Substandard and falsified medicines in African pharmaceutical markets: A case study from Ethiopia.

BACKGROUND: Substandard and falsified (SF) medicines are a global health problem. Their high prevalence is a threat to public health in low- and middle-income countries (LMICs). However, there are few street-level investigations of how this market works. This case study examines the supply and demand for SF medicines in Southern Ethiopia. METHODS: A cross sectional qualitative design, using semi-structured interviews supplemented by participant observation, was adopted. Study participants were selected using purposive, convenience, and snowball sampling techniques. They included pharmacists, physicians, wholesalers, pharmacy owners, regulatory staff, law enforcement agents and the local community. A total of 43 interviews were conducted. The study used Actor-Network Theory (ANT) as an analytic framework. RESULTS: The findings show that efforts to address the problem of SF medicines in Ethiopia struggle because of the lack of a clear framing of the issue and consensus on how it should be understood. The pharmaceutical market in Wolaita Zone, Southern Ethiopia is supplied with a wide variety of SF medicines from diverse sources. This complex supply chain emerges due to barriers to accessing essential medicines that are in demand. Control of SF medicines will require a range of interventions thoughtfully tailored to the local contexts and determinants of both supply and demand. CONCLUSION: The evidence of confusion, ambiguity, and uncertainty in defining the problem of SF medicines suggest that more research and policy work is required to refine understanding of the issue, and of the local market conditions that join demand and supply for different medicines in Southern Ethiopia. These are likely to apply more widely in comparable contexts throughout sub-Saharan Africa. The current global policy emphasis on stricter regulation and enforcement alone does not adequately address the social and economic factors that collectively create and shape user demand that is met by SF medicines.

Real or fake? Sourcing and marketing of non-prescribed benzodiazepines amongst two samples of people who regularly use illicit drugs in Australia.

INTRODUCTION: There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines. METHODS: Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained. RESULTS: Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown. DISCUSSION AND CONCLUSIONS: Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.

Identification of Substandard and Falsified Medicines: Influence of Different Tolerance Limits and Use of Authenticity Inquiries.

Substandard and falsified medicines have severe public health and socioeconomic effects, especially in low- and middle-income countries. The WHO has emphasized the need for reliable estimates of the prevalence of such medicines to efficiently respond to this problem. In the present study, we used 601 medicine samples collected in Cameroon, the DR Congo, and Malawi to assess the rates of substandard and falsified medicines based on different criteria. Based on the specifications of the U.S. Pharmacopoeia for the amount of the active pharmaceutical ingredients, the rate of out-of-specification medicines was 9.3%. By contrast, this rate ranged from 3.3% up to 35.0% if the tolerance limits of other pharmacopoeias or recently published medicine quality studies were used. This shows an urgent need for harmonization. Principal methods to assess the rate of falsified medicines are packaging analysis, chemical analysis, and authenticity inquiries. In the present study, we carried out an authenticity inquiry for the aforementioned medicine samples, contacting 126 manufacturers and 42 distributors. Response rates were higher for samples stated to be manufactured in Asia (52.4%) or Europe (53.8%) than for samples manufactured in Africa (27.4%; P < 0.001). One sample had been identified as falsified by packaging analysis by the local researchers and two additional ones by chemical analysis. Notably, seven additional falsified samples were identified by the authenticity inquiries. The total rate of falsified medicines resulted as 1.7%. Considerations are discussed for assessing the rates of "substandard" and "falsified" medicines in future medicine quality studies.

How Do We Combat Bogus Medicines in the Age of the COVID-19 Pandemic?

The COVID-19 pandemic has brought concurrent challenges. The increased incidence of fake and falsified product distribution is one of these problems with tremendous impact, especially in low- and middle-income countries. Up to a tenth of medicines including antibiotics and antimalarial drugs in the African market are considered falsified. Pandemics make this worse by creating an ecosystem of confusion, distraction, and vulnerability stemming from the pandemic as health systems become more stressed and the workload of individuals increased. These environments create opportunities for substandard and falsified medicines to be more easily introduced into the marketplace by unscrupulous operators. In this work we discuss some of the challenges with fake or falsified product distribution in the context of COVID-19 and proposed strategies to best manage this problem.

