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AuthenticationofTabletsPharmaceuticalWhitePaper

nano4uAGMarktstr.266060SarnenSwitzerland

info@nano4u.nett:+41-41-660-0927

nano4upharmaceuticalwhitepaperonauthenticationoftablets 2

Global trademeans that extra effort is required to protect one's products from themanufacturing line

throughdistributiontothepointofsale.Inparticular,itisnotenoughtotrackandtracepackagedproducts

throughthesupplychainusingprinteduniqueproduct identifiersandserializationsystems,becausenew

serialization requirements in many countries also require proof that the contents of the packages are

actuallygenuine(authentic)andcanbeauthenticatedeasily.This leavesproducerswithnochoicebutto

investinauthenticationtechnologiesiftheyintendtocontinuesellingtheirproductsinthoseterritories.

Unfortunately in the pharmaceutical market at present, individual products are still mostly secured by

logistics, i.e., track and trace systems, which are only useful to track groups of products but not to

authenticate the individual products. By legalizing re-packaging of goods, the current track and trace

systems have become ineffective for the purpose of protection against counterfeit pharmaceuticals.

Criminalenterprisesincreasinglyexploitthisfundamentalweaknesstointroducefakepharmaceuticalsinto

thelegitimatesupplychain.

In thiswhite paperwepresentnano4u's unique authentication solutions to overcome this gap – these

allowtrue-authenticationofpharmaceuticalproductsthemselveswithinasecondarypackagebycreatinga

linkbetweenthephysicalpropertiesofthemedicationitselfwithtrackandtraceinformationcodesprinted

on the package, i.e., the unique product identifier. Using established production technologies, our

authentication solutionsarehighly cost-effective formassproduction . nano4u– solutionsdonotadd

anymarkingagentstoproducts.

nano4u's authentication solutions are fully compatible with all global serialization standards. It

complements them with true authentication capability on the level of the individual product

(pharmaceuticaldosage form). It thereforealsosimplifies inter-operabilityand reliabilityofandbetween

variousdifferentnationalorregionalserializationsystems.

TheStateoftheArt:SerializationandAuthentication

Tofightthegrowingproblemoffalsifiedmedicines,whichformamajorthreattopublichealthandsafety,

differentregionsandcountrieshaveintroducedtheirowntracking,tracing,andauthenticationlegislation.

In theEU, theFalsifiedMedicinesDirective (FMD) requires the introductionofa full trackingand tracing

systembyFebruary2019.Medicinepackswillneedtocontainauniqueproductidentifier(2Dbarcode)and

ananti-tamperingdevice, i.e.,atechnicalmeanstoensurethatthecontentofthepackagehasnotbeen

tamperedwith.Inmanycases,industryistryingtouseso-calledtamper-evidencelabels--thatis,labelsthat

are glued over the closing mechanism of the packaging carton. However, such labels only provide the

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impressionofsafetyandsecurity,astheyareeasilycopiedbycriminalorganizations.Inaddition,genuine

pharmaceuticalcartonboxesquiteoftengetre-introducedintothetradebyhospitalsandotherplayersin

thethirdworld.

The track and trace systems being implemented by pharmaceuticalmanufacturers in Europe and other

parts of theworld aremostly basedon serialization,where, in addition to a drug identificationnumber,

batch number, and expiry date, the unique product identifier (a randomly generated serial number) is

printedon the secondarypackageofpharmaceuticalsasa2Dbarcodeand stored ina centraldatabase.

However, the unique product identifier neither authenticates the package nor its content, because an

originalcodecanbeeasilycopiedand/orthecontentofthepackagecanbeexchanged.Ifaduplicatecode

is scanned in the supply chain, the original cannot be distinguished from the copy, legally requiring the

manufacturertorecallanddestroythebatch.

Thereareliterallyhundredsofsmallandlargercompaniesthatprovidesolutionsagainstcounterfeitgoods,

usingovertandcovertsecurityfeatures.ThesetechnologiesrangefromsecurityhologramstoUV-visible

ink, magnetic pigments, DNA tagging technologies, and RFID chips, to name but a few. Apart from

holographicfoilsonblistersandchemicaltaggantsonor inthetablets, littlehasbeenappliedtodateon

the tablets or the contents of the pharmaceutical package itself. As shown in table I below, most

establishedauthenticationactivitiesarelimitedtosecuringthesecondarypackage(thecartonbox),notits

content.

