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CAUTIONS FOR WOMEN: GLOBAL PANDEMIC OF FALSIFIED MEDICINES – FRAUDULENT MEDICINES, TRAFFICKING

 

http://www.ajtmh.org/content/early/2015/04/16/ajtmh.15-0221.full.pdf+html?utm_source=PassBlue+List&utm_campaign=54c0c8fb67-RSS_NYU_SU15&utm_medium=email&utm_term=0_4795f55662-54c0c8fb67-54981461

 

The Global Pandemic of Falsified Medicines: Laboratory & Field Innovations & Policy Perspectives

 

Gaurvika M. L. Nayyar, Joel G. Breman, and James Herrington*

Johns Hopkins Bloomberg School of Public Health and Johns Hopkins Carey Business School, Baltimore,

Maryland; Fogarty International Center, National Institutes of Health, Bethesda, Maryland; Gillings Global

Gateway, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North

Carolina

 

SUMMARY

 

INTRODUCTION

 

This supplement to the American Journal of Tropical Medicine and Hygiene, entitled “The

pandemic of falsified medicines: laboratory and field innovations and policy perspectives,”

showcases 17 articles on detection technologies and methods, field surveillance data,

multi-sectorial perspectives, and policy interventions and recommendations needed to create a

coordinated and effective response to curb the pandemic of poor-quality medicines. The goal of

this special issue is to alert scientists, public health authorities, and decision makers to the

problem of poor-quality drugs and to take prompt actions to mitigate and resolve the growing

peril.

 

Poor-quality medicines are a real and urgent threat to decades of success in global public

health, particularly for programs combating human immunodeficiency virus/acquired

immunodeficiency syndrome (HIV/AIDS), tuberculosis, and malaria where mortality rates have

seen dramatic declines worldwide.1–3 Safe, effective, high-quality, and affordable medical

products are essential to positive and equitable health outcomes for all, as noted by the U.S. Food

and Drug Administration (FDA) Commissioner, Margaret Hamburg, in her Foreword to this

supplement.4 Although previously thought to be limited to low-income countries with weak

pharmaceutical regulatory systems and problems with anti-malarials (Figure 1), increasing reports

of a large variety of poor-quality medicines and medicinal products, such as vitamin

supplements, in high- and middle-income economies are illustrative of the pandemic nature of

this problem.5–7 It is estimated that falsified medicines result in $75 billion in illegal annual

revenues to criminals and have caused prolonged, severe illness and deaths worldwide; this

figure needs more precision.8 The increasing number of countries reporting breaches of the

supply chain, and products being falsified, along with the recent doubling of articles published

on “fake drugs” every 5 years in PubMed indicate the problem is of pandemic proportions and

growing. However, this may be an underestimate of the problem, given that incidents of

distribution and use of poor-quality pharmaceuticals often go unreported due to poor surveillance

systems and are kept from the public record by governments and pharmaceutical companies.9

 

Further clouding the problem is an ongoing debate and confusion over terms related to poor quality

medicines.10,11 In this summary, we use the term falsified as a synonym for counterfeit,

devoid of considerations of intellectual property. We classify poor-quality drugs into three main

types: falsified (intentional fraudulent manufacturing), substandard (unintentional errors caused

in manufacturing), and degraded (medicines that become poor quality after manufacturing

because of poor storage environments or handling).

 

In 2013, an estimated 122,350 deaths in children under 5 years of age in 39 sub-Saharan

African countries were associated with the consumption of poor-quality anti-malarials,

representing 4% of all under-five deaths, as reported by Renschler and others.12 The impact of

falsified and substandard medicines goes beyond the morbidity and mortality affecting

vulnerable patients and extends to increased microbial resistance, when active drug is in low

amounts in the product; existing drug-resistant microbes in patients can be spread by mosquitoes

and other vectors when no active ingredient is present. In addition, socioeconomic losses and

loss of public trust are associated with poor-quality medicines, all of which jeopardize years of

global public health success and investments.13

 

Over the last decade, many new stakeholders have joined the cause to combat poor-quality

medicines, yet little tangible progress has been made. Moreover, the problem continues to spread

globally, creating an even greater challenge to cooperation among stakeholders, many with

limited resources.8,10,13 The need is urgent for collaboration among those with expertise in policy,

technology, surveillance, and logistics to secure global medicine supply chains.

