natural stimulants for your success. · 2020-02-25 · concept offers appropriate products with 5.0...

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Natural stimulants for your success.Gassolutionsforthepharmaceuticalandbiotechindustries.

Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries. 03Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries.

Gasesareemployedas“invisiblehelpers”inmostareasofindustry.Suchareasinclude,forexample,manyprocessesinthemanufactureofactivepharmaceuticalingredients(API)andpharmaceuticals.Thisalsoincludesresearchanddevelopment(R&D)aswellasproductionandqualitycontrol.LindeGasisnotmerelyasupplierofgasesandgas-relatedhardware.Withourexpertiseandspecialabilities,weatLindeGasarecapableofdoingsomuchmoreforyouwithregardtothesafety,qualityandproductivityofyourprocesses.Wehaveextensiveknow-howandmanyyearsofconsultingexperienceindealingwithawiderangeofenterprises.

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We design and deliver. Fromcalibrationmixturestopharmaceuticalplants.

Thisprofoundknowledgeofgastechnologymeansthatwecanoffercomprehensive,cost-effectivesolutionsforbothexistingplantsandnewprocesses.Ourexpertiserangesfromthedesignandconstructionofpharmaceuticalplantsallthewaydowntoasinglecylinderofcalibrationorhigh-puritygasandfrombulkdeliveriesofnitrogentosamplingandanalysisatyourpointsofuse.Wealwaysworkinclosecooperationwithourcustomersand,nomatterwhatproductorsolutionischosen,wewillhelpyoutoensurethatitissuitableforyourgoodmanufacturingpractice(GMP)requirements.

Inthecomplexworldoftoday,thepharmaceuticalindustrycontinuestodemandincreasinglyadvancedproductsaimedatimprovingmodern-daylife.ThisiswhyLindeGashasanin-depthunderstandingofthemanyregulationsthatgoverntheindustry.

VERISEQ® pharmaceutical grade gases

VERISEQ®Gasesaretraceablepharmaceuticalgradegasesfortheproductionofpharmaceuticalsandactivepharmaceuticalingredients.VERISEQ®Gasesaredevelopedtosuittheneedsofthepharmaceuticalsmanufacturingindustry.Thisuniquerangeofgaseshelpsmanufacturerscomplywiththeapplicableregulationsongasusedinpharmaceuticalproduction.ByturningtoVERISEQ®Gases,producersofpharmaceuticalsoractivepharmaceuticalingredientsareassuredofthequalityandintegrityofthegas.In-housegasanalysiscanbereducedtoaminimum,whichmeansthatstockturnovercanbeimprovedinthelongrun.BychoosingVERISEQ®ProcessGradeGasesfromLindeGas,thepharmaceuticalproducerusesguaranteedgasesthatconformtoagreedandinternationallyharmonisedspecifications.Thegasesareanalysedforidentityandimpuritiesusingqualifiedanalyticalequipment.VERISEQ®ProcessGradeGasesfulfilthemonographrequirementsintheEuropean,JapaneseandUnitedStatesPharmacopoeias.Theanalyticalmethodsareinaccordancewiththesamemonographs,orequivalentvalidatedmethods.WhentraceablepharmaceuticalgradenitrogenwithhigherpuritiesthantheEuropean,JapaneseandU.S.Pharmacopoeiasstatearerequired,theVERISEQ®conceptoffersappropriateproductswith5.0purity,i.e.99.999%,underthenameVERISEQ®ResearchNitrogen.

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Whateveryourgasconsumption,beitlargeorsmall,LindeGascanhelpyoufindtheperfectsupplysolution.Ourofferingextendsfromsinglecylinderstoextensiveon-sitegasproductionplants.LindeGashasdevelopedtraceablegasconceptsthathelpmanu-facturerscomplywithapplicableGMPregulations.TheuseoftraceablegasesthathavebeentestedtocomplywithpharmacopoeiamonographsisareliablewaytoincreasesafetyinthemanufacturingofpharmaceuticalsorAPIs.

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Tailor-made, tested and traceable. Gasestosuityoureveryprocessneed.

Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries.Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries.

