Drug counterfeit- A global menace and its remedial measures
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The manufacturing of fake drugs is a vast and underreported problem, particularly
Nilesh K. Patel
The manufacturing of fake drugs is a vast and underreported problem, particularly
affecting poorer countries.
The counterfeit trade is particularly attractive
to criminal networks because it is extremely lucrative.
It is an important cause of unnecessary morbidity, mortality and loss of
public confidence in medicines and health structures. The term "counterfeit
drug" may be used to describe а drug made by someone other than
the genuine manufacturer by copying or imitating an original product without
authority or right, with а view to deceive or defraud, and then marketing
the copied or forged drug as the original.
According to World Health Organization (WHO), "А counterfeit medicine
is one which is deliberately and fraudulently mislabeled with respect to identity
and/or source. Counterfeiting can apply to both branded and generic products
and counterfeit products may include products with the correct ingredients,
with the wrong ingredients, without active ingredients, with insufficient
active ingredients or with fake packaging1-3. Drug counterfeiting
can be put in practice by various techniques like 4-5,
• Tampering with the expiry date or lot number of original products
• Changing foreign language or low-dosage labels with high-dosage labels
• Diluting active content of drug formulation
• Tampering with original packaging
• Combining bulk active pharmaceutical ingredients (APIs) into a single
batch with a fake certificate of analysis
• Filling API containers with alternating layers of real product
A Few Facts about drug counterfeits
A.
The World Health Organization estimates that 10 % of global
pharmaceutical commerce is in fake drugs. The developing world, mainly Southeast Asia is severely
suffering from drug counterfeiting where traffickers have networks of
distributors as well as laboratories for making pills. Between January 1999 and October 2000, WHO received 46
confidential reports relating to such drugs from 20 countries. About 60% of
these reports came from developing countries and the remaining 40% were
reported by developed countries. WHO classified these products into six
categories1
• Without active ingredients, 32.1%;
• With incorrect quantities of active ingredients, 20.2%;
• With wrong ingredients, 21.4%,
• With correct quantities of active ingredients but with fake packaging,
15.6%;
• Copies of an original product, 1%; and
• With high levels of impurities and contaminants, 8.5%.
B. 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
fake drugs comprise approximately 10% of the global medicine market and estimate
suggests annual criminal sales in excess of US$35,000,000,000. In 2004, FDA
initiated 58 counterfeit drug cases, a significant increase from the 30 cases
initiated in 2003. This is in part due to an increased awareness and vigilance
in drug regulation. The number of fake drug cases has jumped from about five
per year in the 1990s to more than 50 cases since 2004
(see figure-1). The World Health Organization estimates global sales of counterfeit
medicines at $40 billion this year. The Center for Medicines in New
York predicts counterfeit drug sales to reach $75
billion globally in 2010.6-13
Figure-1:-Counterfeit drug cases opened by FDA per year
C. Fake Antimalerial drugs are
biggest problem in developing countries. Phony antimalarials are
becoming a deadly problem, more than 100,000 people die each year from fake
antimalarials in Southeast Asia alone.13-15 Approximately one-third
to one-half of packets of artesunate tablets (pivotal), life-saving
anti-malarial drug, recently bought in Southeast Asia were fakes, containing no
active ingredient at all.16
A countrywide survey in Cambodia
in 1999 showed that 60 percent of 133 drug vendors sampled sold, as the
antimalarial mefloquine, tablets that contained the ineffective but much
cheaper sulphadoxine-pyrimethamine. Another survey found that 38 percent of
tablets sold in five countries in mainland Southeast Asia
as the new antimalarial artesunate were phony.17 Another survey by
the WHO (2003) of seven African countries found that between 20 and 90 per cent
of all anti-malarials failed quality testing. These included chloroquine-based
syrup and tablets, whose failure rate ranged from 23 to 38 %; and sulphadoxine
/ pyrimethamine tablets, up to 90 % of which were found to be below standard.
