Easy-to-use and intuitive interface Reliability: Battery life of at least 1 year Durability: Waterproof, shockproof and dustproof Connectivity: Bluetooth®/NFC/RFID for wireless data transfer Memory: Stores at least 10,000 data points Alarming: Clear visual and audible alarms Reporting: Generates PDF reports with shipment details Cloud: Option to connect to cloud for real-time monitoring Electronic indicators vs data loggers Electronic indicators and data loggers both monitor temperature, but have different functionalities: - Indicators provide a clear PASS/FAIL result for product release. Data loggers require evaluation of

1. Finding the
RightColdChain
Monitoring
Solution
PRACTICAL GUIDE

2. PRACTICAL GUIDE | FINDING THE RIGHT COLD CHAIN MONITORING SOLUTION 2
Step-by-StepGuidetoFindtheRight
ColdChainMonitoringSolutions
Manufacturersoftemperature-sensitivepharmaceuticalproductssuchasvaccines
and other medication – as well as room temperature products – must be able to prove
GxP-compliantproduction,storageandtransportacrosstheentiresupplychain.When
itcomestocoldchainmanagement,theyrelyonthesupportofnumerousplayers.
Packagingandcontainerleasingcompanies,3PLfreightforwardingcompaniesand
logisticsserviceprovidershelptoensurethatproductsreachtheendusersafelyand
efficaciously.Solutionsfortemperature controlalsomakeasignificantcontribution.
Alongtheentiresupplychain,aseriesofcomplextasks
arerequiredtomanufacture,store,transport,andmon-
itortemperaturesensitiveproducts.Eachofthesesteps
requiresadherencetodefinedprocessestoensureproduct
qualityandintegrity,oftencalledstandardoperatingpro-
cedures(SOPs).SOPsincludethemanufacturer’s
guidance andspecificinstructionsforusingtheright
equipmentfor packagingandmonitoring,transporting
productsintime, avoidingexposuretoextremeconditions
andfollowing
thedefinedreleaseprocessateachdestinationalongthe
journey to the end user.
Thisstep-by-stepguideisintendedtogivesupplychain
managers, logistics professionals, QA managers andclinical
researchprofessionals acomprehensiveunderstanding
ofmonitoringsolutions andapplications forpharma and
biopharmacoldchainproductsintransit.Readerswillalso
learnhowtransportmodes,hardwareandsoftwaregoto-
gethertoguaranteeGDPcompliance,andthusprotectthe
safetyand efficacyof your products.
Theseriesofactionsandprocessesinasupplychain
using specialized equipment to controltemperature is
commonly called the “cold chain.”

3. Manufacturer/Filling Hub Distributor/Wholesales Pharmacy/Hospital Patient
Direct Materials/Intermediates Finished Goods
Step 1:
Understanding the Pharmaceutical Supply Chain
Commercialpharmaceuticalproductsarepackagedto
protect the product from bacteria, chemicals, and humidity.
Although they are often less sensitive to temperature
comparedtofoodproducts,thebigchallengewithmost
pharmaceuticalproductsisthatthequalityandlevelof
degradationisnotvisibletothepatient.Forexample,you
cannotseeorsmellifavaccinehasbeenfrozen,haslostits
potency,orhasbecomeharmful.Thismakesitallthemore
importantforpharmaceuticalcompaniestoprovidecom-
pleteproofoftheintegrityandefficacyoftheirproducts–
throughouttheentirepharmaceuticalsupplychain.
Various pharma supply chains
Thepharmaceuticalsupplychainislongandcomplicated
with many different variations to meet a pharmaceutical
company’s needs, for example:
API supply: Active pharmaceutical ingredients and
raw materialsneededformanufacturingareshipped
inbound tothemanufacturingfacilityinspecialbulk
containers.
Fill/finish:AproductisshippedtoaGMPprocessing
facilitytoencasedrugsintofinalprimarypackaging.
Clinicaltrialsupply:Investigationalmedicinal
products (IMP)aremanufacturedinsmallvolumes,and
clinicalkits aredistributedtohospitalsinmanydifferent
countries.
Finished products: After premarket approval, a product
ismanufacturedinbulkbatchesandshippedbyair,sea,
road, or by train through several distribution depots,
often internationally, then locally.
Lastmile:Atthispoint,theproductisinthehandsofa
wholesaler,pharmacy,orhospital.Thislegofthejourney
isthemostdifficulttotrackeachproduct,butitisstill
importantsincepatientsafetyisthetopconcern.
Tomanagecomplexityandbuildresilienceinpharmasup-
plychains,itisequallyimportanttoensurethattheright
processes,people,andinfrastructureareinplacetohandle
andtransportdelicateproductsincompliancewithexisting
regulatory policies.
Simplified version of a pharma supply chain
Technologies and Physical Principles Used in Cold Chain
toMaintainandDocument TemperatureConditions
Insulation and vacuum insulation
Electronic temperature measurement
Database and business process
management software
Wireless data transmission
MobileIoTreal-timetemperature
monitoringandmeasuringdevices
Compressorheatingandcooling
Phasechangematerials (PCM)