On-site supply

Ifyourequirelargeamountsofgas,LindeGascanofferanon-sitesupplybasedontheECOVAR®concept.On-sitemeansthatLindeGaslocatespartofitsproductioncapacityatthesiteofthecustomer.ECOVAR®systemsaredesignedtosupplygascost-efficientlyandreliably–withlessenvironmentalimpactandlesstransportation.TheECOVAR®portfoliofromLindeGasincludesafullrangeofstandardgasgenerationplantsthatarespeciallydesignedforremoteon-siteoperation.PharmaceuticalmanufacturersrequiringlargevolumesofgaswillparticularlybenefitfromtheCRYOSS®productlinethatgeneratesnitrogenofcryogenicpurityforinertingandpurging.LindeGashasgainedexperiencefromdeliveringECOVAR®plantstocustomerswhorequirefullvalidationandFDAapproval.

Microbial contamination is not acceptable

Gasisnormallysterilisedwithafilteratthepointofuse,butsometimessterileliquidgasisrequired.Liquidnitrogenmightbethoughtsterileinitselfduetoitslowtemperature.However,itissometimesusedtopreservelivingmicroorganisms.Noconventionalsterilefiltercanwithstandcryogenictemperaturesforverylong.LindeGascircumventsthisbyliquefyingsterilefilteredgasinitsVERISEQ®SterileLiquidGas(SLG)system.TheVERISEQ®SLGsystembelongstotheVERISEQ®PGC(PharmaceuticalGasConcept).Ithasbeendesignedforuseinpharmaceuticalproduction.

Bulk delivery of liquid nitrogen. On-site supply with the ECOVAR® system.

Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries. 07Natural stimulants for your success. Gas solutions for the pharmaceutical and biotech industries.

HiQ® specialty gas concept

TheHiQ®specialtygasconceptfromLindeGasmeetsmanyoftheneedsofthepharmaceuticalandAPIindustries.HiQ®isourwordforpureandmixedgasesandrelatedgasequipmentaswellasservices.ThisallrestsonthecombinedglobalskillandknowledgeofourHiQ®expertsinthefield,whohavethesoftwaretoolsandnetworkedinformationnecessarytofindtheoptimalsolutionforyourspecificneeds.

Specialty gases

LindeGashastheinfrastructure–dedicatedproductionfacilities,accreditedanalyticallaboratories,mobileanalyticalservices,etc.–thatputstheword“special”intoHiQ®specialtygases.Needlesstosay,allgasproductsarequality-controlledand,whereverapplicable,carryananalysiscertificate.Wemakeitourbusinesstoensurethatthegasormixtureyouuseinyourbusinessisthebestoneforthejob.

Process chemicals – from lab to production

Inadditiontoourstandardassortmentofindustrialgases,LindeGassuppliesarangeofgasesthatarespeciallytailoredtothepharmaceuticalindustry.Theseproductscanbeusedateverystageofthedevelopmentprocess:beginningatthelabbench,throughprocessoptimisationinthepilotplant,andontothefullproductionline.Typicalapplicationsandproductsare:

→ Amination:ammonia(NH3),mono,di&trimethylamine → Bromination:hydrogenbromide(HBr) → Catalysis:borontrichloride(BCl3),borontrifluoride(BF3)

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Approved quality. Gasdistributionandgaspurity.

BASELINE C106 single stage cylinder regulator

Gas distribution systems

TheUSFoodandDrugAdministration(FDA)encouragesascience-andrisk-basedapproachwhendesigning,constructing,commissioningandqualifyingutilitiesandequipment.Thechoiceofmaterialsforgassupplysystemsisdeterminedbythegastobedistributedandthelevelofcontaminationthatcanbeacceptedinthegas.Theinnersurfacefinishofcomponentsisthereforeofgreatimportancetothefinalpurityofthegasatthepointofuse.Gassystemqualificationincludesperformancetesting,wheregassamplesaretakenandthenanalysedaccordingtorelevantCriticalQualityAttributes(CQAs),whichinmostcaseswillbethoselaiddowninthepharmacopoeiamonographs.

