Equipment maintenance, instrument callibration and storage of spare parts is undertaken in this area. The scheduling of work within this function is integrated into the MES.

    Offices

    Head Office, Procurement, Finance, IT, Regulatory Compliance, and Marketing staff are all based in the office block. These staff all have access to the plant information through the MES and also have access to information the 5 other manufacturing sites worldwide together with 42 marketing offices through the MES.

     

    Back to Table of Contents   

    Customers

    The "Miracle Cure Company" supplies to a large number of customers in different countries with both prescription drugs and over the counter (OTC) drugs. In addition to manufacturing its own drugs it manufactures drugs under licence (where it has to supply the drug in the customers own brand packaing) and also manufacturers a number of generic drugs (where the same drug can be sold under different brand names as the patent has expired). The pricing of products is a strategic decision made by "Miracle Cure Companies" senior management - sometimes the cost will be high in order to make sure that the costs of the disruption to the schedule are more than covered, however sometimes the work is done at cost or even at a loss if the new customer is considered strategically important enough.

    Rework

    Just occasionally, and notwithstanding the highly effective scheduling system ,a batch is made which does not meet the critical quality standards of the "Miracle Cure Company".

    This can happen when there is an equipment failure - in general equipment failures can be tolerated by putting the process into hold, repairing the failed item, and then re-starting.

    However, sometimes there are failures which cannot be fixed in time to allow the batch to be completed.

    In these cases it is highly preferable to be able to re-use the batch if possible. This is far more acceptable than disposing of the batch due to its high cost, and can be achieved by either reprocessing in the bulk pharmaceutical chemical production building or by using small percentages of the batch in subsequent batches of similar products provided this is done in time.

    This practise is accepted to a greater or lesser degree by the customers and regulatory authorities (such as FDA, MCA, etc..) depending upon the market for which the drug is intended.

    A further issue with rework is that when a problem does occur and some rework is needed , it can become necessary to change the production schedule to make product which can use up the reclaimed batch.

    Products

    The plant produces a large number of products, in a variety of packaged forms.

    There are three basic categories of products:

    Cancer Cure:

    This includes a cure for both Breast Cancer & Cervical Cancer and is called "Miracle Cancer Cure"

    Alzheimer’s Disease Cure:

    This is called "Miracle Alzheimer’s Cure"

    Hangover Cure:

    This is called "The Miracle Cure"

    Recipe Characteristics

    Each category of product is made in a different way

    Within each general product type there are a large number of specific recipes. The Miracle Cure Company has its own recipes and the products made under licence for other companies have their own recipes.

     

    Packaging

    The product is packed in a variety of ways. Each customer has their own labels for the bottles or cartons which are use, and each customer has their own barcoding standard. Products are packaged for different countries and these have their own languages, some countries also have requirements for different types of packaging and different inserts.

    S88 Analysis

    This section provides an analysis of the plant using S88 Models and Terminology with diagrams to show each of the main S88 entities, such as Plant Area, Process Cell, Unit, Operations and so on. Not all of these are shown in this document but the intention is to show enough for illustration purposes.

    Much more detail is covered in the ControlDraw model

    Back to Table of Contents  

    Plant Area

    The first stage is to draw the entire plant and the Top level of the Physical and Procedural models. This is illustrated the Plant Area diagram below.

    The following Table lists the main S88 entities

    Object S88 Definition
    Raw Material Warehouse Common Resource
    Dispensary Process Cell
    Tank Farm Common Resource
    Liquid Nitrogen Storage Common Resource
    Purified Water Generation Plant Common Resource
    Steam Boiler and Condensate Recovery Common Resource
    Heat Transfer Oil Generation System Common Resource
    Empty Packaging Store Common Resource
    Intermediate Store Common Resource
    Laboratory Common Resource
    Final Product Store Common Resource
    Quarantine Store Common Resource
    Air Emissions Treatment Plant Common Resource
    Solvent Recovery Plant Common Resource
    Water Treatment Plant Common Resource
    Bulk Pharmaceutical Chemical Production Building Process Cell
    Finished Pharmaceutical Production Building Process Cell

     

    We have identified the Process Cell s and the top level Common Resource S88 objects in the plant.

    Note 1

    As this study is concerned with fitting in those parts of a real plant that are not well defined by S88 we have taken the liberty of calling them Common Resources.

    Note 2

    These are all part of the same process cell

    Explanation

    There are 3 Process Cells and 14 Common Resources at the Plant Level. See below for discussion

    Process Cells.

    Why 3?

    Because the batches in each area are not directly related to each other on a one for one basis.

    In this analysis we have enforced a rule that one batch = one process cell (although there may be several in progress) , so making it necessary to split the plant down into several process cells

    Thus :

  • The Solids Processing Cell delivers batches to IBCs

    The Milkshake Cell delivers batches to Product Silos

    The Packaging Cell delivers batches to the Quarantine Store

  • Common Resources

    (S88.01 - common resource: A resource that can provide services to more than one requester.)

