the global threat of
COUNTERFEIT DRUGS
BY THESE AUTHORS
Robert
Cockburn is a writer and formerly a journalist with The
Times, London, United Kingdom. Paul N. Newton is at the
Centre for Clinical Vaccinology and Tropical Medicine, Churchill
Hospital, University of Oxford, United Kingdom. E. Kyeremateng
Agyarko is Chief Executive of the Food and Drug Board, Accra,
Ghana. Dora Akunyili is Director-General of the National Agency
for Food and Drug Administration and Control, Lagos, Nigeria.
Nicholas J. White is at the Faculty of Tropical Medicine,
Mahidol University, Bangkok, Thailand, and the Centre for
Clinical Vaccinology and Tropical Medicine, Churchill Hospital,
University of Oxford, United Kingdom.
PREAMBLE
The production of substandard and fake drugs is a vast and
underreported problem, particularly affecting poorer countries.
It is an important cause of unnecessary morbidity, mortality,
and loss of public confidence in medicines and health structures.
The prevalence of counterfeit drugs appears to be rising (see
“The Scale of the Problem”) and has not been opposed
by close cooperation between drug companies, governments,
or international organizations concerned with trade, health,
customs and excise, and counterfeiting.
In
this article we suggest that many pharmaceutical companies
and governments are reluctant to publicize the problem to
health staff and the public, apparently motivated by the belief
that the publicity will harm the sales of brand-name products
in a fiercely competitive business. Publicly, at least, several
industry sources say the justification for secrecy is to avoid
any alarm that could prevent patients taking their genuine
medicines. We argue that this secrecy, and the subsequent
lack of public health warnings, is harming patients and that
it is also not in the long-term interests of the legitimate
pharmaceutical industry. We urge a change to mandatory reporting
to governmental authorities, which should also have a legal
duty to investigate, issue appropriate public warnings, and
share information across borders. This is not a role for the
pharmaceutical industry, which has a serious conflict of interest.
While
some drug companies have given public warnings to protect
patients, others have been criticized for withholding information
and, in a recent development in the United States, taken to
court for failing to act. The industry is addressing the problem.
In 2003, US pharmaceutical companies made an agreement with
the US Food and Drug Administration (FDA) that they would
report suspected counterfeit drugs to the FDA within five
days of discovery (see “Companies That Have Warned”),
although this remains a voluntary arrangement. In many poorer
countries, where the problem is at its worst, there are no
similar governmental and industry initiatives.
THE
SCALE OF THE PROBLEM
It
has been estimated that up to 15% of all sold drugs are fake,
and in parts of Africa and Asia this figure exceeds 50%. The
FDA estimates that fake drugs comprise approximately 10% of
the global medicine market. This estimate suggests annual
criminal sales in excess of US$35,000,000,000. The number
of investigations of possible counterfeit drugs by the FDA
has jumped from about five per year in the 1990s to more than
20 per year since 2000.
Most
of the literature on fake drugs derives from local investigative
journalism, with little scientific public health inquiry relative
to the enormous scale of this criminal enterprise. The effects
on patients of counterfeit medicines are difficult to detect
and quantify, and are mostly hidden in public health statistics.
The estimate of 192,000 patients killed by fake drugs in China
in 2001 gives an indication of the scale of human suffering.
SECRECY
AND COUNTERFEIT MEDICINES
Most
data on the epidemiology of counterfeit drugs are kept secret
by the pharmaceutical industry and by governmental agencies.
Drug companies employ investigators to track down and facilitate
the shutting down of counterfeit industries, but this occurs
very much in private.
There
are no reliable accessible databases whereby health workers
or the public can access current details of which products
are being faked in a locality. It is obviously correct that
information on anti-counterfeiting strategies and the sources
of undercover intelligence should not be released, but we
believe that the information on what drug is being counterfeited,
and where, should be public knowledge.
GOVERNMENT
RELUCTANCE
Governments
are also often reluctant to publicize problems with the quality
of the drug supply in their country. This is reflected in
the lack of action in much of the world regarding the problem
of counterfeits, relative to their large impact on public
health. The World Health Organization (WHO) has a reporting
system and some of the information is publicly available.
The public information, crucially, does not include the country
or region where the fakes were identified. However, the WHO
has received no reports of counterfeit drugs from member countries
after 2002, and it received only 84 reports between 1999 and
2002.
