PHARMACEUTICAL ANTICOUNTERFEITINGold.iss.it/binary/farm/cont/Pharmaceutical AntiCounterfeiting...

PHARMACEUTICALANTICOUNTERFEITING

DECEMBER 2006

The role of the Pharmaceutical Security Institute

Exploring unlawful trade

Patients – the last barrier to harm

in partnership with

Good balance ofspeakers with a trulyglobal flavor. Good forraising awareness ofthe issues andfostering dialogue andactions.Jim Rittenberg,authentix

Well organised,presentations verygood quality.Rebecca Nordor,Ministiry of Health,Ghana

The Forum deliveredfrank and candiddiscussions.Gerard Norris, African Centre for HIV

Good conference,great speakers!David Schoneker,Colorcon

Powerful stuff!Martin Aartsen, Merck

This is ideal forpharmaceuticalcompanies.Glaxosmithkline

GLOBAL FORUMTHE THIRD

March 13-15, 2007

Prague, Czech Republic

Pharmaceutical AntiCounterfeiting

presentsThe only event which brings together all stakeholders in the fight againstcounterfeit pharmaceuticals

Attended by health professionals, regulators, patients' groups, pharma companies and anti-counterfeiting product and service providers.

Reconnaissance International, PMB 226, 2149 West Cascade, Suite 106A,

Hood River, OR 97031, USA.Fax: +1 541 386 1654 ATN PMB 226. Tel: +1 541 490 7920

Reconnaissance International Ltd.2A High Street, Shepperton, TW17 9AW, UK. Tel: +44 (0) 1932 269917. Fax: +44 (0) 1932 269918.

www.pharma-anticounterfeiting.info

Exhibition and sponsorship opportunities available. Contact Reconnaissance on [email protected]

ON

Making AntiCounterfeiting Policy Effective

Sponsored by

CONTENTS4 Working together for a

solutionAstrid Mitchell introduces usto the third Global Forum onPharmaceuticalAntiCounterfeiting

5 Countering the counterfeiterWho needs to be involved infinding a solution to theproblem of fake anddiverted drugs? Ian Lancasterexplains

6 A deadly tradePeter J Pitts paints a pictureof the global pharmaceuticalcounterfeiting problem

8 Acting on evidencePharmaceutical companieshave joined forces to form thePharmaceutical SecurityInstitute. Ashley Howdescribes its initiatives

10 ‘Grey’ imports, diversion,parallel trade andcounterfeitsGraham Satchwell explainsthe world of unlawful trade inpharmaceuticals, focusing onthe dangers in the UK supplychain

13 Healthcare's truestakeholdersPatients can and should playa key role in the fight againstcounterfeit drugs, says Jim Thomson

14 The counterfeiting andanticounterfeiting ofartesunateThe Wellcome Trust hasundertaken an in-depthinvestigation into counterfeitartesunate in South East Asia.Ian Lancaster and Paul Newton report

Industry Focus

16 Up close and personal:looking beyond RFIDDominic Griffiths describesthe benefits of unique imagetablets, an on-productanticounterfeiting solution

18 Mass serialisationholography for productprotection Mass serialisation holographyhas many advantages overtraditional techniques, explainJoachim Suesse and ClausGrobe

21 COMPANY PROFILES

PHARMACEUTICALANTICOUNTERFEITINGA supplement to Scrip WorldPharmaceutical News in partnership with Reconnaissance International

Editorial: Jenefer [email protected] [email protected] [email protected] Lancaster [email protected]

Sales: Paul [email protected]

Design: Mark Frost [email protected]

Head office: Informa Healthcare, Telephone House, 69-77 Paul Street, London, EC2A 4LQ, UKTel: +44 (0)20 7017 5000© Informa UK Ltd 2006 All rights reserved. Full terms and conditions available on request. Printed by Newman Thomson, Burgess Hill,West Sussex, UK

The views expressed in this supplement arethose of the authors but not necessarily those ofScrip. While information is compiled with all duecare, Informa UK Ltd will not be liable for theconsequences of anyone acting or refrainingfrom acting in reliance on any information.

www.scripsupplements.comwww.reconnaissance-intl.com

Features

www.scripsupplements.com4

Introduction

Pharmaceutical counterfeiting and diversionis a global menace. It threatens not justlivelihoods and company profits, but critically,lives as well. It is estimated that one in 20pharmaceutical products on the market arefake, rising to one in three in somedeveloping countries.

Just as the problem is global, so are thesolutions.And it is only by working togethercan government agencies, law enforcement,public health and regulatory bodies, patientcare organisations and the pharmaceuticalindustry itself develop practicalcountermeasures to prevent the manufacture ofcounterfeit and substandard products and thedistribution of these to the most vulnerablemembers of our societies - the ill and theincapacitated - in developed and developingcountries alike.

Such countermeasures include legislationand regulation, protection and identification,detection and enforcement - none of whichwill be effective in isolation, and all of whichare carried out by different stakeholders.Bringing these stakeholders together todiscuss and implement practical solutions is afundamental necessity for effective action, andthe first and second Global Forums onPharmaceutical AntiCounterfeiting, held inGeneva in 2002 with the World HealthOrganisation (WHO) and in Paris in 2005respectively, were a major step forward in thisrespect.

In the two years since the second GlobalForum on PharmaceuticalAntiCounterfeiting, we have seen a verywelcome increase in the attention being paidto counterfeit pharmaceuticals.The publicsector is paying more attention to theproblem, epitomised perhaps by the Council of Europe's extended investigation.The pharmaceutical industry too is identifying ways to tackle this scourge. PhRMA in the USA has launched its Safe Medicines initiative and

EFPIA in Europe is examining the best waysto protect its members' products.The WHO's new IMPACT initiative,meanwhile, combines the resources of the public and private sectors to develop a cohesive new approach to the problem.

The developing world is also paying more attention to this problem. In India there are newgovernment and industryinitiatives; China isdoing more to protect its citizens,and in Africa thedrug regulators are adopting more stringentpolicies, sometimesbanding togetherfor greatereffectiveness.

And effectivenessis now the keyissue for all theseparties.What needsto be done - andhow - to properlytackle this problem,in hospitals,clinics, pharmacies,border posts andports?

These are thequestions to beaddressed at thethird GlobalForum onPharmaceuticalAntiCounterfeiting.Here, theregulators,manufacturers,distributors,

suppliers and enforcement agencies alike willconsider a range of anticounterfeiting policies -many of them emerging from discussions atprevious Global Forums.

We look forward to seeing you there.

The third Global Forum on Pharmaceutical

AntiCounterfeiting will take place on March 13-15,

2007 in Prague, Czech Republic.

Working together fora solutionAstrid Mitchell announces the third Global Forum on Pharmaceutical AntiCounterfeiting

www.reconnaissance-intl.com 5

Introduction

The global nature of the pharmaceuticalindustry means that counterfeiting is now aworldwide problem. Prescription medicines,OTC or self-medication remedies, traditionalremedies, vaccines, injectables and surgicalimplants are all known to have beencounterfeited somewhere, sometime in the pastfew years.

Counterfeiting is a pernicious crime. Itwould be good to be able to say that it can beprevented by the judicious and committedapplication of an anticounterfeiting strategy,but unfortunately the criminals are too well-organised and the crime is too lucrative forthere to be much hope of that happening.Some criminal elements may be deterred, butthere will always be those who believe theycan get away with it, and whose disregard forhuman life and determination to build theirown bank balance is such that they willcontinue to produce fake pharmaceuticals.Thecost:reward ratio is too much in their favour.

So, for the foreseeable future at least, thefocus of those involved in pharmaanticounterfeiting must be the detection offakes before they reach the patient.Thisrequires the introduction and implementationof a cohesive and comprehensive strategy thatengages many participants.These include allthose involved in the production, distributionand supply of pharmaceutical products: thebrand-owners and the manufacturers (notalways the same entity); importers, distributorsand wholesalers; retail and hospital pharmacistsand self-medication shops, as well as doctorsand nurses. Even patients have a critical role:they, of course, have more at stake than otherslisted here, and they also have the ability tonotice variations in a medicine that they takeregularly for a chronic condition. Many cases offake medicines have surfaced because a patientreported that their new prescription was “notquite right” - it tasted different, felt different onthe tongue, or the packaging looked different.

There are two other groups that have a vitalrole to play in preventing fake pharmaceuticalsfrom reaching the patient, even though they arenot directly involved in the supply chain: lawenforcement agencies and the authenticationand anticounterfeiting service providers.

Three separate law enforcement agencies areinvolved in healthcare: customs (carrying outinspections at ports and border posts); police(and in some countries, specialist consumerprotection agencies); and drug regulatoryagencies (DRAs).