    We have as mentioned identified 14 Common Resources at the Plant Level. That is to say that these are common resources that are hierarchically directly below the S88 Plant Area cell and do not even appear to belong to a Process Cell.

    This is feasible because they provide services to several process cells and so cannot be logically subordinate to them.

    The Raw Material Warehouse serves the entire plant (pharmaceutical actives to building 1, inert excipients to building 2, chemicals to the waste water treatment plant and the purified water generation plant)

    The tank farm serves the entire plant

    The utilities (liquid nitrogen storage, purified water generation, steam and condensate, heat transfer oil generation system and power supply) serve the entire plant

    The Laboratory may be carrying out operations on sample of the batch but is not processing

    The Final Product Store, Intermediate Store, Packaging Store and Quarantine Store are all providing a service to the Plant

    The solvent recovery system, air emissions treatment system and the waste water treatment plant serve the entire plant

    It is debatable that these are all really common resources according to S88, however we need to put all of the equipment in the plant into the physical model in some way.

    The next stage of the analysis involves defining in more detail the objects we have now listed.

     

    Back to Table of Contents  

    Process Cells

    Dispensary

    The dispensary is illustrated in the diagram below:

    Figure 1 - Dispensary

     

    The following Table lists the main S88 entities

    Object S88 Definition
    x Equipment Module
    Weigh Scale Control Module
    Transfer Equipment Equipment Module
    Hoist Equipment Module
    Labelling Machine Equipment Module
    Sampling Tool Control Module
    Testing Equipment Control Module
    MES Terminal Control Module
    Bar Code Reader Control Module
    Raw Material Container Process Input
    Product Container Unit

    Typical phases undertaken within the dispensary as part of the Procedure to prepare a pallet include the following:

      • RECEIVE WORKORDER
      • RECEIVE MATERIAL/CHECK ID
      • WEIGHING
      • SAMPLING & TESTING
      • LABELLING (INCLUDING LABEL RECONCILLIATION)
      • SUB-DIVIDING
      • PALLETISING
      • RELEASE

    The following flow chart gives an indication of the typical workflow required to prepare a pallet of product:

     

    Figure 2 - Typical Dispensary Operation

    The workorder will consist of both production schedule information and recipe information, i.e.

    WORKORDER = PRODUCTION SCHEDULE INFORMATION + RECIPE INFORMATION

    For example:

    Production Planning Information:

      • Product: The Miracle Alzheimer Cure
      • Manufacturing Location: Building 2, Location A & B
      • Time Required at Location A: 10.30 am
      • Components required at location A: Raw Material A & B
      • Components required at location B: Raw Material C
      • Earliest Start: Cannot remove raw materials from cold store to make batch earlier than 9.00am otherwise product quality maybe impaired.

    Recipe Information

    •  
      • Product: The Miracle Alzheimer Cure
      • Raw Material A: 30Kg’s
      • Raw Material A Quality Control Requirements: 80% < 25 microns, 100% < 50 microns, Identity Test
      • Raw Material B: 50 Kg’s
      • Raw Material B Quality Control Requirements: Light Sensitive product, no white light, Identity Test
      • Raw Material C: 200 Litres
      • Raw Material C Quality Control Requirements: Identity Test

    Workorder

      • All of the above.

    The batch as it leaves the dispensary contains multiple process outputs (i.e. pallets and raw materials).

    The production schedule entry defines the batch. Liquid drum material dispensing is the same as solid powder dispensing from the S88 point of view. Gas Bottles are rarely dispensed, it is much more normal that they are simply QC checked for identity and then shipped to the appropriate location for dispensing to the process.

    Workorders may include the requirement to make up raw materials for multiple batches, this is illustrated below with the following information summarised from a workorder:

    Contents of Workorder 1

    Control Recipe 1 (Alzheimer’s Miracle Cure) - Intended Batch Number AMC001

    Material 1, Quantity 1, Time 1, Required at Location 1

    Material 2, Quantity 2, Time 2, Required at Location 1

    Control Recipe 2 (Alzheimer’s Miracle Cure) - Intended Batch Number AMC002

    Material 1, Quantity 1, Time 1, Required at Location 1

    Material 2, Quantity 2, Time 2, Required at Location 2

    Material 3, Quantity 3, Time 3, Required at Location 3

    Control Recipe 3 (The Miracle Cure) - Intended Batch Number MC001

    Material 1, Quantity 1, Time 1, Required at Location 1

    Material 2, Quantity 2, Time 3, Required at Location 2

    Based upon the above workorder there are a number of points to note with respect as to how the dispensary will operate:

    • The dispensary will dispense all of material 1 to three separate sub-lots (one for each control recipe) at the same time to avoid handling the material 1 more than once.
    • The dispensary will send a mixed pallet containing raw materials for control recipe’s 1, 2 & 3 to location 1 at time 1 in preference to sending 3 pallets.
    • The dispensary will send a mixed pallet to location 2 at time 2, even though control recipe 3 does not need material until time 3, providing product stability allows and storage space on the plant exists.