4. Cloud Solution
Deviation Work Flow / Software Based Alarming
Reassessment
Alarm Notification
Missing Logger Notification
Temperature Within
Temperature Profile
TemperatureExcursion
(= ALARM)
E-Mail Notification
Associated
QA Manager
Assessment
Notification
Auto
Assessment
Reassessment
Notification
–196 °C 2–8 °C 15–25 °C
Product
Release
CRYO
Sending Site Destination
Monitoring solutions throughout the pharma supply
chain Monitoringandcontrollingtemperature,humidity
and otherparametersalongtheentirepharmaceutical
supply chain is complex. It requires precision-designed
environ- mentalmonitoringsystemsthathaveproven
reliableand ensure100%compliancethroughtheLast
Miles.Environ- mentalmonitoringsystemstypically
consistofsensorsor probesconductingmeasurementsof
temperatureorother environmentalconditionsinadefined
interval.Thesensor transmitsthevaluestoadatalogger,
whichactsasadata storageandcommunicationbridge
abletoautomaticallyor manuallysendthedatatoa
databasesystem.Thedatabase solutionmaycollectthe
valuesinrealtimeinorderto performvarioustasks,such
asdatastorage,assessmentof thedata,warningand
alarming,visualization,evaluation and analysis, reporting
and archiving.

5. Step 2:
Making the Right Cold Chain Logistics Choices
Keeping the temperature stable during transport is a
questionofchoosingtherightcoldchainlogisticsapproach.
Transportmode(road,air,oceanorrail),size(smallproduct
quantity vs. several pallets), temperature requirements
(ULT,frozen,+2°Cto+8°Cstrict,+15°Cto+25°C)and
triplengthinfluencethechoiceoftechnologytooptimally
protect theproducts.
Temperature-controlled transportation options
Based on the physical properties, typical shipment duration, and
sizes,themaincategoriesfortemperature-monitoring devices
are as follows:
Size Technology Type
Temperature controlled
van or truck
4–50 pallets Insulated vehicle with electrical
heatingandcompressorcooling
+2 °C to +8 °C
+15°Cto+25°C
(+2°Cto+25°C)
Air cargo container
with active temperature
control
LD3: 1 pallet
LD9: 5 pallets
Insulated ULD* with electrical
heatingandcompressorcooling
-20 °C
+2 °C to +8 °C
+15°Cto+25°C
(+2°Cto+25°C)
Air cargo container
with passive temperature
control
1–5 pallets Vacuum-insulated ULD* with
PCM (phase-change material)
-20 °C
+2 °C to +8 °C
+15°Cto+25°C
(+2°Cto+25°C)
Insulated box Various box
sizes, 1–1,000
liters (pallet
size)
Vacuum-insulated box with
PCM (phase-change material)
-20 °C
+2 °C to +8 °C
+15°Cto+25°C
(+2°Cto+25°C)
Thermal cover 1 pallet Insulated cover/hood covering
the pallet
Light insulation
breaking the peaks
Ocean reefer container 20feet:10–20pallets
40feet:20–40pallets
Insulated vehicle with electrical
heatingandcompressorcooling
+2 °C to +8 °C
+15°Cto+25°C
(+2°Cto+25°C)
Dry ice container Various container
sizes, 50–800
liters
Ventilated, well-insulated container for
minimal sublimation losses; wall/
packaging material
-80 °C
Cryogenic container Various sizes,
depending on number
of cryo vials
Vacuum vessels with multilayer
insulation in the annular space;
protectiveshippingcontainer
-196 °C
* ULD = unit load device – a standardized air cargo container built and certified to be connected directly with the aircraft without using cargo
nets.