The role of the law enforcement agencies is todetect fake medicines before they reach thepharmacist or patient, and to investigate cases ofcounterfeits, hopefully to the point of arrest andindictment of those responsible.Their vigilanceand efficacy will help to deter the criminals; thefunction of the authentication andanticounterfeiting providers is to make the job ofdetection as simple and as effective as possible.

In pharmaceuticals, the manufacturer willselect the authentication system or device thatwill be used on its products. Ideally,manufacturers will consult with DRAs toidentify a system that works well for both themanufacturer and the inspectors. Of course,there is a tension between the desire tominimise costs and the need to maximise theefficacy of the inspection process, butfortunately there are authentication systemsthat do not add more than fractions of a centto costs.

The authentication process is at the heart ofcombating fake pharmaceuticals. It is of courseimportant that there is a legislative regime inplace in each country that makes it an offenceto counterfeit medicines and to infringeintellectual property rights; it is equallyimportant that the law enforcement agencies -especially DRAs - are committed to andadequately resourced for the fight against fakemedicines, in order to implement this legislativeregime. Pharmaceutical manufacturers also need

to be committed to combat the counterfeitingof their products, and to work with otherproducers where appropriate to combatcounterfeiting in general.The judiciary mustalso recognise the heinous nature of this crime,and sentence accordingly.

As important as these factors are, theydepend on the ability to detect fakepharmaceuticals.This in turn requiresinvestigative intelligence, corporate monitoringof sales patterns and the application ofauthentication systems appropriate to eachproduct and the distribution procedures ineach country.There needs to be the will andthe way - the will is demonstrated through acommitted DRA implementing a stringentlegislative regime, the way is throughintelligence and detection.

If these measures are applied effectively andconsistently, deterrence will follow.

Recently there have been clear signs atnational and international level thatgovernments are waking up to the seriousnessof pharmaceutical counterfeiting. In the USA,the FDA has issued important guidance on theneed to authenticate medicines and to knowtheir pedigree; in Europe, both the EuropeanCommission and the Council of Europe areexamining the issue; in Asia, with input fromthe World Health Organisation (WHO), theRapid Alert Network and other initiatives helpto raise awareness and share intelligence, andMalaysia in particular has taken radical steps toensure that all medicines available in thecountry are legitimate.

All these initiatives are welcome. Let's hopethat they lead to national and internationalfocus and attention not just on the problembut on solutions, achieved through cohesiveand comprehensive strategies forpharmaceutical anticounterfeiting.

Ian M Lancaster is director of Reconnaissance

International.

Countering thecounterfeiter Ian M Lancaster, introduces us to one of the pharmaceutical industry's biggest problems –

and tells us who can offer solutions


The global picture

A deadly tradeCounterfeit drugs are a growing problem worldwide. Peter J Pitts explains what moves have

been made to counter criminal schemes and what steps must still be taken to protect consumers

Counterfeit drugs account for 8-10% ofglobal medicine supplies, with the proportionrising to a quarter or more in some countries,according to World Health Organisation(WHO) estimates. Meanwhile, the Center forMedicine in the Public Interest expectscounterfeit drug commerce worldwide togrow by 13% a year between now and 2010 -nearly twice the rate forecast for legitimatepharmaceutical commerce. In 2010 this illegalbusiness will generate revenue of US$75billion, up 92% from 2005.The profits are highand the risks are low.That's a deadlycombination.

A large proportion of the world's counterfeitmedicines originate in Asia and end up in theUSA and EU - in the latter, the number ofseizures of counterfeit prescription drugsincreased by 1,000% between 1998 and 2004.Around 12% of drugs in Russia arecounterfeit, according to generally acceptedestimates, and now that the Baltic nations ofLatvia, Lithuania, and Estonia have joined theEU,WHO has warned of an 'obvious' increasein the risk of counterfeits entering the EUsupply chain.

An international epidemicTo watch the international news is to

witness the growth of this insidious criminalepidemic. In China, to take one recent story,11 Chinese nationals and one American werearrested in a counterfeit medicine scheme thatspanned 11 countries and involved 440,000bogus pills and US$4.3 million.The drugsbeing peddled were Lipitor,Viagra, Cialis andLevitra.The USA, the UK, Switzerland andIsrael were all affected.

A registered pharmacist in Hamilton,Ontario, has been charged with sellingcounterfeit Norvasc and the regional coronerin Hamilton is investigating the deaths of fivepeople whose prescriptions for Norvasc werefulfilled by this pharmacy.All five died of aheart attack or stroke.The US Attorney'sOffice meanwhile reports the indictment of 18people alleged to have taken part in a multi-million-dollar international conspiracy tosmuggle cigarettes and counterfeit Viagra to

raise money for the Middle East terroristgroup Hezbollah.

The EU recently went on the record (again)with its concern about the rise of counterfeitdrugs in Europe, and Canadian authoritiesreported arrests made as part of their ongoing'Project Piranha', with the seizure of a Hell'sAngels gang's supply of marijuana, hashish -and counterfeit prescription drugs.

China is a main productioncentre. In 2001, the Chineseauthorities reportedly closed 1,300factories while investigating480,000 cases of counterfeit drugsworth US$57 million. Between200,000 and 300,000 people areestimated to die in China every yearbecause of counterfeit orsubstandard medicine.These are justreported cases: the actual number islikely to be far higher.

There are four underlying causesof counterfeiting in LeastDeveloped Countries (LDCs),according to Julian Morris andPhilip Stevens of the InternationalPolicy Network, and while China isnot classified as an LCD, thecountry needs to address these fourissues.They are:◆ Absent or defective

intellectual propertyprotection. One way to prevent the sale ofunauthorised copies of medicines is to enablecompanies to register and enforce trademarks.Trademark owners have strong incentives toensure that the quality of their product ismaintained, because their reputation andhence future profitability depend upon it. InChina, it is difficult to enforce trademarks,even for local companies.Where trademarkscannot be enforced, cheaply produced copiesof poor quality will typically crowd outgood-quality drugs.

◆ Lack of adequate civil liability. Civil lawprotects the consumer against mis-sold ordefective goods. By enabling consumers toobtain redress from the manufacturer orsupplier of a harmful product, such liability

both compensates those who are harmedand discourages manufacturers and suppliersfrom selling counterfeits. In China, however,civil law is either poorly defined orinadequately enforced.

◆ Inability to resolve disputes overproperty rights and contracts inindependent courts. In China, an

inefficient legal system means that it canoften take years for cases to be heard.

◆ Corrupt courts and regulatoryauthorities. Criminals may be able to bribecorrupt law enforcement agents to turn ablind eye to their activities. If a case doesmake it to court, the criminal may be able topay off the judge.China's lack of adequate drug controls has

inevitably affected Western nations. InDecember 2005 US customs agentsintercepted more than 50 shipments ofcounterfeit Tamiflu.The fake drugs had noneof Tamiflu's active ingredients. Information onthe packages was written in Chinese.

Jeffrey Gren, director of the US CommerceDepartment's Office of Health and Consumer


The global picture

Goods, announced in a recent speech that theUS government is working on stopping theillicit flow of active pharmaceutical ingredient(API), which can be used in counterfeitmedicines.The Commerce Department isfocusing on China and India, Mr Gren said.China, however, maintains that it cannot beheld responsible for API used outside thecountry.While the production and trading ofan API in bulk form should ideally fall underthe same rules that govern the production andtrading of manufactured pharmaceuticals, this isnot currently the case in China - exports ofAPIs are unfortunately not regulated by thestate food and drug administration.

Counterfeit prescription medicines thatenter the EU and the USA from nations suchas Vanuatu, Bulgaria, Latvia and Portugal have

often been produced using phoney APIs, andgovernments on both sides of the Atlantic havetaken significant preliminary steps to addressthis growing problem. In its survey report oncounterfeit medicines and pharmaceuticalcrime, 'Harmonised Provisions for Legislativeand Administrative Procedures Applicable toCounterfeit Medicines in the Council ofEurope Member States', completed in early2005 and published in January 2006, theCouncil of Europe (CoE) identified threepredominant themes - invisibility, biohazardand system failure.

InvisibilityAccording to the CoE report's author, Dr

Jonathan Harper, an 'invisibility' factor masks

the real extent of the presence of counterfeitmedicines in Europe. He cites “a number ofreasons, not least of which are the very natureof medicinal products (counterfeit medicinesare invariably harder to detect compared toother types of counterfeited products), the lackof a commonly agreed and employeddefinition of counterfeit medicines byEuropean States and a lack of awareness (in thecase of several relevant authorities as well as thegeneral public) of the threat that counterfeitmedicines pose.”

BiohazardAdverse Drug Reactions (ADR) associated

with the inadvertent use of counterfeitmedicines may be caused by inappropriate APIdose - no dose at all, or one that is too small

or too large - and quality issues,such as contamination.