    During the transfer of material from the dispensary to the production building the material is "transformed" from being a product of the dispensary (i.e. batches of raw materials on pallets) to becoming raw materials (process inputs) to the production process. The problem as defined inS88 terms results in a situation where there is not a one to one relationship in this respect (i.e. A batch of product from the dispensary (pallet of raw materials) may feed a number of different control recipe’s).

    This transition requires that each pallet contains attributes describing the contents of its pallet and the intended control recipe/batch for which it is intended is identified in order to ensure complete traceability of the batch back to the raw materials supplied to the company from the production process.

    Back to Table of Contents   

    Figure 3 - Dispensary to Production Transition

     

    Bulk Primary Pharmaceutical Process Cell

    The bulk primary pharmaceutical production building process cell is illustrated in block form in the diagram below:

    Figure 4 - Bulk Primary Pharmaceutical Production Building Process Cell

    <This section needs to be further developed, the only aspect so far discussed is gas bottle dispensing to reactors, notes from this include:

    • Procedure for changeover of gas bottles required as more than one may be required per batch (i.e. both partial cylinders and multiple cylinders may feed a batch)
    • Is a batch/lot ID required for the cylinder as it is an input to the process?
  • End notes>
  • Finished Pharmaceutical Process Cell

    The finished pharmaceutical production building process cell is illustrated in block form in the diagram below:

    Figure 5 - Finished Pharmaceutical Production Building Process Cell

    Within the process cell there are 4 main processes, namely:

    • Solution Preparation
    • Powder Preparation
    • Tabletting
    • Vial Filling

    Each of these is described in more detail below:

    Solution Preparation

    <This item has yet to be discussed and developed>

    Powder Preparation

    <This item has yet to be discussed and developed>

    Tabletting

    The tabletting line consists of the following process steps:

    • Granulation (agglomeration of the active pharmaceutical ingredient (powder form), the inert filler component of the tablet (also in powder form) and binder (often in liquid form) to bind the particles together to ensure a uniform mix and a size suitable for tablet compression).
    • Drying (removal of excess solvents used in the binding process above, often a fluid bed dryer or a tray dryer).
    • Tablet Compression & QC Checking (Formation of the tablet itself, different tablet shapes exist (e.g. round, oval, etc…), also different tablet types (e.g. single layer, two layer or 3 layer), this is acheived by re-tooling the tablet compression machine between batches).
    • Coating (the tablet is coated with a film for the purpose of making the drug slow release (changing its dissolution profile), masking of nasty flavours or to aid tablet printing)
    • Tablet Inspection
    • Tablet Printing (printing of batch number and expiry date directly onto the surface of the tablet)
    • Packaging & Issue to Quarantine

    Typically small/medium scale/volume production facilities in order to provide flexibility have each process step above in its own room and product is moved from room to room as required. Not all tablets are coated or printed so these can be left out of the production process if not required. Large scale/volume production processes may have dedicated production lines where each process step follows the other.

    The following Table lists the main S88 entities

    Drawing object S88 Definition S88 Object

    (The name of the specific instance of the S88 object)

    Note
    Granulation Unit Granulation  
    Drying Unit Drying  
    Tablet Compression Unit Tablet Compression  
    Coating Unit Coating  
    Tablet Inspection Unit Tablet Inspection  
    Tablet Printing Unit Tablet Printing  
    Packaging Unit Packaging  
    MES Terminal Control Module MES Terminal  
    Bar Code Reader Control Module Bar Code Reader  

    In defining the units generally it is best to determine which components must run together and which can run independently. As such for each unit above to work independently there must be a facility for Work In Progress (WIP) storage between units, also if unit capacities are not directly matched (e.g. granulation has twice the capacity of tablet compression) WIP areas must be provided to handle the extra product created which must be held until the downstream step can process the material.

