Processing of Rackpacks® Roche Diagnostics Relies on Turnkey Equipment Taking Medication Made Easy! Xstraw® Doses Drugs Via a Straw Page 12

The Customer Magazine by Harro Höfl iger

Edition 1 | October 2015

Processing of RackPacks® Roche Diagnostics relies on turnkey equipment Taking medication made easy! XStraw® doses drugs via a straw Page 12

It melts on your tongue Production know-how for oral fi lm strips Page 22

Processing of RackPacks® Roche Diagnostics relies on turnkey equipment EDITORIAL

5 Assistance via remote diagnostics The Service Portal simplifies many processes

6 Ten plus points Product launch of continuous motion cartoning machine MKC

8 “We wanted to get ear Sir or Madam, started right away” Dear business associates, Roche Diagnostics’ RackPacks® packaging solution I am delighted that you have opened our new D customer magazine. Be “Harro’s” guest once again — this time not as a visitor to our company, but as 12 Taking medication made easy! a reader. Because not everyone can stop by in person on a XStraw® administers drugs via a straw regular basis, we will present useful and interesting facts twice a year in our customer magazine HARRO. In a thoughtful and hopefully attractive fashion, we 14 Inhaling insulin instead of injecting introduce to you some of our most interesting machine Inhalation technology line for MannKind Corporation systems in their practical applications. We also want to inform you about upcoming events and presentation series, and provide news from our company and country. Keeping 17 Patch with a Holiday fragrance in touch with you in this way is a matter close to my heart. heals abdominal pain If you are already somewhat familiar with us, you know that Patch production at Shanxi Yabao Pharmaceutical Group listening is one of our recipes for success. This also applies to our magazine. Therefore, if you have any suggestions, criticism or questions, we look forward to receiving your 20 “Never change a winning team” message at [email protected]. Harro Höfliger accompanies Pfizer during contract manufacturing Incidentally, there is a good reason to explain how we chose to name our magazine. In all of the international language areas, only very few individuals can pronounce the name 21 Inventing according to plan “Höfliger” without a problem. When I introduce myself in Innovation management in specialty machine engineering person, often I am asked “Harro ... who?”. Therefore, our editorial team made a virtue out of necessity, and the magazine received the short and concise name HARRO. 22 It melts on your tongue Production know-how for oral film strips I hope you find this an interesting read!

Warm regards, 24 Success at the ACHEMA Harro Höfliger Customer focus “with all senses”

4 News from Harro Höfliger 25 Trade show calendar

Imprint HARRO, the magazine for customers, interested parties and friends. Editor: Harro Höfliger Verpackungsmaschinen GmbH;Publisher: Thomas Weller, CEO; Overall responsibility: Andreas Streicher, Marketing Director; Editorial management and consulting: Oliver Naucke, nokey communication by Oliver Naucke, Laichingen; Editorial planning and coordination: Denise Dreher; Editorial assistance: Frank Erbach, Stefan Gais, Markus Hänle, Meike Hamm, Jackson Heslop, Harro Höfliger, Frank Naseband, Markus Pfisterer, Dr. Elke Sternberger-Rützel, Hansjörg Schroeder, Dr. Karlheinz Seyfang, Andreas Streicher, Hartmut Thier, Achim Wolf, Daning Zhao;Concept and implementation: pr+co GmbH, Stuttgart; Translation: Gabriele Rosenland, Übersetzungen, Auenwald; Editorial Expert: Ingo Anhenn; Printing: Druckhaus Götz GmbH, Ludwigsburg; Repro: Raff Medien, Riederich; Editor’s address: Harro Höfliger Verpackungsmaschinen GmbH, Helmholtzstraße 4, 71573 Allmersbach im Tal, [email protected]; Circulation: 7,700 (2,700 in German, 5,000 in English) Credits: Title: BB Fotostudio/Janine Kyofsky; Cover flap Atelier Lünig, Harro Höfliger; pp 2/3: BB Fotostudio/Janine Kyofsky, Oliver Naucke, Harro Höfliger

2 HARRO Edition 1 HARRO Edition 1 3 4 With ourowntrainingcenter, theHarro What beganasajointproject onJanuary3,2005 between Service fortheSwiss for in-housetrainingandcontinuing their vocationaltraining.Today, around 60 technology skillsformechanicalengineer- to 110Uhlmannmachinesand60Harro Höfl igerlinesinSwitzer- ten-year anniversary, ManagingDirector RobertoZürcher and Allmersbach imTal. facility Themodern Knowledge Driven by Höfl igerAcademyisnowanidealplatform 300 traineeshavesuccessfullycompleted Offi ceManagerManuelaHummelare stillonboard andhave Harro Höfl igerandUhlmannPac-Systeme,istodaythesuc- ing. Since1981,intensivetraininghas land — this includesconsulting,technicalcustomerservice percent offormertraineescontinuetowork been offered atHarro Höfl iger. Atotalof as professionals inourcompany. offers thebestconditionsforinstructionin education atourcompanyheadquartersin been there sincedayone.Atotalofeightteammembers tend packaging process. pharmaceutical companiesinallmattersrelating tothe metalworking, electricalaswellcontrol and retrofi tting.TheexpertsoftheSwissteamsupportlocal cessful Swissbranchoffi celocatedinArlesheim.Onthe Markus Haener, Marco SpeckerandDr. Sven Borchert Roberto Zürcher, UdoLorenz, Manuela Hummel, Marc Hartzer, JanPaetzold, The UhlmannHöfl igerSchweizteamfrom lefttoright:JörgGentner, Tunisia and Iran.TheModu-Ccapsule The teamhasalready recorded sales inabroad sense MENA countries fi rstorders forwindingmachines and fi But story. llingmachineisasuccess Africa, the pharmaceutical industry is on Africa, thepharmaceuticalindustryison In the Middle East as well as in North In theMiddleEastaswellinNorth Besides installationandproduction Harro Höfl igerMenaS.a.r.l in Tunis. projects fortheinhalation, assembly on record. also and adhesivebandageareas are after-sales serviceprogram intheMENA development ofaneffi cientsalesand excellent foundationforthelaunch of a growth trajectory,an whichwas success in Egypt, Saudi Arabia, Algeria, success inEgypt,SaudiArabia,Algeria, region (MiddleEast&NorthAfrica). support, thecompany’s taskisthe in astrictsense the MENA region On site in Our traineesenjoy their studies HARRO Edition 1

