[e-med] Lutte contre médicaments contrefaits: appel de scientifiques à plus de coopérati

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Lutte contre mÃdicaments contrefaits: appel de scientifiques à  plus de coopÃration	
PARIS, 12 fÃv 2008 (AFP)	

Une meilleure coopÃration entre police et organismes de contrÃle des produits pharmaceutiques est indispensable pour lutter contre les contrefaÃons de mÃdicaments en Asie, plaident des scientifiques dans la revue amÃricaine en ligne Plos One.

Dans leur article, ils lÃvent le voile mardi sur une opÃration qui a permis le dÃmantÃlement d'un rÃseau chinois de contrefaÃon de mÃdicaments contre le paludisme.

RÃalisÃe avec l'aide d'Interpol et de l'Organisation mondiale de la santÃ, avec la coopÃration d'experts lÃgistes, de policiers, de mÃdecins et de pharmaciens, elle devrait servir de modÃle à  de futures opÃrations contre le flÃau de la contrefaÃon, estiment-ils.

Des experts de l'Università d'Oxford et du Wellcome Trust (Royaume-Uni) ont ainsi analysà 391 Ãchantillons de comprimÃs d'artesunate (molÃcule active contre le paludisme) recueillis en Birmanie, Laos, Vietnam, Cambodge et à  la frontiÃre entre Birmanie et ThaÃlande.

La moitià des Ãchantillons (195) ne contenaient pas -ou peu- d'artesunate. Les emballages, dont beaucoup portaient le logo de "Guilin Pharma", sociÃtà pharmaceutique du sud de la Chine, prÃsentaient des anomalies dans la "signature" du laboratoire, un hologramme invisible à  l'oeil nu.

Les experts ont Ãgalement relevà des traces de pollen sur les Ãchantillons et identifià son origine, permettant ainsi d'Ãtablir qu'au moins une partie de l'artesunate contrefait provenait du sud de la Chine.

Les autoritÃs chinoises ont Ãtà alertÃes en mars 2006 et une opÃration de police a permis l'arrestation dans la province du Yunnan (sud-ouest) d'un homme qui avait achetà de fausses boÃtes de "Guilin Pharma" auprÃs d'une fabrique de mÃdicaments contrefaits situÃe dans la province du Guangdong (sud).

Des mÃdicaments contrefaits peuvent augmenter la rÃsistance des maladies aux traitements, parce qu'ils ne contiennent pas ou pas assez de substances actives, et peuvent aussi contenir des produits toxiques. 

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A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia

 <http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050032> http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050032 < <http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050032> http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050032> 

Paul N. Newton1,2*, Facundo M. FernÃndez3, Aline PlanÃon4, Dallas C. Mildenhall5, Michael D. Green6, Li Ziyong7, Eva Maria Christophel8, Souly Phanouvong9, Stephen Howells10, Eric McIntosh10, Paul Laurin11, Nancy Blum9, Christina Y. Hampton3, Kevin Faure5, Leonard Nyadong3, C. W. Ray Soong5, Budiono Santoso8, Wang Zhiguang7, John Newton4*, Kevin Palmer8

1 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom, 2 Wellcome TrustâMahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People's Democratic Republic, 3 School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America, 4 Intellectual Property Crime Unit, International Criminal Police Organization (INTERPOL), Lyon, France, 5 GNS Science, Lower Hutt, New Zealand, 6 Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 7 Intellectual Property Division, Economic Crime Investigation Department, Ministry of Public Security, Beijing, People's Republic of China, 8 Western Pacific Regional Office of the World Health Organization, Manila, The Philippines, 9 United States Pharmacopeia, Rockville, Maryland, United States of America, 10 Therapeutic Goods Administration, Government of Australia, Symonston, Canberra, Australia, 11 Royal Canadian Mounted Police Forensic Laboratory Services, National Anti- Counterfeiting Bureau, Ottawa, Ontario, Canada

Background

Since 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.

Methods and Findings

With evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High-performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to â 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine (âecstasy'). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People's Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.

Conclusions

An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.

Funding: The collection of samples was funded by the Wellcome Trust of Great Britain through the Wellcome Trust-University of Oxford South East Asian Tropical Medicine Research Programme and the United States Agency for International Development (USAID) through its Cooperative Agreement #HRN-A-00-00-00017 with the U.S. Pharmacopeia Drug Quality and Information Program. The work of DCM was funded by the Western Pacific Regional Office (WPRO) of WHO through USAID umbrella grant #AAG-G-00-99-00005. The work of FMF was funded by WPRO through the same USAID grant and the United States National Science Foundation through CAREER grant #0645094. LN is partially supported by a U.S. Pharmacopeia graduate fellowship. PNN is supported by the Wellcome Trust of Great Britain. With exception of the funding of the work of DCM by WPRO the funding agencies had no role in the study design, data collection and analysis, and decision to publish the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Academic Editor: Marcus Reidenberg, Cornell University, United States of America

Citation: Newton PN, FernÃndez FM, PlanÃon A, Mildenhall DC, Green MD, et al. (2008) A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia . PLoS Med 5(2): e32 doi:10.1371/journal.pmed.0050032

Received: September 4, 2007; Accepted: December 21, 2007; Published: February 12, 2008

Copyright: Â 2008 Newton et al. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Abbreviations: DRA, drug regulatory authority; HPLC, high performance liquid chromatography; INTERPOL, International Criminal Police Organization; MDMA, methylenedioxymethamphetamine or ecstasy; MPS, Ministry of Public Security; SE Asia, South East Asia; WPRO, Western Pacific Regional Office (of WHO); XRD, X-ray diffractometry

* To whom correspondence should be addressed. E-mail: paul@tropmedres.ac (PNN) and j.newton@interpol.int (JN)