Impact of substandard and falsified antimalarials in Zambia: application of the SAFARI model.

BACKGROUND: Many countries are striving to become malaria-free, but global reduction in case estimates has stagnated in recent years. Substandard and falsified medicines may contribute to this lack of progress. Zambia aims to eliminate their annual burden of 1.2 million pediatric malaria cases and 2500 child deaths due to malaria. We examined the health and economic impact of poor-quality antimalarials in Zambia. METHODS: An agent-based model, Substandard and Falsified Antimalarial Research Impact (SAFARI), was modified and applied to Zambia. The model was developed to simulate population characteristics, malaria incidence, patient care-seeking, disease progression, treatment outcomes, and associated costs of malaria for children under age five. Zambia-specific demographic, epidemiological, and cost inputs were extracted from the literature. Simulations were run to estimate the health and economic impact of poor-quality antimalarials, the effect of potential artemisinin resistance, and six additional malaria focused policy interventions. RESULTS: We simulated annual malaria cases among Zambian children under five. At baseline, we found 2610 deaths resulting in $141.5 million in annual economic burden of malaria. We estimated that elimination of substandard and falsified antimalarials would result in an 8.1% (n = 213) reduction in under-five deaths, prevent 937 hospitalizations, and realize $8.5 million in economic savings, annually. Potential artemisinin resistance could further increase deaths by 6.3% (n = 166) and cost an additional $9.7 million every year. CONCLUSIONS: Eliminating substandard and falsified antimalarials is an important step towards a malaria-free Zambia. Beyond the dissemination of insecticide-treated bed nets, indoor residual spraying, and other malaria control measures, attention must also be paid to assure the quality of antimalarial treatments.

The Global Wicked Problem of Corruption and Its Risks for Access to HIV/AIDS Medicines.

We discuss how corruption affects access to antiretroviral therapies (ARVs) globally. Recent cases of theft of ARVs, collusion, and manipulation in procurement found in countries such as Central African Republic, Bangladesh, Malawi, and Guinea, show there is still much work to be done to reduce the risk of corruption. This includes addressing the structural weaknesses in procurement mechanisms and supply chain management systems of health commodities and medicines.

Challenges and Opportunities for the Traceability of (Biological) Medicinal Products.

This article provides an overview of the current situation regarding the traceability of medicinal products, with a focus on drug safety and biologics. Limited traceability of biologics, in particular with regard to the batch number, is associated with incomplete recording of exposure information in clinical practice. The current pharmaceutical barcode standards in the EU do not support the automatic recording of dynamic product information, such as batch numbers and expiry dates, by means of electronic barcode scanning in clinical practice. New barcode requirements, such as the 2D DataMatrix with encoded batch numbers and expiry dates, provided on both the primary and the secondary package, can facilitate routine barcode scanning at all points in the supply chain in different healthcare settings. To build a full track-and-trace system for medicines with electronic capture of relevant exposure information, alignment with other topics, such as the Falsified Medicines Directive and initiatives to reduce medication errors, is needed to increase the buy-in from all stakeholders and to solve multiple issues with a joint effort.

Oncology drugs in the crosshairs of pharmaceutical crime.

Oncology drugs clearly have become a target for pharmaceutical crime. In 2016, falsified oncology drugs ranked fifth in the most commonly falsified drug category among the reports received by the Pharmaceutical Security Institute. Although the prevalence of illicit oncology drugs in the legal supply chains appears to be small, these drugs are difficult to detect, particularly in clinical practice. Forthcoming countermeasures to detect illicit drugs in high-income countries include compulsory antitampering devices and product verification technology for a risk-based selection of medicines. Health-care professionals must implement these new procedures into their workflow and remain vigilant about those medicines that are not selected. Although countermeasures should firmly tighten supply chain security, there are concerns about how quickly pharmaceutical crime will adapt to these protections. Because patients and health-care professionals have shown a lenient attitude towards purchasing medicines from unreliable sources, measures against the highly accessible illegal medicine supply chain remain necessary. To improve detectability in clinical practice, reporting of ineffectiveness and unusual drug effects as adverse events or adverse drug reactions is essential.