LindeGasoffersawiderangeofgasdistributionsysteminstallations,including:

→ Industrialinstallations → Specialtygasinstallations(laboratories) → Specialtygasinstallations(GMPproduction) → Ultra-highpurityinstallations(semiconductor)

Gas purity

Thequalityandconsistencyofanygasisonlyasgoodasthedistributionsystem.Itisthereforeessentialthatoneofthegoalsindesigningandbuildingsuchasystemshouldbetheexclusionofimpurities.OurextensiveHiQ®specialtygasportfolioincludesequipmentforlaboratoryuse,butalsoensuresequipmentthatofferstraceabilityandproperdocumentation.Traceableequipmentrangesfromsimplecomponentssuchasvalvesandregulatorstocomplexsystemssuchasgaspanelsandpointsofuse.AllofthesecanbeprovidedwithcertificatesofconformitytoprovecompliancewiththeFDA.TheBASELINE®cylinderregulatorsareGenerallyRecognizedAsSafe(GRAS)andaresuitableforusewithprocessgasesinpharmaceuticalproduction.

Because excellent products lead to excellent results. Specialtygasesforlaboratories.

→ Chlorination:hydrogenchloride(HCl),chlorine(Cl2),silicontetrachloride(SiCl4)

→ Fluorination:hydrogenfluoride(HF),nitrogentrifluoride(NF3),sulphurtetrafluoride(SF4)

→ General chemical:carbondioxide(CO2),sulfurdioxide(SO2),ethyleneoxide(C2H4O),hydrocarbons

→ Insulation:sulfurhexafluoride(SF6) → Methylation:methylbromide(CH3Br),methylchloride(CH3Cl) → Phosgenation:carbonmonoxide(CO),chlorine(Cl2) → Propellants:halocarbons,hydrocarbons. → Reduction:hydrogen(H2),diborane(B2H6) → Refrigeration:halocarbons,ammonia(NH3) → Thiolation:hydrogensulfide(H2S),carbonylsulfide(COS)

AsignificantshareofsalesrevenuesfromthepharmaceuticalindustryisreinvestedinR&D,whichisanarearequiringawiderangeofspecialtygasesforthedevelopmentofchemi-calsynthesis.Pharmaceuticallaboratoriesuseanalyticalinstrumentssuchasgaschroma-tographswithmultipledetectors,liquidchromatographs,UV/VISspectrometersandNMRspectrometers.Theseinstrumentsneedpuregasesandgasmixtureswithanaccuratelymeasuredcomposition.

Keep your cool with cryogenic gases. Innovationsforcooling.

Reactor cooling

TheCUMULUS®FluidTemperatureControl(FTC)systemisdesignedtocontrolthetemperatureofareactororprocessliquidwithexceptionalaccuracy–downtoaslowas-120°C.TheCUMULUS®FTCsystemwillhelpyouachievehigheryields,andthestablecoolingprocessensureseasyrepeatability.Theextra-compactdesignofthesystemmeansasmallfootprint,whichallowsunitstobeinstalledinexistingfacilitiesandmovedaroundtomeetcoolingrequirementsindifferentlocations.

Cryogenic storage and transport

Thankstotheuseofliquidnitrogen,cryo-preservationallowsstorageatatemperaturesufficientlybelowanycriticaltemperature.Thismeansthatbiologicalmaterialcanbestoredalmostindefinitely,sincetherateofdecompositionisextremelylow.LindeGasoffersarangeoffreezersandcontainersofallsizes,engineeredtomaintainspecifictemperaturesbetween-150°Cand-196°C,dependingonwhetherthesampleisinliquidorinvapourphase.Whentransportingfrozenmicroscopespecimens,biologicalmatterormedicines,LindeGascanprovidespecificservicessuchasthemanagementofdryice,packaging,orproducttransportationrequiringstricttemperaturecontrol.


