Presentation on theme: "International Initiatives on Drug Safety"— Presentation transcript:
1International Initiatives on Drug Safety Linda R. HortonPartnerHogan & Hartson LLPBrussels & Washington, DCAugust 23, 20073rd Annual FDA Regulatory and Compliance SymposiumHarvard University Campus, Cambridge, MA
2What we will discuss today EU UpdateTightening Up: “First Time in Humans” Clinical TrialsLightening Up: BiosimilarsMeds Made of Us: Advanced Therapies/Tissue-EngineeringMeds for Kids: EU Pediatrics RegulationTruth or Consequences: EU Penalties RegulationClinical Trials in Developing CountriesCounterfeits and Sub-Standard DrugsThe ProblemIMPACT: WHO InitiativeEU and Council of Europe InitiativesAPEC InitiativesChina Initiatives
3EU Update Tightening Up: “First Time in Humans” Clinical Trials Lightening Up: BiosimilarsMeds Made of Us: Advanced Therapies/Tissue-EngineeringMeds for Kids: EU Pediatrics RegulationTruth or Consequences: EU Penalties Regulation
4To recap from 2005 and 2006:Looking over the Atlantic ≠ looking in a mirror.There is no United States of Europe.There is no EU FDA although, since 1995, there has been a European Medicines Agency (EMEA).Each of the 27 Member States has 1 or more agencies.Although today 70% of new products enter via EMEA route, most products on the EU market were approved by Member State agencies.
5Isn’t the EMEA like the FDA? Not quite. The EMEA is a secretariat for a network of experts.There are (largely) uniform rules on testing, clinical trials, applications, pharmacovigilance, and GMPs.But clinical trial regulation is entirely by Member States.Enforcement is by Member States.Review of EMEA/centrally authorized product occurs chiefly in the national regulatory agency where rapporteur works.European Commission is the one who grants authorization.
6Tightening Up: “First Time in Humans” Clinical Trials - Issues How should the transition from preclinical to first-in-man testing be regulated for novel therapeutic modalities?How to make the transition from preclinical to human studies without creating unnecessary obstacles?How to deal with the question of liability and insurance?Do the national regulatory authorities and the ethics committees carry any responsibility in case of a problem?
7The TeGenero phase 1 trial A sponsor, Tegenero AG, wanted to conduct a human study of a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cellsThe conventional battery of preclinical toxicity tests completed by TeGenero appeared to the UK and German regulators to justify approval of clinical trialEight healthy male volunteers were recruited and dosed by Parexel Clinical pharmacology research Unit (CPRU) on March 13, Two subjects received a placebo. Serious Adverse Events (SAEs) were reported in 6 of the 8 subjects:Within 90 minutes: systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotensionWithin 12 to 16 hours: they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulationWithin 24 hours: severe and unexpected depletion of lymphocytes and monocytes occurredAt 8 and 16 days: intensive organ support was required due to prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patientsDespite evidence of the multiple cytokine-release syndrome, all six patients survived
8Investigations and findings Aim:was the reaction seen due to contamination of the dose, an incorrect dose being administered, or an inherent flaw in the drug?was the short timeframe within which the doses were administered a problem?UK MHRA initial investigation:no errors in the manufacture, formulation, dilution or administration of TGN1412. An unpredicted biological action of the drug in humans was the most likely cause of the adverse reactions in the trial participantsUK MHRA then commissioned an investigation by an expert scientific group committee:the preclinical development studies that were performed did not predict a safe dose in humans, even though current formal regulatory requirements were metGerman regulatory authorities:no deficiencies in the manufacture, testing, storage and distribution of the TGN 1412 could have contributed to the serious adverse effects
9Initiatives - EUCommittee for Medicinal Products for Human use (CHMP): Guidelines on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products dated July 19, 2007 and coming into effect on September 1, 2007Identifies factors influencing risk for new investigational medicinal productsPredicting the potential severe adverse reactions for the first-in-man use of an investigational medicinal product involves identifying the factors of risk. These concerns may be derived from particular knowledge or lack thereof on:the mode of action; and/orthe nature of the target; and/orthe relevance of animal modelsConsiders quality aspects and in particular:The determination of strength and potency, comparability with the material used, and reliability of very small dosesConsiders non-clinical testing strategies and design for first-in-man clinical trialsGives strategies for mitigating and managing risk, including the calculation of the initial dose to be used in humans, the subsequent dose escalation and the conduct of the clinical trial