In
some countries, government officials have been accused of
involvement in the false certification of counterfeit drugs,
while in others, governmental agencies have been criticized
for suppressing information. The WHO in the Western Pacific
region, an area severely affected by counterfeit drugs, is
planning a rapid alert system for expediting the sharing of
warnings and information between governments in the region.
PHARMACEUTICAL
INDUSTRY SURVEY
We
wrote to the Pharmaceutical Security Institute (PSI), which
collates information on fake drugs obtained by the industry,
asking whether they currently forwarded reports of counterfeit
drugs to the relevant governments and the WHO. This question
was not answered, but the PSI (in a letter dated 29 July 2003)
informed us that, “Since its inception, it was recognized
that a great deal of this information it [the PSI] contains
would remain confidential and would not be disseminated. There
is proprietary information that cannot be disclosed, either
to peer member companies or to the general audience. Consequently,
at this time the dissemination of information . . . is restricted
and limited.” The letter added that the PSI encourages
its members to report counterfeiting incidents to the appropriate
authorities, and that it fully supports the voluntary reporting
to the FDA. We also wrote to 21 major companies, of the more
than 70 pharmaceutical companies with offices in the United
Kingdom, asking for information on the companies' policies
on what action should be taken and who should be told when
one of their products was found to be counterfeited. We have
received replies from six companies; one (Merck Sharp and
Dohme) declined to give any information, while three (GlaxoSmithKline
[GSK], Bristol-Myers Squibb, and Novartis) stated that they
would inform the local drug regulatory authority if they were
notified that one of their products was being counterfeited.
PAUCITY
OF WARNINGS ABOUT FAKE DRUGS
That
many pharmaceutical companies, professional organizations
and governments, both in developed and developing countries
are not releasing warnings is manifested by the paucity of
warnings relative to the scale of the problem. The industry's
history of secrecy over data about fake drugs, and claims
of a commercial motivation, go back over 20 years. In 1982,
a spokesperson for the Association of the British Pharmaceutical
Industry said, “It is difficult to declare a [fake drug]
problem without damaging legitimate business.” This
impression of secrecy is supported by historical statements,
such as the following: “The Society [Royal Pharmaceutical
Society of Great Britain] is not issuing press releases [about
counterfeit drugs] because it believes that as much as possible
should be done behind the scenes . . . and that no great publicity
should be sought because it could damage public confidence
in medicines.” But the Royal Pharmaceutical Society
of Great Britain has recently revised its position. David
Pruce, Director of Practice and Quality Improvement for the
organization, told us (E-mail letter, 14 February 2005), “If
there is a risk that a patient has been dispensed a counterfeit
medicine, then it is vital that they are informed. There have
been two recent cases in Great Britain where counterfeit medicines
appeared in the legitimate pharmacy supply chain. The public
announcement of the problem of the counterfeit medicines was
therefore entirely proper and necessary.” He added,
“It is important that news stories of this type are
handled responsibly so that the public's confidence in their
medicines is not undermined. This could deter patients from
taking genuine medicines.”
RECENT
EXAMPLES OF COUNTERFEIT DRUGS
This
assessment, that the dangers of causing alarm amongst the
general public could outweigh the benefits of disclosure,
remains widespread in public statements. A spokesperson for
the Association of British Pharmaceutical Industries, Marjorie
Syddall, wrote (E-mail letter, 20 October 2003), “A
company should be completely satisfied that a medicine is
counterfeit before informing the authorities, but more importantly
still, before it makes this information known to the public
-- so that no unnecessary alarm is caused.”
COMMERCIAL
MOTIVATION – CUT-THROAT COMPETITION
Chris
Jenkins, a founding member of the PSI, now Associate Director
of Pinkerton Consulting and Investigations, told us (E-mail
statement, 9 December 2004), “It is necessary to keep
fake drug information confidential for commercial reasons
. . . to avoid media leaks and to prevent the possibility
of rival drug companies taking unfair commercial advantage
of a victim company.” He explained, “At the outset,
we [the PSI] were against having data online that anyone could
interrogate . . . If a patient came to harm as a result of
a counterfeit product, the company's good reputation is in
danger of disappearing, together with a loss of confidence
in the products . . . The one thing we were trying very hard
to do was to keep it [data] out of the hands of the commercial
people in any of the companies . . . The importance of meeting
sales' targets is such that you can even find cut-throat competition
between different operating divisions of the same company,
let alone between two companies competing in the same market
with similar drugs.”
