WHITE PAPER

ON

THE ANTI-COUNTERFEITING OF MEDICINES

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A. Introduction The EFPIA White Paper is intended to express the views of the European drug manufacturers, associated within the EFPIA to combat counterfeiting effectively as it is described in the EFPIA Position Paper of June 2005 in order to

• address the needs to further develop the European legislation • focus on key European stakeholders in the international collaboration • define the role of suppliers, drug manufacturers, wholesalers, distributors and pharmacies

in the combat against counterfeit medicines • focus on effective and affordable solutions of supply chain control to achieve

transparency • recommend rules and messages for communication to the various stakeholders

B. Executive Summary

1. European legislation The legal system must facilitate close cooperation both nationally and transnationally between the different authorities dealing with anti-counterfeiting. The roles and responsibilities of the latter must therefore be clearly understood and sufficient resources should be made available. Intellectual property right owners, who represent a fundamental element of the European economy, will continue to act responsibly in the fight against counterfeit medicines and they welcome the legislative initiatives aimed at increasing IP rights protection. The medical authorities, which traditionally regulate and control the legitimate activities relating to medicines, will have a major role to play in the joint efforts to combat counterfeit pharmaceuticals. Customs and right holders need to work closely together through training, alerts systems, etc. The assistance of the police is also vital.

2. International collaboration

EFPIA should be the focal point at European level for engagement of key stakeholders from national level. The four main categories of stakeholders are: Government, Industry, Users and Payers (the main ones are listed in this paper). Industry recommends a number of preventative measures as essential to an anti-counterfeiting programme: adaptation of structures, cooperation, awareness and political will.

3. Role of the manufacturers, repackagers, wholesalers, distributors and pharmacies

As the originator of the product, the manufacturer has an obvious role to play in product authentication and supply chain control efforts (new technologies, track & trace initiatives, procedures for counterfeit prevention). Repackagers must also contribute actively to the safety of the supply chain, and so must wholesalers and distributors, through auditing and alert systems. Pharmacies must be a part of the scheme to protect customer health and safety.

4. Supply chain control

All stakeholders in the supply chain should consider participating in a track & trace system in order to ensure transparency of the supply chain. Regulatory tasks should include auditing of the supply chain, a licence system for the sale of medicines over the

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internet, a certificate system for wholesalers and safeguards for the supply of packaging material.

5. Communication

Communication regarding awareness raising on counterfeits towards the broad public should mainly be done by the public authorities. Balanced reporting will include communication to the specialised media and healthcare professionals. Industry may organise alliances and partnerships with healthcare associations / experts as well as with patient organisations. The importance of purchasing medicines through certified distribution channels is already a key message. Member States should be encouraged to adopt stronger criminal measures to combat IP rights offences such as counterfeiting which threatens public health and safety.

1. European legislation 1.1. Legal System The legal system must facilitate close cooperation both nationally and trans-nationally between the different authorities dealing with anti-counterfeiting for example by providing obligatory exchange of information between, customs, public health authorities, police and right holders. Legislation must be reviewed and amended to accommodate this cooperation. Within the Legal Systems in Europe, judges, law enforcement and health specialists should be trained specifically to deal with counterfeiting and in particular pharmaceutical counterfeiting. This will ensure that the seriousness of these offences is clearly understood and they are dealt with appropriately. There must be a clear understanding of the roles and responsibilities of all the authorities dealing with anti-counterfeiting both nationally and at a European level. The legislation dealing with counterfeiting must be enforced consistently. This will also require the backing of national governments and the European Parliament to ensure sufficient resources are available to do so. We endorse the recommendation of the Council of Europe to nationally develop units for investigation and for enforcement comprising for example health specialists, judges, prosecutors, law enforcement, Customs & Excise. These should also be the focus point for international co-operation. 1.2. Intellectual Property Rights Holders The owners of intellectual property rights will continue to act responsibly in contributing to the fight against counterfeit medicines. On the one hand, counterfeiting medicines is a lucrative business and appears to be affecting both developing and developed countries. On the other hand, intellectual property rights represent a central support for innovation and are a fundamental element of the European economy. At the moment there are not adequate legal provisions relating to counterfeit medicines in every European country. Intellectual Property right owners need a legal environment which is unambiguous and clearly targets counterfeiters and deters counterfeiting. The industry therefore welcomes the recent legislative steps adopted at European level to increase the protection of intellectual property rights. In particular the regulation (EC) n° 1383/2003 on customs action, EC directive n°2004/48/EC on enforcement of IP rights and the proposal for a Directive and for a Framework Decision on criminal