Studio Philippi, Harro Höfl iger, Andi Dalferth – Photos “Conference Center”.Theoperatoror “Chat Board” where Board” messagescan beex- “Chat Yes, wewantedatoolthatcan beused the benefi tsofthissystem,andhowitworks. Jackson Heslop:Ourcustomers’desire ventive maintenanceandsupports the via headset, possible solutions can be with themachinemanufacturer. There are which transmitsdetailedpictures ofthe thousands ofpackagesdaily, anditstops. inRemote Service” “We setthestandard HARRO Edition 1 for fasterassistancewhenserviceisre- Excellence United.JacksonHeslop,CustomerServiceDirector atHarro Höfl iger, discusses found quickly. Inmostcases,sendinga fault location.Inreal-time communication Once production isupandrunning,ithastobeeffi cient.Inorder tokeepdowntime a Imagine alinethatproduces several the developmentofExcellence Our ServicePortalcanthenbedirectly Can youclarifythiswithanexample? Remote Service. United ServicePortal? laid thefoundationforanewstandard in identifi edtheneedinaworkshopand Mr. Heslop,whatwasthereason for minimum, Harro Höfl igerdevelopedaServicePortaltogetherwiththepartnercompaniesof Does theServicePortalalsoprovide open theintegrated spare partscatalog. of photosanddrawings,awebcam, planning ofmaintenanceintervals. Inad- prior toamalfunction.Amaintenance maintenance technicianconnectsdirectly machine andprovides amulti-media manager provides instructions forpre- several toolsavailable.Forexample,a saves thecustomertimeandmoney. service technicianisunnecessary. This quired. Together withourcustomers,we activated via the operator panel of the activated via theoperatorpanel of the access themachine documentationor dition, with a few clicks the operator can for the transfer Board” changed, a “White preventive support? The userinterfaceisintuitive, soexten- training fortheServicePortal? ists ofthemachine manufacturer. Does theoperatorneedspecial easy way tocontact the service special- sive trainingisnotnecessary. Theservice request issupposed tobeaquickand “The Service Portal simpliﬁes many Customer ServiceDirector, processes.” Jackson Heslop, Harro Höfl iger Today, roughly 80ofourlinesare inop- The connectiontothelinemanufacturer Where istheserviceportalalready What aboutsecuritywhentransmit- the operator. Thesystemis based onan United ServicePortal.We havealready ting data? SSL-encrypted client-server connection — SSL-encrypted client-serverconnection— is areverse link,whichmeansthema- operator-side service request. This con- eration worldwidewiththeExcellence prove thePortal. nection can be terminated at any time by nection canbeterminatedatanytimeby similar toonlinebanking. in use? chine supplier can connect only after an chine suppliercanconnectonlyafteran and gathered experience tofurtherim- answered numerous servicerequests, video abouttheExcellence United Service Portalwww.hoefl iger.com More informationisavailableina NEWS FROMHARROHÖFLIGER Jackson Heslop when serviceis provide rapid and histeam assistance required 5 6 closures are possible.Labelingsystems,leafl etfoldingandinsertion Customer specifi csolutions can beaddedtothestandard modules. Wide range ofapplications This enablesthepackaging of bottles,bags,tubes,blisters,vials, patches andmore. All standard cartonclosure typesandspecial The continuousmotioncartoningmachineMKCcelebratedaverystrong Ten plus points Here are thetenmostimportanthighlightsofnewversatilecartoner. High performanceindesign,application,versatilityandusability: premiere attheFachPack2015asapartofHarro Höfl iger’s standard portfolio. The cartonercanbeequippedwithdifferent feedingsystems. equipment, bookletandbrochure dispenserscompletethe ergonomic height,thepivotingfoldingunitandextendable and undercontrol: Thecontinuousproduct insertionfrom drawer andpre-insertion. Allthesefeatures offer thebest The operatorhasallcriticalfunctionswithineasyreach, behind, thefoldingcartonmagazinepositionedatan provides forreliable removal ofthecartonfrom the The patentedrotary carton-withdrawalsystem with a4-foldrotor andactivecartonopening Best accessibility magazine andtransferintothechain. Patented operating comfortandeffi ciency. machine’s broad versatility. achieves 250cartonsperminute. At7.5inches, The continuousmotionofthe 5-inchversion Continuity it achieves 200 — smoothlyandsafely.it achieves200— HARRO Edition 1

