• English
• Español
• 中文
• Português

• About USP
• USP–NF
• Food Chemicals Codex
• Pending & Non-US Standards
• Reference Standards
• USP Verified
• Pharmacopeial Education
• USP in Developing Countries
  • Where We Work
  • What We Do
  • Priority Issues
  • What is Drug Quality?
  • Drug Information
  • Continuing Education
  • News & Events
  • Drug Information Updates
    • Archives
  • Resources
  • Support and Partners
• Meetings
• Products

On a monthly basis, USP DQI will supply new information on priority drugs, including antimicrobials, and new therapies that are published in authoritative medical and scientific journals or on reliable Internet sites.

November 2008 Update

Roles for pharmacy in combating counterfeit drugs

Background: The objectives of this study were to describe (1) the international scope of counterfeit drugs, (2) international and U.S. anticounterfeiting initiatives, and (3) the enhanced roles and challenges facing pharmaceutical organizations and individual pharmacists to thwart counterfeit drugs. Data sources included PubMed and Ovid from 1970 to 2008 using the search terms counterfeit drugs, counterfeit pharmaceuticals, and counterfeit medicines, with English as the limiting term. Nonprimary literature sources included the U.S. Food and Drug Administration (FDA) Web site (www.fda.gov) from 1990 to 2008 using the search term counterfeit drugs; presentations from meetings or workshops attended or accessed via the Internet; and Web sites of professional organizations. Additional resources were identified from personal bibliographies collected by the author and bibliographies of gathered articles.

Methods/Intervention/Results: Counterfeit drugs–defined as those containing no active ingredient, an incorrect amount of active ingredients, incorrect ingredient, and/or unapproved labeling and packaging–represent an unquantified problem of international proportions. The existing situation has been facilitated by inconsistent national regulatory oversight, disparate unlinked databases, lack of unified anticounterfeiting actions, and inability to track the distribution of domestically produced or imported drug products between, among, and within nations. In the United States, several important anticounterfeiting initiatives announced by FDA in 2004 have been implemented, but the benefits of others, such as electronic tracking of a drug's movement through the U.S. distribution chain to a dispensing pharmacy, will not be realized in the near future. The role of pharmacists as patient educators, prudent purchasers, and detectors of counterfeit drugs can typically be accomplished with minimal added expense or work; however, the impact of electronic tracking on pharmacies' expenses and workflow is unknown. Pharmacists need to be included in efforts to thwart receipt of counterfeit drugs by patients, but this must be accomplished with minimal negative impact on pharmacy practices.

Authors' Conclusions: Although consistent detection of counterfeit drugs is difficult, pharmacists can take several reasonable measures to lessen the chances they are dispensing counterfeit drugs. However, the increased role of pharmacists is accompanied by several important challenges involving increased expense and altered business practices.

Citation: Ziance RJ. J Am Pharm Assoc 2008: 48(4): e71-88.

Obstacles to prompt and effective malaria treatment lead to low community-coverage in two rural districts of Tanzania

Background: Malaria is still a leading child killer in sub-Saharan Africa. Yet, access to prompt and effective malaria treatment, a mainstay of any malaria control strategy, is sub–optimal in many settings. Little is known about obstacles to treatment and community–effectiveness of case–management strategies. This research quantified treatment–seeking behavior and access to treatment in a highly endemic rural Tanzanian community. The aim was to provide a better understanding of obstacles to treatment access in order to develop practical and cost–effective interventions.

Methods/Intervention/Results: The authors conducted community–based treatment–seeking surveys including 226 recent fever episodes in 2004 and 2005. The local Demographic Surveillance System provided additional household information. A census of drug retailers and health facilities provided data on availability and location of treatment sources.

