pharmaceutical steam generators and water distillation systems
TRANSCRIPT
Kemiterm Pharmaceutical Steam Generators and Water Distillation Systems GETINGE
Multi-Effect Water Distillation EquipmentFor production of Water For Injection (WFI)
Pharmaceutical Steam Generators Clean / Pure Steam* for use in the production of pharmaceuticals.
Clean-Steam Generators Clean Steam* for use in laboratories, hospitals andnon-critical production applications.
Water Treatment Equipment ∆Complete scope including filtration, softening, ROplant, CEDI plant, for production of purified water.
Distribution Systems ∆Storage and handling of treated water and steam;piping & control systems, heat exchangers and storage tanks.
Consultancy and After Sales Services
Design & Integration ServiceInstallation ServiceValidation ServiceComplete After Sales Care
∆ Not included in the scope of this brochure. Details available separately.
*See ‘Definitions’
Located near Copenhagen, Denmark, Kemiterm A/S hasbeen manufacturing water treatment equipment formore than 30 years. After many years as a businesspartner and supplier, Kemiterm joined theGetinge Group in 1998 and became Getinge-Kemiterm A/S.Now an integral part of the InfectionControl business area, Getinge-Kemiterm’s products areglobally distributed andsupported by the GetingeGroup distributionchannels, alongsideexisting channels.
The Getinge Group headquarters and primary factorywithin the Infection Control business area is located inthe town of Getinge on the West Coast of Sweden. Thisstate-of-the-art, 16,500 sq.m (178,000 sq.ft) factory isthe world’s largest of it’s type, and produces the majority of the Group’s pressure vessels, used in sterilizers, steam generators and multi-effect water stills.
The Getinge Group
State-of-the-art production facilities
Getinge WorldwideGetinge is a leading global medical technology groupthat provides complete solutions to clients engaged inthe provision of healthcare.The ‘Infection Control’ business area provides equipment and services to hospitals, laboratories andpharmaceutical companies around the world.As in other business areas, the Getinge Group is theworld market leader in this field, with sales and servicesupport channels in more than 100 countries on all 5 continents.
Getinge-KemitermProducts & Services
Getinge-Kemiterm and theGetinge Group
The guiding Getinge-Kemitermphilosophies are:
Customer Service / SatisfactionReliabilityQuality Control / ValidationRegulatory ComplianceCost-effectivenessEnvironmental Considerations
Pressure vessels are produced in our state-of-the-artproduction facility in Getinge, Sweden using automatedwelding equipment, according to ISO 9001 proceduresand following all appropriate pressure vessel codes.Design, Project Management, Assembly and Testing ofthe equipment is made at the Getinge-Kemitermheadquarters & factory in Lynge, near Copenhagen.
URS
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Quality Assurance / ValidationGetinge-Kemiterm recognize that design, constructionand performance are not the only criteria for selection ofa piece of equipment for pharmaceutical production, butthat quality control and documentation are equallyimportant, and must be an integral part of a project toinstall and validate new equipment. To this end, everyGetinge-Kemiterm water still and pure steam generatoris provided with extensive documentation coveringdesign, function, materials and components used,software programming and test protocols.
Factory Acceptance Testing is also an integral part ofevery project. All equipment is tested in a purpose built,600 sq.m (6,500 sq.ft) testing hall after manufacture.
This state-of-the-art hall is equipped with controllable,quantifiable utilities and data acquisition / monitoringequipment, used in generation of FAT reports.
After installation a Site Acceptance Test may beperformed to verify the FAT results before handover.
BasicsGetinge-Kemiterm understands the importance ofPharmaceutical Water as the most widely usedingredient in drug manufacturing and thatPharmaceutical Water and Steam are the fundamentalutilities for the manufacturing process.
Key D
esign Philosophy
Key DesignPhilosophies
Regulatory IssuesGetinge-Kemiterm closely follows industry trends, practices, guidelines and regulatory requirements;actively participating in working groups and committeesworking in the determination of these. All WFI stills, irrespective of optional features and functions consistently produce WFI that as a minimumcomplies with current USP, EP, JP and otherPharmacopoeial requirements.