D. Lipitor (atorvastatin) is the world's most popular medicine,
with global trade of $12 billion in 2005. Many counterfeits of Lipitior have
been detected in different countries. Pharmacies and dispensing
practices in the UK could
be handing at least £200 million worth of counterfeit medicines18. A drug wholesaler,
distributed over $20 million in illegally imported and counterfeit Lipitor at
Kansas City.12,19 During
2005, three men pleaded guilty in a multi-million dollar Lipitor smuggling and
counterfeiting conspiracy. The counterfeit Lipitor 20mg tablets were
recalled in the U.K. in
200520-22.
E. In 2003, counterfeit Viagra (Sildenafil) with
an estimated value in excess of £2.35 million was seized. In 2004, an individual pleaded guilty to charges of conspiracy and trafficking
in counterfeit goods. The defendant admitted that he conspired with a
manufacturer in Beijing to
import thousands of counterfeit Viagra tablets into the United
States. In January 2005, a
Southern Californian man pleaded guilty
to importing counterfeit Viagra from China and
manufacturing 700,000 counterfeit Viagra tablets at a lab in the U.S. 23-24.
F. A large proportion of the world’s counterfeit
medicines originate in Asia. China in particular is a production centre. In 2001 it was reported that China had 500 illegal medicine factories. In china, A total of 192,000 patients are
reported to have died in 2001 from fake drugs and in the same year Chinese
authorities closed 1,300 factories while investigating 480,000 cases of counterfeit
drugs worth 57 million USD and authorities have found that some products have a
counterfeit prevalence ranging between 50% to 85%. In ,
for example, fake drugs are estimated to make up 13 to 30 % of the
pharmaceutical market24-26 According to the WHO, Cambodia
had 2800 illegal medicine sellers and 1000 unregistered drugs on the market in
2003. The same report showed that Laos
had about 2100 illegal medicines sellers while in Thailand,
substandard medicines account for 8.5 percent of the total market27.
In Haiti, Nigeria,
Bangladesh, India
and Argentina
more than 500 patients, predominantly children, are known to have died from the
use of diethylene glycol formed in the formulation of fake paracetamol syrup28-30.
G. In Africa, Nigeria banned the
import of all drugs from India,
because of the high prevalence of counterfeits amongst the imports31.
In 2002, Nigeria received drugs from
India, 60%
of them were counterfeit, substandard or expired. During the 1995 meningitis
epidemic in Niger, the authorities
received a donation of 88,000 Pasteur Merieux and SmithKline Beecham vaccines
from neighboring Nigeria.
The drugs were found to be counterfeit, with no traces of active product.
Some 60,000 people were inoculated with the fake vaccines32. Recently
counterfeit antiretrovirals (stavudine, lamivudine, nevirapine and zidovudine)
were found in central Africa which weakens the combat against AIDS in sub-Saharan
Africa33.
H. In America, no one knows the mortality or morbidity rate caused by cases
of fake atorvastatin, epoetin, somatropin, filgrastim, olanzipine, immunoglobulin,
oxycodone lamivudine, sildenafil, growth hormone, gemcitabine and paclitaxel.34-37
Counterfeit medicines were also found in Latin America, with instances reported
in Argentina, Brazil, Colombia, Venezuela, Mexico, Peru and Guatemala. Mexico
is a major global source of counterfeit medicines, with the trade standing
at an estimated value of US$650 million per year equal to around 10 % of total
drug sales in the country38.
Factor encouraging Counterfeit of drugs
Non-existent or weak drug legislation and regulation
Anticounterfeiting legislation alone will not solve the problem. The criminals
must be arrested and prosecuted by enforcing existing laws. Merciful punishment
for offences tends to encourage criminal activities such as drugs counterfeiting,
particularly when the penalties for counterfeiting other than drug products
are more severe. At present, out of the 191 WHO member states about 20% are
known to have well developed drug regulation, about 50% implement drug regulation
at varying levels and the remaining 30% either have weak or no drug regulation1.
There must be sufficient resources for drug regulation activities and training
program to eliminate inefficiency and incompetence of drug regulatory authorities.
Each of the activities like development, manufacture, import and subsequent
handling of drug requires specialized knowledge and skills. The authorities
should conform to prescribed standards and their quality should be rigorously
controlled. This would require strong government will and commitment to establish
and operate а drug regulation.