After intensive health education, the biomedical concept of malaria has largely been adopted by the community. 87.5% (78.2–93.8) of the fever cases in children and 80.7% (68.1–90.0) in adults were treated with one of the recommended antimalarials (at the time SP, amodiaquine or quinine). However, only 22.5% (13.9–33.2) of the children and 10.5% (4.0–21.5) of the adults received prompt and appropriate antimalarial treatment. Health facility attendance increased the odds of receiving an antimalarial (OR=7.7) but did not have an influence on correct dosage. The exemption system for under–fives in public health facilities was not functioning and drug expenditures for children were as high in health facilities as with private retailers.

Authors' Conclusions: A clear preference for modern medicine was reflected in the frequent use of antimalarials. Yet, quality of case-management was far from satisfactory as was the functioning of the exemption mechanism for the main risk group. Private drug retailers played a central role by complementing existing formal health services in delivering antimalarial treatment. Health system factors like these need to be tackled urgently in order to translate the high efficacy of newly introduced artemisinin–based combination therapy (ACT) into equitable community-effectiveness and health-impact.

Citation: Hetzel MW, et al. BMC Public Health 2008; 8(1): 317 [Epub ahead of print].

Detecting counterfeit antimalarial tablets by near-infrared spectroscopy

Summary: Counterfeit antimalarial drugs are found in many developing countries, but it is challenging to differentiate between genuine and fakes due to their increasing sophistication. Near–infrared spectroscopy (NIRS) is a powerful tool in pharmaceutical forensics, and the authors tested this technique for discriminating between counterfeit and genuine artesunate antimalarial tablets. Using NIRS, they found that artesunate tablets could be identified as genuine or counterfeit with high accuracy. Multivariate classification models indicated that this discriminatory ability was based, at least partly, on the presence or absence of spectral signatures related to artesunate. This technique can be field–portable and requires little training after calibrations are developed, thus showing great promise for rapid and accurate fake detection.

Citation: Dowell FE, et al. J Pharm Biomed Anal 2008 [Epub ahead of print].

Assessment of hand–held Raman instrumentation for in situ screening for potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy and direct ionization mass spectrometry

Summary: Pharmaceutical counterfeiting has become a significant public health problem worldwide and new, rapid, user–friendly, reliable and inexpensive methods for drug quality screening are needed. This work illustrates the chemical characterization of genuine and fake artesunate antimalarial tablets by portable Raman spectroscopy and validation by FT–Raman spectroscopy and ambient mass spectrometry. The applicability of a compact and robust portable Raman spectrometer (TruScan) for the in situ chemical identification of counterfeit tablets is reported.

Citation: Ricci C, et al. Anal Chim Acta 2008; 623(2): 178-86.

Quality of amoxicillin formulations in some Arab countries

Background:The problem of counterfeit and substandard drugs is recurrent in developing countries where antibiotics account for the majority of such products. The aim of this study was to investigate the quality of locally produced and imported amoxicillin products on the Lebanese, Jordanian, Egyptian and Saudi markets.

Methods/Intervention/Results: One hundred and eleven samples of amoxicillin capsules and suspensions purchased from retail pharmacies were analyzed for their drug content by a validated chromatographic method in order to verify if they complied with pharmacopeial requirements. Suspensions were analyzed for their drug content immediately after reconstitution as well as 7 or 14 days later according to the expiry date.

Fifty–six per cent of amoxicillin capsules did not meet the United States Pharmacopeia (USP) requirements and most had amounts bordering the lower limit. Individual average values as low as 59% of the label claim were detected. Eight percent of the samples of suspensions gave measurements outside pharmacopeial limits. Furthermore, after 7 or 14 days, 38% of the samples were outside the pharmacopeial limits. All the European brands met the pharmacopeial limits except for one.

Authors' Conclusions: The results of this study reveal the high incidence of substandard drugs on some Arab markets where several factors might jeopardize the quality status of medicines: lack of effective quality assurance system during manufacture in both Arab and export countries, and uncontrolled storage conditions, especially unsuitable pharmacy premises. Use of substandard antibiotic preparations increases the risk of therapeutic failure and the emergence of drug–resistant microorganisms.