Gas products – such as liquid nitrogen, liquid carbon dioxide and dry ice – are used to cool various processes and equipment. Cryogenic cooling with gas offers an environmentally-friendly alternative when compared, for example, with mechanical cooling based on halogenated hydrocarbons (HCFCs and CFCs). Many pharmaceutical processes can be enhanced through the use of cryogenic cooling, e.g. grinding, milling, mixing, granulation, freezing, lyophilisation and several others. Temperature control can be integrated into existing processes or equipment to enhance both production and product quality. Some typical parameters are processing times, yield, selectivity, surface structure and particle size. Cooling may be obtained by either direct or indirect contact with a cold-gas flow or with a liquid gas. In cases where the pharmaceutical product must be in direct contact with the cooling medium, Linde Gas can provide sterile liquid gas.

Customer installation of a CUMULUS® PX20 unit.

Freezing

AtLindeGas,wehavedevelopedsophisticatedsystemsforfreezing.Liquidnitrogenandliquidcarbondioxidearebothversatilecoolingagents.Excellentheattransferisachievedthroughdirectcontactbetweenthecryogenicrefrigerantandtheproduct.Ourfreezersystemsensurehigh-speedfreezingforbetterproductquality.Otherbenefitsincludeahighdegreeofreliability,simpleoperationandminimalspacerequirements.

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Laying the foundations for your success. Designandconstructionofpharmaceuticalandbiotechplants.

throughallphases,fromfront-endstudiesorconceptualdesignsuptothehand-overofcompletedplants.AtLinde-KCA-Dresden,wehavetheflexibilitytoprovideeitherselectedservicesortakeonfullresponsibilityforengineering,projectmanagement,procurement,constructionmanagementandcommissioning–includingallstagesofqualification(DQ,IQ,OQ)andvalidationassistance.

Linde-KCA-DresdenGmbHisaleading,full-serviceengineeringcontractor,wellexperiencedinthedesignandconstructionofallkindsofpharmaceuticalplants.Morethan100referencesinthepast10yearsincludeprojectsforbiotechnologicalorchemicalproductionofactivepharmaceuticalingredients,fractionationplantsforbloodplasma,facilitiesforpharmaceuticaldosageforms,andplantsforfoodadditives.Linde-KCA-Dresdenmanagesandexecutesprojects


Interior of a large-scale biopharmaceutical plant, designed and constructed by Linde-KCA-Dresden.

A win-win combination. Maximumsafetywhileoptimisingproduction.

Process optimisation

TheProcessApplicationManagementsystem(PAM)developedbyLindeGascanbesuccessfullyusedforgasoperationssuchaspurgingorblanketing.ByusingPAM,yourLindeGascontactwillbeabletocalculateprocessdataandestimatehowmuchinertgasyouwillneedforanyapplication.Theconvenientlypresenteddatawillhelpyouchoosetheoptimaloperationalmethod.

Inerting

Inertingisacommonprocessinthepharmaceuticalindustry,whereitisusedtoimproveproductqualitybyreducingwatervapouroroxygencontent,therebyavoidingunwantedreactions.Itisalsousedtoincreasesafetybyinhibitingcombustionorbypreventingfireorexplosions.Beinginert,thegascannotinteractwiththepharmaceuticalsubstanceinquestion.Inertingisfrequentlyusedwithrawmaterialsandwithintermediateproductstorageaswellasflammablesolventstorage.Theatmospherewithinprocessreactors,forexample,canbeeffectivelypurgedofoxygenandmoistureatthetimeofstartuporshutdownwiththehelpofnitrogen.

Linde Gas safety system

Notallcombustiblefuelmixturesignite.Itisonlywhentheconcentrationofcomponentsfallswithincertainlimitsthatignitionandaresultingfireorexplosionispossible.LindeGashasdevelopeduniquePCsoftwaretohelpyoucalculateflammabilitylimitsforalmostanymixtures.Theflammabilitytrianglethatisgraphicallypresentedmakesitpossibletodeterminehowtoalterthemixturesoastoavoidignition.

AtLindeGas,wehaveextensiveknow-howwhenitcomestoworkingwithinertgases–nitrogen,argonorcarbondioxide.Handlingthesegasesrequirescaution,andLindeGascanhelpyouwithtraininginthesafehandlingandstorageofgases.

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Let nothing go to waste. Savingtheenvironmentforfuturegenerations.