The
WHO 1999 guidelines for the development of measures to combat
counterfeit drugs states that “the reluctance of the
pharmaceutical industry, wholesalers and retailers to report
drug counterfeiting to the national drug regulatory authorities
could impede the national authorities from successfully taking
measures against counterfeiting,” and suggests “the
compulsory reporting to the relevant authorities of any incidents
in which counterfeits are detected or involved.” A recent
review of the law and counterfeit drugs calls for the “eradication
of the clandestine status of records and counterfeit drug
information.” At the International Conference of Drug
Regulatory Authorities in Madrid in February 2004, it was
stated by the WHO that “the drugs industry had a great
deal of data but was ‘very reluctant to make them available.’”
INFORMATION
STRICTLY CONFIDENTIAL
In
the US it was reported that it had been “very difficult
to obtain citable factual information about the extent of
the problem of counterfeit drugs. Drug companies keep the
information they have strictly confidential.” In 1989,
the British Department of Health and Glaxo (now a part of
GlaxoSmithKline) were criticized for not publicizing information
about the discovery in Britain of fake Glaxo Ventolin asthma
inhalers. London's The Times obtained the fake Ventolin's
licence and batch numbers for a story, prompting the release
of the information. Warning letters, drafted by Glaxo and
the Department of Health, were sent to all 14,000 pharmacists
in Britain five weeks after the fake's discovery. In 1998,
the company Schering do Brasil was accused of keeping secret
the discovery of oral contraceptive pills made of wheat flour
for 30 days while they carried out their own investigation.
According to the Far Eastern Economic Review, the
company was fined US$2.5 million by the Brazilian government.
Schering do Brasil informed us (E-mail letter, 17 February
2005) that “Federal Justice cancelled the fine in 2002
after the company appealed.” In Niger, in 1995, one
of the fake meningitis vaccines originating from Nigeria was
labelled as made by SmithKline Beecham, but Le Monde
reported that the company did not act against the counterfeiters,
afraid that it might damage trade.
FAKE
PAEDIATRIC ANTI-MALARIAL DRUGS
The
need to release fake drug information is acute in Africa,
where a resurgence of malaria is killing an estimated one
million people a year, the vast majority of them children
under five. One example highlights the problems encountered.
One of us (K. Agyarko) found counterfeits of the GSK paediatric
anti-malarial syrup halofantrine (Halfan) in August 2002 in
Ghana. That month he prepared a public health warning. Agyarko
and his deputy told the BBC that he also alerted GSK's Ghana
agent, who visited him with staff from GSK's London headquarters
and took away samples of the fake Halfan. Agyarko publicly
stated (on 23 September 2002, at the First Global Forum on
Pharmaceutical Anticounterfeiting in Geneva, Switzerland)
that he was asked by GSK to withhold his public warning because
it would “damage” their product. After his meeting
with GSK, no warning was issued. In a written statement (E-mail
letter, 24 October 2003), GSK denied receiving Agyarko's fake
Halfan alert and said the company was “not provided
with any samples of fakes by the authorities in Ghana.”
THE
PHARMACEUTICAL SECURITY INSTITUTE
The
PSI is a not-for-profit corporation formed by the major drug
companies to collate their fake drug information to cooperate
in fighting the racket. Based in Vienna, Virginia, United
States, the PSI holds the only known comprehensive and updated
source of fake drug information. The PSI Web site (www.psi-inc.org)
states, “On a daily basis, many individuals unknowingly
risk death or serious injury to their health by taking counterfeit
pharmaceuticals.” But its databank, which health workers
see as holding key information to prevent patients from taking
life-threatening fakes, is not accessible to the WHO, health
authorities, or the public. Such is the secrecy of the PSI's
information, that access is restricted even between its member
companies, which include the 15 largest drug manufacturers.
After
a year of inquiries, resulting in a BBC Radio programme (BBC
Radio 4, “File on 4”, 5 October 2004), GSK reversed
its position and said that its local agent had “bumped
into” Agyarko and had received his alert and samples
of fake Halfan syrup. In a new statement (E-mail letter, 5
October 2004) GSK said: “At no point was any pressure
put on the Ghanaian authorities not to issue a public warning
on fake Halfan.” GSK's vice president of communications,
Louise A. Dunn, told us (E-mail letter, 6 October 2004), “There
was some confusion over the interactions with Mr Agyarko.
The key point here is that there was no wrong doing . . .”