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measures (July 2005) aimed to make the rules more accessible for right holders and provide a more effective legal instrument against fraud. In particular we support the following:

• clear definitions of “counterfeit medicine” and “pharmaceutical crime” • harmonised sanctions commensurate with the level of the crime • complete codification of existing Member State legislation which has been recommended

by the Council of Europe • strengthening and harmonising the criminal law dealing with counterfeiting

1.3. Medical Authorities Pharmaceutical counterfeits represent a major risk to consumer’s safety and health. For this reason, the Medical Authorities, who are entrusted by governments with the task of monitoring and securing the safety of pharmaceutical preparations, have a major role to play in the joint efforts to combat pharmaceutical counterfeits. At the moment the role of the Medical Authorities, as defined by national and Community legislation, is on the whole too narrowly defined. It often does not allow them to actively and effectively take action against these illegal activities that represent a major threat to patients’ safety and public health. For historical reasons, the role of Medical Authorities focused on regulation and control of the pharmaceutical industry, i. e., the “legal” activities relating to the manufacturing and trade of pharmaceutical goods, not the illegal trade. The present serious situation is not taken into consideration in the regulations governing the authorities. To change this situation three priorities have to be tackled:

• Redefine the role of the Medical Authorities. In particular, their investigative and prosecution capacity in relation to counterfeits must be reviewed and clearly and consistently put in place;

• Manufacturing and dealing with counterfeit pharmaceuticals must be criminalised under the medical legislation, so counterfeiters can be held fully accountable for damaging or threatening public health.

• Voluntary alert systems to the national medical authorities. 1.4. Customs & Excise We need to pursue our cooperation with the Customs authorities to combat the international phenomenon of counterfeit medicines. In order to facilitate speedy action by Customs it would help to remove the current obstacles preventing the transfer of information between Customs and the rights holders. This would enable a fast response from the right holders which would in turn stimulate Customs to act quickly. We need to encourage the industry to make use of the EU Customs Watch notices and customs to halt suspicious shipments and to early inform right holders about potential infringements. In particular we would suggest the following:

• Company specific drug lists to Customs • Company hotlines for Customs

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• “Sector-specific training” (eg. Offered by PSI) • More general information about exporters, importers, normal routes of supply chain • Information based “case oriented” • Voluntary alert system

1.5. Police The Police are integral in the investigation and collection of evidence to ensure that the counterfeiters are duly prosecuted. Counterfeiting is a serious crime, which must be fought by all means available. The assistance of the police is vital in order to efficiently fight against counterfeiting. A harmonised set of rules must be established for the police to operate efficiently at a consistent level across Europe. This should include:

• Extension and strengthening of competence and knowledge e.g. by establishment of

special national/EU counterfeit police units. • Clarifying responsibility for investigations and giving the police the appropriate authority. • Increased availability of seizure orders and prosecution. • Trans-national cooperation. • Cooperation between the police and other authorities and private intellectual property

right owners. 2. International collaboration 2.1. Key Stakeholders There are many key stakeholders at local, national and international level that are essential to effective international collaboration. EFPIA is positioned as a focal point at European level and so, therefore, for engagement of key stakeholders at local level the feed should be through EFPIA to the appropriate body/association. For engagement of key stakeholders at an international level the feed should be through EFPIA to the International Federation of Pharmaceutical Manufacturers Associations, (IFPMA). Key Stakeholders at European Level There are four main categories of key stakeholders, which are Government, Industry, Users & Payers. A variety of stakeholders exist within each category, too many to list in this paper. The main ones are:

• Government EU Institutions •EU Commission and EU Parliament

•DGs for Health & Consumer Protection, Enterprise, Justice Freedom & Security (former JHA), Research, Trade, Taxation & Customs Union (“Taxud”) •OLAF (European Anti-Fraud Office)

•EMEA (European Medicines Evaluation Agency) •EPO (European Patent Office)

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Council of Europe •Parliamentary Assembly •Public Health Committee •Ad hoc Pharmaceutical Questions group •Ad hoc Anti-Counterfeiting Group •EDQM (European Directorate for Quality Medicines) network •OMCL (Official Medicines Control Laboratory) network

Law Enforcement Agencies •EU Customs – DG Taxud & Task Force Experts •Interpol - Europe •Europol •EMEO (European Medicines Enforcement Officers) •National enforcement agencies

Other •WHO - Regional Office Europe • OECD (Paris) •UNECE (United Nations Economic Commission Europe) • ICC (Paris)

• Industry

•EFPIA •Wholesalers/Distributors/Retailers/Suppliers/Forwarders •PSI – Europe (Pharmaceutical Security Institute) •IPEC – Europe (International Pharmaceutical Excipients Council •APIC (Active Pharmaceutical Ingredients Committee) •CEFIC (European Chemical Industry Council) •EGA (European Generics Association) •AESGP (Association of the European Self-Medication Industry) •GIRP (European Association of Pharmaceutical Wholesalers) •FECC (European Association of Chemical Distributors)

• Right Holders AIPPI – Association Internationale pour la Protection de la Propriété Intellectuelle ECTA – European Community Trademark Association PTMG – Pharmaceutical Trade Marks Group GRUR – Deutsche Vereinigung Gewerblicher Rechtsschutz und Urheberrecht Marques REACT

Users Users are identified as an important collaborative partner in any anti-counterfeiting programme. Users include patient organisations and institutions, healthcare professionals such as doctors’ organisations and medical councils, pharmacists’ organisations and nurses’ organisations. At European level they vary in size and focus and are too numerous to list here.

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Payers Payers are recognised as an important stakeholder and include organisations such as health and care insurers, medical industry insurers & re-insurers and the providers of subsidised medicines programmes. 2.2. Effective Anti-Counterfeiting Programmes The EFPIA Anti-Counterfeiting Ad hoc Group acknowledges the work carried out by the Council of Europe Committee of Experts on pharmaceutical questions and its multisectoral Ad Hoc Committee on counterfeit medicines. The same applies to the very comprehensive work produced by Dr Jonathan Harper. We agree with all of the recommendations & binding instruments in the Harper Report. We have recommended the following preventative elements as essential to an anti-counterfeiting programme:

Adaptation of structures and systems to detect counterfeits at international and multisector level

Identification of liaisons for an information network Cooperation between laboratories (see below) Raise awareness of stakeholders Create political will to support concerned agencies and centres Encourage national, regional and international cooperation Foster cooperation between/within concerned groups Accessible and valid information

define requirements for reporting define confidentiality parameters guarantee data reliability determine means of transmission

Cooperation between laboratories requires :

Mutual support Supply test methods Provide analytical techniques Provide test samples where equipment & finance are available Provide reference materials

Exchange of expertise

Database on counterfeits (rapid alert data base) Who has examined What ? Information on usefulness of analytical techniques Information on impurity profiles

Identify & use centres of expertise

Identify official laboratories (OMCLs) that have specific experience Provide information about special competences at OMCLs Create network of centres of expertise

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3. Role of Manufacturers, Repackagers, Wholesalers, Distributors and Pharmacies 3.1. Manufacturers As the originator of the product, the manufacturer is the logical starting point for product authentication and supply chain control efforts. Additionally, the manufacturer is already GMP certified, is regularly GMP audited and routinely performs incoming material control procedures. Additionally, manufacturers are encouraged to:

• Intensify efforts to accurately define the extent of the counterfeiting problem by improving internal reporting to include the submission of reports concerning counterfeiting incidents and the collation of these reports in a central location.

• Seek to protect the supply chain through careful analysis of new technologies and the scalable deployment of these technologies consistent with the known level of risk associated with not only the pharmaceutical product but also the geographic area.