    So, for instance, sometimes granulation and drying takes place in series because of the machinery installed and as such the granulation and drying should be grouped together into one unit called granulation/drying. Similarly tablet compression and tablet inspection can also be integrated into two machines in series and a unit could be defined called tablet compression/inspection. In summary the number of WIP areas define the number of units and hence the number of unit procedures and associated control recipes. This is illustrated below:

    Back to Table of Contents 

    Figure 6 - Tabletting Process Cell

    A single batch of product which is produced in the granulator could become multiple batches of product in the tablet machine which in turn could become multiple batches of packaged product. For example, the granulator/dryer could produce 2,000 Kg’s of granulated product which was made from 200 Kg’s of pharmaceutical active ingredient, 1,000 Kg’s of inert filler and 800 Kg’s of solvents. These 2,000 Kg’s of granulated product could be used to make:

    Batch 1 - 100,000 number 20mg (active) tablets, oval shape (uses 20 Kg active)

  • Batch 2 - 200,000 number 30mg (active) tablets, round shape (uses 60 Kg active)

    Batch 3 - 100,000 number 20mg (active) tablets, round shape (uses 20 Kg active)

    Batch 4 - 250,000 number 40 mg (active) tablets, oval shape (uses 100 Kg active)

  • In addition each batch of tablets produced above could be put into multiple types of packaging,. For example batch 1 above could be used to make:

    Packaging Batch 1 - 1,000 number blister packs, 10 tablets per pack, own brand

  •  

    packaging, English Language, no inserts, primary outer carton contains 10 blister packs, secondary outer carton contains 10 primary outer cartons, 10 secondary outer cartons per pallet

  • Packaging Batch 2 - 2,000 number blister packs, 5 tablets per pack, own brand

  • packaging, English Language, no inserts, primary outer carton contains 2 blister packs, secondary outer carton contains 10 primary outer cartons, 5 secondary cartons per pallet
  • Packaging Batch 3 - 20,000 number blister packs, 3 tablets per pack, third party brand

    packaging, French Language, "Vignette" insert (type of insert

  • specific to French market), primary outer carton contains 5 blister

    packs, secondary outer carton contains 100 primary outer cartons,

    20 secondary cartons per pallet

    Etc…

  • The packaging process can be summarised in the following diagram:

    Figure 7 - Packaging

    Vial Filling

    <This item has yet to be discussed and developed>

    Back to Table of Contents   

    Plant Level Common Resources

    Tank Farm

    The liquids used in the production process in large quantities are generally held in the tank farm in bulk storage tanks. The typical arrangement for the bulk storage tanks is as follows:

     

    Figure 8 - Typical Bulk Storage Tank

     

    The following Table lists the main S88 entities in the Tank Farm:

    Drawing object S88 Definition S88 Object

    (The name of the specific type of the S88 object)

    Note
    T1 Unit Bulk Storage Tank  
    P1 Equipment Module Tanker Unloading Pump  
    P2 Equipment Module Bulk Storage Tank Discharge Pump  

    The bulk storage tank may receive bulk liquids from multiple suppliers, usually a delivery docket is checked prior to allowing the tanker to charge its contents to the bulk storage tank.

    In addition the tank is not usually fully emptied before the next load is charged and as such the raw material from different suppliers is mixed over time.

    Some bulk storage tanks may have agitators to keep the contents mixed, others may have the liquid pumped around a recirculation loop to keep the contents mixed. Some tanks may be required to be maintained above a certain temperature (often by electrical heat tracing) as some substances may solidify on cold days (e.g. glacial acetic acid).

    Possible phases associated with this common resource include:

    • Receive from Tanker
    • Discharge from Bulk Storage
    • Agitation (if required)

    Liquid Nitrogen Storage

    <This item has yet to be discussed and developed>

    Purified Water Generation Plant

    <This item has yet to be discussed and developed>

    Steam Boiler and Condensate Recovery

    <This item has yet to be discussed and developed>

    Heat Transfer Oil Generation System

    <This item has yet to be discussed and developed>

    Compressed Air Generation System

    <This item has yet to be discussed and developed>

    Power Supply

    <This item has yet to be discussed and developed>

     

    Empty Packaging Store

    <This item has yet to be discussed and developed>

    Intermediate Store

    <This item has yet to be discussed and developed>

    Laboratory

    <This item has yet to be discussed and developed>

    Quarantine Store

    <This item has yet to be discussed and developed>

    Final Product Store

    <This item has yet to be discussed and developed>

    Air Emissions Treatment Plant

    <This item has yet to be discussed and developed>

    S88 Entities

    The following Table lists the main S88 entities in the Tank Farm:

    Drawing object S88 Definition S88 Object

    (The name of the specific type of the S88 object)

    Note
    Liquid/Liquid Extraction Column Equipment Module Liquid/Liquid Extraction Column  
    Distillation Column Equipment Module Distillation Column  
    Waste Water Stripper Equipment Module Waste Water Stripper  

    The units are essentially continuos units in terms of their operation with a changeover required as each tank of raw feedstock is emptied. Given that a tank of feedstock could contain (say) 50,000 Litres and the column could operate at (say) 1,000 Litres per hour, the operation could be running continuosly for 50 hours before the feedstock supply tank would need to be changed. This is typical of this type of operation and is frequently considered as continuous control.

    Waste Water Treatment Plant

    <This item has yet to be discussed and developed>

    Back to Table of Contents