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Design &Manufacture
Autoclave IntegrationThe combination of separation systems and the rapidresponse of the falling film technique enable the Getinge-Kemiterm steam generators to operate under a widervariety of operational conditions than generators with onlygravity and/or demister separation and ideal forapplications with fluctuating flow and pressurerequirements, such as the supply of steam to autoclaves.Getinge-Kemiterm steam generators may be supplied‘stand alone’ or may be integrated with any Getinge steamsterilizer. A degasser option is available to ensure non-condensible gas content remains below 3.5%. This togetherwith the precision control and separation systems ensurescompliance with EN 285 and HTM 2031 irrespective offeedwater quality.
Basis Of DesignGetinge-Kemiterm CSG and PFS Generatorshave the same basic construction andoperating principle. The CSG incorporatesa labyrinth baffle system to remove waterdroplets, whereas the PFS uses the 3+
separation system to guarantee puresteam quality irrespective of
feedwater quality.
Pharmaceutical Steam
DefinitionsGetinge-Kemiterm follow the concepts established inthe ISPE Baseline® Guide for Pharmaceutical Steam.For the purpose of defining our product range we usethe terms Clean Steam Generator (CSG) and PureSteam Generator (PFS) as follows:
CSG: Produces steam by evaporation of ‘clean’water. The properties of the steam are generallysimilar to those of the feedwater.
PFS™: Produces pure steam whereof the condensatemeets the pharmacopoeial requirements of Water forInjection, irrespective of feedwater quality.
FeaturesCommon Features
316L stainless steel pressure vessel – shell & tube Unique single port double tube sheet designPressure fed ‘falling film’ evaporation system304 stainless steel frame and electrical enclosureElectrical or plant steam heatingStandalone or integrated with Getinge™ autoclavePure steam pressure control systemGAMP compliant PLC system
CSG FeaturesTube in tube external preheaterLabyrinth separation system
PFS FeaturesUnique Ω internal preheatersUnique 3+ separation system
Steam generators are available in a variety of capacitiesfrom 100 to 8,000 kg per hour (220 to 17,600 lbs perhour).
An 8000 kg per/hourpure steam generatorinstalled at Getinge’s
test facility in Sweden.
Allen BradleySiemens Mitsubishi
Unique 3+ Separation SystemAt the exit of the evaporation tubes the clean steam turnsthrough 180°. Unevaporated feedwater and largedroplets are separated and fall to the bottom of thecolumn. This effluent (typ. 5-10%) is continuouslydischarged to drain as ‘blowdown’, carrying awayimpurities from the separation system. Heat may berecovered by cooling the effluent with incomingfeedwater via a heat exchanger.
The clean steam continues at low velocity upwardsthrough the central tube within the column. Lowerweight droplets continue to separate under gravity.
The clean steam enters a tangential port to the cyclonechamber and accelerates at high velocity within thechamber. This centrifugal action further removes waterdroplets and impurities, which drain to the base of thecyclone chamber and from there to the base of thecolumn via a discharge port.
Finally the steam turns again through 180° and exits aspure steam from the top of the column.
PFS FunctionThe generator consists of a 316L stainless steel shell andtube heat exchanger (column). The shell is heated by anexternal energy source, such as utility steam orelectricity. As it flows to the evaporation tubes,feedwater is preheated to boiling point via inverted Utubes (Ω preheaters) within the column. At the top of thecolumn the feedwater is distributed uniformly into theevaporation tubes, creating a thin film on the internalwalls. This ‘falling film’ is rapidly evaporated, creatingclean steam.
1+
1
2
3
TM
Pharm
aceutical Steam
PT
CT
Unique single port double tubesheet.
Stainless steel frame and control enclosure – as standard, not optional extras
Vertical condenser for complete drainability
GAMP Compliant PLC Systems
GAMP Documentation available21CFR Part 11 capable when combined with supervisory systems
Eliminates stress cracking Reduced external piping
Water For Injection (WFI)
Production is controlled according to distillateconductivity and temperature. These parameters, plusoutlet valve position are continuously monitored andrecorded during production.
No Moving PartsLow MaintenanceQuiet OperationEnergy EfficientMinimal Pretreatment RequirementsSteam or Electrical Heating
Basis Of DesignGetinge-Kemiterm consider assurance andmaintenance of product quality as theprimary factor in the design, construction
and control of the MS WFI stills.