Under-reporting of possibleADRs related to counterfeitmedicine is likely to be significant,considering that ADRs are knownto be under-reported even in thecase of authorised medicinalproducts. A weakness in theexisting Europeanpharmacovigilance system is that itis not explicitly geared to detectionof 'drug ineffectiveness'.The directimpact of the inadvertent use ofcounterfeit medicines on publichealth in Europe is thereforedifficult to gauge from currentlyavailable data.

System failureAccording to Dr Harper, a

number of inter-related factorsmake Europe vulnerable to theproblem of counterfeit medicines:

◆ Lack of awareness and perception of theproblem at many authority/stakeholder levels;

◆ Regulatory gaps, particularly in the areas ofAPI and the packaging and distributionchain

◆ Weak export/transit regulations;◆ Lack of coordination between relevant

authorities, both nationally and internationally,and an inconsistent approach; and

◆ Inefficient cooperation between stakeholderswithin the supply chain and between thosein the supply chain and authorities.

The problem of the internetThe internet has the very real potential to

become the international drug cartel of the21st century.When the 'learned intermediary' -

a doctor or pharmacist - is replaced by agreedy intermediary, such as an unregulatedinternet site, there is significant danger topublic health. Profiteers masquerading aspharmacists threaten both safety andeffectiveness. 'Let the buyer beware' is badhealthcare practice and even worse healthcarepolicy.When patients go outside any givennational regulatory system and enter theinternet's grey zone, they assist those who putprofits before patient health.The online arenais often favoured not only by profiteersmasquerading as pharmacists, but also bycriminals intent on feeding counterfeit drugsinto the marketplace.

The US FDA has developed a framework fora pharmaceutical supply chain that would bemore secure against modern counterfeitthreats.This includes the following elements:◆ Implementation of new technologies to

better protect the US drug supply;◆ Adoption of electronic track and trace

technology;◆ Adoption and enforcement of strong, proven

anti-counterfeiting laws and regulations byindividual states;

◆ Increased criminal penalties to detercounterfeiting and more adequately punishthose convicted;

◆ Adoption of secure business practices by allparticipants in the drug supply chain;

◆ Development of a system that helps ensureeffective reporting of counterfeit drugs tothe FDA and that strengthens the agency'srapid response to such reports;

◆ Education of consumers and healthprofessionals about the risks of counterfeitdrugs and how to protect against them; and

◆ Collaboration with foreign stakeholders todevelop strategies to deter and detectcounterfeit drugs globally.The last is particularly important because, as

the Chinese proverb says,“An ant may welldestroy a whole dam.”

Counterfeit drugs are a global challenge toall nations and criminal counterfeitingoperations are increasingly operating acrossnational borders.The FDA has stated that it intends to work with WHO, Interpol and other international public health and law enforcement organisations to develop and implement worldwide strategies to combat counterfeit drugs. Now is the time to address and defeat this very real public health threat.

Peter J Pitts is director of the Center for Medicine in

the Public Interest and a former associate

commissioner at the FDA.


PSI initiatives

The traffic in counterfeitpharmaceuticalsworldwide,especially indevelopingcountries,can result inserious harm such asinjuries and deaths due toineffective or toxic treatments.However, the availability of counterfeitingdata is limited, and all too often the problem isdefined with reference to just a few well-known cases.At other times, dubious, overly optimistic orpessimistic and highly questionable estimatesare presented as fact.

Policymakers at government agencies andinternational organisations struggle todetermine the precise extent and nature of thisproblem.This year the World HealthOrganisation (WHO), having recognised theproblem for some time and having highlightedthe importance of timely exchanges ofinformation with the active participation ofpublic and private stakeholders, has developedthe WHO International Medical ProductsAnti-Counterfeiting Taskforce (IMPACT).

Meanwhile, pharmaceutical companies havehad to work out how to respond to the well-organised criminal groups that manufacture,transport and distribute medicinesindiscriminately and without regard to currentgood manufacturing practices. Several leadinginternational research-based manufacturershave responded by establishing thePharmaceutical Security Institute (PSI), the

world's onlyorganisation devotedexclusively to the collectionand analysis of information onpharmaceutical crime. At present themembership of the PSI consists of 23international pharmaceutical manufacturers. It maintains a close affiliationwith the International Federation ofPharmaceutical Manufacturers' Associations(IFPMA), whose director-general serves as its president.

The institute is combating a range of illicitactivities including counterfeiting, illegaldiversion and theft. Multilingual analysts, in co-ordination with experienced investigators,manage a consistent flow of information asdata is collected, analysed and disseminated insupport of individual or co-ordinatedinquiries. More broadly, it regularly producesstrategic trend information, which is essentialif the nature of the counterfeiting threatposed by international criminal conspiracies isto be fully understood.

The Counterfeit Incident SystemA unique incident-based reporting mechanism,the Counterfeiting Incident System (CIS), wasinaugurated by the PSI in 2002.The CISincludes pharmaceutical crime reports fromopen sources such as press releases, academicjournals, media articles and governmentwarnings, as well as member company reports.While an incident will be defined more fullybelow, generally it can be viewed as a singleevent which, when discovered, includesdetailed information on a specificpharmaceutical crime. For example, a membermay learn of the discovery of a counterfeitmedicine following a government inspection.The member, using the web-based system,

The Pharmaceutical Security Institute is using a

unique incident-based reporting scheme to

tackle counterfeit medicines and other

forms of pharmaceutical crime.

Ashley How reports

Acting on evidence

submits critical data points needed for theanalysts to positively identify this incident aseither a new incident or an event relating to aone submitted previously.

The critical data points necessary foreffective analysis include fields such as the date,time and place of the incident. Informationregarding the product's characteristics,therapeutic category, quantity involved, and any

details concerning the individual suspectsand businesses responsible for

counterfeiting is included. Injust a few years, the CIS

has become a reliablesource of

counterfeiting

information for its members andgovernment investigators from around

the world.

Counterfeit medicine PSI's definition of counterfeit medicines isbuilt upon that used by the WHO1.Counterfeit medicines are products deliberatelyand fraudulently produced and/or mislabelledwith respect to identity and/or source to makeit appear to be a genuine product.Thisdefinition applies to both branded and genericproducts.

Counterfeit products appear with a widerange of deficiencies. For example, counterfeitmedicines have been found to contain less thanor more than the required amount of activepharmaceutical ingredients (APIs) used in theauthentic version.The product may evencontain the correct amount of API buthave been repackaged in counterfeit packaging to extend the expiry date.

Illegal diversion Illegal diversion occurs when a genuinepharmaceutical product is approved andintended for sale in one country, but is thenillegally intercepted and sold in another.Theseschemes are often accomplished through the

use of false statements or declarations.Sometimes drug regulators in the secondcountry have not approved the use of thediverted drug.

Illegal diversion may also occur within thesame geographic area, the same country or thesame city. Discounted medicines are divertedfrom one intended group of consumers toanother which buys medicines in anunregulated open market. For example, inLatin America, illegal diversion occurs when agovernment purchases drugs at discountedprices for use in state hospitals and thesedrugs are then diverted to the street or open air markets.

Pharmaceutical theft Pharmaceutical theft is defined as an illegaltaking of medicines.Thefts include burglary,robbery and embezzlement of goods.Those responsible may be insiders such asemployees, or outsiders such as professionalthieves.The theft may occur anywhere in the distribution chain, such as at the site of manufacture, freight forwarder,distribution centres, warehouses, pharmaciesand hospitals.

PSI believes that an intensive, systematicapproach to the collection and analysis ofcounterfeiting incident data yields a moreaccurate assessment of the situation and willover time foster a clear understanding of thisproblem by the authorities.Timely sharing ofthe information/intelligence to its members,law enforcement agencies and drug regulatoryauthorities, as appropriate, will enable promptaction to be taken and successful conclusionsachieved.

Other PSI initiatives.Apart from the collection and analysis of data,PSI is also responsible for a range otherinitiatives, all of which it is hoped will increasethe impact that its members, law enforcementand regulatory authorities have on thispervasive crime.

These initiatives include the following:◆ Development of a training programme with

PSI members which:

- focuses on all aspects of counteractingthe problem of counterfeiting;

- is aimed at customs, police andregulatory authorities; and

- is strategically directed◆ Representation of the pharmaceutical

industry at various groups and forums, e.g.the WHO, the World CustomsOrganisation, Interpol, the Council ofEurope, the European Federation ofPharmaceutical Industries and Associations,(EFPIA) and the Pharmaceutical Researchand Manufacturers of America (PhRMA);

◆ Working closely with national drug andhealthcare regulatory authorities;

◆ Presenting to various governmental andnon-governmental bodies and groups and atappropriate conferences;

◆ Providing a point of consultation for theindustry; and

◆ Working with the Partnership for SafeMedicines, a coalition of patient, provider,non-profit and industry organisationsdedicated to the safety of patients and thedrug supply chains.This initiative wasstarted in the USA and is now expandingto Europe and beyond.