Harro Höfl iger HARRO Edition 1 system. The4-fi ngersupport guaranteesprecise and fi xed Surface damageisstrictlyavoided,evenwhenprocessing The cartonsare transportedcarefully withacarrierchain There are very fewformatparts,andchangeoverscan positioning ofthecartonduringpackagingprocess. mechanical aswelltheelectronic level.Theformat indicators ensure reproducible formatchangeovers. The machine’s designandconfi gurationprovide for parameters are centrally administered andposition fast formatchangeovers.This appliestoboththe Fast change-over refi ned,glossy, mattorsensitivecartons. be carriedout with almostnotools. Accuracy safety glass.Thisensures anoptimalviewofthework applicable safetyregulations. Theergonomic machine On thenewlydesigned,movable17.3”colordisplay the materialdoesnotbuildup staticcharges andis industrial PCallowsforeasyintegrationofmarking process andGMP-compliant cleaning.Inaddition, feed area withseparatecomponentsforproduct The guarding completely consistsofsinglepane design withsmoothsurfacessetsnewstandards. with touchfunction,theoperatorcanconstantly observe andmonitorallparameters.Astandard and inspectionsystemsintotheuserinterface. confi gurationandcanbeeasily integrated into Intriguing design Thanks tothemodulardesigninproduct Best materials construction — inaccordance withGMPand construction — The cartoner is designed in modern balcony balcony The cartonerisdesignedinmodern chain, product insertionandfoldingcarton closure, themachinehasaveryfl exible a widevarietyofpackaginglines. Total control Modular scratch resistant. TOP INNOVATION 7 Atelier Lünig, Oliver Naucke, Harro Höfliger 8 at RocheDiagnostics Erecting ofcartonblanks HARRO Edition 1 startedright away” “We wanted toget Yes, sure! We hadalready beenusingtwo olderlinesforthis Were there anyparticular challengesduringimplementation? What doyouconsiderspecialaboutthisline? formats. Theline’s outputisalsoratherimpressive: 150cycles and experiencesofthisproject. Roche inadialogueaboutthechallenges Qualification Director SiteEngineeringat Diagnostics inMannheim.RainerWäsch, the processing ofRackPacks were required forthisenormousline intensive developmentandcooperation ready byHarro Höfliger:Two yearsof combined andhandedoverturnkey meters underonecentralcontrol system– Ten different machineson650square in thefinishingarea andupto100cyclesperminuteinthe packaging concept,whichweimplementedinthisline. Itis product. Itwasnecessarytoanalyze theweakpointsofthese cartoning section. capable ofprocessing atotalof65products withfourdifferent about 650square meters.Then,ofcoursetheoutstanding machines and oftheproduction process, andto develop Rainer Wäsch: First,theimpressive size.Itcoversanarea of well asproject Mannheim as Rainer Wäsch, leader forthis Director Site Qualification Engineering assembly and packaging line ® atRoche BEST PRACTICE

9 10 instruction leafl ets without extensiveadjustmentandtrainingactivities. this newline—naturallyatthehighestpossibleoutput.Plus, Satteldorf inorder toqualifythelineonsite,documentits Harro Höfl igerinstalledthecompletelineinitstechnology unpleasant surprisesavoided.Two ofourteamstravelledto installation atourpremises. How was the turnkey handoverachieved? How wastheturnkey be connectedtoworktogether. Inaddition,wewantedto disassembly and to provide guidance and support later during of ouroperatingstaff and couldbeextremely shortened— conditions atourpremises. Indoingso,thequalifi cationphase ensured areliable operationrightfrom thebeginningunderreal center inSatteldorfandreproduced ourinfrastructure. This after installation,weimmediatelywantedtogointoproduction combine twodifferent insertswithtwodifferent RackPackson dard andspecialtymachinesfrom Harro Höfl igeraswell machines from other manufacturers. All these machines had to solutions forabetterperformance.Thelineconsistsofstan- Loading of toploader cartons Package closingof loading theRackPacks Toploading machinefor into thepackage ® four possibleformatversions Erecting ofcartonblanks in always astonished about open and clear commu- “I particularly value the level of technical problem solving expertise.” Harro Höfl iger’s high Höfl iger — and I am Labeling ofpackages nication with Harro Qualifi cationDirector SiteEngineering at RocheinMannheim Rainer Wäsch, RackPacks Labeling of ® HARRO Edition 1 product combinations cartridges fordefi ned Feeding ofindividual Test) aswellqualifi cationwithIQ(InstallationQualifi cation) years. Ofcourse there are points of friction when developing We followtheproject managementapproach, whichisspeci- We havebeencooperatingonthisproject foratotaloftwo we initiated aso-calledsteeringcommitteealready atthe initiated we What specifi cationsdoyoufollowwhendevelopingsuch fi edbyRoche.Milestonesare thedevelopeddesignof packages palletizing of Grouping and HARRO Edition 1 line withthefi naldetaileddesign review, thepre-Factory Ac- How wasthecooperationwithHarro Höfl iger? beginning oftheproject. Thiscommitteemeetsoncea always beenwell-prepared andthediscussionswere con- and implementingsuchahugepackagingline.Thisiswhy month anddevelopssolutionsforissues.Allmembershave and fi nallythevalidation. documented dismantlingandinstallation,anacceptancerun and OQ(OperationalQualifi cation).Thisisfollowedbythe ceptance Test (pre-FAT), theFAT andSAT (SiteAcceptance a project? structive, goal-orientedandopen. automation robot) cartridges (4-unit De-palletizing of diagnostic frame (forRackPack 3-fold formatwithaconnecting Assembly ofcartridgesina ® ) This iseasytoanswer:theopenandclearcommunication. were putonthetableanddiscussed.Moreover, Iamalways What doyouvaluemostaboutthecompanyHarro Höfl iger? frame. But the milestones have been reached and we could the engineers fi nd waysto reach thegoal. Areas needingim- Are yousatisfi edwiththecourseofproject? Despite theline’s highcomplexityweare on target. Of course, Nothing waswithheldorsugarcoated. Allstumblingblocks lem solvingexpertise.Evenwhenfacedwithdiffi culttasks, provement were quicklyaddressed andresolved. Allproject critical moments occurred again and again in our given time time given our in critical momentsoccurred againand astonished aboutHarro Höfl iger’s highleveloftechnicalprob- members havebeenveryfl exibleandopentoourwishes. start upthelineonscheduleinJulythis year. Users: laboratories andhospitals the analysis of different diseases two carton erectors, top-loaders, folding to 65combinations of RackPacks andtwo Mannheim Product: RackPack with small bottles for Interlinked machines: de-palletizer, Options: Operating company: Roche Diagnostics, Output: up to100cartons/min. beler for RackPacks, intermediate storage, RackPacks with upto65combinationsof Four different foldingcartons depending on theproduction mode different inserts carton closers with labeler, palletizer connecting machinefor RackPacks, la- Key factsoftheassemblyand packaging line: Four different cartons with up BEST PRACTICE 11