Principle Equipment Features
Advantages of Multi-effect Distillation
Combination of separation systems allows use oflower grade feedwater6 log10 reduction in endotoxin concentration
Allen BradleySiemensMitsubishi
AISI 316L for all piping and components Choice of surface finishes.Dead legs less than 3D.Sanitary clamp connections with FDA approved gasket materials
Stills are available in a variety of capacities from 100to 15,000 liters per hour (26 to 4,000 gallons per hour).
Modem for remote monitoring/troubleshooting
All stainless steel piping system
Unique Ω internal feedwater preheater system
Superior and unique 3+ stage separation system forimpurity removal
MS™ FunctionGetinge-Kemiterm MS stills are designed to produce Water
For Injection by evaporating, purifying and condensingfeedwater. Due to the unique 3+ separation system, MS stills do not
require high quality water as a precondition to reliably produce WFIsatisfying USP, EP, JP or other pharmacopoeial requirements.
The feedwater is sequentially evaporated and condensed in a series of columns,or effects. The design of each column is fundamentally the same as a Getinge-Kemiterm Pure Steam Generator. Only the first effect is heated by externalenergy. Each subsequent effect uses pure steam from the previous effect asheating media, and the condensate is collected as WFI. Pure Steam from thefinal effect enters the shell of a heat exchanger, which uses cooling water tocondense the steam to WFI.
The size and design of each column determines the output capacity of the still,the number of columns determines the efficiency; the greater the number ofeffects, the lower the consumption of utilities. Thus the selection of the numberof effects (min:3, max:8) is a balance between initial capital cost and runningcost, and must be evaluated case-by-case based on local conditions such asutility costs and environmental concerns.
Multi-Effect Stills
The steam from the final effectprovides a slight overpressureto raise the distillate to adegassing chamber.
In this uniquely designed feature, the distillate gentlyboils to release dissolved gases.
When required, distillate flows undergravity from thedegassing chamber.
The temperature,conductivity and outlet valve positions arerecorded.
The temperature and conductivity is continuouslymonitored and if not withinappropriate parameters, thedistillate is discharged todrain.
The WFI produced in eacheffect and the condenser is collected in the condenser.
In normal production, the still may be operated manually, or remotely according to the level in the downstream storagetank. In the latter case, on reaching the upper level, the still may either stop, or enter a ‘hot standby’ mode where itremains heated and available for immediate production. In stop mode, the still will cool and will vent via a built in0.2µm sterilizing grade filter in a heated stainless steel housing.
Water for Injection
Getinge-Kemiterm products may be combined with otherGetinge equipment to provide our customers withcomplete solutions to their process needs.Getinge takes complete responsibility for the design andfunction of these combinations. We provide the customerwith complete peace of mind, saving the time and cost ofdesigning, selecting, purchasing and validating discretecomponents.
Combination Systems
Multi-media FilterWater SoftenerActivated Carbon FilterRO PlantCEDI Plant (PW production)Multiple Effect Still (WFI Production)
Storage TanksDistribution PipingPoint of Use Heat ExchangersUser Points
Typical Water Treatment andDistribution System
Pure Steam Generator with condensing system(produces WFI on demand or during night-time)Storage Tank, Distribution Pump, Loop PipingPoint of Use Heat Exchanger and User PointGetinge GE 66xx autoclaveGetinge 8666 washing machine
Typical Laboratory System
Examples
Combines features and techniques of PFS and MSsystems and may be configured over the same capacity rangesUnique Ω internal preheating for optimum efficiencyand longevity3+ separation system guarantees Pure Steam and WFIqualityPure Steam pressure is precision controlled accordingto process requirements, including supply of steam toautoclaves.Shared use of components, control system and skidframe reduces equipment cost and space requirements.Single unit design reduces time and cost of validationand maintenanceMulti-mode control allows use as steam generator ormulti-effect still or both
PFS-CFor small scale production and laboratory use it is notcost effective to use multiple effect distillation plant.The cost advantages / energy savings that can be madeby the ME principle cannot offset the capital cost.However, frequently there is a requirement for bothWater for Injection and Pure Steam in such facilities.In these cases, the PFS-C is a sensible choice. This maybe regarded as Single Effect (SE) distillation. A PFS generator produces pure steam, for use with anautoclave and SIP processes. Alternately the pure steamis condensed in a water cooled condenser to produceWFI. The controls may be configured according to theusage pattern – for example, during the day, pure steamis constantly available and by night, the pure steam iscondensed and the collected WFI is stored in a tank foruse during the day.