 

NEW AND PROMISING DETECTION TECHNOLOGIES

 

Diagnostics are at the heart of any successful epidemic response effort; they are crucial to the

ability of national regulatory agencies and the global health community to take action against the

pandemic of falsified medicines by identifying them before market entry and contact with

patients. Testing for poor-quality medicines is challenging because of the high cost of traditional

laboratory-based analytic chemistry methods, lack of training in forensic techniques for

packaging and chemical analysis, and the large sample sizes needed to conduct representative

and generalizable studies in the field.13 Fortunately, over the last 5 years, research in detection

technologies has expanded with over 42 unique detection technologies available to address poor quality

medicines, of which over half are commercially available.14 However, there are a lack of

harmonized, agreed-upon detection standards and a scarcity of effective, affordable, rapid, and

portable detection technologies that can be readily brought to scale; this is allowing poor-quality

medicines to continue to contaminate national drug supply systems. This supplement includes

research on four novel technologies that are promising in this field.

 

Weaver and Lieberman introduce a library of chemical color tests embedded on an

inexpensive paper card to presumptively identify formulations corresponding to low-quality

antimalarial drugs. Although this test may be relevant to low-income settings because of its

portability and low-cost profile, it requires comparison to authentic colorimetric samples, many

of which are not currently available from antimalarial pharmaceutical manufacturers.15

Green and others share a novel colorimetric assay for the simultaneous assessment of both

lumefantrine and artemether in Coartem™ tablets. They take a three-tiered approach to test for

falsified medicines, including image analysis, and integrating the technology with two other

novel, low-cost, fluorescence scanning devices. This very promising simple combination

intervention for field settings requires caustic acids for the assay, which can be difficult to

manage in remote, low-income settings.16

 

Another novel assay technology in early-stage development, described by Ho and others,17

consists of a detection reagent (probe) and a micro-fluidic platform to test for active

pharmaceutical ingredients (APIs) of antimalarial drugs with the potential for integration into a

fully automated field-ready system. Kaur and others have used chemical and bioassay techniques

to test the quality of the antileishmanial drug miltefosine, a drug that has played a role in the

elimination program for visceral leishmaniasis (kala-azar) in India, Nepal, and Bangladesh.18,19

Overall, these four new and promising proof-of-concept technologies face similar challenges—

an absence of needed funding for field setting validation and scalability. Importantly, there is a

necessity for evidenced-based policy guidance on the role of these new tools in field

surveillance.

 

FIELD REPORTS OF POOR-QUALITY MEDICINES

 

Representative and generalizable epidemiological surveys on poor-quality medicines are

scarce. For example, no reliable global estimates are available describing the prevalence of poor quality

medicines, in large part due to the lack of consensus on harmonized international

definitions of poor-quality medicines and surveillance methods.20 World Health Organization

(WHO) has attempted to develop a consensus on definitions, but there is yet no globally

recognized, actionable resolution to date. No globally harmonized standards or statistically

representative sampling schemes and testing protocols exist for surveillance to inform a

regulatory and legal response against those who knowingly and deliberately distribute falsified

and substandard medicines.7,9,10 Adding to this complexity, national regulatory authorities are

inadequately trained, equipped, and funded to conduct routine and systematic surveillance of

their drug supply systems. Limited funding from donors to provide support for regulatory

systems strengthening and medicines quality monitoring affects the capacity of progressive

governments and engaged civil society organizations to collect statistically representative

samples of medicines to test for product quality.21 Ultimately, this creates a vicious cycle of a

poor evidence base perpetuating the lack of political will and global accountability in responding

to this scourge. This supplement offers insight into this issue from seven high-quality field

surveys, each using unique and robust sampling methodologies and testing protocols, thus

offering an important snapshot of recent field data on the quality of lifesaving medicines in lowand

middle-income economies.

