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3 The Magnitude of the Problem
Pages 85-136

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From page 85...
... There are few epidemiologically rigorous, peer-reviewed studies on the prevalence of falsified and substandard drugs. This chapter presents the results of a cross section of government and industry data and peer-reviewed and gray literature about the global burden of falsified and substandard drugs.
From page 86...
... The interconnectedness of the drug supply chain makes it imperative that countries share information on falsified and substandard drugs. The Pharmaceutical Security Institute Incident Reporting System The Pharmaceutical Security Institute (PSI)
From page 87...
... Some countries with serious problems never appear in incident reports because there is little political will for action. For the same reason, some countries with transparent and accountable governments consistently appear in the ranking of numbers of seizures by countries (PSI data shared with the committee, Thomas Kubic, PSI-Inc., July 11, 2012)
From page 88...
... Analysis of PSI data supports two main conclusions. First, falsified and substandard drugs are a global problem that affected at least 124 countries in 2011 (PSI data shared with the committee, Thomas Kubic, PSI-Inc., July 11, 2012)
From page 89...
... bIncident reports include thefts worth roughly $100,000 or more. SOURCE: PSI data shared with the committee, Thomas Kubic, PSI-Inc., July 11, 2012.
From page 90...
... Much of their information about falsified and substandard drugs is confidential, but their publications give a sense of the types of violations regulators find. The FDA Office of Criminal Investigations The FDA Office of Criminal Investigations takes action against criminal violations of the Food, Drug, and Cosmetic Act, such as illegal drug manufacture, manufacture and sale of unapproved drugs, illegal importation, drug adulteration, and promotion of off-label uses for approved products (FDA, 2009a,b)
From page 91...
... SOURCE: BMI, 2012. Latin America 16% Middle East 5% Africa 3% Asia 51% North America 10% Europe 15% FIGURE 3–3 Geographic distribution of Pharmaceutical Security Institute incident reports, affected countries, 2011 data.
From page 92...
... Interpol has raised international awareness about falsified and substandard drugs through their media campaigns and work with police (Interpol, 2011a; Mullard, 2010)
From page 93...
... THE MAGNITUDE OF THE PROBLEM 93 TABLE 3–3 Operation Pangea Against Online Pharmacies, 2008-2012 Number of Operation Countries Name Participating Duration Year Results Pangea V 100 1 week 2012 • 3.75 million pills confiscated • Estimated value: $10.5 million • 18,000 websites shut down • 133,000 packages inspected and 6,700 confiscated • 80 suspects under investigation or arrest Pangea IV 81 1 week 2011 • 2.4 million pills confiscated • Estimated value: $6.3 million • 13,500 websites shut down • 45,500 packages inspected and 8,000 confiscated • 55 suspects under investigation or arrest Pangea III 44 1 week 2010 • 2 million pills confiscated • Estimated value: $6.77 million • 297 websites shut down • 87 suspects under investigation or arrest Pangea II 25 5 days 2009 • Identification of 1,200 websites engaged in pharmaceutical crime • 153 websites shut down • 59 suspects investigated Pangea I 10 1 day 2008 • Commercial websites taken down • Postal deposits monitored and parcels examined, packages containing suspected counterfeit medicines intercepted • Thousands of medicines withdrawn from circulation SOURCE: Adapted from Interpol, 2012b.
From page 94...
... Newspapers, court documents, and other gray literature sources also contain valuable information about drug quality lapses. Convenience surveys and case reports can be useful for identifying a problem in particular product lines or building momentum for further research.
From page 95...
... •  onvenience surveys suggest serious problems with antimicrobial C drug quality in low- and middle-income countries, and especially with antimalarial quality in sub-Saharan Africa and Southeast Asia. Case Reports A great deal of literature on falsified and substandard drugs describes problems that emerge only after patients have been harmed (Ravinetto et al., 2012)
From page 96...
... An overview of case studies and gray literature is helpful to understanding falsified and substandard drugs. Gray literature compendiums and peerreviewed case studies indicate where and in what product lines drug quality problems occur.