10Initiatives - UKUK expert scientific group committee on phase one clinical trial recommendations:Pre-clinical Development:The strategy should be to have science-based decisions made and justified on a case-by-case basis by investigators with appropriate trainingSharing and strengthening the collection of informationTransition From Preclinical to Clinical developmentBroader approach to dose calculationMaximum reduction of riskStarting dose and dose escalation should be made on a case-by-case basis and should be scientifically justifiableClinical DevelopmentDecision on whether to conduct a first-in-man trial should be carefully considered and fully justifiedPrincipal Investigators and staff should have appropriate levels of training, expertise, and qualificationWhere there is a predictable risk of certain types of severe adverse reaction, a treatment strategy should be considered beforehand
11Initiatives - UKUK expert scientific group committee on phase one clinical trial recommendations:New agents should be administered sequentially to subjects with an appropriate period of observation between dosingA similar period of monitoring between sequential dosing of subjects during dose escalationRegulatoryMore communication should be encouraged between developers and the regulator at an earlier stage before an application is filedThe regulator should have access to additional opinion from independent, specialist experts with research knowledge in their fields. An Expert Advisory Group (EAG) of the Commission on Human Medicines, or a similar body, might undertake this roleFutureAvailability of ‘hands-on’ experience in the planning and conduct of clinical trials should be widenedFeasibility of developing specialist centers for phase one clinical trials of higher risk and for advanced medicinal products should be exploredRegulatory process for first-in-man trials of higher risk agents and advanced medicinal products should be subject to frequent review
12Lightening Up: Biosimilars – EU Regulatory Pathway Article 10(4) of the Community Code on Medicinal Products (Directive 2001/83/EC):“Where a biological medicinal product which is similar to a reference biological product does not meet the conditions in the definition of generic medicinal products, owing to, in particular, differences relating to raw materials or differences in manufacturing processes of the biological medicinal product and the reference biological medicinal product, the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The type and quantity of supplementary data to be provided must comply with the relevant criteria stated in the Annex and the related detailed guidelines. The results of other tests and trials from the reference medicinal product's dossier shall not be provided.”
13General GuidelinesOverarching Guideline on Similar Biological Medicinal ProductSimilar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality IssuesSimilar Biological Medicinal Products containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical IssuesOther guidance documents such as the recently adopted EMEA document: “Questions and Answers on biosimilar medicines”
14Specific Product Guidelines Recombinant Human ErythropoietinRecombinant Human Growth HormoneRecombinant Human InsulinRecombinant Human Granulocyte-Colony-Stimulating-Factor
15Status of biosimilars Authorized biosimilars: Omnitrope® (somatropin) (Sandoz): Recombinant human growth hormone - Reference product Pfizer’s Genotropin®.Valtropin® (somatropin) (BioPartners): Recombinant human growth hormone - Reference product Lilly’s HumatropePositive opinions from Committee on Medicinal Products for Human Use (CHMP); all with reference product Jansen’s Eprex/ErypoBinocrit® (epoetin alfa) (Sandoz): ErythropoietinHexal® (epoetin alfa) (Hexal Biotech Forschungs): ErythropoietinAbseamed (epoetin alfa) (Medice Arzneimittel Pütter): ErythropoietinRejected as biosimilar (received a negative opinion from CHMP):Alpheon (BioPartners): Recombinant interferon alpha – Reference product Roche’s Roferon-A
16Naming and interchangeability INN International Nonproprietary Name (for marketing in EU and Japan)USAN United States Adopted Name (for marketing in the U.S.)Role: Identifies the compound within a family of compounds based on chemistryImpact on:prescription,substitution of drugs, andadverse event reporting process
17Naming and interchangeability Similar and not identical g entails problems that are not prevalent as to small-molecule generic medicinesFor pharmacovigilance, it is important for records to be kept to distinguish between events associated with innovator products and biosimilarsShould there be special restricted substitution rules for biosimilars?Does the EMEA possess the authority to recommend such rules? Can the Commission impose such rules?New system of nomenclature?