• Products or regions with the highest counterfeit risk should be addressed first. o If considered at risk, individual packages should be marked with overt and covert

technologies for authentication o Ideally, both exterior (cartons) and interior (blisters) packaging should be marked. o A technology evolution plan should be developed in case the chosen technology

is defeated. o Tamper evident features should also be included.

• Manufacturers should be prepared to play a role in determining the cost/benefit performance of track and trace initiatives and to participate in officially sanctioned track and trace initiatives.

• Manufacturers should have effective procedures in place that prevent counterfeiters to work with non-used material from e.g. trial batches and to work with no longer used machines and tools

3.2. Repackagers Repackagers have also to contribute actively to the safety of the legal supply chain. If they receive a tamper proof packaging for repackaging operation, they have to apply the same safety standard as the package had before repackaging. This might include:

• Re-boxing shall be discouraged. • If only the exterior packaging is marked, the authorized repackager shall continue to use

the original security feature or code • If the pharmaceutical packaging is tamper proof the authorized repackager shall repack

again in a tamper proof packaging

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3.3 Wholesalers and Distributors Wholesalers and Distributors have also to contribute actively to the safety of the legal supply chain. Together with the manufacturers and the pharmacies wholesalers and distributors are also stakeholders in the pharmaceutical supply chain. This might include:

• Participation at a pan European supply chain track & trace system • Actively or passively participate in a supply chain auditing and alert system

3.4 Pharmacies Pharmacies normally are the point of dispensing and therefore they have a special role to play in supporting customers health and safety. As most close to the customer, pharmacies as well as other points of dispensing are ideal locations for product authentication. This might include:

• Participation at a pan European supply chain track & trace system • Actively participate in the drug authentication system

4. Supply Chain Control The suitable starting point of any supply chain control should be at the drug product manufacturer’s level as there are GMP certificates available, quality systems in place, as well as established control of all incoming starting materials such as actives, excipients, packaging materials and security features. The drug product manufacturer therefore will be a major partner in any system of track & trace based supply chain control and authentication of drug products in the market. The supply chain control is most effective if the system is at least designed supra-nationally, an international focus is the most effective. All stakeholders in the supply chain, drug manufacturers, wholesalers, distributors and pharmacies have to be legally obliged to participate in a track and trace based supply control system.

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24

Supply Chain Control : Desired stateSupply Chain Control : Desired state

Manufacturertoday

Certified&Audited

Repackager

Point ofdispensingDistribution

20 –50 stepsIncl. customs

API

Excipients

PackagingMaterial

Securityfeatures

Regular Supply Chain

Internet

forTransparency&

Prosecution Mainauthentication

Counterfeitresistant

technology

QC

Referenceto original

code!

forInternetSupply

Customer

AuditedSupplyChain Control

Counterfeit penetrationbyirregular & uncontrolledSupplyChain

Tab 1. The desired state of the legal supply chain: a “closed shop” 4.1. Regulatory tasks 4.1.1. Auditing Any supply chain control has to be audited to ensure that the implemented measures are working in the desired way. Governments or authorities should be responsible to set the legal framework for extending the existing GMP auditing system by including auditing of the supply chain. The existing Good Manufacturing Practices (GMP) and the Good Distribution Practices (GDP) could work as an adequate basis for this. 4.1.2 Internet The most critical supply chain is the internet supply of drugs as there is no qualified personnel who can act to ensure patients health and safety. Therefore there shall be equivalent systems in place in order to ensure that the drugs offered via the internet do not represent a risk to the patient. A pan European license system with authorized internet pages for internet pharmacies shall be established. 4.1.3. Wholesalers A license or certificate system for wholesalers can also contribute to raise the hurdle for counterfeiters. If pedigrees are required, it should be considered that paper based pedigrees can be penetrated by counterfeiters, therefore electronic systems are preferable.