From page 97...
... . Antimalarials in Southeast Asia and sub-Saharan Africa  There is consistent survey evidence that antimalarial drugs, medicines bought around 200 million times per year, mostly for children under the age of 5, are often of poor quality (WHO, 2011b)
From page 98...
... For these reasons, they are often the target of criminals and unscrupulous manufacturers. A WHO study of antimalarial drug quality in six African countries4 used a stratified convenience sample (WHO, 2011a)
From page 99...
... of one or more active ingredients less than the pharmacopoeial limit (Q) minus 25%.
From page 100...
... . Investigators classified all drugs failing packaging analysis as falsified, as well as those substandard drugs that contained no active ingredient or an ingredient not listed on the label (Nayyar et al., 2012)
From page 101...
... . Researchers in southeast Nigeria attempted to include unlicensed private medicine dealers in their sample of antimalarial drug quality (Onwujekwe et al., 2009)
From page 102...
... Though most epidemiologically rigorous research on drug quality has tested antimicrobial drugs, there is some information about other essential medicines. In a 2012 study, Stanton and colleagues prepared an exhaustive sampling frame of formal and informal drug sellers in three districts in Ghana (Stanton et al., 2012)
From page 103...
... . More research adhering to the checklist in Table 3-8 would allow for a better understanding of the burden of falsified and substandard drugs, and it would facilitate valid comparisons of the problem among countries and over time.
From page 104...
... This lack of clarity impedes coordinated international action. • The WHO rapid alert system is a promising program to track falsified and substandard drugs in low- and middle-income countries.
From page 105...
... What did the collector say in buying the medicines? Statistical methods 8 Describe the data analysis techniques used Ethical issues 9 Whether ethical approval was sought and whether the study encountered any ethical issues Packaging 10 Packaging examination and reference standards Chemical analysis 11 Chemical analysis and dissolution testing procedures and location(s)
From page 106...
... Do these outlets differ systematically from those in which samples were obtained? Packaging and chemical 16 • Packaging and chemistry results and their results relationship • Details of products sampled -- how many, in what drug classes, countries of origin, batch numbers, manufacture and expiry dates • Results for each analysis -- packaging, % active ingredient, dissolution • Additional information could be included in supplementary material Category of poor-quality 17 A clear statement for each medicine sample medicine detected, whether the investigators class it as genuine, counterfeit, substandard, or degraded, with an explanation as to why and whether the medicine was registered with the government in the location(s)
From page 107...
... The committee sees great promise in this system for other developing countries. The WHO Global Capacity-Building Project There are currently no accurate estimates of the global burden of falsified and substandard drugs.
From page 108...
... poorly equipped for surveillance or enforcement. A recent WHO project attempts to correct this problem by building a "coordinated, continuous, and ongoing global surveillance and monitoring system" for falsified and substandard drugs (WHO, 2012b, p.
From page 109...
... Regulators from the 10 pilot countries testing the rapid alert form and incident investigation system had training on the system in September 2012. The pilot testing ran until December 2012 (personal communication, Michael Deats, WHO, October 12, 2012)
From page 110...
... For example, if the data indicate that substandard medicines are the main drug quality problem in one part of the world, then better regulation of manufacturers can do much to improve the problem. Similarly, if it becomes clear that a country has a problem with diverted medicines in commerce, then some of the distribution chain improvements presented in Chapter 5 would enhance the national drug safety program.
From page 111...