18Naming and interchangeability: use of INN The EMEA guideline on Similar Biological Medicinal Products recommends that the specific medicinal product which is prescribed to the patient needs to be “clearly identified”The EMEA guideline does not specifically address the suitability of using the same INN for both a biological product and any related biosimilar. It does, however, acknowledge that concerns exist as regards the differences that may materialise between biological products and related biosimilarsThe 44th Consultation on International Nonproprietary Names (INNs) for Pharmaceutical Substances was held at WHO Headquarters in Geneva on May The INN Expert Group noted the nomenclature systems in this field are generally working well. There appears to be no consensus for change
19Meds Made of Us: Advanced Therapies/Tissue-Engineering: Issues Lack of an EU-wide regulatory framework for tissue engineered products led to divergent national approaches, creating obstacles to the internal marketThe EU Regulation on Advanced Therapy Medicinal Products aims to address this regulatory gapIntroduces specific rules for the authorization and supervision of advanced therapy products for human use in the EUGoverns three types of advanced therapies: gene therapy, somatic cell therapy and tissue engineeringGene and somatic cell therapy products had previously been defined and classified as medicinal products in the EUTissue engineered products had not
20What are advanced therapies? Defines advanced therapy products for human use including tissue engineered products as medicinal productsThis means that their authorisation for marketing in the EU will be governed by the Community Code on Medicinal ProductsDetermines that cells or tissues are "engineered" if they have been subject to substantial manipulation, so that biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement are achieved, or if they are not intended to be used for the same essential function or functions in the recipient as in the donorWhere a medical device contains a tissue engineered product, irrespective of the role of the medical device, the pharmacological, immunological or metabolic action of these cells or tissues should be considered to be the principal mode of action of a combination productSuch combination products should always be regulated under the RegulationNevertheless, the medical device element should also meet the essential requirements of the Medical Devices Directives
21Advanced Therapies: Ethics, procedure and requirements A controversial subject of debate during the adoption procedure for the draft Regulation was the potential application of the Regulation to advanced therapy medicinal products that contain or are derived from human embryonic or foetal cells, primordial germ cells or cells derived from those cellsThe final text does not address this issueEstablishes a compulsory centralized procedure for marketing authorizations for advanced therapy productsThis includes the establishment of a new European Medicines Agency (EMEA) Committee for Advanced Therapies (CAT)Introduces stringent requirements on risk management and post-authorisation traceability requirementsClarifies the requirement that clinical trials on advanced therapy medicinal products including tissue engineered products must be conducted in accordance with the Clinical Trials Directive
22Advanced Therapies: Status Regulation approved by Council of Ministers on May 31, 2007Regulation now needs to be translated in all EU official languages and formally adopted, signed and publishedIt will apply from 1 year after entry into force
23Meds for Kids: EU Pediatrics Regulation: Issues More than 50% of medicines used to treat children in Europe have not been tested for use in children and have not been authorized for use in the care of childrenThe EU Paediatrics Regulation (Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use) aims to balance:the ethical issues raised by conducting trials on children; withconcerns arising in treating children with products which have not been tested on themIt imposes extensive system of requirements on companies and offers rewards and other incentives
24Meds for Kids: Requirements Requires applications for marketing authorizations for new medicines and line extensions to:include results of studies in the paediatric population carried out in accordance with an agreed Paediatric Investigation Plan (PIP); orproof of having obtained a waiver (e.g. because likely to be ineffective or unsafe in part or all of the paediatric population) or deferral from this obligationRequirement applies irrespective of whether or not the medicine for which authorization is sought is intended to be administered in childrenRequirement does not apply to generic products, biosimilars, hybrids, products containing substances acknowledged to have well-established medicinal use, herbal medicines and homeopathic medicinesThe PIP must be agreed with a new expert Paediatric Committee (PDCO) within the European Medicines Agency (EMEA)
25Meds for Kids: Benefits For newer medicines benefits include:six months extension of the SPC to which the product is entitledtwo years extension of market exclusivity for orphan medicinesoptional access to the centralized EU level procedure for marketing authorization applications that include one or more paediatric indications on the basis of studies conducted in accordance with the agreed PIPFor older medicines, a new type of marketing authorization, a Paediatric Use Marketing Authorisation (PUMA) will be availableThis type of authorization, for which eight years’ data protection and ten years’ market protection are provided, will apply solely to products for which the patent has expired and which are not protected by an SPCIt covers therapeutic indications developed exclusively for use in the paediatric population in accordance with an agreed PIP