Harro Höfl iger 12 XStraw with adrug,enablesmore comfortableintake for children andforpatientshavingdiffi culty easy! made medication Taking and howitworks. a drinkingstraw. Thestraw, whichispre-fi lled swallowing. Theimageillustratesthebenefi ts ® isthenameofanewdosageformusing “playful” drinkingensures safeadministration. method isespeciallywellacceptedbychildren, since and guaranteessimpleintuitiveintake.This developed forapplicationinpediatricsandgeriatrics This newdrugdosageformhasbeenparticularly Patient HARRO Edition 1 HARRO Edition 1 guaranteed. for one-timeuse:There isnocleaningrequired andhygienicapplicationis during transportandstorage.Thisnewdrugdosageformhasbeendeveloped juice, teaorotherbeverages.Aclosingcapandthepackingprotect thedrug The drinkingstrawenablescomfortableintakeofthedrugwithwater, fruit Straw withprotective cap function. the userorcaregiver apracticalcontrol — indicating completedrugconsumptionto is appliedandremains intheupperposition, for theliquid.Itmovesupward whensuction of themedication.Howeveritispermeable drinking strawandprevents leakageorloss The fi lterislocatedatthelowerendof Filter provides taste-maskingproperties. the drug.Foractiveingredients withabitterorunpleasanttaste,pelletcoating The fi llingtechnologydevelopedbyHarro Höfl igerensures precise dosing of Pellets transported thatway dispersed intheliquidand In thestraw, thepelletsare The three XStraw This entity markets theneworal drug All services andmore details canbefound Raumedic andHarro Höfl iger. Experi- technologies, competence indosing and Raumedic: Extrusion of drinkingstraws, Harro Höfl iger: Delivery of fi lling and pellets andgranules, pharmaceutical pharmaceutical industry, worldwide packaging technology, especially inthe packaging lines,development of new implementation of theentire production individual components for fi lling in injection moldingof caps, customized Glatt: Development andproduction of line on-site at thecustomer’s location. laboratory andtheclinical stage,give helpful tips during product launch andare bed systems. at at are thecooperating partnersGlatt, and production of granulation andfl uid enced expertswho oﬀer support inthe dosage form XStraw system partnersduring installation and development, production anddelivery of contract manufacturing, development cleanrooms. DS Technology GmbH service. www.d-s.technology pellet withmulti-layercoating Cross-sectional viewofa ® ® . In thebackground partners TOP INNOVATION 13

Atelier Lünig 14 Powder inhalershelpdiabetics:Harro Höfligerdesignedandbuilttwofillingassembly systems fordry-powderinhalation fortheUSbasedMannKindCorporation. of therapeuticproducts forthetreatment ofdiabetesandcancer, withtechnologies MannKind isabiopharmaceutical company, focusingonthedevelopment that allowpulmonary absorption ofdrugs(through thelungs). instead of injecting Inhaling insulin The dry-powder with cartridges for individual application inhaler “Dreamboat”

HARRO Edition 1

BB Fotostudio/Janine Kyofsky, Harro Höfliger HARRO Edition 1 Al Mann(centre) launch intheUS during thevisit to theproduc- Harro Höfliger tion facility (right) and

“Dreamboat” andapowderfilledcartridge.This Technosphere The uniquefeatures ofFDKPisitsabilitytoform A yellow. with insulin.By inhaling thepowder, theinsulin the lunganditseliminationfrom thebodywithout ter theinhalationprocess. Theinhalerisre-used troduced tothemarketin2015.Thetherapeutic Drug Administrationin2014,thedrughasbeen undergoing metabolism. lungs. MannKindutilizesaTechnosphere passes intothebloodstream through thepatient’s diabetes. Afterapproval bytheU.S.Foodand der formulationwhichisbasedonanorganic dose application, and discarded by the patientaf coded according tostrength, inblue,green and amounts ofpowder. Thecartridgelidsare color can bedosedusingcartridgescontainingdifferent over a15dayperiod.Various amountsofinsulin cartridge isinsertedintotheinhalerforasingle- high bloodsugarinadultswithtype1and2 molecule calledFumarylDiketopiperazine(FDKP). system consistsofadrypowderinhalercalled The cartridgescontainpowderparticlesloaded FREZZA insulin. Inabout60clinicaltrialsin volving more than5,300volunteers, ® MannKind wasabletoshowthat particles, its rapid dissolution in AFREZZA ® isanew, fast-acting,inhaled ® canbeusedtocontrol ® pow - - - -