6. False Deviations
Basedonourcustomers’experienceofmillionsofpharmaceuticalshipments,weknow
thatinlessthan10%ofallcasesatruetemperaturealarm(deviationoutsidethedefined
shippingconditions)isfound.Usually, halfofthecasesareduetodelays orother errors
thathappenatthedestination,whichcanbe definedas“falsedeviations.”
Passive vs. active equipment choices
Whenchoosingthepackagingfortheirvaluableshipment,
pharmaceuticalmanufacturershaveachoicebetween
activeandpassivecontainers.Thedecisionforoneorthe
othersolutionhasabigimpactonmaintainingtherequired
temperatureoftheshipmentthroughoutthesupplychain.
Activecontainershaveelectricallycontrolledcoolingand
heatingsystemsorallowcoolingwithdryice.Whenpassive
containersarechosen,theshipmentispackedininsulated
boxes or containers without active temperature control.
Thechoiceofpackagingisbasedonthetemperatureprofile
oftheproduct,shippingmodeandtriplengthaswellas
ariskassessmentregardingexcursionsfromthedefined
transport conditions.
Risk Active Containers & Trucks Passive Boxes
Wrong loading The equipment must be “ready for use” and
electrically powered. Airflow must never be
blocked.
Minimal risk (< 0,5%)
Passivecontainerstypicallyrequireavery
specialtypeofloadingthatincludesmany
elements, such as vacuum-insulated panels
andphase-changematerial(PCM).
Moderate risk (< 1%)
Extreme weather Extreme weather conditions outside
the container/box specification can always
occur.
Medium risk (1%–5%)
Extreme weather conditions outside
the container/box specification can
always occur.
Medium risk (1%–5%)
Technical failure
during shipment
Active containers/trucks contain hundreds
of different mechanical parts that can fail.
Moderate risk (< 1%)
Passiveboxescontainnomechanical
parts andthereforealmostneverfail
during shipment.
No risk (0%)
Handlingerrors
during transport
Therearevariousrisksin
handling errors:
Rerouting (shipment takes different route than
planned)
Delays(shipmenttakeslongerthan
planned)
Wrong ambient temperature (e.g. container left
on tarmac for too long)
Malfunction during battery charging
Medium risk (1%–5%)
Rerouting (shipment takes different route
than planned)
Delays(shipmenttakeslongerthan
planned)
Wrong ambient temperature (e.g. container left
on tarmac for too long)
Medium risk (1%–5%)
Late stop Atthedestination,sitepersonneloftenforget
topressthestopbuttononthedatalogger.
Medium risk (1%–5%)
Atthedestination,sitepersonneloftenforget
topressthestopbuttononthedatalogger.
Medium risk (1%–5%)
Overview of different risks and the impact on active and passive equipment

7. Step 3:
FindingtheRightHardwareforYourRequirements
Coldchainmonitoringofpharmaceuticalsismorethan
justmonitoringaproductintransitfrompointAtoB.Over
the years, many different applications and supply chain
variations haveemerged.
One way with product (single-use)
Onewayonproductandcoldroomstorage(single-use)
One way with product and return
(single-use or electronic temperature indicators)
Sample collection
(box-level temperature monitoring indicators)
Continuous on mobile equipment
(real-time on containers and/or transport vehicles)
Multi-step cold chain depots (multi-use)
End-to-End on product
(box-level temperature monitoring indicators)
One-Way Continous
Real-Time Real-Time
PDF Report PDF Report
WithProduct|Single-UseDataLoggers OnProductandStorage|TransportandStorage
Real-Time Real-Time
PDF Report PDF Report
OnProductandStorage|TransportandStorage OnMobileEquipment|DataLoggersforContainersandTrucks
Multi-Step
Real-Time Real-Time
PDF Report
PDF Report
With Product and Return | Transport and Storage ColdChain|Multi-UseDataLoggers
End-to-End
Real-Time
PDF Report
PDF Report
Sample Collection | Box-Level Monitoring On Product | Box-Level-Monitoring
CRYO

8. Differenthardwareoptionsareavailabletopharmaceutical
manufacturersformonitoringthesescenarios:chemical
indicators, electronic “smart” indicators and data loggers have
differentadvantageswithinthesupplychain.
Application
One-way
transport
on
product
One-way
transport
on
delivery
unit
or
in
transport
vehicle
One-way
transport
on
product
and
during
storage
En-to-end
on
product
One-way
transport
on
product
with
return
Collection
on
product
Round-trip
on
container
Continuous
in
transport
vehicle
Continuous
in
remote
rooms
or
equipment
Process
monitoring
Temperature
mapping
Data Logger
Hardware Type
Description
Multi-use
temperature data
logger
Classic data logger with battery life
ofatleastoneyearandtypically
with Bluetooth®/USB interface for
generating PDFreports
Single-use
temperature data
logger
Low-cost classic datalogger
withbatterylifeof110days
and typically with Bluetooth®/USB
interface for generating PDF reports
Real-time
data
logger
Multiplesensorswithbatterylife
ofatleastoneyearandcloud
connectionviapublicnetwork
(GSM or Mobile IoT)
End-to-end
temperature
indicator
Ultra-thin and compactelectronic
temperatureindicatorwithlong
batterylifeandmonitoringofthe
stabilitybudgetofaproduct
Data
logger
with
external sensor
Dataloggerwithexternalsensor
withtemperaturerangefrom
–200°Cto+200°Candbatterylife
ofatleastoneyear,usuallywith
Bluetooth®/USB interface for
generating PDFreports
Dry ice
temperature data
logger
Single-usedataloggerwith
specialhardwaredesignand
larger batteries;engineered
to be exposed directly to dry ice
Humidity
data
logger
Dataloggerfortemperatureand
relative humidity, typically with
Bluetooth®/USB interface for
generating PDFreports
Overview of different cold chain applications and hardware options for data monitoring