26Meds for Kids: Status Entered into force on 26 January 2007 Some provisions enter into force later on:Obligation to agree a PIPFor medicines not authorised by 26 January 2007, enters into force on 26 July 2008For line extensions enters into force on 26 January 2009In the meantime, companies may approach the Paediatric Committee, which will be established by 26 July 2007, to agree a PIPThe PUMA will be available from 26 July 2007Should lead to increased assurance concerning the quality, safety and efficacy of medicinal products prescribed for paediatric useHowever, obligations are strict and it remains to be seen whether industry will consider that the benefits provide adequate compensation for the additional studies undertaken and costs involved
27Truth or Consequences: EU Penalties Regulation Commission Regulation (EC) No 658/2007 was finally adopted on 14 June 2007, and will enter into force on 5 July 2007Commission can now impose fines, for breaches of certain regulatory obligations, on companies whose medicinal products have been authorized in accordance with the central authorization procedure laid down in Regulation 726/2004
28Penalties for breach of certain obligations Penalties can be imposed for breaches of certain obligations, such as:the obligation to provide accurate and complete information in the marketing authorization application;failure to comply with the conditions or restrictions included in the marketing authorization;failure to notify the EMEA about the date of placing the product on the market; or about any prohibition or restriction imposed by the competent authorities of any country in which the medicinal product is marketed;failure to supply the EMEA with any information that may influence the evaluation of the risks and benefits of the product;breach of labelling and packaging obligations;breach of pharmacovigilance obligations, etc.
29Types of penaltiesThe Regulation provides for two types of financial penalties: fines and periodic penalty paymentsWhere the marketing authorisation holder has committed, intentionally or negligently, an infringement, the European Commission may impose a fine of up to 5% of the authorisation holder’s Community turnover in the preceding year. The Regulation provides that in determining whether to impose fines and in determining the appropriate fines the European Commission shall be guided by the principles of effectiveness, proportionality and dissuasivenessWhere the marketing authorisation holder does not terminate the infringement, the European Commission may impose periodic penalty payments per day not exceeding 2.5 % of the holder’s average daily Community turnover in the preceding business year
30Non-cooperation penalties The Penalties Regulation also permits the European Commission to impose fines on marketing authorization holders not exceeding 0.5 % of their Community turnover in the preceding business year where, intentionally or negligently they do not comply with requests by the EMEA or the European Commission during the investigation or they supply incorrect or misleading information in response such a requestMoreover, where non-cooperation of the marketing authorization holder continues, the European Commission may also impose periodic penalty payments per day not exceeding 0.5 % of the holder’s average daily Community turnover in the preceding business year
31Clinical Trials in Developing Countries The continued supply issueLiability issues for sponsors
32The continued supply issue – World Medical Association Paragraph 30 of the WMA Declaration of Helsinki :"At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.“* Paragraph 30 was added at the 52nd WMA General Assembly, Edinburgh 2000Note of clarification on paragraph 30):“The WMA hereby reaffirms its position that it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review.“The note of clarification was added at the 55th WMA General Assembly, Tokyo 2004
33U.S. approachForeign studies performed under an investigational new drug application (IND) or investigational device exemption (IDE) must meet the same requirements of 21 CFR Part 312 or 21 CFR Part 812, respectively, that apply to U.S. studies conducted under an IND or IDEUnder 21 CFR (c)(1), FDA will accept a foreign clinical study not conducted under an IND only if the study conforms to the ethical principles contained in the Declaration of Helsinki (Declaration), as set out in 21 CFR (c)(4), incorporating the 1989 version of the Declaration, or with the laws and regulations of the country in which the research was conducted, whichever provides greater protection of the human subjects
34U.S. approachThe U.S. has not incorporated in its clinical trial regulations the amendments to the Helsinki declaration added at the 52nd WMA General Assembly in Edinburgh in 2000The U.S. regulations follow the 1989 version of the WMA declaration, which does not incorporate paragraph 30The EU Clinical Trials Directive 2001/20/EC refers to the 1996 version of the WMA declaration, which does not incorporate paragraph 30. However, the EU Community Code as amended by Directive 2003/63/EC refers more generally to the Declaration of Helsinki without specifying which version.