The MannKind Powder Filling and Assembly Machine The MannKindPowderFillingandAssemblyMachine let, 200mmpitch).Inthismachineplatform,atray is basedontheHarro HöfligerFLP-200machine platform (Fillingmachine,Lengthwisetransport,Pal development projects like management provided have tobeconsidered, our production lines, Corporate VicePresident ofOperations influencing factors in which countless by Harro Höfliger is indispensable.” the solid project and ChiefOperatingOfficer “Especially for of MannKindCorporation Jürgen A.Martens,

BEST PRACTICE

- 15 BEST PRACTICE

serves as the transport medium. At the end of the machine, after cleaning and complete product removal, the tray is returned to the start of the process. “The courage to Vibrating conveyors feed the cartridges and explore new avenues, corresponding lids into the line. A Pick & Place system positions each cartridge in the trays. A so- combined with the called ‘walking beam’ transports the trays from station to station. Two vacuum drum fi ller systems Swabian perseverance provide high-precision dosing of the powder into to see things the cartridges. Every dosing system is equipped with an through to the end, AMV-sensor (Advanced Mass Verifi cation), for one distinguishes hundred percent weight verifi cation of the powder dosing. That means the AMV-sensor verifi es 400 Harro Höfl iger and individual doses of powder per minute. In the event makes them stand out.” of under-dosing or over-dosing, the machine sorts out the affected cartridge and moves it to the fail Jürgen A. Martens, part ejection area. Corporate Vice President of Operations The fi lled cartridges are sealed with color-specifi c and Chief Operating Offi cer lids and subsequently coded with laser markings. of MannKind Corporation Every machine work step is followed by a control step, which checks the previous operation. Correct- ly fi lled cartridges that have been fully closed with the proper colored lid and have received a legible LOT-coding, are moved to the pass part discharge are packaged at a time. Already three machines of the machine. were delivered and are running smoothly. The fi rst From there, the cartridges are transported into an machine was used in the production of the required intermediate storage. From there into an automatic sample quantities during clinical development phase blister machine. Fifteen (3x5) Cartridges per blister then converted to supply commercial product. Patch with a Holiday fragrance heals abdominal pain Production line by Harro Höfl iger The commissioned production line meets the following requirements: • Powder dosing in 400 cartridges/min. Harro Höfl iger manufactures traditional patches for the Shanxi Yabao Pharmaceutical Group • Filling weights: 3–15 mg per cartridge • Filling tolerance max. +/-5% • 100% verifi cation of each powder dose • Fitting the lid on 400 cartridges/min. • Cartridge color verifi cation (green, blue, yellow — according to strength) • Laser marking of cartridges and crosscheck of markings Even the unopened folding carton entices with a scent of cin- • Intermediate storage of at least 3,200 fi lled and assembled cartridges for namon and anise. Then there is the content, which carries an approximately 8 minutes of accumulation aroma of spicy gingerbread. This product enjoys great popu- • Filling machine under laminar fl ow larity in China. The patch is coated with a herbal paste and helps infants and small children who suffer from abdominal pain and diarrhea. It is produced and distributed by the Shanxi Yabao Pharmaceutical Group Co., Ltd., headquartered in the Chinese Shanxi province, and is manufactured on a Packing and Four-Side Sealing Machine from Harro Höfl iger. The so-called “gingerbread” patch has been available in China since 1992. The Yabao patch is readily available in pharmacies and costs about 1 Euro each. At fi rst it was hand- made. Today, about 150 million pieces are sold per year — a magnitude that can no longer be manufactured by hand but requires automated machine processing. A look at patch production at the Shanxi Yabao Pharmaceutical Group in China

16 HARRO Edition 1 HARRO Edition 1 17 BEST PRACTICE

Re-use without waste: The remaining punched-out grid is returned Non-slip: Application of protective fi lm Properly shaped: Processing by means of a rotary die-cutter Well packed: The pouches on their way to the cartoning machine to the extruder

Flashback: In 2007, Harro Höfl iger received a development four-side sealed pouch. The fi nished patch is applied to a in a light-proof and air-tight pouch – ready for transport to the contract from Yabao. For two years, possible ways to process pre-printed aluminum fi lm and closed by another fi lm from pharmacies. active ingredient paste were tested. The fi rst attempt was the “The excellent service and above. An inkjet printing unit applies batch numbers and Since Yabao is very pleased with the automated packaging vertical slicing of an active ingredient strand of paste with a hot prompt support by the Chinese expiration dates before the completed pouch is conveyed to- process, another PMK machine was ordered in 2011. To date, blade. However, this method failed at high speeds, due to the wards the cartoner. The cartoning machine processes 200 downstream cartoning has been a manual process, but in tough and sticky texture. Not until 2009, were the developers as well as the German Harro cartons per minute. Each carton will contain three patches and 2015 these operations will also be automated. Two more able to fi nd a stable process: The paste was rolled out fl at and Höfl iger team on site in China an instruction leafl et. The option with two patches per carton complete lines will follow so that the patches can be the appropriate quantity applied to the patch carrier fi lm using will be processed at an output of 250 folding cartons per min- produced on a total of four packaging lines – with automatic a punching process. This method was presented to the deci- has convinced us, and led us to ute. Prior to the onward transport, a camera controls the cartoners from Harro Höfl iger and full wrapping machines sion makers at Yabao who then ordered a PMK Patch and order additional machines.“ quality and contents of the imprint. Now the patch is sealed from a third party supplier. Pouch Packaging Machine. In 2010 it passed the Factory Ac- ceptance Test with the customer present. Ren Wuxian, President, Shanxi Yabao Pharmaceutical Group Co., Ltd. Technology in detail. The line’s centerpiece is the continuous packing process with the integrated four-side sealing machine The gingerbread patch in TCM PMK 300. It receives the fl attened active ingredient mass from Traditional Chinese Medicine (TCM) relies on alter- herbal substances the upstream extruder. The paste is processed on a carrier ma- air, the paste is easily removed from the punches and sticking native healing methods, which have proven eﬀ ec- such as roots, bark terial in three adjoining webs, with a width of about fi ve centi- of active ingredient particles is prevented. The remaining active tive in the Far East for several thousand years. TCM and tubers. The meters each. ingredient grid is returned to the extruder for re-use. considers the abdominal region as the vitality and natural active ingredi- Using a method specifi cally developed by Harro Höfl iger, the The punched out active ingredient slices are placed on two well-being center of the entire body, the navel as one ent can quickly enter the machine punches out round active ingredient slices. The punch fi lms. The fi rst fi lm prevents moisture, the second fi lm serves of the most important acupuncture points. It is on bloodstream and body through and compressed air shape the sticky paste properly. A cooled as a carrier for the glue which adheres to the skin later. Anoth- the navel, where the so-called “gingerbread patch” is the thin layer of skin at the navel climate area, which is kept at a constant temperature, prevents er protective fi lm is pre-printed and encloses the paste placed. The patch contains a paste made from pure since there is little underlying fat. the punch from becoming contaminated. Thanks to the cooled including the adhesive side. Now the patch is packed in a