Thecurrentstateoftheartthereforecanbesummarizedasfollows:

• Theserializationnumberdoesnotauthenticateapharmaceuticalproduct

• If themanufacturer can not authenticate the content of a pharmaceutical package, it has to bedestroyedbylaw

Thedrawbacksofcurrentlyavailableantitamperingandauthenticationmeasuresare:

• canbeeasilyfaked(securitylabels)

• areprohibitivelyexpensive

• trackproductionbatchesatbest

• requireexpensiveequipmentandtimeforauthentication

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TableI:Overviewofexistingauthenticationtechnologiesandtheirapplicationtopharmaceuticalpackaging

Technology Appliedto Comments

SecurityInks,UV,DNA,magneticparticlesetc.

• Secondarypackage(cartonbox)

• Blister

• Canbehighlysecure

• Doesnotauthenticatedosageform

• Expensive

• Requiresdedicatedinstrumentationforauthentication

RFID • Secondarypackage

• Blister

• Dosageform(Tablets)

• Prohibitivelyexpensiveeveninlargequantities

• Easytofake

• Althoughvariantsfortabletsexist,marketpenetrationvirtuallynon-existent.

SecuritypapersandLabels,hologramsetc.

• Secondarypackage

• Blister

• Commonlyavailable

• Veryeasytofake,ashundredsofcompaniesdothesamething

• Costsatleastaround1cent/packageeveninlargequantities

Taggants • SecondaryPackage

• Blister

• DosageForm

• Authenticatesproductionbatches

• Highlysecure

• Requiresnewregulatoryapprovaloftablet

• Requiresdedicatedinstrumentationforauthentication

Inkjetprintableinks • SecondaryPackage

• Blister

• Notpracticalondosageformbecauseofslowprintingspeedandrequiredregulatoryapproval

• Expensive

Digitalwatermarks,etc. • SecondaryPackage • Easilyfaked

• Accesstodatabaseneeded

• Doesnotauthenticateproduct

• Economicsolutionatlargevolume

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nano4u:ABetterWay

In nano4u’s unique approach, pharmaceutical dosage forms are microscopically marked in the tablet

pressusingminutegeometricalchanges inthepressingtools.Oncethetablets fromdifferenttoolshave

been placed in a blister, the sequence of thesemarks in the blister is a unique truly random code that

identifies this particular blister itself. This truly random code is read on the blister line with industrial

camerasathighspeedsandcryptographicallysecured.Astheblistersareplacedinthesecondarypackage,

theirsecuredrandomcodeservesasabasistogenerateauniquetrulyrandomproductidentifierprintedon

the package.A cryptographically secured link is created between the physical properties of each tablet,

theirarrangement inablister,andthesecondarypackage.Any illegalattempt tobreak this link iseasily

detectedby takingaphotographofablisterandsecurelychecking itagainst thecodeon thesecondary

package.

TableII:Manufacturingofaself-authenticatedpharmaceuticalpackage

Tableting

Coating Blistering

Insideatabletpress,stampspresspowderinto tablets. A single press contains up to160 stamps. As every stamp is slightlydifferent, these variations are transferredto the tablet and serve as a uniquefingerprintforeverytablet.

The unique fingerprint of tablets can bemeasured even on coated tablets usingnano4u’s proprietary technology.Bymixingtogethermillionsoftabletsfromhundreds of different tools in production,the coating step actually guarantees thattablet positions in the final blisterpackagingaretrulyphysicallyrandom.

The tablets are placed into a regulararrangement in each blister where theyform a truly random physical sequence.Measuringthefingerprintsofthetabletsonthepackagingline,thisrandomsequenceisread and cryptographically secured withadditional information about the package,such as time of manufacturing, batch nr.etc. A truly random product identifier isgenerated and printed on the primary orsecondarypackage.

Allinformationrequiredforauthenticationisontheproductanditspackage.Aself-authenticatingpackage

does not require connection to any external database for authentication. The authentication works

anywhereintheworldwherethereisaccesstoasmartphonewiththecorrectcryptographicauthentication

software(app)installedonthedevice.

Ascryptographyisusedtolinktheactualdosageformstotheirpackaging,pharmaceuticalcompaniescan

alsobettercombatillegalre-imports.Individualcryptographickeyscanbeprovidedtoeachmanufacturing

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site and quickly changed should a problembe detected. Illegally repackaged content can thenbe easily

identified.

TableIII:Self-authenticationinthefield

Anywhereintheworld,thesequenceoffingerprintscanbereadwithamobilephoneandcomparedwiththeprintedserializationcodeonthepackage.