 

Collectively, across the seven quality survey studies in the supplement, ~16,800 samples of

anti-malarials, anti-tuberculosis medicines, antibiotics, and anti-leishmaniasis medicines were

tested for quality and an estimated 9–41% of specimens failed quality specifications.22–28 These

studies used unique sampling and data collection strategies, including samples drawn from

nationally representative surveys, government and Interpol seizures, “mystery shoppers”

(unknown to the vendor), convenience samples, and overt and repeat randomized surveys. For

instance, Yeung and others conducted sampling using mystery shoppers and overt surveys in the

epicenter of antimalarial drug resistance in Cambodia. Survey results showed that, of 291

samples tested, mystery clients were more likely to receive an oral monotherapy, which is

banned in the country. Results also found that over 30% of the medicines collected did not fall in

the 85–115% range of the stated API and that there were no falsified anti-malarials; most of these

failures (58, 19.9%) were in the 75–84% unacceptably low range.22 Overall, the findings of this

study reflect the positive impact of the country’s effort to ban monotherapies and to control drug

quality. Also noted at the country level, Lalani and others randomly sampled 134 anti-malarials

from 60 outlets (public and private) in Afghanistan and found 26% failed disintegration testing,

as outlined in the Global Pharma Health Fund-MiniLab®, and a subsample of

sulfadoxine/pyrimethamine and quinine compounds failed U.S. Pharmacopeial (USP) tolerance

limits (32.4%, 12/37) when assessed by in vitro dissolution testing. This study suggests that

substandard drugs need to be considered within the context of poor bio-availbility, as well as

insufficient API, and highlights a need for a regular and systematic medicines quality

surveillance program in Afghanistan.23 The Artemisinin-based Combination Therapy (ACT)

Consortium Drug Quality Project Team/IMPACT2 study tested the quality of artemisinin-based

Anti-malarials from a nationally representative sample of Tanzania’s private sector. They found

that while none of the 1,737 anti-malarials were falsified, a minority were of poor quality;

medicines lacking WHO prequalification status were more likely to be poor quality.24 Of the

seven quality studies, results from the Medicines Quality Database at the USP Convention

contributed the largest sample of medicines; 15,063 samples were collected from 17 countries of

Africa, Asia, and South America. The highest proportion of failure was among anti-malarials,

6.5% between 2003 and 2013 (478/7,333).25 Tabernero and others used a random sampling

design and conducted a follow-up survey to detect poor-quality medicines in Lao People’s

Democratic Republic, assessing changes over time from 2003 to 2012. Although an overall

reduction in the number of poor-quality medicines was observed, the study detected that 25%

(9/37) of samples were outside pharmacopeial limits.26

 

Fadeyi and others tested 35 samples of antibiotics purchased in Ghana, Nigeria, and the

United Kingdom that were manufactured in six countries (China, Ghana, India, Nigeria, Ireland,

and the United Kingdom) using MiniLab® thin layer chromatography (TLC), in vitro dissolution,

and high-performance liquid chromatography photodiode array detection (HPLC-PAD). All

samples of amoxicillin released the expected amount of API within time and met the USP

tolerance limits. Of the 15 co-trimoxazole samples purchased, six (40.0%) (two from Ghana and

four from Nigeria) met USP tolerance limits but nine (60%; three from Ghana and six from

Nigeria) did not. Test results using MiniLab® TLC were inconsistent, highlighting the need to

invest in techniques such as HPLC and dissolution testing.27 On the other hand, Yong and others

obtained samples of antibiotics and anti-malarials from seizures conducted by Interpol and

medicine regulatory authorities and observed that one-third of all antibiotic and antimalarial

samples had API compositions outside pharmacopeial specifications (< 85% or > 115% API).