9. Chemical indicators
Chemical time and temperature indicators are small
chemical-based labels indicating (alarming) if time and
temperature limits are exceeded. Most chemical indicators
provideasmoothprogressionoftheindicatedstatusfrom
“Good-to-use” to “Don’t use.”
Beforechoosingachemicalindicator,youshouldaskyour-
self the following questions:
Does it cover my temperature range?
Doesithavetherequiredcertifications?
What do you know about thefailure rate?
Is the lifetime sufficient?
Isiteasyforthereceivertoread/understandtheresults?
DoIrequireastabilitybudgetformyshipments?
Wouldusingastabilitybudgetsave timeandmoney?
CanIsharetheresultsoftheindicatoreasily?
Doesitprovidemewiththerelevantdatanotonlyto
evaluate the result but also to improve?
Electronic “smart” indicators
Anelectronictimeandtemperatureindicatorisasmall, thin,
anddurable,battery-operateddevicewhichmea- sures
temperature,butalsoknowsallowedtemperature limits and
times and indicates a clear, visible, digital result (GREEN/OK
=productcan beusedorRED/ALARM =don’t use
product).
Electronic “smart” indicators provide the following benefits:
TheyhaveLEDsand/orLCDscreensthatareeasytoread
and see the product status.
Theymonitorproductsatanypointinthesupplychain,
whichiscrucialforhigh-pricedgoodsintransit.
Theyallowyoutomonitorthetemperaturevariations
andtimetakenduringshipmentorstorage.
They’reeasilycustomizedtoyourspecifications,hence
ensuring customer satisfaction by eliminatingdeviations.
Six Chemical Indicator Classes
Class 1: Ideal for monitoring high-end items.
Class2:Custom-madetotestandunderstandairremoval
andsteampenetrationusingtheBowie-Dickstest.
Class3:Specificvariablesusedtoexposeasingle
sterilization product procedure.
Class4:Comprisemultiplevariationsandreact
to various sterilization processes.
Class5:Reactwithallthepossibleandessentialvariables.
Class6:Emulatingindicators,usuallyverifythesteriliza-
tioncyclewhilereactingwithallcriticalvariables.
Functionalities Electronic Indicator Data Logger
Chemical Indicator
Indicate(alarm)iftimeandtemperature limitsareexceeded
Multi-levelassessment(multiplealarmlevelsandtimeranges)
Keep the measurement chain for further processing

10. 10 Must-Have Features of an Electronic Indicator
Compliance: Developed and produced according to
GAMP®5guidelines;withcalibratedandaccuratetem-
perature sensor (with NIST-traceable calibration certifi-
cates)
Traceability: Equipped with a unique ID-number
Low cost: Cantensofthousandsofkitsbeequipped
for less than $5 USD per piece?
Size and Thickness: Must be <3 mm thick, small
enough for use even on boxes and clinical kits (e.g. less
thanthe size of a credit card)
MountingandStarting:Easyattachmentandactivation
directlytokitwithself-adhesiveback;orbythethousands
on an automated packaging line
Battery Lifetime: Enough battery capacity to cover the entire
lifetimeofatypicalkit(upto4years)
SeamlessTracking:Continuouslymonitorstemperature
and keeps track of remaining stability budget; tracks statis-
tics(e.g.timepertemperaturezone,highestandlowest
value)aswellasdate/timeofalarmforfurtheranalysisby the
sponsor
Easytoreadstatus:OK/Alarmvisibilityatanytimewith-
outadditionalequipment;intuitiveandeasyforhealth-
care professionals and patients to us
CompliantDocumentation:Documentsandarchivesthe
statusincompliantway(nomanipulationpossible);allows
foreasydownloadandfeedbacktosponsorincasethe
stability budget is used-up (ALARM)
WHO Pre-qualified Status: WHO PQS E006
Data loggers
Adataloggerisadevicethatmeasuresandstorestempera-
tures and other environmental parameters. Most devices
haveaninternalassessment(allowedtemperaturelimits
andtimes)andindicateacleardigitalresult(OK=product
canbeused,ALARM=don’tuseproduct).However,some
dataloggersjustmeasure,storethemeasurementrowand
providethemtoasoftwaresolutionwheretheycanbe
assessed, analyzed and even archived.
Dataloggershelpyoumanagetemperaturecontrolduring
everyphaseofyourpharmaandlifesciencesupplychain
fromfirsttolastmiles:APIs,production,packaging,distri-
bution,clinicaltrials,directtopatient.Yourchoiceofdata
loggershasasignificantanddirectimpactonlogisticscosts,
efficienciesinsupplychainprocesses,andcompliancewith
regulatory guidelines.
PDFdataloggerswithUSB
and Bluetooth®LowEnergy
(BLE)
PDFdataloggersareaproven economicaltechnology to
monitormillionsofcoldchainshipmentsthesimplest,
fastestwaypossibleandtodocumentthereleasedecision
basedonmeasurementdata.Theyhelpyoumanageevery
pharmaceuticalandlifescienceapplicationfromfirstto last
miles,includingrefrigerated,dryice,humidityand
cryogenics.
Measurementrange:-200°Cto+200°C
Measures: Temperature, Humidity
Single use, multiple use
Battery-powered (No Lithium)
Readout:PDFreportwithalarmstatistics,
graph and raw data embedded
Software options: LIBEROConfig, SmartStart,
elproVIEWER, LIBERO Cloud
Readingoutthedataloggersafterarrivalatthedestination
canbeperformedviaaUSBportorviathewirelessdata
transmissiontechnologyBluetooth®LowEnergy(BLE).
Communication via Bluetooth® consumes very little energy,
whichisofcourseimportantforabattery-powereddevice.
USB Data Logger Bluetooth® Data Logger Real-Time Data Logger
Start Manual Wireless with smart device Automated with geofence
Intervention during shipment – Yes
–
Stop Manual Wireless with smart device Automated with geofence
Readout/upload Manual Wireless at arrival Automated in real-time