If the sequence of tablet fingerprints in the blister matches thecode,thepackagehasnotbeentamperedwith,asanytamperingwill destroy the cryptographic link between the physical tabletsequenceandthecode.Thistrueauthenticationdoesnotrequireanyexternaldatabaseaccess.

Our cryptographic solutions and smartphone-based reading apps can use the aggregation of coding on

product and blisters (primary packaging) aswell as serialization-compatible coding on carton boxes (2D

barcode)tocreatefullyself-authenticatingpackages.Thesecanbetrulyauthenticatedinthefieldwithout

requiringcentraldatabaseaccess,whilebeingfullycompatiblewithexistingdatabasesolutions.nano4u’s

uniqueapproachprovidesreliablecompatibility/interoperabilitywithcustomersupply-chainmanagement

andespeciallyERPsystems.

The linking (or data aggregation) solution between physical product properties and packaging is highly

secure, and it is the only means available to truly authenticate pharmaceuticals without requiring the

destructionofthepackageormedication(suchas inthecaseofchemicalanalysis)oraddingtaggantsto

theformulation.

Fastandfullysecureauthenticationisespeciallyimportantincasesofproductrecalls.Forinstance,where

counterfeit products have been detected in the supply chain, self-authenticating packages allow the

manufacturerstodistinguishbetweenillicitandlegalproductsanywhereintheworld.Manufacturersand

distributors can therefore avoid return shipments and the destruction of large quantities of legitimate

products, because their authenticity can be truly established on the dosage form level.

Self-authenticating pharmaceutical packages therefore improve the resilience of complex supply chains

effectively, as the approach is easily scalable globally and does not require additional physical

infrastructureaftermanufacturing.

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Self-authenticatedpackage:Easytouseandverycosteffective

Proprietaryproduction-proventechnology isusedforourauthenticationsolutions.Fortabletproduction,

absolutelynothingischangedfromapprovedandvalidatedprocesses.Forimageacquisitionandscanning,

establishedtechnologypreviouslyusedinotherindustriesisapplied.

Our field-levelsimpleauthenticationusesestablishedsmartphonecameras,combinedwithdigital image

analysis and cryptography. This provides a first level of authentication. Whilst this is not forensic, the

reliabilityoftheauthentication,especiallyifmorethatoneblisterinacartonischecked,isextremelyhigh.

For forensic-level analysis (analogous to analyzing the paper of a bank note), microscopic features on

tablets, includingsurfaceandsub-surface,arerapidlymeasuredthroughtheblisterbyopticalhigh-speed

scanners.Thistechnologyallowsrapidacquisitionof3Dtomographic informationofthetablet insidethe

blister.Withinsecondsouruniquealgorithmsthenallowauthenticationofindividualtabletsontheforensic

levelwithoutphysicalcontacttothetablet.Theblisterandthepharmaceuticalpackageremainfullyintact.

Our systems are highly cost effective, as they do not require any changes to existing production or

packaging lines.Theyworkwithoutusinganyadditionalmaterialonthepackageorproduct.Thecostof

manufacturing using our solutions for large quantities of pharmaceutical tablets is converging towards

zero,instarkcontrasttoallotherexistingtamperevidencesolutions,whicharecharacterizedbyanalmost

linearcorrelationbetweencostandoutput(mainlybecauseoftherelativelyhighcostoftamper-evidence

labels).Ourauthentication solutionsare fully compatiblewithFMD regulationsandcanprovide for fast,

reliableandfulltrackingandtracingalongthesupplychainwithouttheneedtodestroytheproductduring

authentication,whileenablingtrueauthenticationontheproductlevel-notjustthepackage.

nano4u-SupportYouCanCountOn

nano4u has the expertise and integrated products/technological know-how to help you protect your

product’s integrity and security across the global supply chain. We understand the complexities of

internationalsecurityregulationsandcanhelpyoumaintaincorporatecomplianceatreasonablecost.Our

integratedtechnologysolutionscanhelpyoutoprotecttheintegrityandsecurityofyourproductsandto

maintainyourbrand’sreputation.

nano4uhasverypowerful tools available toauthenticatepharmaceuticals anywhere in theworld, even

withamobilephone,andwithoutcentraldatabaseaccess.Havingfast,simple,andreliableauthentication

capabilitiesthroughoutthesupplychainstronglyincreasessafetyandsecurityofpharmaceuticalproducts,

andthesesolutionsmakeitmuchmoredifficultfororganizedcrimetodistributefakemedication.

Copyright©nano4uAG,Sarnen,Switzerland,January2018