In summary, the challenge posed bycounterfeiting is clearly evident from theinstitute's data.There have been documentedincreases in the number of incidentsworldwide, more countries are experiencingcounterfeiting than ever before, and an evenwider variety of pharmaceutical products isbeing counterfeited, illegally diverted orstolen.Working together in an innovativepublic-private partnership is the mosteffective way to safeguard patients fromexploitation by criminal counterfeiters.

References 1.World Health Organisation Fact Sheet No

275 on Counterfeit Medicines (February2006), available athttp://who.int/mediacentre/factsheets/fs275/en/ print.html

Ashley How is european director of the

Pharmaceutical Security Institute.


PSI initiatives

A brand new approach to life science law. Take a tour today. Visit www.lslawonline.com


UK supply chain threats

It is difficult to understand the problemscaused by unlawful trade, whether incounterfeit or fraudulently obtained goods, without being clear about the terms used. People often talks of the 'greymarket', 'diversion' and 'parallel trade' as if they were synonymous. So here is a quick reminder.

Diversion refers to the movement ofbranded goods from one international marketto another without the consent of theintellectual property rights (IPR) holder andcontrary to their wishes. It can be illegal incertain circumstances, for instance where thegoods were obtained from the IPR holder bydeceiving them into believing the goods werefor sale in one country when in reality theywere always bound for another.

'Grey' goods are those that have beendiverted in this way. Often, grey market goodswill not violate the law but will be of interest

to the rights holder as a breach of companypolicy - after all, each company seeks tomaximise the price it can obtain in particularmarkets, and employees or contractors whofacilitate export to cheaper markets to linetheir own pockets do so contrary to corporate interests.

'Diversion' and 'grey' goods are distinctlydifferent from counterfeiting and have nothingin themselves to do with parallel trade. Paralleltrade refers to trade that goes on legally withinand across all member countries of the EU,which is fundamentally a free market withoutinternal borders. By definition, therefore, therecan be no 'diversion' of goods that haveremained with the EU.

However, it is clearly not in the commercialinterests of pharmaceutical manufacturers tosell their goods into southern and easternEurope at lower prices, only to see them turnup in more expensive markets such as the

UK, competing against identical products that those manufacturers market there athigher prices.

There are two main protagonists on thisstage. On the one hand we have so called'ethical' manufacturers, and on the other wehave European parallel traders, whoserepresentative association suggests that they tooare manufacturers (simply because they re-package the products made by majormanufacturers).

Major manufacturers call themselves 'ethical' because originally they invested inR&D to develop their own products withoutrecourse to copying the off-patent products of their rivals.Well, those days are gone and some very well known manufacturers of patented medicines also produce generics - even if they set up separatecompanies to do so.The description 'ethical' is outmoded, if not actually misleading.

'Grey' imports,diversion, paralleltrade and counterfeitsBuying diverted goods is a

recipe for disaster, and

wholesalers who do so should

be aware that they could be

furthering the trade in

counterfeit medicines, says

Graham Satchwell



Most people would be wary of courting thecompany of an individual who wore a badgedeclaring themselves 'ethical', so why shouldthe public be any more trusting of a corporation that does so?

Major pharmaceutical manufacturers shoulddrop the 'ethical' tag and instead market theidea that we have no right to expect makers ofmedicines to be any less commercially driventhan makers of software. Both software andpharmaceutical manufacturers need to beproperly constrained by the law, although one(because of the nature of the goods) to agreater degree than the other.

As for the parallel traders, it is misleading touse the term 'grey goods' in relation to theirtrade: parallel traded goods are 'white', notblack (market) or any shade in between.Whenthe term grey is used, the implication is clear:the goods are not 'white' but a bit shady.Parallel trade properly conducted is nothingother than 'white'. It certainly does not deservethe tag that suggests it falls somewherebetween legal and illegal.

We all benefit from parallel trade - whetherby buying cheaper jeans or shampoo - andmoving goods from one part of Europe toanother where a better price can be achievedhas been at the centre of business activity forEuropean countries since biblical times.

Solving the problemsSo far so good - the distinctions are clear.

However, significant problems have arisenwhich pose a continuing threat to the health ofthe British public (and the same situationprevails in other countries). It is surely time toshed some light on the fundamental issues, andto concentrate on solving the problems.

Every matter referred to hereafter is a matterof public record, known to, or within thepotential grasp of, the UK Medicines &Healthcare Regulatory Agency (MHRA),which in this contest between two parties has,or should have, the role of referee, mediatorand policeman.

There have been occasions when UKwholesalers holding parallel trader licences havebought products from sources importing fromoutside the EU, which were apparently'diverted' and yet turned out to be counterfeit.Buying products from outside the EU withoutspecific regulatory approval is in itself illegal.Buying and selling counterfeit medicines is ofcourse potentially lethal. Despite that, whenfound out, wholesalers have not had theirnames published and some continue to tradewhilst others have voluntarily relinquished theirwholesaling licence.

What lesson can we draw from this? That buying apparently 'diverted goods' is arecipe for disaster, and that it has offered,and will continue to offer, the opportunity for counterfeits to enter the legitimate supply chain.

No wonder manufacturers become keen tocite such cases: every diversion harmsmanufacturers' profits, while the selling ofcounterfeit goods masquerading as 'grey' addsinsult to financial loss and boosts the possibilityof loss of reputation, litigation, lost sales andshare price damage

Counterfeiting parallel traded goodsThere have also been occasions when those

holding parallel trading licences have beenoffered, and have purchased, goods purportingto be parallel traded goods from those whohave also supplied counterfeit medicines.Theimplication is clear, and this is important - to asuccessful but unscrupulous businessmaninvolved in the sale of counterfeit medicines,there can be no better bet than to counterfeitparallel traded goods.

Think about it:◆ The (re)packaging of parallel traded

medicines is always less sophisticated thanthe brand-owner's original packaging (andtherefore easier to copy);

◆ It rarely if ever carries any anti-counterfeiting features (hologram, micro-text or shifting ink); and

◆ No parallel trader employs investigators andanalysts to search for and detect counterfeitsin the way that major pharmaceuticalcompanies do.In addition, given the (small) price

differences between parallel and non-paralleltraded medicines, one can see the growingpotential for counterfeiters to exploit thisopportunity. Repackaging is currently oftendone abroad, with goods reaching UK shoresready for distribution.

The lesson? We should insist thatrepackaging is conducted to certain minimumstandards including the use of anti-counterfeiting design features.All repackagingfor the UK market should be undertakenwithin these shores and therefore subject toMHRA supervision.

There is no point whatsoever in demandingthat major manufacturers do more in terms ofpackaging and supply chain security, whenthose who also call themselves manufacturers(because they hold repackaging licences, orsimply because they do a little purchasing ofgenerics and have their own company nameadded by the supplier in Asia) do absolutely or

virtually nothing. Small wonder majormanufacturers feel less than warm towards'repackagers'.The MHRA must ensureregulatory change to provide better protectionfor the public.

One cannot escape the fact that the role ofthe MHRA is pivotal in all this.The agencywas set up (originally as the MCA) in thewake of the awful thalidomide tragedy.Thattragedy was caused by corporate greed.Understandably, the agency's raison d'être wasto ensure that such a catastrophe could neverhappen again. During the 50 years since, thathas remained its focus.

The MHRA polices the pharmaceuticalmanufacturers and the market with specialattention to new drugs, and this is of coursenecessary. But it needs to look up and lookaround: it has begun to see the dangers thatcounterfeit medicines pose, now it needs a shiftin culture. It needs not only to police themanufacturing industry, but to properly policethe pharmaceutical market with a view toidentifying and dealing with threats fromoutside the legitimate market.

At the moment the agency takes actionagainst vendors selling products such asunlicensed Chinese herbs and steroids, but thisis very easy. Such action is no substitute foracquiring sufficient resources and adopting astrategy to curb the rough end of thewholesale and parallel trade market.

So what else can be done? If there was aglobal price for each medicine, diversion andparallel trade would stop instantly and the doorto counterfeit medicines would be closed alittle. But will there ever be global pricing? Ofcourse not.

So, with price differentials remaining,manufacturers can act against diversion byapplying quotas to particular markets andmaking the appearance of medicines sodifferent for particular markets that divertedproduct is quickly identified. Both these thingshave increasingly been happening over the pastfive years. However, neither will preventcounterfeiting.The only way is to havemanufacturers, major and minor, invest more inunique and randomised mass serialisationsystems. But even that will not in itself beenough.

At the beginning of 2006 the ease withwhich a wholesale dealer licence can beobtained in the UK was clearly illustrated andexposed in a public television broadcast. Itpointed out that in the UK there is no checkon the background of the company applyingor its directors, in fact no check at all on theidentity of the applicants, no need for any



trading history, nor even the need for theapplicant to be a limited company.That needsto change.