Innovations in cylinders

AnyonenotwishingtodiscardemptycompressedgascylindersornotwantingtopayexcessivedisposalfeeswillvaluethebenefitsofECOCYL®,ourPortableCalibrationGas(PCG)container.Thishasbeendesignedtoreplacenon-refillableor“disposable”cylindersthatoftenendupassolidwaste.ECOCYL®comprisesalightweight,high-capacityrefillablecylinderwithacap-protectedintegralcylindervalve,aregulatorandavariable,selectableflowmetertomeetallyourcalibration-flowneeds.

Air treatment

CIRRUS®VapourEmissionControl(VEC)systemsfromLindeGasofferaflexible,compactandefficientairtreatmentsolutiontohelpyouminimisetheemissionofVolatileOrganicCompounds(VOC).LiquidnitrogenisusedtocondensetheVOCvapourfromgasstreams.TheultimateaimistopreventtheunwantedreleaseofVOCsintotheatmosphere.Forlarge-scaleprojects,LindeGasisalsoabletooffercustomisedcryocondensation.

Wastewater treatment

Pureoxygeniscommonlyusedinbiologicalwastewatertreatmentplantstoimproveaerobicactivity,whichreducesdissolvedoxygen(DO)levelsandunpleasantodours.Oxygencanalsopreventtheformationofhydrogensulfideinbuffertanks,lagoonpipingandseweragesystems.Wherestandardbiologicaltreatmentisnotapplicable,LindeGasalsoofferssolutionsemployingwetoxidation.


Linde Gas received the 2004 Gases and Technology Magazine Product Innovation Award for gas delivery systems with ECOCYL® – a portable, refillable, integrated calibration gas cylinder and gas delivery system.

Cleaning and extraction with CO2.

Dry ice blasting

Thesolidstateofcarbondioxideisknownasdryice.Itissimilarinappearancetonormalicewithahardnessclosetoplaster.Atatmosphericpressure,itsublimatesatatemperatureof-78°C.CRYOCLEAN™fromLindeGasisadryiceblastingprocessthatiseasytouseandrequiresnoelectricalpower.Furthermore,itleavesnocleaningagentresidues,nowastewater,andnosolvents.

Supercritical extraction

Carbondioxideinitssupercriticalstateisincreasinglyusedforextraction.Suchsupercriticalextractionisforexampleappliedinthepharmaceuticalindustrytorefinecompoundsandtoextractactivenaturalproductsfromplants.Supercriticalcarbondioxideisparticularlyinterestingbecauseitssolubilitypropertiescanbechangedbyvaryingthepressureandtemperature.Ithasalistofotherbenefits:itisnon-toxic,taste-free,solvent-freeandnon-flammable.LindeGascansupplycarbondioxideandothergasesforsupercriticalextraction,fulfillingarangeofspecifications.

Ithasbeensaidthatwehavenotinheritedtheearthfromourancestors,butthatweborrowitfromourchildren.ThisiswhyLindeGasoffersarangeofproductsdesignedtohelpyouminimiseyourimpactontheenvironment.Theveryairyoubreatheisourrawmaterial.

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LindeGas,foundedover125yearsago,todayrepresentsthefirstchoiceformorethan1.5millioncustomersinmorethan55countries,allofwhombenefitfromourgasapplicationtechnology,widerangeofhardwareandprovenspecialistservices.

WithbusinesssegmentssuchasLinde-KCA-Dresdeninitsportfolio,Lindeisavaluablepartner,providingextensiveknow-howandstate-of-the-artapplicationsforthepharmaceuticalandbiotechindustries.Anothersubsidiary,LindeGasTherapeutics,isitselfapharmaceuticalmanufacturer,soithasitsownstoreofin-houseknowledge.

AtLindeGas,severalengineersconcentratesolelyongas-relatedinnovationsforpharmaceuticalmanufacturers.OurongoingR&Dactivityconvertsideasintonewtechnologiestohelpyou,ourcustomer,securecompetitiveadvantagesandopennewmarketopportunities.