18 HARRO Edition 1 HARRO Edition 1 19 awinningteam” “Never change 20 This conceptwaswellreceived and the Research andDevelopmentarea. trolley system which enables the use of tainment topic.Especiallythepatented tain degree ofrisk.Thisiswhywedecid- In addition totheexperiencealready the followinginterviewwithDr. ClemensStief,Teamleader atPfi zerinFreiburg. manufacturers forthefi llingofhard capsules.Harro Höfl iger’s contributionisexplainedin Pfi zerproduces andpackagesinnovativedrugs fortheglobalmarket,nowalsoascontract In Germany, Pfi zeremploysmore than2,000employeesatthree sites.AttheFreiburg plant, ment ofnewdrugs.Thecore elementofthisbusinessmodelisfocusingonhumanhealth. The enterprisePfi zerisinvestingmore than7billionUSdollarsinthe research anddevelop- Harro HöflHarro iger. in theproduction process involvesacer- important tous.We knewthattheuseof partner whoisnotafraidtoimplement contributed toourdecision infavorof anteeing thehighestlevelofqualityand and useofcontainmentsystems.Guar- drugs andconsequentlytheapplication opment andproduction ofhighlypotent a varietyoffi lling media,particularlyin gy andpragmaticapproach tothecon- convinced by theirinnovativetechnolo- gained withHarro Höfliger, wewere can lookbackonalong-standingpart- ed foradependableandtrustworthy a newprincipleforexposure prevention mented severalsuccessfulprojects. nership. Together wealready imple- new concepts.WithHarro Höfl iger, we ronment duringproduction, wasandis safety forouremployees,andtheenvi- ments were thedevel- Dr. Stief,whatmade Pfi zer’s main require- you decideinfavor Höfl iger? gies from Harro of thetechnolo- This isabuildingblockfor the highde- The capsulefi lling systemModu-Cthus Were there anyotherdecisioncriteria? the trustalready gained,thetarget-orient- tion, minimizedexposure andoffers the projects. Inaddition,proximity played tems, wenotonlyservePfi zer’s require- the systemmeetyourrequirements? fl exible retrofi tting. The patented trolley fl exibility, makestheModu-CMSstand Of course.Worth mentioningiscertainly By enteringintocontractmanufacturing, uncomplicated communication during its kind,where flexibility, cleaningor Production hasalready started.Does production anddevelopmentrequire- batch sizesoftenplayanimportantrole. ed cooperation and the fast, simple and ed cooperationandthefast,simple our customers. gree offl exibility, owe whichweinturn changeovers ofthedosing systems. out. This system provides safe produc- at anadequatespeed,inadditiontohigh quantities aswellmedium-sizedlots offers exactlytherightsolutionforour during theproject planningphase. a role. Thisisespecially advantageous ments. Thecapabilitytohandlesmall of ourcustomers.Thecontainmentver- a strategicmovetobetterutilizeoursys- ments but also have to meet the demands ments butalsohavetomeetthedemands system allowsforfastand simple sion oftheModu-Cisfi rstsystemof velopment unitwithroutine production With Harro Höfl igerwehavefound ade- worst comestotheworst,Harro years now. Would youdecideagainfor winning team.“ What, ifaservicetechnician fast response timesandanuncomplicat- far. We can rely on short-term availability, tasks, reliability combinedwithfl exibility this company? Höfl provide quickand technicians iger Our experiencehasbeenverypositiveso Before Iansweryourquestionwould (e.g. fi llingavarietyofmediaintoone ularly inthehighcontainmentsector. Dr. Stief,youhavebeenworkingwith like togobackabit:Asanadvancedde- keeping withthe motto:“Neverchangea back toyourquestion:Yes, wewould pendable partner, alsoforthedevelop- over thephone. closely withmi- oura Often, employees. ed andconstructivecooperation.Ifthe nor problem can quicklyberesolved capsule) is of great interest to us, partic- again collaboratewithHarro Höfl igerin quality, safetyand flexibility. Coming quirements are alwaysthesame:high developed on a joint basis. The basic re- ment of new processes. Each machine straightforward supportonsiteandwork is needed? supplied tousdatehasbeenfurther machines from Harro Höfl igerformany HARRO Edition 1