11. Real-time data loggers
Adataloggerisadevicethatmeasuresandstorestem-
peraReal-timemonitoringisthedeliveryofcontinuously
updateddataatzeroorlowlatency.Real-timedataloggers
provide end-to-end global visibility of product location,
temperature,humidity,tilt,lightandotherparameterson
roadorrailways,intheair,ontheocean,andinrooms,
containers,warehousesandmore.Receivingdataabout
productsintransitviareal-timedevicesprovidestheop-
portunitytorespondproactivelyandimmediatelytoavoid
temperatureexcursions,delaysinshipmentor,worsecase
scenario,totalproductloss.Whenusedincombination
withpredictiveanalysissoftwareandvirtualtwintechnol-
ogy,real-timedataloggersarepowerfullogisticstoolsthat
aredramaticallychangingsupplychainefficiency.
Using public 4G LTE mobile networks and new NB-IoT
technology, LIBERO G offers longerbatterylife and deeper
connectivity into trucks, boxes andwarehouses.
The Advantages and Efficiencies of
Real-Time Data Loggers
Instantalerts:Helpsassessthesituation’sseverityandin
finding solutions to save products
Accuracy: Risk of human error can be eliminated due to
thefastandreliableautomatedprocessesofcollecting
data independently
Customized configuration: With real-time temperature
monitoring system, it’s possible to customize data loggers
based on product types at any time.
Efficient supply chain management: Processes at sender
andrecipientcanbeautomated(automated start,auto-
mated stop, automated upload).
Reportsandanalytics:Real-timedatacanbeusedto
predicttrendsovertimeandhelpmanageandmitigate
risk before situations become critical.
Assetlocationtracking:Byprovidingtemperature/hu-
midityandpositioninthesamedevice,newopportuni-
tiesinassetlocationtrackingcanbeoffered(i.e.proac-
tive intervention, improved fleet management)
Accessibilitytodata:Keepingtrackoftemperaturefluc-
tuationsthroughoutthesupplychainwithouttheneedto
retrievedataloggers,installsoftware,ortrainpersonnel
in uploadingfiles.
Reduced administrative costs: Aggregated temperature/
humidity and position data can be used to manage risk,
improvethecoldsupplychainandreducecost(heat
maps, insurance, and litigation).

12. Humidity data loggers
How relevant are humidity data loggers in cold chain
monitoring?Pharmaceuticalproductsarehighlysensitive
inopenformasactivepharmaceuticalingredients(APIs) or
duringprocessingandfillingwithregardtovariousenvi-
ronmentalfactors,suchastemperatureandhumidity,but
alsowithregardtoaircontaminationbyparticles.Assoon
asthepharmaceuticalproductisinitsprimarypackaging
(blisterpack,syringe,orvial),itspotencyandqualityisgen-
erallynolongeraffectedbyhumidity.Inwarehouseswitha
temperatureof+15°Cto+25°C,ithasprovenusefultoadd a
measuringpointforhumidity.However,itisraretomon- itor
humiditycontinuouslyduringtransportation.Ifthere are
problemswiththedewpointwhenopeningincoming
containers, selective humidity measurements can be useful.
Dry ice data loggers
Dryiceisthesolidformofcarbondioxide.Asacoolant, it
iscost-effectiveandwidelyavailableatairportsandin
industrialized zones as blocks, discs, or pallets. Where there
arenomechanicalcoolingoptionsduringtransportandlow
temperaturesareimportant,dryiceistheperfectcoolant.
Many frozen pharmaceutical products are transported on
dryicesinceitissafeandinexpensive.However,dryice
can produce much lower temperatures than expected.
Duetovariousphysicaleffects,thetemperatureindryice
containerscandroptoaslowas-95°C.Thedevelopmentof
adryicetemperaturedataloggerthatisdirectlyexposedto
temperaturesof–78°C(orlower)isahugechallenge.Such
lowtemperaturesrequireagreatdealofengineeringto
reducepowerconsumption,sincethelowerthetempera-
tures,thelesspowerthebatteryprovides.Whenthedevice
isremovedfromthedryiceatthedestination,thedisplay
mustbereadyforimmediateuseandprovideareliable,
efficientreadingandthusacorrectreleasedecision.
Special Requirements When Using
Data Loggers for Air Freight Shipments
IATAbatterycompliance:Lithiumbatterycellsarecon-
sidereddangerousgoodsandmustbedeclaredinthe
shipping documents. However, devices containing lithium
batteriesintheformofbuttoncellsoralkalinebatteries
areexcludedfrom theIATAlithiumbattery regulation.
Thereisno restriction onthenumber ofdevices pership-
mentforthistypeofdevice.Theyalsodonotneedtobe
declared in the shipping documents.
Airlineapproval for real-time devices: Real-time data
loggerscommunicatingactivelyviaGSMorLPWAN
aresubjecttoapproval.Theremustbeatleasttwo
independentwaysto completely shut down the device
inflight,shutdownthecellularfunctions,orcompletely
shutdownboththecellular functionsandthedevice. A
combination of acceleration and pressure measurement
isatypicalexample,sincetheseparameterschangesig-
nificantly during takeoff and landing.

