The role of constraints and information gaps in driving risky medicine purchasing practices in four African countries.

Substandard and falsified (SF) medical products pose a major threat to public health and socioeconomic development, particularly in low- and middle-income countries. In response, public education campaigns have been developed to alert consumers about the risks of SF medicines and provide guidance on 'safer' practices, along with other demand- and supply-side measures. However, little is currently known about the potential effectiveness of such campaigns while structural constraints to accessing quality-assured medicines persist. This paper analyses survey data on medicine purchasing practices, information and constraints from four African countries (Ghana, Nigeria, Sierra Leone and Uganda; n > 1000 per country). Using multivariate regression and structural equation modelling, we present what we believe to be the first attempt to tease apart, statistically, the effects of an information gap vs structural constraints in driving potential public exposure to SF medicines. The analysis confirms that less privileged groups (including, variously, those in rural settlements, with low levels of formal education, not in paid employment, often women and households with a disability or long-term sickness) are disproportionately potentially exposed to SF medicines; these same demographic groups also tend to have lower levels of awareness and experience greater levels of constraint. Despite the constraints, our models suggest that public health education may have an important role to play in modifying some (but not all) risky practices. Appropriately targeted public messaging can thus be a useful part of the toolbox in the fight against SF medicines, but it can only work effectively in combination with wider-reaching reforms to address higher-level vulnerabilities in pharmaceutical supply chains in Africa and expand access to quality-assured public-sector health services.

Alertas sanitarias de productos médicos subestándares, falsificados y no registrados al inicio de la pandemia de COVID-19 en las Américas / Health alerts for substandard, falsified, and unregistered medical products at the onset of the COVID-19 pandemic in the Americas / Alertas de saúde para produtos médicos abaixo do padrão, falsificados e não registrados no início da pandemia de COVID-19 nas Américas

[RESUMEN]. Objetivo. Identificar y analizar los incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia de COVID-19. Métodos. Búsqueda detallada en los sitios web de las autoridades reguladoras de las Américas. Identificación de los incidentes de medicamentos y dispositivos médicos (incluidos los de diagnóstico in vitro) subestándares falsificados, no registrados y robados. Se determinaron los tipos de productos, las etapas de la cadena de suministro en las que se detectaron y las medidas tomadas por las autoridades. Resultados. Se identificaron 1 273 incidentes en 15 países (1 087 productos subestándares, 44 falsificados, 123 no registrados y 19 robados). La mayor cantidad de incidentes corresponden a dispositivos médicos, desinfectantes y antisépticos. El punto en la cadena de suministro con mayor frecuencia de informes fue la adquisición a través de internet. Las medidas tomadas por las autoridades reguladoras corresponden en su mayoría a: alerta, prohibición de uso, prohibición de publicidad y fabricación, retiro del mercado y seguimiento de eventos adversos. Conclusiones. Se evidenció un número destacable de incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia por COVID-19. La escasez de insumos, la flexibilización en los requisitos regulatorios y el aumento de la demanda son factores que pueden favorecer el incremento del número de incidentes. Las autoridades reguladoras nacionales de referencia presentaron mayores frecuencias de detección de incidentes y de aplicación de medidas sanitarias. Se observó que se debe abordar el canal de venta por internet con alguna estrategia reguladora para garantizar la distribución segura de productos médicos.

[ABSTRACT]. Objective. Identify and analyze incidents of substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic. Methods. Detailed search of the websites of regulatory authorities in the Americas. Identification of incidents of substandard, falsified, unregistered, and stolen medicines and medical devices (including in vitro diagnostics). The types of products were determined, as were the stages in the supply chain where they were detected, and the actions taken by authorities. Results. A total of 1 273 incidents were identified in 15 countries (1 087 substandard, 44 falsified, 123 unreg- istered, and 19 stolen products). The largest number of incidents involved medical devices, disinfectants, and antiseptics. The most frequently reported point in the supply chain was online purchasing. The principal measures taken by the regulatory authorities were: alerts, prohibition of use, prohibition of advertising and manufacture, recall, and monitoring of adverse events. Conclusions. A substantial number of incidents involving substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic were identified. Shortages of supplies, easing of regulatory requirements, and increased demand are factors that may have led to an increase in the number of incidents. The national regulatory authorities of reference reported more frequent detection of incidents and more frequent application of health measures. A regulatory strategy is needed in order to address online sales and ensure the safe distribution of medical products.