35Latin American countries’ approaches vary Brazil has enacted legislation (ANVISA Resolution ) which provides that the sponsor must guarantee the subjects of the trial access to the medicines under study if these prove to be superior to conventional treatments. More recently ANVISA has published a recommendation on how the sponsor should proceed, under certain circumstances, with the donation of the product to the subjects of the study once the clinical trial is overArgentina follows the current version of the Helsinki declaration, but in practice the ANMAT and the Ethics Committee decide, on a case by case basis, whether the sponsor is required to continue the supply of the tested drug once the trials is over. In taking this decision the ANMAT and the Ethics Committee will take into account factors such as the availability of the drug in the market or the chronic character of the diseaseChile follows an approach similar to that of ArgentinaOther countries like Mexico have no continued supply obligations
36Liability for International Activities: Abdullahi v. Pfizer Abdullahi v. Pfizer is an ongoing case about whether U.S.-based researchers and clinical trial sponsors can be held accountable in the United States for torts arising out of international clinical trials. This case arises out of a 1996 trial conducted in Nigeria to test Trovan on children with brain infectionsBackgroundPlaintiffs, who are Nigerian residents, sued Pfizer under the Alien Tort Claims Act (ATCA), 28 U.S.C.A. 1350, which allows U.S. courts jurisdiction over a tort action committed in violation of the “law of nations or a treaty of the U.S.”Plaintiff argue Pfizer violated international laws and ethical standards – including the Nuremberg Code, the Declaration of Helsinki, and other guidelines – when it, among other things, failed to secure informed consent when conducting a clinical study involving Trovan in NigeriaPlaintiff’s are seeking almost $2 billion in compensatory and punitive damages for allegedly causing injuries or death to 64 children and an injunction that would prevent Pfizer from conducting any testing without proper informed consent
37Abdullahi v. Pfizer: Current status In August 2005, the Southern District Court of New York granted Pfizer’s motion to dismiss the case for the second time after it was remanded by the U.S. Court of Appeals for the Second CircuitAfter a closer consideration of the facts surrounding the decline of jurisdiction by Nigerian courts in the similar case, the District Court held that Nigeria was an available adequate forum for the litigationIn light of recent Supreme Court and Second Circuit precedent concerning the ATCA, the District Court held that there was no right of action under ATCA because the Nuremberg Code, the Declaration of Helsinki, and the other guidelines do not impose obligations sufficient to give rise to a private right of action under the ATCAOn September 6, 2005, the Plaintiff’s filed a notice of appeal, but there has been no decision from the Court of Appeals and oral argument was scheduled for July 12, 2007
38Abdullahi v. Pfizer: Current status In May 2006, the Washington Post obtained a copy of a previously unreleased report completed by a panel of Nigerian Medical Experts who investigated Pfizer’s Trovan trial in NigeriaThe panel allegedly corroborated the Plaintiff’s allegations as disclosed in their Court of Appeals briefIt is alleged that::Pfizer Inc., developed the protocol in the U.S. and did so in 6 weeks (ordinarily, this takes over a year)Pfizer did not receive government authorization to conduct the clinical trialsThe protocol was not reviewed or approved by an Ethics Committee prior to conducting the trialThe “approval” letter that Pfizer submitted was backdated and possibly forgedThe protocol “allowed the doctors the discretion of their clinical judgment,” but the panel who investigated judged some deviations to be serious deviations that compromised patient care
39Abdullahi v. Pfizer: Nigerian cases Pfizer is facing four separate lawsuits in Nigeria, two launched by State of Kano, where the trials took place, and two by the Federal Government of NigeriaThese cases have faced a number of delays due to procedural issuesIn early July, 2007 the civil case filed by the State of Kano seeking 2.7 billion has been adjourned until July 30 to allow both parties to study their positions. Pfizer asked for it to be dismissed because of lack of jurisdictionOn July 20, 2007, at the request of the Federal Government, the Federal High Court struck the Federal Government’s 7 billion federal suit instituted. This was apparently a strategic move to allow the government to fix defects in the complaint as the government expressed its intention to re-file another suitOn July 25, 2007, the criminal case was delayed to allow prosecutor more time to prepareOn July 26, 2007, the Federal Government filed a criminal case against Pfizer International and Pfizer Nigeria and several individuals accusing them of bribing officials, forging documents, and illegal importation of the drug