Exploring the feasibility of obtaining mifepristone and misoprostol from the internet.

OBJECTIVES: We aimed to document the experience of buying abortion pills from online vendors that do not require a prescription and to evaluate the active ingredient content of the pills received. STUDY DESIGN: We searched the internet to identify a convenience sample of websites that sold mifepristone and misoprostol to purchasers in the United States and attempted to order these products. We documented price, shipping time and other aspects of ordering. We sent the samples received to a testing laboratory that measured the amount of active ingredient in individual tablets. RESULTS: We identified 18 websites and ordered 22 products: 20 mifepristone-misoprostol combination products and 2 that contained only misoprostol. We received 18 combination products and the 2 misoprostol products from 16 different sites. No site required a prescription or any relevant medical information. The time between order and receipt of the 20 products ranged from 3 to 21 business days (median 9.5 days). The price for the 18 combination products ranged from $110 to $360, including shipping and fees; the products without mifepristone cost less. Chemical assays found that the 18 tablets labeled 200 mg mifepristone contained between 184.3 mg and 204.1 mg mifepristone, while the 20 tablets labeled 200 mcg misoprostol contained between 34.1 mcg and 201.4 mcg of the active ingredient. CONCLUSIONS: Obtaining abortion medications from online pharmaceutical websites is feasible in the United States. The mifepristone tablets received contained within 8% of the labeled amount of active agent. The misoprostol tablets all contained that compound but usually less than labeled. IMPLICATIONS STATEMENT: Given our findings, we expect that some people for whom clinic-based abortion is not easily available or acceptable may consider self-sourcing pills from the internet to be a rational option.

Awareness of the implementation of the Falsified Medicines Directive among pharmaceutical companies' professionals in the European Economic Area

Background: The Falsified Medicines Directive (FMD) is a response of the European Union to the increasing number of falsified medicines present in the legal supply chain within the Member States of the community. Effective implementation of the new regulations will depend on the effective cooperation of all parties involved in the distribution of medicinal products including the managers of pharmaceutical companies. Objective: The objective of the study was to examine awareness of the Implementation of the FMD among pharmaceutical company professionals in the European Economic Area. Methods: Sampling was conducted using a method called purposive sampling. An appropriate research tool in the form of an original questionnaire was made available to the respondents in electronic form. During the period from January 2016 to June 2016, 1,496 e-mail messages were sent. The response rate was 17.37%. Results: The study included 99 women (39.3%) and 153 men (60.7%). In the study group, 95.7% of people had heard of FMD. Doctors had rarely heard about the falsified medicine directive when compared to pharmacists (p=0.0063), people working in the pharmaceutical industry (p=0.0014), and respondents with a different professional profile (p=0.0114). In the study group, 89.6% of people were aware of the role of National Medicines Verification Organization in the process of implementing the provisions of FMD into the national system of distribution of medicinal products. The number of the respondents who knew the deadline for the implementation of FMD was significantly higher in the study population, i.e. 91.9% (p=0.0001). Both the younger respondents and those with lower level of education were less aware of the time requirements posed to national regulators (p=0.0003, p=0.0023, respectively). Conclusions: Awareness of the regulations related to the implementation of the FMD, although relatively high among pharmaceutical company professionals in the EEA, is still insufficient (AU)

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Legal aspects of counteracting the trafficking of falsified medicines in the european union.