In addition, we need a harsher approach by the MHRA to exposing wholesalers whohave been found in possession of counterfeit or otherwise sub-standard medicines.We needto adopt the precautionary principle in orderto deter 'chance taking' by those fewwholesalers and parallel traders who have noplace doing business in the supply ofmedicines. Most of all we need an alliancebetween honest parallel traders andpharmaceutical manufacturers.

Now is the time for decent wholesalers andparallel traders (the majority) to help ensurethat parallel trade does not continue to providean open door for inadequately re-packaged andpotentially counterfeit products.

To date, British wholesalers and paralleltraders have been even more secretive and'closed' than the major manufacturers, and thisneeds to change.We need to see just how theassociations that represent these businesses goabout policing their membership. Opennessand honesty is required.

We have now had several known cases of

counterfeit medicines entering the legitimatedistribution chain in the UK. I say 'known'because anyone who has worked in this fieldwill be aware of the high probability that manymore incidents of counterfeiting have goneundetected than detected.

Manufacturers (properly so called, not'repackagers') need to bite the bullet and workat shortening the supply chain.As I reportedmore than two years ago, supply chains inEurope often have more than 20 links, andeach link represents an opportunity for erroror infiltration.This needs to stop.

It is understood that late in 2006 membersof the MHRA gave talks and presentations atwhich they described a classification fordifferent 'types' of counterfeits.They areapparently now divided by that agency into'dangerous' and 'non-dangerous'.

This action represents an approach to theproblem by our regulators which I had hopedhad disappeared. Undoubtedly they have madesome progress recently, particularly with theappointment of the new head of investigations.He needs to take a firmer line and ensure thateach member of his team understands thatthere are, by definition, no safe counterfeits.

Clarity and action neededDiversion, parallel trade, grey product,

counterfeit goods - these are all differentthings, but they come together in a dangerous way where the supply of medicinesis concerned. Clarity before action is necessary, but any further delay before theMHRA, manufacturers (of whateverdescription), wholesalers and parallel traders take bold action is unwarranted and dangerous.

Both the public and the bodies referred toabove will suffer if confidence in ourhealthcare system is undermined by counterfeitmedicines. It is time to stop playing fast andloose with a lethal issue.

Graham Satchwell has written extensively on the

subject of counterfeit medicines and diversion and

is an acknowledged expert. He is a former director

of corporate security for GSK responsible for

Europe, Middle-East and Africa. He is a law

graduate, former detective superintendent and

Fellow of the Royal Society of Arts. (Copyright

owned by Graham Satchwell. To be reproduced in

whole or part with the specific written permission of

the author only.)

Why not take a free trial today and see how Scrip information differs from the rest

www.scripnews.com/trial

JSN0013A

CS5766


The patient’s role

Here's a quick test. Have a look at anygovernment policy document, promotionalbrochure for a major conference or, Godforbid, an internal briefing document from amajor pharma company. I guarantee the wordthat will leap from the page with monotonousregularity is 'stakeholder'. Don't even bother tolook at anything from a PR company - theword will be all over it like a rash.

Stakeholder is one of the most over-usedwords of our age. It has acquired meaningsbeyond what it actually says. For example, Ioften hear manufacturers, distributors,pharmacists, regulators et al. referred to asstakeholders in anti-counterfeiting. But what istheir stakeholding? If a fake version of amanufacturer's medicine turns up in thesupply chain, the share price might wobble fora day or two, or they may have to recall abatch.These are painful to the company - butlife goes on. If a distributor or pharmacist isfound to have counterfeits in their stock, theirreputation may suffer - but life goes on.Indeed, in today's climate, they are veryunlikely to suffer any substantive hardship atall. If the regulator fails to identify acounterfeit medicine in the supply chain, lifegoes on. However, if that fake medicinereaches a patient, it is entirely possible that lifewill not go on. Or that a chronic conditionmight not be managed as it should be. Or thata GP might wrongly attribute a setback tolack of efficacy and needlessly change atreatment regime.

These and other outcomes harm not onlythe patient, but also their confidence in theirmedicine - and therefore the likelihood ofconcordance with the treatment plan.Thismay not seem important until we understandthat by taking the seemingly simple step ofusing a medicine as prescribed, patients wouldincrease pharma profits by 25%. Mostreasonable people would think that reasonenough for taking seriously this particulargroup of stakeholders.

In the murky world of counterfeit andsubstandard medicines, the only personguaranteed to suffer is the patient. Now that'swhat I call a stakeholding.Yet patients are

often the last ones considered whenstakeholders discuss how best to combatcounterfeits. It is felt by some that patients arenot sophisticated enough to understand theissues, or that if they are made aware of thepatient safety risks of counterfeit medicines,confidence in medicines will be shaken. Ofcourse, this is palpable nonsense. Confidencein fakes, not medicines, would be shaken and confidence in our porous supply chainjust might be as well. Neither of these is a negative.

The last barrier to harmIn the campaign for safe medicines for all,

the stakeholder best placed to protect thepatient, is the patient.The one who puts themedicine in their body.The one who knowswhat to expect of it.The one with the livedexperience of what the real medicine does fortheir condition.The patient is the last barrierto harm and we need to accept this and use itagainst the crooks.

Surely, in the fight against counterfeiters, it isbetter to have several million investigators(each with a strong vested interest in their ownsafety) than it is to have a few dozen.Thestatus quo isn't fit for purpose. In the ten yearsto 2005 the UK medicines regulator, theMHRA, randomly sampled 25,000 packs ofmedicine.At last year's prescribing level, thatequates to 0.000385% of the supply - aminiscule needle in a very big haystack.Obviously the MHRA works in other ways,but is clearly hampered by lack of resources.

If we accept that the patient is the lastbarrier to harm, then the only remainingquestion is how best to involve them in thefight against bad medicine.The obvious answeris through the relevant patient groups and therepresentative bodies of the health professions.These groups are trusted sources ofinformation and support, and many are readyand willing to be part of the solution.

At its global congress last spring,TheInternational Alliance of Patients'Organizations (IAPO) ran a workshop oncounterfeit medicines.The most-requestedresource was a guide for patient groups to

distribute to patients.The InternationalCouncil of Nurses last year published anexcellent toolkit for its members and madecounterfeits the focus for International NursesDay.The Washington-based Partnership forSafe Medicines publishes an eight-step guidefor patients, as well as a global email alertsystem and a massive library of information oncounterfeit medicines.A UK company has justlaunched a service that delivers batch-authenticated medicines direct to the patient.Various technology developers are workingfeverishly to put in the hands of patients in thedeveloped and developing world, the low-costmeans to authenticate their medicines.All ofthese developments directly address the statedneeds of patient groups and associatedprofessions, eager to help protect theirconstituents.And this is set to mushroom inthe coming months.

In January 2007, an alliance of, sorry,'stakeholders' will come together to takestrategic, pan-European action to combatcounterfeits and campaign for a secure supplychain.The alliance will include, inter alia,patient groups, the healthcare professions andthe pharma industry.Their work will build onprevious initiatives and will feed into others -for example the World Health Organisation’s(WHO’s) IMPACT. It will be action-orientated and will work towards specificpositive outcomes.The seemingly disparateinterests within the alliance will be united by acommon charter. Of course, each member ofthe alliance will have their own priorities butthey are coming together as allies in order totake real and lasting action to improve patientaccess to safe medicines.This developmentplaces, at the heart of the fight against fakemedicines, those who have the greatest vestedinterest: patients, the last barrier to harm.

Jim Thomson is CEO of the Centre for Mental

Health, a UK group representing patients and

those working in mental health. He is also

European liaison for the Partnership for Safe

Medicines and a member of the Institute for

Health Law Studies, California Western School of

Law, IHLS.

The true stakeholdersIf patients are the only people guaranteed to suffer from the use of substandard medicines,

why are they the last to be considered in the fight against counterfeiting? Jim Thomson reports


Focus on SE Asia

Artesunate was discovered in the 1970s bythe Chinese, who were examining traditionalherbal remedies used to treat malaria.Theyfound the artemisinin in the leaves of artemisiaannua bush to be the active ingredient thatmade one of these herbal treatments effective,and developed a process to synthesise it,creating the compounds now known asartesunate. In combination with lumefantrine,this is now the treatment for malariarecommended by the World HealthOrganisation (WHO) in all areas where thereis chloroquine resistance.This means that thisChinese-manufactured drug is the leadingmalaria treatment in SE Asia, China and partsof Africa.