40Counterfeits and Sub-Standard Drugs The ProblemIMPACT: WHO InitiativeEU and Council of Europe InitiativesAPEC InitiativesChina Initiatives
41The Problem According to WHO: Fake packaging, correct quantity of correct ingredient (clone)Fake packaging, wrong ingredientFake packaging, no active ingredientFake packaging, incorrect quantity of correct ingredientGenuine packaging, wrong ingredientGenuine packaging, no ingredientGenuine packaging, incorrect quantity of correct ingredient
42Scope of the Problem WHO Survey 60% of counterfeit medicine cases occurred in poor countries and 40% in industrialized countries from January 1999 to October 2000Counterfeits make up more than 10% of the global medicines market and are present in both industrialized and developing countries.Up to 25% of the medicines consumed in poor countries are counterfeit or substandardAnnual earnings from the sales of counterfeit and substandard medicines estimated at over US$ 32 billion globallyUp to 25% of medicines consumed in developing nations are estimated to be fake or substandard
43The Counterfeit Drug Market SOURCES OF COUNTERFEITSPhotos courtesy of Lewis Kontnik
44What can be done in the United States? Trafficking in counterfeit, unapproved, adulterated, or misbranded products is a felony violation of the U.S. Federal Food, Drug, and Cosmetic Act (FDCA)FDA’s “Long Arms”Cease & Desist OrdersImport AlertsWarning LettersCivil Monetary Penalties“Cybersmuggling”Patent InfringementBusiness & Professional Code Violations
45Jurisdiction Under FDA and Other U.S. Laws FDA Jurisdiction over Foreign Entities (including “Internet Pharmacies”)If impact in U.S. (example: shipping products to U.S.)Injunctions against or criminal prosecutions of foreign nationalsSeizures of product, injunctions, criminal prosecutions, and civil penaltiesConspiracy Laws18 USC 1001 (False Reports to the Government Act)18 USC 542 (relating to entry of goods by means of false statements)18 USC 545 (relating to importation contrary to law and smuggling)Money laundering charges
46COMBATING COUNTERFEIT DRUGS FDA’s February 2004 ReportCOMBATING COUNTERFEIT DRUGSSource:
47FDA Recommendations – Summary Multilayered approach; no “magic bullet”New TechnologiesStricter Licensing RequirementsTougher PenaltiesMore Secure Business PracticesReporting and ResponseIncrease EducationInternational Collaboration
48Securing the U.S. Drug Supply Technology:Unit-of-Use PackagingTamper Evident PackagingAuthentication TechnologyIdentification of Products likely to be counterfeitedRadio-frequency Identification (RFID Technology)FDA Conclusion:Mass serialization and RFID would provide better protection if adopted as the standard track-and-trace technology
49Much teamwork is needed to stop counterfeiting FDA will collaborate with foreign stakeholders to develop strategies to deter and detect counterfeit drugs globallyFDA will work with WHO, Interpol, and other international organizations on worldwide strategiesFDA suggests that drug producers, distributors, and dispensers ensure legitimacy of business partners and refuse to do business with unknown or suspicious persons.
50What is being done?: WHO WHO: international framework convention Concept paperGoal:To establish norms that countries should adopt and incorporate into drug laws and the manner in which to implement themTo include:Development of national measures to strengthen drug regulatory authoritiesMeasures to ensure quality of drug supplyPenalties and sanctionsParticipants agreed that further development neededRecommendations:Make counterfeiting specific crimeRaise public awarenessIncrease cooperation
51IMPACT: WHO Initiative In February 2006, the WHO launched the International Medical Products Anti-Counterfeiting Taskforce (IMPACT) in response to the growing public health crisis of counterfeit drugsAims to build coordinated networks across and between countries in order to halt the production, trading and selling of fake medicines around the globeA partnership comprised of the major anti-counterfeiting players, including: international organizations, non-governmental organizations, enforcement agencies, pharmaceutical manufacturers associations and drug and regulatory authoritiesComprised of working groups to address the areas where action is needed: legislative and regulatory infrastructure, regulatory implementation, enforcement, technology and communicationExpert group of lawyers, of which I am member, met in Brussels in July 2007 to work on draft legislative concept paper.