INTRODUCTION: The paper identifies key risks associated with the illegal production and sale of medicines. Also there were generalized features of criminal responsibility for acts related to the trafficking of drugs in some Member States of the EU and analyzed legal means of combating the falsified drugs today. The problem concerning falsification of medicines is particularly acute not only in developing countries but also in developed ones. Fake is one in ten - twenty drug. The largest share of falsified drugs comes from the so-called «Asian tigers¼, already from which they come to the EU market. THE AIM: In this publication authors have set following objectives: - to determine the risks associated with illegal production and sale of medicines; - organize legal means of combating the falsified medicines in the EU member states; - clarify features of criminal responsibility for acts related to the trafficking of drugs in the EU countries. MATERIALS AND METHODS: The article bases on the works of scholars and experts, statistical information and other sources. Particular attention is paid to the analysis of regulations of the EU institutions and national criminal laws. So, provisions of the criminal codes of 10 EU member states were taken into account. RESULTS: There is a system of legal measures which counter the circulation of falsified medicines in the EU and consists of general and specific regulatory requirements, mainly of economic and legal nature. The most important role among the last play package labeling requirements for drugs and license conditions. DISCUSSION: In the article were discussed factors that stimulate the production and sale of falsified drugs and the risks associated with these. Demarcated the concept of «falsified medicinal product¼, «counterfeit drug¼, «substandard drug¼. CONCLUSIONS: Although there are guidelines for patients to identify falsified drugs, still a major role in this process should play public authorities and enterprises. In all the countries illegal circulation of falsified drugs is prohibited under threat of criminal or administrative responsibility.

Surveillance for falsified and substandard medicines in Africa and Asia by local organizations using the low-cost GPHF Minilab.

BACKGROUND: Substandard and falsified medical products present a serious threat to public health, especially in low- and middle-income countries. Their identification using pharmacopeial analysis is expensive and requires sophisticated equipment and highly trained personnel. Simple, low-cost technologies are required in addition to full pharmacopeial analysis in order to accomplish widespread routine surveillance for poor-quality medicines in low- and middle-income countries. METHODS: Ten faith-based drug supply organizations in seven countries of Africa and Asia were each equipped with a Minilab of the Global Pharma Health Fund (GPHF, Frankfurt, Germany), suitable for the analysis of about 85 different essential medicines by thin-layer chromatography. Each organization was asked to collect approximately 100 medicine samples from private local medicine outlets, especially from the informal sector. The medicine samples were tested locally according to the Minilab protocols. Medicines which failed Minilab testing were subjected to confirmatory analysis in a WHO-prequalified medicine quality control laboratory in Kenya. RESULTS: Out of 869 medicine samples, 21 were confirmed to be substandard or falsified medical products. Twelve did not contain the stated active pharmaceutical ingredient (API), six contained insufficient amounts of the API, and three showed insufficient dissolution of the API. The highest proportion of substandard and falsified medicines was found in Cameroon (7.1%), followed by the Democratic Republic of Congo (2.7%) and Nigeria (1.1%). Antimalarial medicines were most frequently found to be substandard or falsified (9.5% of all antimalarials). Thin-layer chromatography according to the Minilab protocols was found to be specific and reproducible in the identification of medicines which did not contain the stated API. Since only samples which failed Minilab testing were subjected to confirmatory testing using pharmacopeial methods, this study did not assess the sensitivity of the Minilab methodology in the detection of substandard medicines, and may underestimate the prevalence of poor-quality medicines. CONCLUSIONS: Surveillance for poor-quality medicines can be carried out by local organizations in low- and middle-income countries using a simple, low-cost technology. Such surveillance can identify an important subgroup of the circulating substandard and falsified medical products and can help to prevent them from causing harm in patients. A collaboration of the national drug regulatory authorities with faith-based organizations and other NGOs may therefore represent a promising strategy towards the Sustainable Development Goal of "ensuring access to quality medicines".

A review of existing and emerging digital technologies to combat the global trade in fake medicines.

INTRODUCTION: The globalization of the pharmaceutical supply chain has introduced new challenges, chief among them, fighting the international criminal trade in fake medicines. As the manufacture, supply, and distribution of drugs becomes more complex, so does the need for innovative technology-based solutions to protect patients globally. Areas covered: We conducted a multidisciplinary review of the science/health, information technology, computer science, and general academic literature with the aim of identifying cutting-edge existing and emerging 'digital' solutions to combat fake medicines. Our review identified five distinct categories of technology including mobile, radio frequency identification, advanced computational methods, online verification, and blockchain technology. Expert opinion: Digital fake medicine solutions are unifying platforms that integrate different types of anti-counterfeiting technologies as complementary solutions, improve information sharing and data collection, and are designed to overcome existing barriers of adoption and implementation. Investment in this next generation technology is essential to ensure the future security and integrity of the global drug supply chain.