As the leading treatment for such awidespread disease, widely available and widely taken, artesunate has become a targetfor counterfeiters.The first known counterfeits were discovered in 1998, and by2001 the public was being warned about fakes and given information on how toidentify them. For example, The New Light ofMyanmar Online published the following storyon November 9 2001:

“During post market surveillance, theregistered 'Injection Artemether'produced by Kunming PharmaceuticalCorporation, China is found to be animitation.The comparison of the genuine(registered) and fake (imitation) InjectionArtemether are noted as follows:

The colour on the lower left side of theouter front package of the genuineInjection Artemether is previously dark-blue and recently red and the fake is

bluish; the manufacturing date andexpiry date of the genuine drug arestated on the back of the outer packageand there is no statement on package ofthe fake drug; Myanmar RegistrationNumber is stated on the back of theouter package of the genuine drug andthere is no statement on the package ofthe fake drug; liquid in the ampoule ofthe genuine injection is oily and liquid inthe fake injection is watery.Thelaboratory analysis of the fake (imitation)drug is found to have no activeingredient of Artemether.”

At this time, an early random shopping surveyrevealed that 38% of shop-bought artesunatewas counterfeit, containing no active drug.Asecond, more rigorous survey in 2003 foundthat 53% of 188 items of shop-bought blister-packed artesunate were fakes, with no activeingredient. In Laos, an incredible 89% of 27samples were fakes, with no active ingredient.

The Wellcome Trust SE Asian collaborationteam assessed the incidence of fake artesunatein the region, based on their purchases. In onlyfive of 27 locations did they find no incidencesof fake artesunate. In 15 locations only fakeswere available.

Such depth of knowledge about thepenetration of counterfeit drugs in a givenregion is unusual.Very few similar studies - ifany - have been conducted in such detail andwith such rigorous methodology.

The bigger pictureWhile the information gleaned from this

study is important, it is not possible to

extrapolate from this data that more than50% of all medicines available in this region are counterfeit. Nor can we say thatmore than 50% of artesunate in othercountries is fake.This is a particular regionwith a particular health problem with aparticular treatment regime and a particularregulatory and enforcement regime, in closeproximity to places where fake drugs areknown to originate.The unique combination of these factors causes very high levels of fake artesunate.Nonetheless, these are alarming figures which indicate the seriousness of thisproblem and we can conclude that it isprobably not confined to this region and this one medicine.

Fit for purpose?The discovery of fake artesunate prompted

Guilin Pharmaceuticals, the manufacturer ofthe product in blister-packed form, toinvestigate the measures they could take tocombat counterfeiting.They elected to use ahologram incorporated into the blister foil.Atthe time, there were not many producers thatcould incorporate holograms into blister foil.This in itself was thought to be something of adeterrent to the counterfeiters.The hologramitself though was a relatively simple design,although it incorporated certain hidden imageelements.

The first artesunate with a counterfeithologram appeared within months of theintroduction of the hologram blister pack.However, it was very crude and anyonefamiliar with the genuine hologram would

The counterfeitingand anticounterfeitingof artesunateIan M Lancaster and Dr Paul Newton report on the Wellcome Trust's investigation

into fake artesunate in South East Asia and discuss what can be learnt from

the problem of counterfeit drugs in this region


Focus on SE Asia

have no difficulty in differentiating the fakefrom the genuine.

That last statement raises critical questionsabout the design and introduction of ananticounterfeiting feature:Who is familiar withthe genuine hologram? Who will pay attentionto the hologram anyway? What is the purposeof the hologram - or any anticounterfeitingfeature? Is it to be examined by the patient, thebuyer of the drug, or is it designed to beexamined by a knowledgeable team ofinspectors (perhaps customs officers or drugregulators), trained and equipped for thispurpose? If so, who are those inspectors andwho is responsible for training and equippingthem?

An anticounterfeiting feature should notstand alone. It needs to be part of a holisticstrategy that draws on the resources ofcommercial sector (the drug manufacturer andlegitimate distributors), the public sector

(police, customs and drug regulatory agencies),and the patient/customer. But this is often notthe case.

The WHO estimates that only 20% of DrugRegulatory Agencies (DRAs) worldwide havea “well-developed functioning capacity” while30% have “no drug regulation or a capacitythat hardly functions.” It doesn't take muchimagination to realise that most of those 20%are in the developed world and that the 30%with no drug regulation are in the developingworld.

So Guilin Pharma has adopted a hologramto its mark its genuine product, but who isthere to examine it in the markets of SE Asia?The patient, who - no matter how much efforthas gone into educating the customer aboutthe characteristics of the hologram - is notproperly trained to do so?

Furthermore, the counterfeiters areincreasingly familiar with the artesunate

hologram and with hologramproduction techniques: 12types of fake hologram havenow been identified and theremay be more not yet found;each is 'better' than theprevious fake (in that it iscloser in appearance to thegenuine hologram). None -yet - is a 100% accurate copy;all the fakes are identifiable assuch - if only there were the inspectors who weretrained and equipped to spot them.

A health disaster Anticounterfeiting, and

pharmaceuticalanticounterfeiting inparticular, cannot depend onthe efforts of themanufacturer to useanticounterfeiting devices orsystems.These are necessary,but are most effective whensupported by a suitableinspection regime.The WHOencourages DRAs to adopteffective policies, but oftenthe resources to make thesepolicies effective are notavailable. Patients are veryoften left to make their owndecision about whether agiven medicine is genuine orfake. But they may not evenbe aware that fakes are in

circulation. And in many parts of the worldthey don't have the education, never mind thetraining, to examine and identify fakeproducts.

This is a potential health disaster. It can becontained, but only with the right resourcesand, above all, the will to do so.Thecounterfeiters are greedy and determined andfaking medicines is often easy and lucrative.But if the health sector and enforcementagencies put enough resources and effort into identifying fake medicines and trackingdown those responsible for them, thecounterfeiters will turn their attentionselsewhere.

Pharmaceutical anticounterfeiting canprobably never stop the counterfeits, but it canreduce them - significantly.

Ian M Lancaster is director of Reconnaissance

International.

Fake anti-malarials - as big a risk to public health as malaria itself?

The global extent of counterfeit medicines isa subject of intense debate (and is being dealtwith elsewhere in this supplement).While theprecise prevalence depends upon whom youask there are a number of points on whichthose involved in the debate agree:◆ Counterfeit medicines were historically

perceived to be an issue for the developingworld. Recent well publicised incidents ofcounterfeiting demonstrate that this is nolonger the case;

◆ Since the US FDA Task Force report in20041 the pharmaceutical industry has beenmaking efforts to address counterfeiting andtraceability throughout the supply chain;

◆ That, of the myriad anticounterfeittechnologies, radio frequency identification(RFID) is emerging as the front runner,particularly in the USA;

◆ That there is no 'silver bullet' - a multi-pronged approach to this problem isrequired; and

◆ Counterfeiting is on the increase and a lotmore needs to be done by governments,regulatory agencies and industrystakeholders to prevent it.From a patient perspective, how damaging

are counterfeit medicines? In the developedworld adverse events from taking knowncounterfeit medicines are thankfully theexception rather than the rule. It is thedeveloping world that has suffered most at thehands of counterfeiters and remains the marketin most need of a solution. In these countriesit is the life-saving - anti-malarials, anti-HIV,for example - rather than lifestyle drugs thatare most often prone to illegal copying.

From a brand owner (i.e. the pharmaceuticalcompany) perspective, if a patient suffers anadverse event following consumption of acounterfeit dose that was mixed amongstauthentic medicine it could be very difficult to

prove which tablet caused the side-effect - andtherefore who is liable for the harm caused tothe patient. For example, Bristol-Myers Squibband Eli Lilly were reported to have paid anestimated US$71m in 2002 to settle more than200 lawsuits that arose as a result of apharmacist distributing diluted doses ofGemzar and Taxol to cancer patients in theUSA2.

So what is the pharmaceutical industrydoing about this growing problem? Manypharmaceutical companies have establishedinternal taskforces, and have been advised bythe FDA to consider combining both 'overt'and 'covert' approaches to anticounterfeiting.To date most companies have focused onelements of the packaging process to make itharder for counterfeiters to penetrate thesupply chain. Due, at least in part to the FDA’srecommendation of track and trace solutions,the leading contenders for broad-scaleanticounterfeit protection centre on RFID.

The objectives of RFID are straightforward:to allow manufacturers and distributors toprecisely track products as they move throughthe supply chain from the point of manufactureto the point of dispensing.The technologycreates electronic ‘pedigrees’ that shouldimprove patient safety by allowing wholesalersand retailers to rapidly identify, quarantine, andreport suspected counterfeit drugs.

RFID involves the tagging ofpharmaceutical packaging material usingtransmitters.The need to detect the signal fromsuch transmitters places technologyrequirements on each element of the supplychain. Implementing RFID is therefore by nomeans straightforward. Indeed, in 2006 theFDA stated that it was unlikely that thepharmaceutical industry would meet its targetdeadline of 2007 for RFID implementation3.However, notable successes including Pfizer's

tagging of Viagra bottles in the USA indicatethat progress is being made (although Pfizerhas stated that this initiative alone will noteliminate counterfeiting)4.

