E-DRUG: Counterfeit artesunate investigation
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The results of the following study are available from PLoS medicine
http://medicine.plosjournals.org/archive/1549-1676/5/2/pdf/10.1371_journal.pmed.0050032-S.pdf (published 12 February 2008)
The article includes interesting maps and illustrations
and the editor's summary appears below
A Collaborative Epidemiological Investigation
into the Criminal Fake Artesunate Trade
in South East Asia
Paul N. Newton1,2*, Facundo M. Ferna´ndez3, Aline Planc¸on4, 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
Editors' Summary
Background: Malaria is one of the world's largest public health problems,
causing around 500 million cases of illness and at least one million
deaths per year (the estimates vary widely). The most serious form of
malaria is caused by the parasite Plasmodium falciparum, which has
become resistant to multiple drugs that had previously been the
cornerstones of antimalarial regimens. One group of drugs for treating
malaria, the artemisinin therapies including artesunate, are based upon a
Chinese herb called qinghaosu; these have now become vital to the
treatment of P. falciparum malaria. But counterfeit artesunate, containing
none or too little (''subtherapeutic levels'') of the active ingredient,
is a growing problem especially in South and East Asia. Fake artesunate is
devastating for malaria control: it causes avoidable death, reduces
confidence in the drug, and takes away profit from legitimate
manufacturers. Of major concern also is the potential for subtherapeutic
counterfeit artesunate to fuel the parasite's resistance to the artemisinin
group of drugs.
Previous estimates have suggested that between 33% and 53% of
artesunate tablets in mainland South East Asia are counterfeit. In this
paper the authors report on an unprecedented international collaboration
and criminal investigation that attempted to quantify and source
counterfeit artesunate among some of the most malarious countries in
Asia.
Why Was This Study Done? Previous reports have identified the
problem of fake artesunate, but as of yet there have been few reports on
the potential solutions. Concerned health workers and scientists, the
regional World Health Organization (WHO) office and the International
Criminal Police Organization (INTERPOL) got together to discuss what
could be done in May 2005 when it became clear the counterfeit
artesunate situation was worsening in the Greater Mekong Sub-Region
of South East Asia (comprising Cambodia, Lao People's Democratic
Republic, Myanmar, Thailand, Vietnam, and Yunnan Province in the
People's Republic of China). Their subsequent investigation combined
the goals and methods of a range of concerned parties---police,
scientists, and health workers---to identify the source of counterfeit
artesunate in South East Asia and to supply the evidence to help arrest
and prosecute the perpetrators.
What Did the Researchers Do and Find? The researchers conducted
forensic analyses of samples of genuine and counterfeit artesunate. They
selected these samples from larger surveys and investigations that had
been conducted in the region beginning in the year 2000. Genuine
samples were supplied by a manufacturer to provide a comparator. The
authors examined the physical appearance of the packages and
subjected the tablets to a wide range of chemical and biological tests
that allowed an analysis of the components contained in the tablets.
When comparing the collected packages and tablets against the genuine
samples, the researchers found considerable diversity of fake artesunate
in SE Asia.
Sixteen different fake hologram types (the stickers contained
on packages meant to identify them as genuine) were found. Chemical
analysis revealed that all tablets thought to be fake contained no or very
small quantities of artesunate. Other ingredients found in the artesunate
counterfeit tablets included paracetamol, antibiotics, older antimalarial
drugs, and a range of minerals, and there were a variety of gases
surrounding the tablets inside the packaging. Biological analyses of
pollen grains inside the packaging suggested that the packages
originated in the parts of South East Asia along the Chinese border.
What Do these Findings Mean? The results were crucial in helping the
authorities establish the origin of the fake artesunate. For example, the
authors identified two regional clusters where the counterfeit tablets
appeared to be coming from, thus flagging a potential manufacturing
site or distribution network.
The presence of wrong active pharmaceutical ingredients (such as the older antimalarial drugs) suggested the counterfeiters had access to a variety of active pharmaceutical ingredients. The presence of safrole, a precursor to the illicit drug ecstasy, suggested the counterfeits may be coming from factories that manufacture ecstasy. And the identification of minerals indigenous to certain regions also helped identify the counterfeits' origin. The researchers concluded that at least some of the counterfeit artesunate was coming from southern China. The Secretary General of INTERPOL presented the findings to the Chinese government, which then carried out a criminal investigation and arrested individuals alleged to have produced and distributed the counterfeit artesunate.
The collaboration between police, public health workers and scientists
on combating fake artesunate is unique, and provides a model for others
to follow. However, the authors note that substantial capacity in forensic
analysis and the infrastructure to support collaborations between these
different disciplines are needed.
Additional Information. Please access these Web sites via the online
version of this summary at http://dx.doi.org/10.1371/journal.pmed.
0050032.
The World Health Organization in 2006 created IMPACT---International
Medical Products Anti-Counterfeiting Taskforce---with the aim of
forging international collaboration to seek global solutions to this
global challenge and in raising awareness of the dangers of
counterfeit medical products. The task force membership includes
international organizations, nongovernmental organizations, enforcement
agencies, pharmaceutical manufacturers' associations, and drug
and regulatory authorities. IMPACT's Web site notes that trade in
counterfeit medicines is widespread and affects both developed and
developing countries but is more prevalent in countries that have
weak drug regulatory systems, poor supply of basic medicines,
unregulated markets, high drug prices and/or significant price
differentials. IMPACT holds international conferences and maintains
a rapid alert system for counterfeit drugs.
The drug industry's anticounterfeit organization, Pharmaceutical
Security Institute, works to develop improved systems to identify
the extent of the counterfeiting problem and to assist in coordinating
international inquiries. Its membership includes 21 large pharmaceutical
companies.
The Web site of David Pizzanelli, a world expert on security
holography, contains a PowerPoint presentation co-authored by Paul
Newton that illustrates the different types of fake holograms found on
fake artesunate packages, and their implications for artemisinin
resistance (http://www.pizzanelli.co.uk/content/artesunate.html).