52EU InitiativesCouncil Regulation (EC) No 1383/2003 of July concerning customs action against goods suspected of infringing certain intellectual property rights and the measures to be taken against goods found to have infringed such rightsIdentifies two categories of goods that infringe property rights: counterfeit goods and pirated goodsEnables customs authorities, in cooperation with right-holders, to improve controls at external borderSets up a more efficient system by laying down:the conditions for customs action where goods are suspected of infringing intellectual property rights; andthe measures to be taken against goods that have been found to infringe intellectual property rightsSimplifies the procedure for the lodging of applications for action with the customs authorities, in particular for small and medium-sized enterprises (SMEs), and for the destruction of fraudulent goodsExtends the scope of application of Community action to cover new types of intellectual property rights: new plant varieties, geographical indications and designations of origin
53EU InitiativesDirective 2004/48/EC of the European Parliament and the Council of April on the enforcement of intellectual property rightsHarmonizes national legislation on enforcement of intellectual property rights to ensure equality of rights for all rights holders in the EUEstablishes an effective information exchange system between the competent national authoritiesThereby aims to:promote innovation and business competitivenesssafeguard employment in Europeprevent tax losses and destabilization of the marketsensure consumer protectionensure the maintenance of public order
54Other EU InitiativesDraft Directive amending Directive 2004/48/EC on the enforcement of intellectual property rightsAdopted by the European Parliament on April 27, 2007If agreed by the European Council, Member States would be obliged to adjust their penal codes and to establish harmonized criminal sanctions against IPR-infringersLaunch of coordinated customs actions at major EU ports and airportsEstablishment of an Anti-Counterfeit Task Force of Customs experts to improve targeted customs controlsIntroduction of an Integrated European Risk Management framework to target and prevent the entrance of high-risk goods at EU bordersEfforts to share intelligence with third countries, such as the US and China, on trafficking developments and the detection of high-risk consignments
55Council of Europe Initiatives Council of Europe Draft Convention on Counterfeit medicine/pharmaceutical crimes March 30, 2007Classifies pharmaceutical offenses as serious crimesProvides that Member States must penalize the manufacture and distribution of counterfeit medicinesEstablishes a network of a Single Point of Contact in all sectors concernedRequires the adoption at national level of provisions to control the quality of components for pharmaceutical use, packaging material and manufacturing processes in accordance with the standards laid down by the PharmacopoeiaIntensifies co-operation between law enforcement agencies at the national and European level
56Asia-Pacific Economic Cooperation (APEC) Initiatives On 3 June 2005 APEC Trade Ministers endorsed a series of Anti-Counterfeiting and Piracy measures including guidelines for authorities to seize and destroy pirated goods and support to increase the capacity of economies to deal with counterfeitingThe APEC Anti-Counterfeiting and Piracy Initiative is part of efforts intended to strengthen intellectual property protection and overcome damage caused to regional innovation and commercial competitiveness, especially for small businesses
57APEC Initiatives It includes a range of measures to: Reduce Trade in Counterfeit and Pirated Goods - Economies aim to reduce counterfeit and pirated goods trade and combat transnational networks that produce and distribute these items. Actions include establishing guidelines for authorities to inspect, suspend, seize and destroy goods and equipment used in counterfeit and pirated goods tradeReduce Online Piracy - Appropriate legal regimes and enforcement systems will be enacted to curtail online piracy and to undermine the online trade in counterfeit goods. This includes the development of guidelines to prevent Internet sales of counterfeit goodsIncrease Cooperation to Stop Piracy and Counterfeiting - Operational contact and the sharing of information between customs and law enforcement agencies will be increased to combat counterfeiting and piracy networksIncrease Capacity Building to Strengthen Anti-Counterfeit and Piracy Enforcement - Member Economies' ability to develop and manage effective anti-counterfeiting and piracy enforcement systems will be increased through education and training throughout the region
58China InitiativesIn 2006, China reportedly investigated over 300,000 reports of counterfeit drugs worth about $6.3 million and closed 530 factoriesChina is reportedly currently investigating the issue of fake drugs in a number of Chinese hospitals:Suspicion was raised in Jilin, where nearly 60 hospitals and many pharmacies were found selling a fake version of albuminOver 2000 bottles of albumin, all packaged in legitimate boxes, have been seizedThere are suggestions that large Chinese counterfeit gangs, who also manufacture fake credit cards, weapons and narcotics, are involved
59Technology FDA’s Recommendation Chipless ID Issues A multilayered approach that includes radio frequency track-and-trace and authentication featuresChipless IDIssuesCostAvailabilityReliabilityOther Security MechanismsPedigree???
60THE END Linda R. Horton Partner Hogan & Hartson L.L.P. Brussels & Washington, D.C.