FotocreditsPfi zer, Harro Höfl iger, Atelier Lünig HARRO Edition 1 Form meetsfunction:Scetchingthe disc-fi ller The result: ideasfrom employees,suppliersandcustomerslead The term“innovation”islikeacurrency: Ifusedcarelessly, it according toplan Inventing for example,inthepharmaceuticalindustry. to clearprocesses, andexpertsare includedbasedontheir tomer requirements, andtoimplementfuture developments, How doesinnovationmanagementinspecialtymachineengineeringwork? inthemarket pilotsystems Our innovationprocess passesthrough fourphases: utilizing thisinnovativecapacitytoreliably meetcurrent cus- innovations are priceless,sinceeverycustomerinquiryre- process hasbeengeared towards thestrengths ofHarro Höfl iger. provided further motivation to introduce innovation manage- becomes worthless.Inspecialtymachineengineering,actual quires highlyindividualsolutions,whichcanrarely bepre-engi- ment asastaff function. Thus,theresearch anddevelopment medium-sized company in 2009 in the TOP-100 competition neered. Thisemphasizestheimportanceofsystematically specifi knowledge. c Phase 3:Implementationofthemachinetechnology Phase 2: Phase 1: Testing theconceptforfunctional viability Phase 0: Testing theideaforinnovativepotential The award giventoHarro Hofl igerasthemostinnovative Further developmentofthetechnologythrough This culminated inapatent appli- The approach wastominimizethe which led tothefi rstpreliminary Asthma patients expecttheirporta- Höfl iger hasdeveloped theDisc- tests and construction of aprototype. production. ThenewDisc-dosing pre-dosed powder portions insmall properties andvery small dosing inhalation powder within ados- followed bybrainstorming sessions, market developments wereanalyzed, impact of thedosing process on the fi ller inatargetedinnovation project. ing of such powders isanextremely is often fi lling all 30to60chambers month. Onesolution is toplacethe ring, theso-called disc.Thediﬃculty ral shaped andlocated on aplastic Result: Adosing technology that ly aspossible. Thehandling anddos- ble powder inhalers tobeassmall as possible, but at thesametime development continued with afocus quantities. For thisreason, Harro demanding taskdue topoor fl ow cavities with thedesireddose of the system canaccurately fi ll up to60 can bescaled-up andisready for on targetcustomers. cation. Subsequently, consistent sensitive powder. First, therelevant of thediskasprecisely andeﬀective- chambers, which arecircular or spi- contain medication for anentire How aboutsomepowder? ing cycle. Thefi lling level canbe adjusted asdesired,thus giving pharmaceutical companies more flformulat- in exibility ing theirproducts. KNOW-HOW 21 22 yourtongue! It melts on of webmaterialscontainingactiveingredients. well-established machineprogram fortheprocessing Harro Höfl igerhasbeenknowninthemarket fortheir dollars intheyear2018.Formore than20years, to grow from 182billiondollars(in2013)to218 the growing pharmaceuticalmarket,whichisexpected Oral andbuccalfi lmstripsoffer agreat potentialfor Oral (ODF)andbuccal(MBF) release oftheactiveingredient istimedelayed. addition ofwater. MBFare suitableforhigherdosesand within averyshorttime—entirely withoutchewing orthe released andtransferred viatheoralmucosatobody Once incontactwithsaliva,theactiveingredient is be reduced. Finally, thedrug’s effectiveness isincreased. pills iseliminated.Also,gastro-intestinal sideeffects can offers great advantages.Thepatient’s fearofswallowing dissolve quicklyanddistributetheactiveingredient. This once placedonyourtongueorinsidecheek,they of thehighlypromisingtomedicationintake: alternatives fi lmstrips represent one HARRO Edition 1