This study offers a model example of how multiple national and international enforcement and

regulatory agencies have come together to respond to poor-quality medicines.28

 

The majority of the publicly accessible rapid alert, reporting, and response networks and

databases for detecting, storing, and sharing information on global breaches in supply chain

security are voluntary, including among others the WHO Rapid Alert System, Medicines Quality

Database, WHO Western Pacific Region Rapid Alert System, and Worldwide Antimalarial

Resistance Network (WWARN) AQ Surveyor.21,29,30 However, while reporting is improving,

few countries submit their full complement of notable drug-quality events reports to these

databases due in part to not understanding the benefits of such reporting. This prevents decision

makers and the public from taking action, because data are incomplete, non-representative,

fragmented, and/or confidential. This complicates the challenge of gathering and galvanizing the

necessary evidence for technical assistance and regulatory action.9 Fortunately, Mackey and

others report on novel results from the Pharmaceutical Security Institute’s Counterfeit Incident

System (CIS), a nonpublic database collecting information on incidents of diversion, theft, and

fraud from 28 pharmaceutical companies. Of the 1,510 identified CIS reports involving falsified

medicines, 28% reported China as the country of origin of the incident/detection. In line with

other trends, the most prevalent falsified medicines were anti-infectives, mostly from Asian and

Latin American regions ( reported geographically) and from middle-income markets (reported

economically).31

 

POLICY PERSPECTIVES

 

The pandemic of poor-quality medicines requires an urgent and coordinated international

response. The authors in this section of the supplement argue that this can be achieved via a

multi-sectorial response, including a global convention32 and through tailored national model

laws.33 For example, Attaran argues that poor-quality medicines, as a criminal enterprise, exists

because present laws are unbalanced: “… the free trade laws that cause medicines to be globally

traded are not matched by criminal laws to prosecute those who illicitly traffic medicines, seize

their assets, and better secure the medicine supply chain.” Trade that is both open and free yields

benefits to many who would not otherwise have access to lifesaving drugs. When open and free

trade fails to have adequate legal oversight, the end user can be harmed, not infrequently

resulting in death, because criminality in the production and distribution of falsified and

substandard medicines is left unchecked.8 Attaran suggests that to protect public health and

secure the national drug supply chain require law reform that both stigmatizes the crimes as evil

and punishes the criminals in proportion to the harm they cause. Even in developed economies,

the penalties for producing and distributing falsified and substandard medicines are lamentably

weak. Until recently, Canada imposed a maximum penalty of 3 years’ imprisonment and a

$5,000 fine for adulterating a medicine, France levels only 3 years’ imprisonment and a €75,000

fine, while in Norway incarceration is just 4 months for this crime. In the Netherlands, the crime

for production of a substandard medicine requires that the perpetrator commit the act twice in 2

years—the first violation is excused—and then the prison term is only 6 months maximum.

Attaran argues that countries should ideally “have laws that target and suppress the harmful

elements of the global medicine trade—the substandard and falsified medicines—without

interfering with the legitimate trade in either branded or generic medicines. This is a goal that the

public health community, the law enforcement community, and the pharmaceutical industry

should all be able to agree on.” To this end, a Model Law on Medicine Crime has been drafted

that stresses compatibility with a country’s existing laws and is available free online at

http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2530087.

 

Similarly, Nayyar and others suggest that to have a lasting and sustained impact, this

response must focus on increasing the information on, and availability of, standardized detection

technologies, national legislation bolstered by an international law/convention addressing

technical–financial–legal dimensions, and, most urgently, a leading organization, with technical

expertise and influence similar to that of the FDA, that can coordinate cross-sectorial

stakeholders and mobilize resources in a transparent manner. These recommendations have

notable and effective precedents for using international law in this way. For example, a 1929

international treaty criminalized counterfeit currency and the Framework Convention on

Tobacco Control (FCTC), and its associated protocols, prohibited illicit trafficking of tobacco

products. Indeed, the FCTC has realized over $250 million in new funding for global tobacco

control efforts and reduced the availability of health-harming tobacco products, thus

demonstrating that an international treaty can both raise needed operational revenues and have a

health impact. The FCTC provides an excellent model for combatting falsified and substandard

medicines.32,34

 

Finally, Cinnamond and Woods,35 of the Global Fund to Fight HIV/AIDS, Tuberculosis and

Malaria (GFATM), describe the newly established Joint Inter-Agency Task Force and Global

Steering Committee for the Quality Assurance of Health Products. These two proactive units,

based within a major supplier of antiretroviral, anti-tuberculosis, and antimalarial drugs, offer a

systematic and coordinated approach to promoting and protecting access to safe and effective

medicines in low- and middle-income countries that are recipients of the GFATM financing

mechanism.