However,
the Ghana incident needs to be viewed in the context of the
wider illegal trade in fake Halfan syrup identified in West
Africa, and GSK's reluctance to give us details about this
trade. We asked GSK whether it had issued any public warnings
about fake Halfan syrup, but the question was not answered.
The only reference to counterfeit halofantrine syrup that
we have been able to find in the public domain was published
in a specialist technical journal that described the mass
spectroscopy analysis of fake halofantrine syrups by the GSK
Medicines Research Centre and demonstrated that the fake syrups
contained two potentially harmful sulphonamide drugs, but
no halofantrine. We wrote to GSK (letter, 20 June 2003) asking
when and where discoveries of fake Halfan were made, and whom
GSK had informed about them. GSK told us only that “counterfeit
Halfan is present in Nigeria and Sierra Leone” (letter,
21 July 2003). It gave no details of preparation type or discovery
dates.
Fake
GSK Halfan syrup was discovered in Nigeria in June 2002 by
the Nigerian National Agency for Food and Drug Administration
and Control. NAFDAC alerted GSK and issued a public health
warning in June 2002 in the regular NAFDAC fake drug bulletin,
giving the fake Halfan syrup's identifying details. The NAFDAC's
Dora Akunyili told BBC Radio (5 October 2004): “It is
more dangerous not to alert the public. We will still issue
a warning even if we find it in only one shop. If you find
any fake drug product in only one shop you can be sure it
is in many villages . . . We don't defend companies. We are
defending the people.”
The
Pharmaceutical Board of Sierra Leone, which handles fake drug
cases, was not informed by GSK of any discoveries of fake
GSK Halfan syrup, according to its director Michael J. Lansana
(E-mail letter, 21 January 2004), although it did receive
a report of counterfeit adult Halfan caplets from GSK. Later,
GSK told us (E-mail letter, 6 October 2004) the fake Halfan
syrup it had tested was found in Sierra Leone in late 2001,
and that it had informed Sierra Leone's Minister of Health
and Sanitation of the find.
Only
a single report of counterfeit halofantrine, which does not
specify details of preparation type or location, is given
in the WHO Counterfeit Drug Reports for 1999–October
2000.
The
fake Halfan syrup cases highlight the importance of communication
and cross-border cooperation, and the need for industry and
governments to inform neighbouring countries when a fake is
found. The global distribution and the scale of the racket
in fake adult Halfan capsules was clear in December 2000,
when Belgian customs seized 57,600 packs of fake GSK Halfan
capsules (and 4,400 packs of fake GSK Ampiclox [ampicillin]
and 11,000 packs of fake GSK Amoxil [amoxicillin]) en route
from China to Nigeria. The counterfeiters in China were found
to be preparing to export 43 tons of 17 brands of drugs from
seven international pharmaceutical companies.
COMPANIES
THAT HAVE OWNED UP
Sometimes
pharmaceutical companies have publicized information to alert
health workers and patients and governments to the dangers
of counterfeited or tampered products. For example, Johnson
and Johnson, Serono, Hoechst, Wellcome Foundation (now part
of GSK), GSK, and Genentech have publicized information on
their drugs that have been counterfeited or tampered with.
In 1982, cyanide-laced paracetamol killed seven people in
the US. The pharmaceutical company whose product had been
tampered with, Johnson and Johnson, issued alerts and cooperated
with the investigation, and although the financial cost to
the company was large, its long-term reputation was probably
enhanced. Other companies, at least initially, did not take
advantage of the disaster for their own financial gain. In
2002, Johnson and Johnson issued 200,000 letters to health-care
professionals in the US warning them of fake Procrit (erythropoetin)
within one week of being notified of a severe counterfeit
problem. In 1982, Hoechst voluntarily took out magazine adverts
in Lebanon to warn pharmacists and customers of a fake of
its drug Daonil (glibenclamide) for the treatment of diabetes
mellitus. In 2001, Serono was told by the FDA to issue a public
warning to hospitals, clinics, and patients in seven US states
after the discovery of a counterfeit of its drug Serostim,
a human growth hormone used in the treatment of AIDS and other
conditions. In 1984, in Thailand, the Wellcome Foundation
(now part of GSK) publicized the discovery of fakes of its
antibiotic Septrin (co-trimoxazole) that lacked any active
ingredients, and the company's efforts to stop its production.