The limitations of RFID would appear to be:◆ That it is currently proving difficult to apply

RFID across an entire product range;◆ The IT required to support RFID is

complex and costly - and not easily availablein some territories; and

◆ RFID does little to convince patients that aproduct is authentic.While RFID remains a technically elegant

way of monitoring units of product throughoutthe supply chain, it is not failsafe, nor is itsuitable for all. So what else is out there?

Closing in on the productA fundamental limitation of RFID and

many other packaging-based counterfeitmeasures is that they do not enableidentification of counterfeit product at thelevel of the dose form.This is relativelyunimportant if the final packaging unitprovided to the patient contains thecounterfeit measure. However, even indeveloped markets such as the UK and USA,packages released from the manufacturer areoften re-packaged as they move through thesupply chain - for example, to provide a setnumber of tablets for a course of treatment.

It makes sense therefore to either morerigorously control the supply chain tominimise the likelihood repackaging or tomove the anticounterfeit measure even closerto the individual dose form. In anunprecedented move, Pfizer is pursuing theformer strategy, recently announcing a deal inthe UK which makes UniChem the soledistributor for its products in the UK market5.This has triggered a predictably negativeresponse from other supply chain participants,


On-product solution

Up close and personal:looking beyond RFIDWith Pfizer stating that its recent RFID initiative isn't going to solve the problem of counterfeit

Viagra, what else is out there? Dominic Griffiths explains how an on-product anticounterfeit

measure has many benefits for patients, doctors and pharmaceutical companies alike


On-product solution

and at the time of writing the UKgovernment is considering whether or not thismove constitutes anticompetitive behaviour6.

So what about the dose form? Swallowingthe tablet is the final patient experience ofconsuming a medication. Ultimately it is thedrug, rather than the packaging, that must betrusted by the patient to be authentic. Surely,then, customised and difficult to imitate tabletdesigns that can easily be recognised by thepatient would be the best way to provide animmediate visible indication of tabletauthenticity? Every tablet would be protected,rather than every tablet pack.

In the past, implementation of tablet-levelanticounterfeit measures was prevented by the widespread availability of tablet presses and coating equipment. Counterfeiterscould, therefore, fairly easily make tablets that appear authentic in shape and colour.Indeed, counterfeit tablets are perhaps the most common form of abused medication.

Today, companies offer technologies thatcan coat tablets in a way that providesexcellent protection from counterfeit (seeFigure 1).The main advantages of these'unique image tablets' are that, as well as beingvirtually impossible to counterfeit, they can becustomised for a given territory giving thepharmaceutical company the ability to trackproduct diversion and re-importation withoutthe need for extensive and expensive ITinfrastructure. In addition, the technology usedto create such tablets is:

◆ Proprietary - theproduct's appearance isprotected by intellectualproperty and considerableknow how.

◆ Restricted - thetechnology ownercontrols the machinesupply and the rawmaterials used in themanufacture - giving thepharmaceutical companyincreased confidence inthe safety of theirproduct.

◆ Cost-effective - becauseimplementation of thisanticounterfeit measureinvolves the replacement,rather than the addition,of a processing step, thecost implications of thetechnology are minimised.

Brand benefits In addition to providing an excellent

anticounterfeit measure, unique appearancetablets offer pharmaceutical companies theopportunity to strengthen their products' brands.Tablet appearance can be used to enhance brandimage in two ways: by 'passive' association,where a patient associates a particular tabletdesign with the manufacturing company andlinks their positive experience of the medicationwith its proprietor, and by 'active' associationwhere unique appearance tablets are seen to addvalue to a product. For example, elderly patientsare typically required to administer several drugsper day, each often having a different dosingregimen. Distinctive tablets could help them(and other poly-pharmacy patient groups) tomore easily tell one tablet from another, leadingto improved compliance and therefore increaseddrug effectiveness.And if the patient recognisesthese benefits (and consequently requests aspecific medication), it is likely that their doctor will too.

Furthermore, several studies havedemonstrated an association between tabletcolour and the perceived effect and efficacy ofa treatment. For example, in one study patientssuffering with rheumatoid arthritis receivedred, blue, green, or yellow placebo tablets7.Patients reported significant pain relief whentaking the red tablets - in contrast to the blue,green, or yellow tablets, where little or no painrelief was observed. Matching expectationwith appearance could therefore add brandvalue by improving a product’s perceived

benefit - and therefore compliance.It is also of particular note that, in a recent

US survey of 150 pharmacists,8 79% ofrespondents blamed look-alike medications fordispensing errors - errors that cost in excess of7,000 lives per year in US hospitals.

No silver bulletKey players in the regulation, manufacture

and distribution of pharmaceuticals worldwideare putting in place measures to combat theprevalence of counterfeit drugs.The mostproactive market is the USA where the FDAhas recommended a range of anticounterfeitingmeasures, the lead one of which is RFID.However, the FDA's targets will not be metand RFID will not deliver the 'silver bullet'that solves the problem globally. It has beenrecognised by all that no single solution exists,however taking counterfeit protection to thetablet level offers the pharmaceutical industry acost-effective option that empowers the patientto join the fight against counterfeit drugs.Thistechnology can give patients and prescribersalike the confidence that the dose form itself isauthentic (rather than having to trust thepackage it came in).That the technology alsoenhances brand value is a considerableadditional advantage of this innovativetechnology.

References1. Combating Counterfeit Drugs. (February,

2004).A report of the Food and DrugAdministration.

2. 'National Briefing: Midwest: Missouri:Drug-Watering Suits Settlement' (October2002). New York Times.

3. 'FDA Counterfeit Drug Task ForceReport: 2006 Update' (June 2006).A reportof the Food and Drug Administration.

4. 'Pfizer Introduces Radio FrequencyIdentification Technology to CombatCounterfeiting, Protect Patient Health'.(February 2006). www.pfizer.com

5. 'UniChem Appointed as Sole DistributionPartner for Pfizer Prescription Medicines inthe UK' (September 2006).www.unichem.co.uk

6. 'OFT looks at Pfizer's distribution deal withUniChem' (October 2006).The Times.

7. Hutchison E. BMJ, iv:196-200, 19748. 'Survey shows pharmacists believe

distinctive tablet appearance reducesdispensing and patient medication errors'.(June 2006). www.colorcon.com

Dominic Griffiths is director of business

development at Phoqus Pharmaceuticals.

Figure 1: Unique image tablets take counterfeit protection and brand

recognition to the level of the tablet


Tracing and authentication

Effective counterfeit protection forpharmaceuticals can only be achieved withsecurity technologies that are inaccessible tocounterfeiters and prohibitively difficult toimitate. For product protection on a broadscale, the application of mass-serialised codes israpidly becoming a key security requirement.It enables the pharmaceutical industry to traceproducts through the supply chain and toverify their identity by means of an electronic'pedigree'.While the security effect of apedigree is self-evident, mass-serialised codes(for example, barcodes) are, unfortunately, oftenapplied with printing technologies that aretechnically easy to replicate or manipulate.Consequently, incremental protection may berequired for high-risk products or countries.

Fulfilling the additional protection

requirements of the pharmaceutical industrywith traditional holography - a common andwell known tool for product authentication -is difficult because of technological limitationsrelated to security and the inclusion ofindividualised tracing data. Being produced ina batch embossing process, images arereproduced from a master and are identical ineach batch; in other words, they lackindividualised holographic features(see Figure 1). Furthermore, productiontechnologies for embossed holograms arewidely available today and therefore accessibleto counterfeiters.

Mass serialisation holography however, amore effective anti-counterfeiting tool,provides the option to secure individualisedproduct tracing data within one system.

Holospots An example of

mass serialisationholography istesa scribos’s‘Holospot’lithography.Holospotlithographyproducesindividualised,computer-generatedholograms,which areinscribed into apolymeric, self-adhesive security

label by a high-resolution lithographic laser.Asthe holographic information is stored insidethe material - and not on its surface - it isespecially protected against counterfeiting ormanipulation.

The smallest Holospots are just 1mm2 insize, thus being well suited for small-sizedpharmaceutical products with limited space forsecurity features, such as vials or ampoules.Data storage capacity is sufficient to store serialnumbers, brand names, and company logos.Variable data can be included in every singlesecurity feature, giving each pharmaceuticalproduct its own secured identity.

With Holospot lithography, security data isstored in up to four different levels ofinformation in order to address individualprotection needs (see Figure 2). Overtholographic information visible to the nakedeye can be combined with high-resolutionmicro text as well as hidden information,which is stored in analogue and digital form.