... TABLE 3–5 The Pharmaceutical Security Institute's 2011 Open-Source Review Therapeutic Country Action Justificationa Quantity Category Drugs Value Arrests Afghanistan Destroyed Substandard & 32 tons Unknown Unknown $- 0 expired Angola Seized-arrests Illegal 1,000 kilos Unknown Unknown $- 419 Bangladesh Arrests Counterfeit Unknown Unknown Unknown $- 2 Brazil Seized Diverted Cytostatic, Cancer and $120,000 0 metabolism transplant Brazil Sentence Counterfeit $2.5 million in damages Unknown Androcur $- 0 Brazil Seized Counterfeit 46,688 dosage units Multiple Multiple $- 0 Brazil Seized Unknown 168 seizures Unknown Unknown $- 0 Canada Seized-arrests Counterfeit 100,000 dosage units Genitourinary ED $1,000,000 1 Chile Seized-arrests Illegal 12,000 dosage units CNS Psychotropic $- 2 China Destroyed Counterfeit & 60 tons Genitourinary, ED & diabetes $6,000,000 0 substandard metabolism China Sentence Counterfeit Cytostatic Oncology $- 1 China Sentence Counterfeit Cytostatic Oncology $- 11 China Seized-arrests Counterfeit Unknown Unknown $3,000,000 263 China Seized-arrests Counterfeit 6,900,000 dosage units Genitourinary ED $- 15 China Seized-arrests Counterfeit 201 types of drugs Unknown Unknown $- 23 China Seized-arrests Counterfeit Unknown Unknown $314,000,000 1,770 continued 111
From page 112...
... TABLE 3–5 Continued 112 Therapeutic Country Action Justificationa Quantity Category Drugs Value Arrests China Sentence Counterfeit Unknown Unknown $- 1 China Seized-arrests Counterfeit Unknown Unknown $29,884,160 114 China Sentence Counterfeit 840,000 dosage units Unknown Unknown $4,720,000 8 China Seized-arrests Counterfeit Unknown Unknown $33,000,000 121 China Seized Counterfeit 800 boxes, 121 types of Unknown Unknown $253,440 0 drugs China Seized-arrests Illegal 14,000 dosage units Hormones Abortion $- 1 Colombia Seized Adulterated & 7.5 tons Unknown Unknown $- 0 expired Colombia Sentence Unknown Unknown Unknown $- 288 Colombia Seized Illegal 436,180 dosage units Unknown Unknown $- 0 Colombia Seized-arrests Counterfeit 150,000 dosage units Cytostatic, Cancer & HIV/AIDS $- 22 anti-infective Cyprus Seized Counterfeit & 7,500 dosage units Unknown Unknown $- 0 illegal Czech Republic Seized-arrests Counterfeit Unknown Hormones Anabolic steroids $- 11 Dominican Seized-arrests Adulterated Unknown Unknown $31,000 3 Republic Ghana Arrest Illegal Anti-infective Antimalarial $- 1 Ghana Arrest Illegal Anti-infective HIV/AIDS $- 0 Ghana Detection Illegal Anti-infective Antimalarial $- 0
From page 113...
... India Seized-arrests Counterfeit 32 packs Unknown Blood glucose test $- 3 strips India Seized-arrests Counterfeit 250,000 dosage units Respiratory Coscold (cough $- 3 tablets) India Arrests Counterfeit Unknown Glucose-D $- 3 India Seized-arrests Counterfeit Unknown Unknown $74,800 3 India Seized-arrests Counterfeit 600 boxes Unknown Crocin suspension $- 2 India Seized-arrests Counterfeit Unknown Unknown $5,610 5 India Arrests Unknown Unknown Unknown $- 4 India Seized Spurious 388,000 dosage units Anti-infective Antibiotics $- 0 India Arrests Unknown Unknown Unknown $- 4 India Seized-arrests Spurious & Unknown Unknown $48,620 2 contraband India Seized-arrests Illegal CNS Psychotropic $4,114,072 10 India Seized Counterfeit Unknown Unknown $233,754 0 Indonesia Seized Illegal Unknown Unknown $8,899 0 Israel Seized-arrests Counterfeit 230,000 dosage units Metabolism, Weight loss & ED $- 1 genitourinary Israel Sentence Unknown Genitourinary ED $- 1 Israel Seized Counterfeit 100,000 dosage units Genitourinary ED $- 0 Kenya Detection Counterfeit 1,340 batches Anti-infective HIV/AIDS $- 0 Lebanon Seized-arrests Counterfeit 200 large boxes Unknown Unknown $- 2 Mexico Theft Stolen 98 cases Unknown Unknown $- 0 113 continued
From page 114...