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4.1.4 Suppliers Suppliers can also contribute to raise the hurdle for counterfeiters. They should be fully integrated into the existing system of GMP auditing and ISO certification. Suppliers of packaging material should ensure the identity and credibility of their customers. The access to printed packaging material and to security features shall be controlled by suitable measures e.g. documentation of customers or the check of the credibility of the customers. 4.2. Industry’s tasks 4.2.1 Track & Trace System All stakeholders in the supply chain shall consider establishing a track & trace system in order to ensure the transparency of the supply chain enabling the identification of the point of penetration of counterfeits into the legal supply chain. Prosecution of offenders to the Anti counterfeiting rules will be facilitated by those systems. The business processes, the database and the ownership for business processes, database and contents as well as the funding still have to be defined between all stakeholders of the supply chain. The cost per packaging line at manufacturers level, for the pan European database as well as for the authentication point (bar code readers) have to be calculated. The total impact on the Cost of Goods sold shall not be higher than 1 Eurocent per individual pack. Industry can support authorities by also doing audits of supply chain control, e.g. by doing inspections at the respective suppliers level before and after the factory. 4.2.2 Technology and Process The track and trace system shall be based on a pan European Barcode standard. This standard should be able to work on the basis of the EPC (= Electronic Product Code), as this is the only available global product standard description, which is also compatible with different bar coding standards and with RFID (=Radio Frequency IDentification). Due to its current development status RFID is considered as a mid term to long term solution only. The content of the barcode information shall comprise at least manufacturers name, product name, batch number and expiry date. The bar code number shall be randomized in order to make copying of sequential numbers for counterfeiters impossible. 5. Communication Industry generally supports initiatives to provide consumers with information about counterfeit medicines but is conscious of the fact that respective communication activities towards the public should not create anxiousness or fears from consumers and patients. Therefore EFPIA is advocating a pragmatic approach: Communication regarding awareness raising on counterfeiting towards the broad public should mainly be done by public authorities.

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Pharmaceuticalindustry

Health Experts:•Raise awareness of existing counterfeited products and

HCP’s possibilities to support anti-counterfeiting actions

(Alliance,

partnerships)

Broad Public (Patients,

consumers, end users, press)

•Communication and awareness raising should be done by

authorities

•Stress importance of certified drug

distribution channels

•Raise awareness at patient level on the dangers of internet

sales

Authorities/European and National Politics:

(involving healthcare sector and other sectors)•Support investigative activities

•Increase penalties for counterfeiters

Supply Chain:•Develop uniform effective

and affordable track & trace system for Europe to prevent

counterfeiting•Do not enforce any system if above criteria can not be met!

Communication of pharmaceutical industry to key stakeholders with key messages

Tab 2. The desired state of communication: authorities should be first contact to public Industry recommends communication on counterfeit medicines be targeted mainly vis-à-vis specialised media and healthcare experts in order to contribute towards balanced reporting. Existing industry activities concerning political involvement and development of technical solutions should be communicated proactively. 5.1. Alliances and Partnerships Industry can organize alliances and partnerships with healthcare associations / experts as well as patient organizations. Common approaches have to be identified with the various key stakeholders. Messages to be communicated will depend on the respective alliance, while emphasising the importance of public health and safety. What seems to be useful is the development of guidelines in the form of templates or tool kits which develop awareness, increased vigilance and as a consequence can set up a reporting system on suspected counterfeit medicines. On their websites, patient organizations can alert consumers to counterfeit drugs. The main message will be to stress the importance of purchasing medicines through certified distribution channels. Due to practical reasons, authentication of products should be done by wholesalers and pharmacies. Patients and consumers can only play a limited role in this context. What seems to be realistic is a telephone “hotline” access to report anomalies detected concerning a product, dosage form, patient leaflet or package. Local authorities responsible for authorization and regulation of medicines have to be involved in these common efforts.

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5.2. Messages to public authorities / European and national Authorities Main industry message towards European and national authorities should be, that increased penalties will help to deter counterfeiting and more adequately punish those convicted. Member States are to be encouraged to adopt legislative measures on stronger criminal measures as foreseen in the EU proposals for a Directive and a Framework Decision (July 2005). Industry also asks public authorities to increase investigative activities, especially at customs level (see messages to stakeholders above). 5.3. Communication within the Supply Chain Industry has to advocate the proposals for technical solutions with the other members of the supply chain as indicated in the sections above and to be developed in a business case.

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