Citation: Kyriacos S, et al. J Clin Pharm Ther 2008; 33(4): 375-9..

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

Summary: Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed.

Authors' Conclusions: Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drug supply. International donors must help support and coordinate these efforts.

Citation: Amon JJ. Global Health 2008; 4: 5.

A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia

Background: Since 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.

Methods/Intervention/Results: With evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High–performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to approximately 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine ('ecstasy'). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People's Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.

Authors' Conclusions: : An international multi–disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross–disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.

Citation: Newton PN, et al. PLoS Med 2008; 5(2): e32.

Bad medicine in the market

Summary: Counterfeit medicines are an insidious threat to global health, and the risks they pose have been largely underestimated to date. Apart from failing to cure disease, they can cause mental and physical damage–and even death. Fake drugs containing insufficient active ingredients breed resistance, which can make standard drugs useless. No area of the world is unaffected, but mounting evidence shows that the problem is disproportionately severe in developing and emerging–market countries, which also have the highest burden of infectious diseases. Countries have the primary responsibility–both in stopping criminal manufacturing and distribution and in protecting their citizens from counterfeit products–but multilateral organizations such as the World Health Organization (WHO) must do more to expose the problem and help countries tighten regulatory controls. While monitoring of outright fakes is improving and arrests of those trading in them are increasing, some global agencies are promoting drugs they assume to be good copies of branded drugs but which are probably substandard.

Authors' Conclusions: Global agencies must stop this double standard and develop effective methods of improving detection of all substandard products.

Citation: Roger B, et al. World Hosp Health Serv 2007; 43(3): 17–21.

An LC method for the simultaneous screening of some common counterfeit and substandard antibiotics validation and uncertainty estimation

Summary: Pharmaceutical counterfeiting is a worldwide public health problem, often under–recognized, especially in developing countries where the percentage of counterfeit and substandard medicines is dramatically high. Antibiotics, among the most widespread drugs, have been particularly targeted by counterfeiters. World Health Organization emphasizes the need for development and distribution of screening methods explicitly targeted to counterfeit drugs. In this paper a single method is presented for the simultaneous analysis of some of the most commonly counterfeited essential antibiotics: ampicillin, amoxicillin+clavulanic acid, doxycycline, cloxacillin, chloramphenicol. A full validation was performed in terms of linearity, precision, robustness and trueness; an assessment of uncertainty was carried out exploiting these data. A wide linearity range was investigated considering the specific nature of counterfeit and substandard drugs, whose content in active substance may be rather far from the declared amount.

Authors' Conclusions: A large span in robustness parameters was considered and a complete intermediate precision assessment was conducted, envisaging the possibility of transferring the method to quality control laboratories, hopefully in developing countries. Finally, the method was successfully applied to the analysis of antibiotics purchased on the informal market in Chad, among which counterfeit and substandard samples were detected.

Citation: Gaudiano MC, et al. J Pharm Biomed Anal 2008; 48(2): 303-9.

Establishment of an HPLC identification system for detection of counterfeit steroidal drugs

Summary: A set of simple HPLC methods employing UV detection were developed for detection of counterfeit drugs by the qualitative and quantitative analysis of nine steroidal drugs: ethinylestradiol, diethylstilbestrol, norethisterone, norgestrel, methyltestosterone, medroxyprogesterone acetate, progesterone, testosterone propionate and nilestriol. The methods were based on studies of the relationships between the retention factors (k) of the nine compounds and the percentages of water to methanol in the mobile phases on a reverse phase Alltima C(18) column giving reliable separation of the compounds under three sets of chromatographic conditions.

Authors' Conclusions: The methods were validated using statistical tests and were used on nine commercial samples for detection of possible counterfeit drugs.

Citation: Shi YQ, et al. J Pharm Biomed Anal 2008; 46(4): 663–9.