... TABLE 3–5 Continued 114 Therapeutic Country Action Justificationa Quantity Category Drugs Value Arrests Mozambique Seized-arrests Diverted Anti-infective HIV/AIDS $5,200 9 Nigeria Seized Illegal Anti-infective Antimalarial $- 0 Nigeria Seized Counterfeit & 844 cartons Unknown Unknown $1,906,577 0 unregistered Nigeria Arrest Illegal Unknown Unknown $- 0 Nigeria Seized Counterfeit Unknown Unknown $- 0 Nigeria Seized Illegal Unknown Unknown $- 5 Nigeria Seized Illegal Unknown Unknown $- 0 Nigeria Arrests Illegal Unknown Unknown $- 30 Nigeria Seized Illegal Anti-infective Antibacterial $1,900 0 Nigeria Detection Counterfeit Unknown Unknown $12,710 0 New Zealand Arrests Unknown Unknown Unknown $- 1 Pakistan Charged Unlicensed & Unknown Unknown $- 0 spurious Pakistan Arrests Spurious & Unknown Unknown $- 1 substandard Pakistan Seized-arrests Counterfeit Anti-infective Antibiotics $- 3 Pakistan Charged Spurious Unknown Unknown $- 0 Pakistan Arrests Spurious & Unknown Unknown $- 4 unauthorized Pakistan Sentence Spurious & Unknown Unknown $- 1 substandard
From page 115...
... Pakistan Seized Spurious Anti-infective Vaccine $- 0 Pakistan Seized-arrests Counterfeit Anti-infective Antibiotics $220,535 12 Pakistan Charged Spurious & Unknown Unknown $- 11 substandard Peru Seized Unknown 15,000 dosage units Unknown Unknown $7,000 0 Peru Destroyed Adulterated & 22 tons Unknown Unknown $7,000,000 0 expired Philippines Seized Counterfeit 1,000 boxes Genitourinary ED $70,375 0 Portugal Seized Unknown 133,000 dosage units Genitourinary, ED & weight loss $- 0 metabolism Russia Seized Illegal 2.9 million counterfeited Unknown Unknown $- 0 goods Singapore Seized Illegal Metabolism, Weight loss & $10,896 0 hormones birth control Slovakia Seized Counterfeit 128,000 dosage units Hormones, Steroids & ED $- 0 genitourinary South Korea Charged Counterfeit Genitourinary ED $- 15 Spain Seized-arrests Counterfeit & 710,000 dosage units Hormones, Steroids & ED $- 26 illegal genitourinary Spain Seized-arrests Illegal 23,000 dosage units Hormones Anabolic steroids $- 1 Taiwan Seized-arrests Counterfeit & Metabolism, Weight loss & ED $- 168 illegal genitourinary Tanzania Detection Illegal Anti-infective Antibiotics & $- 7 antimalarial continued 115
From page 116...
... TABLE 3–5 Continued 116 Therapeutic Country Action Justificationa Quantity Category Drugs Value Arrests Thailand Seized-arrests Counterfeit Metabolism Weight loss $969,932 10 Thailand Seized-arrests Illegal CNS, genitourinary Sleeping & ED $3,233 2 UAE Seized Illegal 1,000,000 dosage units Genitourinary ED $- 0 UAE Arrest Illegal 70,000 dosage units Genitourinary ED $- 0 Uganda Detection Counterfeit Anti-infective Anti-malarial $6,072 0 UK Sentence Counterfeit & Unknown Genitourinary ED $- 1 illegal UK Sentence Illegal Unknown Hormones, HGH & ED $- 1 genitourinary UK Seized Counterfeit & 8.5 million dosage units Genitourinary ED $- 0 illegal UK Seized-arrests Counterfeit & Unknown Unknown $1,615,600 3 illegal UK Sentence Counterfeit Genitourinary ED $- 5 UK Sentence Counterfeit 896,000 dosage units Multiple Multiple $- 1 UK Sentence Counterfeit Genitourinary ED $- 2 UK Sentence Counterfeit 800 dosage units Respiratory Inhalers $- 1 UK Arrest Illegal CNS Pain management $- 1 UK Sentence Counterfeit Genitourinary ED $- 1 UK Sentence Stolen Multiple Multiple $- 1 UK Seized Counterfeit & 1.2 million dosage units Multiple Multiple $- 0 illegal
From page 117...