13. Step4:GetEverythingUnderControl
With the Right Software
Intheworldofpharmaceuticalsupplychainswherecost
reductioniskingandagrowingnumberofproductsare
temperaturecontrolled–collecting,communicatingand
analyzingtemperatureandlogisticsdataiscriticaltosuc-
cess.Dataarethefoundationofbusinessintelligence.Pro-
videdtheyconvergeatacentrallocationandareavailable
inaformatthatcanbeeasilyaccessedandanalyzed.
Intelligent database solutions can support companies in
numerousways:supplychaindigitalization,alerting,data
collectionandanalysis,riskmanagement,administration
andfurtheranalysis(e.g.oflogisticsdata)viainterfacesto
allstakeholdersinthesupplychain.Coldchaindatabase
solutionshelppharmaceuticalcompaniesgainend-to-end
complianceandmaximumvisibilitytocomplexsingleor
multi-stagepharmaceuticalsupplychains.Theyprocess
datafromconventionalPDFdataloggerstothelatestgen-
erationofmobileIoTreal-timetemperatureandposition
trackers. Thanks to customized integrations and processes,
criticaloperationalneedsaremetandqualified.
Requirements to an environmental monitoring
database solution
Whensearchingforasuitabledatabasesolution,stake-
holdersoftenaskimportantcriticalquestions:HowcanI
automate, improveandspeedupmy processes?How
can Icreateandmaintainstabilityinthesupplychainfor
full
transparencyatanytimeandanyplace?CanIintegratethe
technologytomyexistingsystems?Isitascalablesolution
thatwillgrowwithmydemand(fromstandardizedtools
to collect, archive, visualize and analyze data to complex
bespoke solutions for specific processes, automation
andintegrationtoothersystems)?Whocanhelpdesign,
implementandqualifymydatamonitoringsolutionand
database?
Toprovidesatisfactoryanswerstothesequestions,
databasesolutionsmustmeetthefollowingminimal
requirements:
24/7dataaccessinthecloud;combiningshipment
and storageinformation
Smartglobalworkflowswithautomated
email/SMS alert notifications
Dashboardsandliveupdateswithreal-time
mobile IoTmonitoring
CustomAPIsandERPintegrationforbig
data management
Quality control via end-to-end visibility for immediate
action and proactivity.
Datasecurityandintegrity;FDA21CFRPart11
compliant; GAMP® 5 validated
Scalablefromafewdepartmentstoanentire
global enterprise as needed