Feeble regulation of exporting countries
Many a times
pharmaceuticals made for export are not regulated by exporting countries to the
same standard as those produced for domestic use. The immense majority of APIs used by US drug manufacturers come from
overseas, approximately 80 % for branded medicines and 90 % or more for
generics. In addition, pharmaceuticals
are sometimes exported through free trade zones where drug control is lax. The
repackaging and relabeling operation in such zone can provide better
opportunities for counterfeiters to introduce illicit material into the
distribution chain even when the system is highly regulated. In 2000, US Food
and Drug Authority (FDA) had linked adverse drug reactions in 155 US citizens to
drug ingredients originating from China and
found that 4,600 foreign bulk drug suppliers to the US had not been inspected3.
In December 2000, Belgian customs seized 57,600 packs of fake GSK Halfan
(halofantrine) capsules, 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 companies39.
Lack of cooperation between regulatory authorities
Cooperation
between regulatory authorities, police, customs services and the judiciary is
essential for effective control of the drug market and enforcement of drug
legislation. The cooperation of the pharmaceutical industry, wholesalers and
retailers is necessary to report cases of counterfeit drugs in combating
counterfeit drugs. Where such cooperation is lacking the national drug
authority may not be able to take measures against counterfeiters hence
counterfeit medicines tend to flourish. There are no reliable and accessible
databases whereby health workers or the public can access current details of fake
drugs in a locality. It is obviously correct that information on
anti-counterfeiting strategies and the sources of undercover intelligence
should not be released but the information on what drug is being counterfeited
and where drug is being counterfeited, should be public knowledge5.
Corruption and difference in interest
Corruption and
conflict of interest many a times adversely affect the working ability of
regulatory personal and results in criminals not being arrested, prosecuted and
convicted for their crimes. It is necessary to empower public awareness and
consumer groups to take part in drug regulation and to make regulatory
authorities accountable and their decisions transparent. 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.40-41 In 2002, a pharmacist at USA pleaded guilty to diluting
cancer drugs and later admitted that he had diluted at least 98,000
prescriptions since 199242.
Commercial interest and political reluctance
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. 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. If
a patient faces any 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 its products. 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”43. A recent review of the law
and counterfeit drugs calls for the eradication of the clandestine status of
records and counterfeit drug information44. 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 available45.
Stipulation and high cost of medicines
High cost of
medicines may be a deterrent in their manufacturing by genuine means. Therefore
is become profitable to counterfeit them as it decreases the cost and the cost
conscious consumers may further boost their demand. As there is a greater incentive
in supplying these cheap counterfeits, the traders also tend to it. Even the
hospitals and the pharmacists may be attracted in their purchase due to pries
differential
Involvement of intermediaries
As in other
consumer goods sectors pharmaceutical trade also utilizes intermediaries
between the manufacturing and the importing countries. In some instances this
may involve re-packaging and re-labeling which may be carried out without
fulfilling GMPs requirements Counterfeit medicines are a growing problem in
many countries and are increasingly being supplied over the internet. The internet is an excellent medium for both
retail and commercial scale counterfeiting. For example, the Canadian web
pharmacies are not found to be based in Canada but in places such as in Jamaica
or Pakistan. At the commercial level, the internet gives counterfeiters a means
for trading in fake products and components.
Approaches to Combating Counterfeit medicines
Investigation with aid of Technologies
At а national level, each country
should develop appropriate medicines policy options, legislation and
enforcement strategies in view of its own situation and availability of
institutional framework, professional and financial resources. Many technologies
are available to rescue counterfeiting like holograms, tamper-evident
closures, and part of blister pack foils or bottle-induction seals. There are
color-shifting inks, invisible bar codes, in-product tracers and portable x-ray
composition testing systems. There is even a technology for printing 2-D bar
codes directly on pills with FDA-approved colorants. Electronic track
and trace mechanisms and radio-frequency identification (RFID) is the most
promising technology to combat against phony drugs. RFID technology uses a tiny
radio frequency chip containing essential data in the form of an electronic
product code (EPC). Among recent
anticounterfeiting technologies, electronic product code is a next-generation
bar code system that goes much further than any system available today. The EPC
identifies not only the product, as with current SKU bar codes, but gives a
unique number to each case, box or bottle of product. This would help
secure the integrity of the supply chain by providing an accurate drug
"pedigree," a record documenting that the drug was manufactured and
distributed under secure conditions. The
European Union and San Raffaele University in Milan, Italy, recently completed an even larger scale test
project, the Drug in Virtual Enterprise (DRIVE), based on a slightly different
technology and documented substantial systems savings. The “Manual of Anticounterfeiting
Solutions”, published by Reconnaissance International, gives details about most
of those technologies and explains the management systems that companies need
to use them effectively.