... SOURCE: PSI data shared with the committee, Thomas Kubic, PSI-Inc., July 11, 2012.
From page 118...
... Analyzed Country Drugs Studied Substandard Drug Hu et al. Not reported China Macrolides: FCIS consisting of two color (2006)
From page 119...
... . In total, 3% versus 1% contained no active ingredient, 12% versus 4% had too little or too much active ingredient and 35% versus 14% had weight variation outside pharmacopoeial limits.
From page 120...
... Analyzed Country Drugs Studied Substandard Drug Prazuck et al. 21 Northern Antimicrobials Drug quantitative analysis was (2002)
From page 121...
... No metronidazole suspension met pharmacopoeial specifications. Several antibacterial preparations contained very low quantities of active ingredient (ampicillin and amoxicillin 24% to 40%)
From page 122...
... Drug quality was Hogerzeil of 26 benzylpenicillin, measured by level of active (1998) brands of amoxicillin, ampicillin, ingredient as percentage 13 essential doxycycline, phenyl- of stated content and by drugs methoxypenicillin, and compliance (pass/fail)
From page 123...
... substandard, including two (15%) content of active ingredient with low rifampicin content, one (8%)
From page 124...
... Analyzed Country Drugs Studied Substandard Drug Roy 137 brands Bangladesh Ampicillin, TMP–SMX Not reported (1994) Taylor et al.
From page 125...
... Chemical estimation of seven The dissolution rate and Not reported different marketed brands of disintegration time of tetracycline/HCl capsules for substandard drugs were tetracycline content showed that in accordance with USP six brands were not meeting specifications. The bioavailability the pharmacopoeia prescribed of substandard product as standards.
From page 126...
... , mass spectroscopy, pollen analysis, X-ray diffraction, packaging analysis U.S. Pharmacopeia China 2004 Artesunate, quinine, HPLC, thin layer (2004)
From page 127...
... Not tested NA private outlets continued
From page 128...
... Senegal, Uganda combination quality testing treatment, according to U.S. sulfadoxine- Pharmacopeia pyrimethamine standards WHO Cameroon, 2008 Artermisinin- Compendial (2011)
From page 129...
... Not tested NA private outlets Private Random 284 119/284 (42%) Not tested NA and public pharmacies and outlets Public and Random 27 15/27 (56%)
From page 130...
... Ghana, Kenya, Not provided Artesunate, Thin layer (2008) Nigeria, Rwanda, artemether, chromatography Tanzania, Uganda dihydroartermisinin, or dissolution artemether- analysis lumefantrine, sulfadoxine pyrimethamine, mefloquine, amodiaquine Ofori-Kwakye Ghana Not provided Artesunate Colorimetric tests, et al.
From page 131...
... Not tested NA private outlets Private Stratified 225 60/225 (27%) Not tested NA and public random pharmacies sampling and outlets continued
From page 132...
... , unless otherwise indicated. Samples failing chemical assay analysis might have failed packaging analysis; HPLC = high-perfomance liquid chromatography; NA = not applicable; NS = not specified.
From page 133...
... * ¶ private and public pharmacies ‡ 115 samples from Laos were randomly selected.
From page 134...
... http://www.interpol.int/Crime-areas/Pharmaceutical-crime/ Operations/Operation-Storm (accessed November 6, 2012)
From page 135...
... PSI-Inc. (Pharmaceutical Security Institute)
From page 136...
... 1999. Counterfeit and substandard drugs in Myanmar and Viet Nam: Report of a study carried out in cooperation with the governments of Myanmar and Viet Nam.


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