14. Cold chain management dashboard
Ultimately, a digitized supply chain and the controls applied to
itareonlyasgoodasthedatarelayandcontrolthat
underpinsyourexperienceasanend-user.Totrulysucceed,
youneedanexcellentqualitydigitaldashboardthatcan
displayallcollectedcrucialdataassimple-to-understand
readouts,chartperformance,andcreatemapvisualsthat
showwherecargoisatanygivenpointinthechain.With
coldtransport,youalsoneedahostcloudplatformthat
canmanagefastfeedback,multipleuserinput,andremote
‘login anywhere’capabilities.
When itcomes toensuring outgoing management works,
seamless integration is also essential. Communication lines,
actionablealerts,andremoteadjustmentsallneedtobe
presentasaccessible,linkedtoolsonavirtualdesktop.
Manyoff-the-shelfdigitalsupplymanagementdashboards
aren’tcomprehensive,detailed,orfocusedenoughto
managesomanyindependent,tightlycontrolledvariables
demanded in cold supply chain.
Acustomizedcoldchainmanagementsoftwareshould
ideallycoverthefollowingfunctionalities.
Data collection, visualization, and analysis
Combinationofincomingposition,temperature,andpub-
licaccessdatatocreatethebestpossibleactiveoverview
Creationofagraphical,zoomableroad(orrail)mapplot-
tingroutesandcurrentlocationofallshipments
Clickable overview of all origins, destinations, packaging
modes, supply chain partners, and trade lanes
Displayofthecurrentjourneyprogress,currenttempera-
tureand/orhumidity(ataminimum)pershipment
Read-outofdashboarddataasscrolling,searchablelists
aswellasgeneralperformancechartsloggedovertime
Availability of metadata summaries, charts, and auto-tar-
getstohelpwithKPIcreationandattainment.
APIandERPintegrationforfurtheranalysis(e.g.oflogis-
tics data)
Command, control, and administration
Creation of automatic receipts and distribute automatic
notifications when a ‘step’ transition occurs (e.g., ware-
house to van, van to delivery point).
Personalized modular customization that allows individ-
ual components and tracked metrics to be pinned to the
dashboardandmonitoredaseachuserseesit.
Integration of direct communication (i.e. SMS, e-mail,
phone) links to all relevant staff.
Waystoimportandexportdatafrombackups and
third-party files.
Remotely enable and disable sensors as needed.
Checkallmovementsagainstexpectedschedulingand
adapt if new changes appear.
Deliveryofdailyschedulestoallrelevantstaffand
report back periodically on expected performance.
Warningserviceprovidersaboutanyspecialrequire-
ments (e.g., fragile medicines, extremely low-tempera-
ture crates).
Incorporates emergency planning strategies to better
cope with unexpected transport disruptions, larger
accidents, and natural disasters.
Alarms,assessments,and“falseexcursion”
corrections Temperaturealarmsarebroughttothe
attentionofthe productownerduringashipment(when
usingreal-time devices)oraftertheshipmenthasbeen
completed.Those temperaturealertsshouldsend
automatic,urgentwarnings via SMS ande-mail toservice
providers andmanagers when faultsorabnormalheat
stressaredetectedsothatthereis time for corrective
action.

15. Thefinalassessmentshouldbeusedtomakeadecisionto
release(orquarantine)aproduct.Toperformanautomated
assessmentagainsttheremainingstabilitybudgetandre-
leasetheproductuponarrivalatdestination,thefollowing
data are needed foran immediate decision:
Completemeasurementrecordfromacalibratedsensor
Start time stamp (clear date and time)
Stoptimestamp(cleardateandtime)
Stability budget (assessment criteria) with clear condi- tions
oftemperaturezones/limitsandallowedtimes
Common causes of “false alarms” and possible cold-chain database
interventions
With this data the temperature monitoring database solu-
tioncanperformanassessmentandaclearOK(=release)
orALARM(=quarantine)decisioncanbetaken.
In cases where there are “false/positive” discrepancies (false
alarms)withashipment,thusnodefinitiveresultis available, cold
chain databases can enable fast and reliable interventio
Cause of False Excursion Cold Chain Database Intervention
Early start, sensor measures too early
(before product has been loaded or conditioned)
Coldchaindatabasecanreassessthedata
using the correct time stamps
Notemperaturevaluesavailableduetosensorfailure
(sensor not started or no sensor added)
Iftheshipmentcontainsmorethanonedevice,itmightbe
possibletouse thedatafromthe othersensorstorelease
the entireshipment
Minor temperature excursion during shipment Coldchaindatabasecanreassessthedata
using the stabilitydata of the product
Wrong sensor setting triggers a temperature alarm Coldchaindatabasecanreassessthedata
using the correct stability data
Latestopatdestination,sensorcontinuestomeasure
(at roomtemperature)
Coldchaindatabasecanreassessthedata
using the correct time stamps