The visible holographic structures, such as aserial code, have a diffractive, shimmeringappearance and are suitable for authenticationby pharmacists, customs officials or patients.Asimple magnifier gives access to the micro text,which serves as a second step ofauthentication, for example for wholesalers orother distribution partners. Special readingdevices are required to gain access to thehidden analogue and digital information,which is stored in a projection hologram andactivated by laser light.These devices should berestricted to internal specialists or investigators,so that access to covert data is always under thecontrol of the brand owner. Hidden analogue

Mass serialisationholography forproduct protectionMass serialisation holography provides secure item-specific coding. This is an effective tool

for securing product tracing data applied to pharmaceutical packages that are susceptible

to counterfeiting or misuse, explain Joachim Suesse and Claus Grobe

Figure 1: Production processes: serialised holography and standardholograms

tesa Holospot®

Standardhologram


Tracing and authentication

information serves as a third security layer forauthentication, while the inclusion ofmachine-readable digital data in the projectionhologram, such as data matrix codes, allowsproduct tracing information to be secured.

All information levels can be logicallylinked to each other, for instance by usingalphanumeric coding, or they canindependently carry information that isunique to the item being labelled.

High-risk scenariosMass serialisation - identifying each single

product package with a unique code - is beingimplemented throughout the pharmaceuticalindustry today.

Some identification systems depend onprinted barcodes or data matrix codes and, insome test projects, radio frequencyidentification (RFID) technology.In each case, a connection to a databank isrequired for product identification,verification, and product matching with thestored code.

In some countries or regions, however, the

technicalinfrastructure toauthenticateproducts via adatabase may belimited.Additionalsecuring of printedtracing data may alsobe necessary forthosepharmaceuticals, forwhich counterfeitingof the barcode ordata matrix codeitself has beenobserved orsuspected. Bothscenarios requireadditional protectionmeasures to allowreliable productauthenticationwithout the need -and the risk - ofdatabank-basedverification systems.

Mass serialisationholography makespossible the productprotection requiredin these high-riskscenarios. Individualproduct codescontained in a

barcode are linked with the holographicinformation contained in a Holospot, which isapplied next to the barcode tracinginformation (see Figure 3).The barcode

Figure 3: Linking Holospots and barcodes

data is effectively secured againstcounterfeiting and, at the same time provideson-the-spot, easy authentication of theholographic security features, without theneed for databank access.

Proven efficacy Holospot lithography is in use in a variety of

industries and countries. One of the bestdocumented cases of the Holospot systeminvolved counterfeiting of a personal carebrand - Nivea - in Russia, a country where

counterfeiting activity has grown enormouslywithin recent years. Counterfeit Niveaproducts were first discovered in 2003,exhibiting a packaging appearance virtuallyidentical to genuine products; however, thecounterfeit product contents were of lowquality, jeopardising the overall brand’sreputation. In 2004, the counterfeit rate of theaffected product group reached 30% and adecision was made to introduce the Holospottechnology for product protection.

Products were secured with Holospot labels(see Figure 4), containing the brand name andan individual serial number in the micro text,while additional coded information was storedin the projection hologram.The supply chainwas informed about the security measure andthe visible features for authentication. Fieldinvestigation was activated for store checks andmarket analysis. In 2005, turnover shot up by40%, and no counterfeits of the securedproduct have been found in the market todate. Payback period with respect totechnology cost was less than seven months.

Figure 4: Holospot applied on Nivea Hair Careproducts in Russia

Joachim Suesse has been managing director of

Germany-based tesa scribos since its foundation in

2001. Before joining tesa in 1992, he worked in the

pharmaceutical industry for more than 10 years,

holding various marketing and sales positions with

Eli Lilly and Baxter Healthcare. Claus Grobe has

been head of marketing at tesa scribos since 2005,

focusing on security and identification solutions in

the fields of counterfeit protection, protection

against product diversion, and theft protection. He

worked in the chemical industry for more than eight

years, holding various marketing and R&D positions

with tesa AG.

Figure 2: Serialised holography offers up four different levels ofauthentication

A UniQ way tocombat counterfeiting

UniQ brand enhancement extends brandidentity, helping to build customer loyaltyand improve patient compliance

UniQ distinctive on-product brandingtakes counterfeit protection to thedose form

You’ve spent $500m getting your tablet to market

It's time to protect it – and your patients

Phoqus Pharmaceuticals LimitedUK Telephone: +44 (0)1732 870227 Fax: +44 (0)1732 870228

E-mail: [email protected] www.phoqus/com/anticounterfeit


Company profile

Proprietary tablet coating that stands out from the crowd

Phoqus Pharmaceuticals

COMPANY DESCRIPTIONPhoqus is a drug delivery and tablet coating company based in the UK. Phoqus has developed aproprietary solution for anticounterfeit and product branding — UniQTM — based upon itsplatform technology of electrostatic dry powder deposition. Tablets coated using UniQTM arenovel in appearance and can be used to create or enforce a specific product or corporate brand.These tablets cannot be copied by existing tablet coating systems. UniQTM therefore provides an effective on-product, overt counterfeit deterrent that delivers protection to every singletablet. Phoqus controls the supply of materials and equipment to the pharmaceutical industrywhich provides further protection from would-be counterfeiters. The UniQTM system can becombined with other anticounterfeit measures such as secure packaging, tablet printing, orcovert markers

Phoqus is collaborating with Cardinal Health, a global provider of services to thepharmaceutical industry, to offer contract manufacturing services for products developed usingthe Phoqus technology.

PHOQUS’ SERVICES:• Formulation development

• Tablet manufacture

• Tablet coating

• Contract manufacture

CONTACT INFORMATIONContactDominic Griffiths – director business development

Telephone+44 1732 870 227

[email protected]

Website addresswww.phoqus.com/anticounterfeit

Drug Delivery22

Protecting your brands and interests

tesa scribos

COMPANY DESCRIPTIONtesa scribos is an affiliate of tesa AG, one of the world's leading providers of adhesive tapes andlabels. Its products offer effective anti-counterfeiting and product tracing capability, as well asmanipulation protection and document security.

tesa scribos offers expert advice, practical security measures and a wide range of modernsecurity technologies. As part of the global tesa network, tesa scribos is able to provideinnovative security support on a worldwide basis.

TESA SCRIBOS’ EFFECTIVE TECHNOLOGIES ARE:• tesa Holospot®, a discreet, forgery-proof information carrier label that can be attached easily

to any product. It features human and machine readable data that is individualised on itemlevel in conjunction with a distinctive optically variable appearance. Brand owners benefitfrom multiple overt and covert security levels for maximum counterfeit protection with thepossibility of identifying every single product individually. Authentication is possible with orwithout special devices and can be adapted to the brand owner’s needs.

• tesa IdentSeal®, a security label material for standard industrial laser markers. It offersexcellent contrast for clearly visible text or high density bar codes. Easy to use overt productprotection and identification is combined with effective tamper-evidence. Brand owners canchoose between specific surface structures, non-removable imprints or fluorescent UVfeatures to further enhance security.

• tesa® SecuritySeal adhesive tapes and labels for protection against manipulation and theft bymeans of an irreversible optical proof of first opening.

• tesa® SecurityPrint labels with security print, such as guilloches, luminescent inks,thermoreactive and color-shifting inks, and anti-copy protection.

• Customer-specific security labels that incorporate a number of security features.

CONTACT INFORMATIONContactClaus Grobe – marketing manager

Telephone+49 40 4909 6330

[email protected]

Website addresswww.tesa-scribos.com

Company profile

Today’s Seal with Tomorrow’s Technology

3749

westpharma.com

West Spectra ID is the only seal that provides multiple layers of protection for your packaged drug product. West Spectra ID enhances patient safety with point-of-use instructions, combats drug counterfeiting and helps keep your supply chain secure.

• West Spectra ID seals with spectroscopic inks pro-vide covert protection and rapid authentication.

• West Spectra ID seals with full-color graphics and text provide item-level information such as a vial’s contents, product or brand name, dosage or strength of the drug, cautionary statements and storage instructions.

• The unique characteristics of Spectra ID seals help deter drug counterfeiting.

• West Spectra with an embedded RFID tag provides electronic item-level track-and-trace identifi-cation and read/write capabilities for product authentication.

• West Spectra technologies are integrated into West’s existing tamper-evident Flip-Off® seals.

To find out how West Spectra ID can provide security for your drug product, call your West account manager.

West Spectra™ is a trademark of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.Flip-Off® is a registered trademark of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

Copyright © 2006 West Pharmaceutical Services, Inc.

Denmark France Germany Italy +45 (7561) 6000 +33 (1) 39 21 54 00 +49 (24 03) 7960 +39 02 6703079

Singapore Spain U.K. U.S.A. +65 6 862-3400 +34 (91) 656-1415 +44 (1726) 6 35 63 +1 610-594-2900

PHARMACEUTICAL ANTICOUNTERFEITINGold.iss.it/binary/farm/cont/Pharmaceutical AntiCounterfeiting...

Documents

Transcript of PHARMACEUTICAL ANTICOUNTERFEITINGold.iss.it/binary/farm/cont/Pharmaceutical AntiCounterfeiting...