Enhancing regulatory and legislative oversight
Ineffective or weak drug regulatory
control could promote unregulated importation, manufacture and distribution of
drugs, leading to the proliferation of counterfeit drugs in the national
market. Legislation and regulations form
the basis for drug regulation. Where legislation and regulations do not exist
for proper control of medicines, the otherwise criminal activity of counterfeiting
of medicines is not treated as а crime. Governments of each country
should show political will or commitment for evolving and implementing programs
for combating counterfeit medicines. Governments must establish new drug laws
or update existing drug laws to combat against fake medicines. The power, duties and responsibilities of the
institutions must be clearly defined to enforce drug laws and drug regulation.
There must be some necessary correction for easy availability of financial and
other resources. The
industry, along with pharmacists, health workers and governments, needs to
extend the fight against fakes to a public collaborative approach with a legal
responsibility to report suspected counterfeits to drug regulatory authorities.
Internal and external education
Alone governmental
agencies can not stop counterfeiting of medicines; it is а shared
responsibility of non-governmental groups and consumer associations.
Non-governmental organizations or community based organizations should be
informed about the problem of counterfeiting and the possible presence of
counterfeit drugs in the national distribution chain. Educating consumers about
the risks of counterfeits is a critical piece of the effort to stop
counterfeits from entering the stream of commerce. They should be provided with
information and methods for detection so that they are able to report cases to
the national drug regulatory agencies.. Education and information campaigns
directed at the general public should be established and the public should be
advised to buy medicines from legitimate sources rather than from peddlers and
hawkers or from unauthorized market places. Many other sources like magazines,
medication leaflets and webpage are best option to increase consumer awareness
regarding fake drugs. Consumers should also be encouraged and advised to report
to their prescribers or physicians any lack of improvement in their health
status in spite of the treatment or any adverse reactions experienced.
Cooperation with other pharmaceutical and non-pharmaceutical organization
Drug policies for fake drugs will not be
effective without harmonized efforts of the pharmaceutical industry, the
government, its agencies, drug importers, drug distributors, the pharmaceutical
profession, governmental organizations, public interest groups and consumer
groups etc. Measures are often effective when carried out by all concerned
working together. The prevalence of counterfeit drugs appears to be rising and
has not been opposed by anyone due to non cooperation between drug companies,
governments or international organizations concerned with trade, health,
customs and excise and counterfeiting.
Worldwide collaboration
Globalization of the world economy and
activities relating to trade encourage fake drug phenomena. Smooth business across
national and international borders also increased promotion and sale of drugs
through several means. The internet is
going to lead to increased circulation of counterfeit drugs in national and
international markets. This problem can only be resolved by increase in
awareness and cooperation at subregional, regional and international levels.
Cooperation should include harmonization of measures to prevent the spread of
counterfeit drugs, developing common strategies and timely exchange of
information. All countries should adopt uniform strategies and common
definition of fake drug to improve fight against counterfeit drugs.
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About Authors
1Nilesh K. Patel*, 1Ashish D. Mishra, 2Bhanubhai N. Suhagia 1Dinesh
R. Shah, 3Shailendra S. Bhatt and 1Bhavin P. Marolia
1Department of Quality Assurance, Maliba Pharmacy College, Tarsadi, Surat-394350,
Gujarat, India
2Department of Quality Assurance, L.M. College of Pharmacy, Navarangpura,
Ahmedabad-380009, Gujarat, India
3Department of Pharmacology, Maliba Pharmacy College, Tarsadi, Surat-394350,
Gujarat, India
Corresponding author
Nilesh K. Patel
M. Pharm, Lecturer, Department of Quality Assurance, Maliba
Pharmacy College,
Tarsadi, Surat-394350, Gujarat, India,
Tel: +912625255882, Fax: +912625255882, nkpatel99@gmail.com
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