WeatLindeGasstrivetosimplifyyourGMPcompliancebyprovidingyouwiththerightproductsandtherightservices–rightontime.Boththepharmaceuticalindustryandthebiotechnologyindustrysetveryhighstandardsforsafetyandquality.Thisisreflectedinthedemandsplacedongasesandontheirapplications.Whichiswhyweoffermorethanmerecataloguecontent.YourlocalLindeGasrepresentativewillhelpyoufindoutmoreabouthowyourcompanycangetthemostoutofourexpertiseandinnovativesolutions.

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Not just a gas supplier. Safety,training,servicesandmore–fromLindeGas.

Automatic gas ordering

Thankstooursophisticatedlogisticsandmanagementsystems,weareabletooffercylindertrackingandfollow-upservicesunderthenameACCURA®.WealsoofferSECCURA™–ourfully-automatedgassupplyservice–toensurethatyouwillneverrunoutofgas.

Total gas management

Ourtotalgasmanagementsolutionaimstomeetalltheneedsofthecustomer,thusallowingyoutofocusonyourcorebusiness.Totalgasmanagementspanseverythingfrominventorycontroltoremotemonitoring,coveringeverythingfromautomaticorderingandcylinderreplacementtoincominginspections.

Safety first

SafetyconsciousnessisanoverridingaspectofourcompanycultureatLindeGas,anditisgiventoppriorityinallgasinstallations.Anyrisksconnectedwithpotentiallyhazardousgas,thegassupplysystem,collectionordisposalareminimisedthroughpreventiveaction.LindeGasoffersextensivesecurityandmaintenanceservices,andwecan,insomeareas,offerqualifiedon-sitepersonnelandthesecurityofanemergencyresponseteam.

Education and training

LindeGascanrecommend,andassistin,thedevelopment,implementation,controlandfollow-upofappropriatesafetymeasuresandproceduressuchasenhancingawarenessandthetrainingofpersonnel.EducationandtraininginapplicableprocessesisconsideredtobeoftheutmostperformanceinGMP.LindeGascanassistyouinyoureducationalrequirementsconcerninggasesandgas-relatedapplications.

Sampling and analysing

ToverifythecontentsofgassystemsatfactoriesoperatingunderGMPrequirements,acompletegasanalysisshouldbecarriedoutatleastonceayear.OuranalyticalservicesinvolveLindeGaspersonnelregularlytakinggassamplesfromthefactory’sgassystemandanalysingtheminaccordancewithappropriateregulations.


Our quest for quality goes on. Getthemostoutofinnovationsingastechnology.

AtLindeGas,weoffervariousvalue-addedservicesalongwithourproducts.Wehavemanyyearsofexperiencewithsituationssimilartoorexactlylikeyours.Wecan,forinstance,simplifyyourqualificationprocessthroughcorrectdocumentation,andwecanperformfactoryandsiteacceptancetests(FATandSAT).Wecanalsohelpyouwithinstallationandoperationalqualifications(IQandOQ)ofourequipment.

Getting ahead through innovation.

With its innovative concepts, Linde is playing a pioneering role in the global market. As a technology leader, it is our task to constantly raise the bar. Traditionally driven by entrepreneurship, we are working steadily on new high-quality products and innovative processes.

Linde offers more. We create added value, clearly discernible competitive advantages, and greater profitability. Each concept is tailored specifically to meet our customers’ requirements – offering standardized as well as customized solutions. This applies to all industries and all companies regardless of their size.

If you want to keep pace with tomorrow’s competition, you need a partner by your side for whom top quality, process optimization, and enhanced productivity are part of daily business. However, we define partnership not merely as being there for you but being with you. After all, joint activities form the core of commercial success.

Linde – ideas become solutions.

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CRYOCLEAN™ and SECCURA™ are trademarks of the Linde Group. HiQ®, VERISEQ®, ECOVAR®, CRYOSS®, CUMULUS®, CIRRUS®, ECOCYL®, BASELINE® and ACCURA® are registered trademarks of the Linde Group.

Linde AGLinde Gases Division, Seitnerstrasse 70, 82049 Pullach, Germany Phone +49.89.7446-1661, Fax +49.89.7446-2071, [email protected], http://hiq.linde-gas.com

natural stimulants for your success. · 2020-02-25 · concept offers appropriate products with 5.0...

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