Wellcome also had reports that the fakes were being imported
into the UK, which it made public along with the warning that
it sent to the British Embassy in Bangkok. In 2001, GSK made
public the discovery of fakes of its AIDS treatment Combivir
(zidovudine + lamivudine), and Genentech publicized information
on fakes of Neupogen (filgrastim).
The
Pharmaceutical Research and Manufacturers of America announced
in April 2003 that, from 1 May 2003, its 60 members would
voluntarily report to the FDA “within five working days
of determining that there is a reasonable basis to believe
their product has been counterfeited.” This is an important
local development but it should be mandated by law and become
a global standard. Indeed, we have not found one country where
drug companies have a legal duty to report discoveries of
counterfeits of their products to public health or trade authorities.
We
suggest that the pharmaceutical industry, which is such a
benefit to our health, is harming both patients and itself
by not vigorously warning the public of fake products when
they arise. Apart from the moral imperative, there is the
prospect of growing legal pressure on drug companies to take
responsibility for fakes of their products. In Britain, there
are proposals to introduce a charge of “corporate killing”
for companies who have contributed to the deaths of customers
that could also apply to drug companies if they do not take
reasonable steps to warn the public of a fake product.
DRUG
COMPANIES SUED IN THE UNITED STATES
Already,
the US has seen the first court case brought against two drug
companies for allegedly failing to act to protect customers
over a fake drug discovery. In 2002, a Kansas City pharmacist
was jailed for diluting the anticancer drugs Gemzar (gemcitabine)
and Taxol (paclitaxel). The victims and dead patients' families
sued the drug companies, Eli Lilly and Myers Squibb, for not
taking steps to stop him. The companies argued that they had
no duty to protect the plaintiffs from the pharmacist's criminal
acts, but a newspaper reported that Eli Lilly and Myers Squibb
settled out of court, apparently for US$72 million, avoiding
a legal precedent that would hold drug companies liable for
not disseminating such information.
Chris
Jenkins suggests that the PSI could face a legal challenge
to open its fake drug databases (E-mail, 9 December 2004):
“Only the PSI had an overview of the known racket…In
theory, every fake drug case reported by the companies should
be on there.” He is concerned that private investigators
could be liable for fake drug data they obtain for client
companies.
GOVERNMENTS
MUST ENFORCE A LEGAL RESPONSIBILITY
We
believe that the industry, along with pharmacists, health
workers, and governments, needs to extend the “behind
the scenes” fight against fakes to a public collaborative
approach with a legal responsibility to report suspected counterfeits
to drug regulatory authorities, in a similar way to the reporting
of “notifiable” infectious diseases. The drug
regulatory authorities, accountable to the consumers of drugs,
should have a statutory duty to investigate and disseminate
the information, with the interests of patients as the prime
concern. Drug regulatory authorities in economically poor
countries will need additional financial support.
We
recognize that false information could seriously damage a
company and that information should be verified and used prudently.
We also recognize that careful public information measures
will be needed to prevent patients from stopping the use of
genuine products, but suggest that this is possible as pharmaceutical
companies can, and have, alerted the public in collaboration
with government agencies (see above). However, the decision
to warn the public should not be made by the pharmaceutical
industry alone, which has a serious conflict of interest.
We believe that the long-term interests of both the industry
and patients are best served by more openness and social responsibility
to public health. Company staff and shareholders should not
be in a position to adjudicate conflicts between commercial
gain and public health—such adjudication should be in
the hands of government departments accountable to the public.
The
pharmaceutical company is also a victim of the counterfeiter
and should be supported by governmental authorities if it
reports promptly. Individuals who report information on counterfeit
drugs should remain anonymous and be protected from the criminal
counterfeiting underworld, which may exact retribution. International
agreements between companies to avoid taking advantage of
competitors' misfortunes, when precipitated by rumours or
confirmed reports of fake drugs, may facilitate enhanced cooperation
within the Convention against Counterfeit Drugs
The
effective control of the global epidemic of counterfeit and
substandard drugs will not be easy, and will need a multifaceted
approach: the provision of effective, available, and inexpensive
drugs; the enforcement of drug regulation; more openness by
governments as to the scale of the problem; more effective
police action against the counterfeiters and those who may
be corrupt allies within government and industry; enhanced
cooperation between the industry, police, customs, and drug
regulators; and enhanced education of patients, drug sellers,
and health workers. We urge the industry and governments to
act, through the sharing of crucial public health information,
to facilitate the protection of patients and improve the quality
of an apparently deteriorating drug supply.
For
sources and documentation, click
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