 

CONCLUSIONS

 

The threat of poor-quality medicines presents a real and present danger to decades of effort

and success by many governments, multilateral organizations, philanthropies, and private sector

groups in fighting HIV/AIDS, tuberculosis, malaria, and many other conditions that have

witnessed steady and significant declines in mortality worldwide. These public health triumphs

are due in part to access by families to safe, effective, high-quality, and affordable medicines and

medicinal products, as articulated by the FDA Commissioner. However, as shown in this

supplement, survey data from over 17 countries reveal that poor-quality medicines and medicinal

products represent a pandemic of grave concern to the health and well-being of populations

globally, but especially those living in low- and middle-income nations where national drug

regulatory systems and policies are weak or ineffective for lack of enforcement. Fortunately, new

techniques for sampling and detecting falsified and substandard medicines proposed in this

supplement merit further study for validity in field settings and, if proven effective, should offer

venture capitalists and other funders opportunities for investment to bring these tools to scale so

governments can secure their medicine supply systems. Nonetheless, no tool or technique is of

any value if not backed by good governance and the rule of law. To this end, a global convention

that addresses the technical–financial–legal dimensions of the pandemic of falsified and

substandard medicines, coupled with a Model Law on Medicine Crime offers national

governments valuable tools to address these weaknesses through normative guidance, evidence based

policies, and tough legal and financial penalties for those who manufacture and/or

distribute falsified and substandard medicines and medical products. We hope this clarion call to

action will be heard and acted upon by policy makers and leaders at international and national

levels.

 

REFERENCES PROVIDED AT WEBSITE LINK: http://www.ajtmh.org/content/early/2015/04/16/ajtmh.15-0221.full.pdf+html?utm_source=PassBlue+List&utm_campaign=54c0c8fb67-RSS_NYU_SU15&utm_medium=email&utm_term=0_4795f55662-54c0c8fb67-54981461

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WUNRN

http://www.wunrn.com

 

UNODC - UN Office on Drugs & Crime

 

http://www.unodc.org/unodc/en/fraudulentmedicines/introduction.html

 

UNODC Resolution on FRAUDULENT MEDICINES

http://www.unodc.org/documents/organized-crime/FM/Resolution_20_EN.pdf

 

FRAUDULENT MEDICINES - TRAFFICKING +

June 4, 2014 - Fraudulent medicines pose a considerable public health threat as they can fail to cure, may harm and even kill patients.  These threats to public health have led the international community to call for a stronger and more coordinated response. Compounding this public health risk is the fact that the supply chain for medicines operates at a global level, and therefore, a concerted effort at the international level is required to effectively detect and combat the introduction of fraudulent medicines along this supply chain.

The 20th session of the Commission on Crime Prevention and Criminal Justice (CCPCJ) adopted resolution 20/6 on fraudulent medicines, otherwise referred to as falsified medicines due to concern about the involvement of organized crime in the trafficking in fraudulent medicines. At the same time, resolution 20/6 highlights the potential utility of the United Nations Convention against Transnational Organized Crime (UNTOC) for which UNODC is the guardian, in re-enforcing international cooperation in the fight against trafficking, through, its provisions, inter alia, on mutual legal assistance, extradition and the seizing, freezing and forfeiture of the instrumentalities and proceeds of crime.

As with other forms of crime, criminal groups use, to their advantage, gaps in legal and regulatory frameworks, weaknesses in capacity and the lack of resources of regulatory, enforcement and criminal justice officials, as well as difficulties in international cooperation.  At the same time, the prospect of the comparatively low risk of detection and prosecution in relation to the potential income make the production and trafficking in fraudulent medicines an attractive commodity to criminal groups, who conduct their activities with little regard to the physical and financial detriment, if not the exploitation, of others.