16. Cloud-based temperature monitoring solutions
A temperature monitoring solution consists of hardware
collectingtemperaturevaluesandsoftwareevaluatingthe
data, triggering alarms, compiling reports and archiving the
harvesteddatainacompliantmanner.Butwhereisthis
softwarerunning?Inthepast“onpremise”wastheusual
answer.TodaymoreandmoreGxP-compliantcloud-based
temperaturemonitoringsolutionsarebeingutilized.
Cloud computing utilizes distributed remote servers
accessibleviatheinternettostore,manage,andprocess
data–ratherthanrunninganapplication onalocalserver
onpremise.Asarule,adistinctionismadebetweenthree
cloudmodels,whichdifferintheoutsourcedareasof
responsibility.SoftwareasaService(SaaS),alsoknownas
cloudapplicationservices,representsthelargestcloud
market. SaaS delivers applications that are typically
accesseddirectlyviawebbrowseranddonotrequireany
downloads orinstallations ontheclientside.
Obvious advantages of cloud-based solutions are:
Availableandaccessibleknow-howtorun
adatacenterbythecloudprovider
High security standards in facility, equipment,
SWtools(e.g.firewalls),processesandpersonnel
Fast and easy scalability of all resources
(performance, storagespace)
Built-in backup and recovery functionalities
Reduced maintenance efforts due to synergy effects
Allthosebenefitsusuallyleadtosignificantcostsavings
comparedtorunningsoftwareonpremiseatthesame
security and performance levels. However, before opting for
SaaS,companiesshouldanswertwoveryimportant
questions:
1) Have you prepared a clearly structured and detailed
agreementandawell-definedexitscenario
toavoidlock-ineffectsresultingin
dependencies on the solutions provider?
2) Haveyouevaluated yourpartnerextensively
andscheduledregularauditstobeableto
delegate control andavoid security
concerns?
Public versus private cloud
WhatistherightSaaSmodelforyourrequirements?SaaS
has three sub-types differentiating if the application is dedi-
catedtoonecustomerorifmanysharetheapplication:
PublicCloud:ApplicationisprovidedbytheSaaSprovider
andusedbymanycustomerswiththeirownusernames
andpasswords,butsharedinfrastructureandsoftware.
PrivateCloud:Applicationisdedicatedtoasinglecus-
tomer.Comparedtothepubliccloud,theprivatecloudis
significantlymoreexpensivesincetheresourcesneedto
be multiplied with each new customer.
HybridCloud:Mixofpublicandprivatecloudsolutions.
Theresourcesaretypicallyorchestratedasanintegrated
infrastructure environment. Hybrid Cloud takes “the best of
bothworlds,”butismorecomplextooverlookand
manage.
While a public cloud will deliver the lowest total cost per
temperature measurement point, there are risks related
tohostingaGxP-complianttemperaturemonitoring
solution in the public cloud that need to be considered and
mitigated.
On-Premise
Infrastructure as a
Service (IaaS)
Platform as a
Service (PaaS)
Software as
a Service
(SaaS)
Applications
Data
Runtime
Middleware
Operating System
Virtualization
Servers
Storage
Network
Managed by you Managed byothers

17. Checklist to Mitigate Risks Resulting From
UsingaPublicCloudSolution
Data safety and data protection
- Data is protected from unauthorized access. Data is backed-up
regularly.
- System is aligned with privacy regulations (GDPR).
Validation
- Hard-andsoftwarecomponentshavebeenvalidatedaccordingtotheGAMP®5 includingvalidationplan,
risk analysisandvalidationreports.
- Supplier has provided IQ documentation of the cloud software.
- Efficient tools for qualification of customer-specific hardware components are available.
Change management
- ServiceLevelAgreement(SLA)clearlydefineshowtodealwithupgrades, patches andchanges.
Supplier dependency
- Suppliertakescareofthemaintenanceandassuranceoftheaccuracy, consistencyand
completenessofdataoveritsentirelifecycle.
- There is a meaningful notice period prior to service termination.
- Clientremainsownerofthedataandthatdataisavailablefordownload before the service ends.
- Youkeepacopyofthedatainahumanreadableformat(e.g.PDF/A) at yourpremises.
- Rawdata(measurementvalues)cannotbechangedormanipulated. Anaudittrailkeeping
trackofeverychangeisimplemented.
Business continuity
- SLAguaranteestheperformanceandavailabilityofthesolutionandthatthesupplier monitorstheavailabilityand
performanceofthesolutionandprovidesreportsthereof. System and data are backed up regularly and
recoveries are exercised and documented regularly.
Data archiving
- “Freshdata”whichisusedfortakingbusinessdecisionsisavailableelectronically for visualizations (e.g.
zoom, overlay).
- It is possible to draw statistics easily (e.g. calculate MKT).
- Itispossibletoaddcommentsinthesystemandgeneratereports (e.g. releasedecision).
- Itispossibletoexportthedata(e.g.toahigherbatchmanagementsystem). “Archivedata”isavailableforat
least10yearsandfulfilsthefollowingrequirements: It is clearly labeled (e.g. monthly report per sensor).
- It is recorded in a “human readable” form (e.g. PDF/A report).
- Itisstoredinasecurearchive(e.g.inadrivethatisbackedupregularlyto a different physical
location).

18. Summary
Whetheraproductreachesitsdestinationintactornotis
affectedbymanyfactorsthatcanonlybepartiallyinflu-
enced (i.e., the safest packaging, the most reliable logistics
provider,theoptimalshippingroutes,thefastestmeansof
transport).However,thankstotheever-increasingamount
ofdataavailable,moreandmoreunforeseeablefactorscan
alsobemadepredictable.Animportantrolehereisplayed
byenvironmentaldata,whichcanbestbecollectedand
evaluated using ideally coordinated hardware and software
solutions.Nomatterwhichlogisticschoice,hardwareand
softwareyoudecideupon,GxP-compliantmanufacturing,
storageandshippingoftemperature-sensitivepharma-
ceuticalproductsrequirecloselycoordinatedcooperation
betweenallstakeholdersinvolvedinthecoldchain.
ThispracticalguideispartoftheColdChain
MonitoringSolutions&Logisticswebsitecontent
forsupplychainandQAprofessionals.Topics
includeinformation on differentlogistic choices,
hardwareoptionsanddatabasesolutions.