Studio Philippi, Atelier Lünig, Harro Höfl iger HARRO Edition 1 aging be clearlyrecognizable. should beintuitive,andthe dose itselfmust account. Openinganduseof thepouches ability andeconomiccostsmustbetakeninto design, lengthystorageperiods,goodprint- of thesealmustbeensured. Also,package ed againstmoisture andoxygen,theintegrity work step.Sinceallmaterialsmustbeprotect- sion andpackagingmustbecontrolled inone consumption. Ambientenvironment, conver- of theproduct aswellprotection until diffi culttohandle. eliminate thesedisadvantages,andtheyare fast dissolvingtabletsdon’t completely unpleasant, orhavediffi cultyswallowing.Even Patients mayfi ndhaptics,tasteortabletsize active ingredient maybenegativelyaffected. years. However, theeffi ciencyto release the established oraldrugdosageformsformany Dosing sizes Tablets, capsulesandthelike dosage. adapted tothedesired of thefi lmstripcanbe weight. Thedimensions percent ofthetotal concentration typicallycorresponds to30 thickness. Asarule,theupperlimitofdrug limited byitspolymermatrixandthestrip the mouth.Thedrugquantityforfi lmstripsis in order toimprove comfortoftheMBFwithin increased. MBFsnormallyhaveround shapes the thicknessofcarriermaterialcanbe and 10square centimetersinsize.Ifnecessary, A typicalODFisrectangular andbetween2 As withtabletsandcapsules,theODF mustgenerallyensure bothsafeusage have beenthe pack- During carefully. as production andpackaging costsmustbeconsidered handling andeffectiveness, thetherapeuticbenefi taswell market. Inorder todemonstrate theirsuperioreaseof ODF andMBFoffer hugepotentialforthepharmaceutical Conclusion The of thefi lmstrip. requirements forthickness,surfaceproperties orweight which layerapplicationprocess complieswiththe exact the fi lmstripinfl uence releaseoftheactiveingredient, or fi ed.Forexample,howsurfaceanddissolutionspeedof polymer formulation,furtherquestionshavetobeclari- steps. Afteranalysisandqualifi cationoftheaqueous identify theimpactofdifferent fi lmtypesandprocess Proof-of-Principle testingisoftenrequired inorder to be foreseen duringthelaboratorystage.Thisis why the high machinespeeds,effects canoccurwhichcannot enable asmoothscale-uptoproduction level.During packaging procedures mustbeconsidered upfront to scale, factorssuchasproduction, conversionand rolling orprintingmethods. sion, extrusionofanamorphoussoliddispersion,and pouches. Optionalproduction methodsare meltextru- is convertedintostripsandpackedindividual taste-masking coating.Thefi nished fi lmpolymermatrix strate, thendried.Itisalsopossibletoapplya polymer formulationisprintedorsprayedontoasub- production principleforfi lmsisapplied.Theaqueous mal patchtechnologyforwhichthetypicalcasting material of theODFtopackaging Precise andfi xedtransfer production development ofODFandMBFisbasedontransder- ofnewproducts onalaboratory and spreading longitudinal cutting Precision during KNOW-HOW 23 24 The ExcellenceUnitedpartnersappeared togetherinHall3.Three ofthefive Visitors were abletoexperienceHarro Höfliger“withallsenses” (Managing Director, Uhlmann),SiegfriedBullinger(Managing Partner, Harro Höfliger), from lefttoright, were allvisibly pleasedwiththe results ofthe Bausch+Ströbel) andHarro Höfliger(ManagingDirector andCompanyFounder, Excellence UnitedPartnersparticipated attheACHEMA:SiegfriedDrost exhibition Eventful. Informative.Competent.Theopen-designboothdrew visitorsalmostlikemagic forms were ondisplay. from AllmersbachimTal completelyagrees withtheorga the show.” Foran“experience withallsenses”Harro Höfliger the chemical,pharmaceuticalandfoodindustries tomers spent a considerable amount of time to learn moretomers spentaconsiderableamountoftimetolearn try for fivedays.From June15-19,2015, theworld’s lead trade show world’s leading Success at the Höfliger, summarizes: “Highlyqualified prospective cus Once again,Frankfurtwasthecenterofprocess indus in the middle of the action was the team from Harro Höfliger ing tradeshow, ACHEMA,attracted 3,813exhibitorsfrom production of oral and inhalable pharmaceutical dosage presented exciting live shows.Robot-Show-Actsand3-D animation ontouchscreens inspired thetradeshowvisitors. and ourExcellenceUnitedpartners.Theexhibitionteam around 167,000tradevisitorstotheMainmetropolis. Right about ourinnovations.“ markable, andseveralcontracts were finalizeddirectly at nizer’s conclusionofthetradeshowashavingbeen“from satisfaction toexcitement”.ThomasWeller, CEOofHarro The sharp increase trade visitors was re of international A professional focus where newtechnologiesforthe HARRO Edition 1 - - - - -

Studio Philippi

7 EXHIBITION TRENDS*

∞ The trend is shifting from batch to continuous processes ∞Biopharmaceutical drugs are experiencing significant growth ∞ Aseptic filling is becoming increasingly important ∞ Modern formulation technologies are increasingly in demand ∞ Batch sizes continue to decrease and demand high system flexibility ∞ Trend towards modular standardized system solutions ∞ Demand for a dust-free environment when handling powder

*Compiled by specialized journalists of PROCESS magazine.

Innovations ataglance:Thepowderlaboratory next tradeshow Team Harro Höfliger thanksyouforyourvisitandislooking forward to the HARRO Edition 1

and granules Listening. Understanding.Inspiring.High-leveldiscussionswithexperts!

World ofEnergySolutions Visit us: January 25 –2016 January 28, Shanghai, China,November17 – 20, 2015 Stuttgart, Germany, October12 – 14, 2015 Arab Health AAPS Algiers, Algeria,September29–October01,2015 Analytica Almersbach i.T., Germany, April19 – 20, 2016 Göteburg, Sweden,October20 – 23, 2015 Madrid, Spain,October13 – 15, 2015 Mumbai, India,December01 – 03, 2015 Moskau, Russia,November24 – 27, 2015 München, Germany, May10 – 13, 2016 Düsseldorf, Germany, November16 – 19, 2015 Paris, France,February10 – 11, 2016 Dubai, UnitedArabEmirates, CHINA-PHARM COMPAMED Orlando, USA,October25 – 29, 2015 CPhI /P-MEC Hannover, Germany, October06 – 08, 2015 Las Vegas, USA,September28–30,2015 Kintex, SouthKorea, April26 – 29, 2016 Open Days2016InhouseShowHarro Höfliger October 01,2015 Nürnberg, Germany, September29 – Nürnberg, Germany, April19 – 21, 2016 New York City, USA,April26–28,2016 SCANPACK Pharmtech Interphex Pharmapack P-Mec India BIOTECHNICA FachPack Maghreb PharmaExpo Expo Expo /Pharma Pack Powtech KoreaPharm

SHOP WINDOW 25 Inventive. Qualiﬁ ed. Reliable.

Driven by Innovation Strength and Knowledge

At Harro Höfl iger we foster a culture of understanding. This product. From the planning stage to implementation, our mar- contributes to the success of our business partners. We are ket specialists, creative designers and experts work hand- engineering system partners for individual production processes, in-hand with you — the innovators of new products. We as well as standard machines and platforms. This combina- provide support every step of the way, from laboratory phase tion allows us to tailor processes to precisely suit the customer through completion of your production line.

Harro Höfl iger Verpackungsmaschinen GmbH · www.hoefl iger.com