Resolution 20/6 contains nine action points among which paragraph nine requests that UNODC, in cooperation with other United Nations bodies and international organizations, such as the International Narcotics Control Board (INCB), the World Health Organization (WHO), the World Customs Organization (WCO) and the International Criminal Police Organization (ICPO/INTERPOL), as well as relevant regional organizations and mechanisms, national regulatory agencies for medicines and, where appropriate, the private sector, civil society organizations and professional associations, assist Member States in building capacity to disrupt and dismantle the organized criminal networks engaged in all stages of the illicit supply chain, in particular distribution and trafficking, to better utilize the experiences, technical expertise and resources of each organization and to create synergies with interested partners.

While focus has been given to the health and regulatory aspect of this problem, it appears that less attention has been given to the issue from a criminal justice perspective.  Given its expertise and work to build effective and transparent criminal justice systems and to support states to prevent and combat all forms of organized crime, UNODC can support the fight against the illicit manufacture and trafficking of fraudulent medicines in coordination with other stakeholders.

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http://www.fraud.org/learn/counterfeit-drugs

 

COUNTERFEIT DRUGS

Consumers have lots of choices in buying prescription drugs these days. But as you search for the best price or most convenience, be careful about the source of your medications. Counterfeit drugs are on the rise, so you need to be vigilant about the quality and integrity of the drugs you buy. You might throw your money away on ineffective drugs, or even worse, you could be harmed by taking drugs that aren’t what they pretend to be.Learn more to protect yourself and your loved ones from the dangers of counterfeit drugs.

• Know your medications. If you know the size, shape, color, taste, and side effects of the prescriptions you take, you will more easily identify possible counterfeits. Contact your pharmacist or doctor if you notice anything different about a medication.
• Pay attention to packaging. Check for altered or unsealed containers, or changes in the packaging or label. Contact your pharmacist or doctor if you notice any changes.
• Only buy prescription medications from a safe, reputable source. If the seller is unfamiliar check with your state board of pharmacy or the National Association of Boards of Pharmacy atwww.nabp.net or call 847-391-4406. These sources can tell you if the pharmacy is licensed.
• When you buy medications online, make sure the seller is properly licensed. Check with your state board of pharmacy or the National Association of Boards Pharmacy at www.nabp.net or call 847-391-4406. These sources can tell you if the online seller is licensed. You should check the state board of pharmacy where the online seller is located, and your own state board of pharmacy. Some sites display a seal, such as the National Association of Boards of Pharmacy’s VIPPS seal, as proof that the site has met state and federal requirements. Dealing with pharmacies that display the VIPPS seal, which means they are Verified Internet Pharmacy Practice Site, or other similar certification seals, gives you more confidence that they and the products they sell are legitimate. See a list of VIPPS-accredited pharmacies.
• If you believe you have bought a counterfeit drug, report it. Contact the pharmacist who sold you the medication. Your pharmacist will know if there has been a legitimate change in the color, shape, taste or packaging of the medication. You can also report your suspicions to the Food and Drug Administration (FDA). If you bought the drug by mail, by telephone, or in person, contact the FDA’s Medwatch program at 1-800-332-1088 or at http://www.fda.gov/medwatch. To report a counterfeit drug that you bought on the Internet, use this online form or call the Medwatch number. In addition, ask your doctor for medical advice if you have taken drugs you suspect are counterfeit.

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USA Food & Drug Administration - FDA

http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/default.htm

 

MEDICATION HEALTH FRAUD

 

In general, health fraud drug products are articles of unproven effectiveness that claim to treat disease or improve health. In addition to wasting billions of consumers' dollars each year, health scams can lead patients to delay proper treatment and cause serious—and even fatal—injuries. FDA is very concerned about these fraud products, and removing these products from the market remains one of the Agency's top priorities.

Health Fraud and Consumer Outreach Branch¹

Health Fraud Scams²

Cracking Down on Health Fraud³

Weight Loss Fraud⁴