The ‘COMBI’,A UniqueSolutionAll Multiple Effect water stills may be used to generatePure Steam. However, the quantity is limited to a smallproportion of the capacity of the first effect. Steam mayonly be extracted during WFI production and extractionproportionately reduces the WFI capacity of the still.Furthermore, the pure steam production cannot respondto large fluctuations in demand, such as provision ofsteam to an autoclave.The Getinge-Kemiterm COMBI solves these problems,allowing simultaneous production of Pure Steam andWFI in specified flow rates. Pure Steam and WFI maybe produced either simultaneously or independently.
Storage&
Distribution
PFScor
Combi
WasherAutoclave
The ‘Combi’: note the larger first effect.
Com
bination Systems
Features and Benefits
Testing, Commissioning and Qualification
Quality is an intrinsic feature of every Getinge-Kemiterm product. From the design specification,through component selection, fabrication, assembly andfactory acceptance testing, every aspect of themanufacturing process is examined and documented toensure and prove that the product is designed, built and tested according to the customer specification and performance requirements.
Our objective is to demonstrate and document that weadhere to a cohesive quality control regimen in accordance with Good Engineering Practice. Thus our documentation package should contribute to the commissioning and validation of our clients’ system,saving time and cost in the overall validation exercise..In-Process CheckingDuring procurement and production, in-process checksensure that only the specified materials and componentsare being used. Datasheets and certificates are collected,verified and stored for later inclusion in the project documentation.
During assembly, a variety of inspections are performedto the appropriate systems, including but not limited to:
On completion of assembly, the column and pipingsystem are passivated, rinsed and sealed. We only usestainless steel in our workshop, so avoiding the risk ofcontamination of stainless steel with ferrous materials.
Pressure and leak testingInspection of all welds (NDE)Videoboroscope reportSurface finishPiping SlopeDead Legs
Quality Philosophy
Factory Acceptance Testing (FAT)On completion of manufacture, every Getinge-Kemiterm product is tested in our state-of-the-art, 600sq.m testing hall. Here the utilities are set to emulateactual site conditions and are monitored whilst theequipment undergoes stringent tests and checks. Utilityconsumption and equipment output are monitored andrecorded for the FAT report. 24 hour performance testingwith simulated usage patterns is also available.
By default, we perform a ’PRE-VALIDATION’ of theequipment, carrying out the same test procedures asdefined in the IQ-OQ protocols, which will later be performed on site as part of the validation exercise. Thisexhaustive procedure identifies the inevitable minorissues with equipment and documentation and ensures atrouble free start-up and site acceptance testing later on.Chemical (incl. TOC), Microbiological (incl. LAL) andparticle testing may also be performed on request.
DocumentationOur objective is to provide a documentation packagethat may be used as an integral part of the clients’qualification support documentation thus saving timeand cost. Unless otherwise specified the documentationpackage comprises:
PLC SystemsAll our PLC systems are designed and programmedaccording to current GAMP guidelines. Completedocumentation of all software modules, test proceduresand reports are available.
Site ServicesAfter delivery factory trained technicians are availableto supervise and assist with start up and Site AcceptanceTesting.
Layout, dimension and appearance checkComponent identification / verification of design CalibrationCapacity and consumption check, confirmation ofperformance specificationAlarm checksExternal signal checkOperating mode confirmation & I/O check
Material CertificatesIsometric Weld Identification DrawingsWeld Parameter ReportsWelders CertificatesPassivation ReportDesign QualificationFAT Protocol and ReportComponent DatasheetsOperation & Maintenance ManualQA ReportSAT Protocol and Report
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FAT Contents
Getinge-Kemiterm A/SPhone: +45 48 16 33 33
Fax: +45 48 18 91 04 Email: [email protected]
www.getingeproducts.com/scientific
Getinge International A.B.Phone: +46 35 15 55 00
Fax: +46 35 16 63 92 Email: [email protected]
www.getingeproducts.com/scientific
Japan: Maquet-Getinge K.K.Phone: 03 3599 8366
Fax: 03 3599 8365Email: [email protected]
www.getinge.co.jp
U.K: Getinge U.K. LtdPhone: 01623 510033
Fax: 01623 440456Email: [email protected]
www.getingeproducts.com/scientific
Americas: GetingeCastle IncPhone:1 716 475 1400
Fax:1 716 272 5116Email: [email protected]
www.getingecastle.com