[RESUMO]. Objetivo. Identificar e analisar incidentes de produtos médicos abaixo do padrão, falsificados, não registrados e roubados no início da pandemia de COVID-19. Métodos. Foi realizada uma busca detalhada nos sites das autoridades reguladoras das Américas. Foram identificados incidentes envolvendo medicamentos e dispositivos médicos (incluindo para diagnóstico in vitro) abaixo do padrão, falsificados, não registrados e roubados. Foram determinados os tipos de produtos, os estágios da cadeia de abastecimento em que foram detectados e as medidas tomadas pelas autoridades. Resultados. Foram identificados 1 273 incidentes em 15 países (1 087 produtos abaixo do padrão, 44 falsificados, 123 não registrados e 19 roubados). O maior número de incidentes estava relacionado a dispositivos médicos, desinfetantes e antissépticos. O ponto na cadeia de abastecimento com a maior frequência de relatos foi a de aquisição pela internet. As medidas tomadas pelas autoridades reguladoras foram principalmente alertas, proibições de uso, proibições de publicidade e fabricação, recolhimento de produtos do mercado e monitoramento de eventos adversos. Conclusões. Houve um número significativo de incidentes envolvendo produtos médicos abaixo do padrão falsificados, não registrados e roubados no início da pandemia de COVID-19. A escassez de insumos, a flexibilização das exigências regulatórias e o aumento da demanda são fatores que podem levar a um maior número de incidentes. As autoridades reguladoras nacionais de referência informaram um aumento na frequência de detecção de incidentes e implementação de medidas sanitárias. O canal de vendas pela internet precisa ser abordado com alguma estratégia regulatória para garantir a distribuição segura de produtos médicos.

Quality Assessment of Selected Essential Antimicrobial Drugs from Drug Retail Outlets of Selected Cities in Eastern Ethiopia.

The prevalence of substandard and falsified (SF) antimicrobial drugs is increasing around the globe. This poses a great concern for the healthcare system. The consumption of SF antimicrobial drugs has the potential to result in treatment failure, emergence and development of antimicrobial resistance, and ultimately a rise in mortality rate. The objective of this study was to assess the quality of four commonly used antimicrobials marketed in the cities of Dire Dawa and Jijiga and the town of Togo-Wuchale, which have high potential for illegal drug trade activities in Ethiopia because they are located near the border with Somalia. A total of 54 brands/samples of amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, and norfloxacin formulations were collected covertly from 43 facilities using a convenience sampling strategy from March 16 to March 29, 2022. The samples were first screened using Global Pharma Health Fund (GPHF)-Minilab protocols and then analyzed using U.S. Pharmacopoeial and British Pharmacopoeia official methods. The quality evaluation detected no falsified product; however, it showed that 14.3% of the samples failed the GPHF-Minilab screening test semiquantitatively. Overall, 22.2% of the products analyzed did not meet any of pharmacopoeial specifications assessed: 13%, 12.2%, and 11.1% of the products failed in assay, dissolution, and weight variation, respectively. Additionally, 56.3% of amoxicillin samples, 60% of amoxicillin/clavulanate, 20% of ciprofloxacin, and 54.5% of norfloxacin samples were found to be pharmaceutically nonequivalent with their respective comparator products regarding dissolution profiles. The study showed the presence of substandard antimicrobial medicines in the eastern Ethiopian market.

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains.

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global 'Prevent, Detect and Respond' strategy.

Substandard and falsified antimicrobials in selected east African countries: A systematic review.

BACKGROUND: Globally, millions of people have been affected by fraudulent pharmaceutical products, particularly those in developing countries. Although the problem of falsified and substandard drugs is acknowledged, the extent of the issue is ever-changing, has a dynamic nature, and should be quantified and captured in a recent snapshot. OBJECTIVE: This systematic review seeks to examine the data that can quantify and provide a current snapshot of the prevalence of SF antimicrobials in selected east Africa countries. METHODS: Scientific studies on antimicrobial quality were searched in PubMed, Embase, Scopus, and Google Scholar from 2017 to February 2023. The search strategy focused on scientific articles published in peer-reviewed scientific journals written in English and the studies exclusively done in any of the selected countries of east Africa. The articles were carefully reviewed by two individuals for inclusion independently, first by title followed by abstract and the full-text retrieval. To minimize bias associated with the methodology used for data collection, the quality of the studies was assessed for quality according to the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). The reporting of this systematic review was done following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). RESULTS: Fifteen studies that estimated the prevalence of poor-quality antimicrobial medicines in selected four east African countries were included. The overall percentage of samples of antimicrobials that failed at least one quality test was 22.6% (151/669) with each class's prevalence of 17% in antibiotics (73/432), 24% in antimalarial (41/171), and 56% in anthelmintics (37/66). Quality control parameters of API content were the most commonly examined in the included studies, accounting for 14/15 (93%) studies. Fifty (33.1%) of the failing samples failed assay API- content determination, while 26.5% (n = 40) failed the visual inspection and packaging analysis; 19.2% (29) failed dissolution; 14% (n = 21) flawed hardness or friability; 4%(n = 6) failed uniformity, as well as 3.2% (n = 5) failed disintegration test of the quality control parameter. CONCLUSION: It was found that this review was general in these selected east African countries and was a catalyst for combating the menace of poor-quality medications that affect millions of lives.

The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance.

Approximately 10% of antimicrobials used by humans in low- and middle-income countries are estimated to be substandard or falsified. In addition to their negative impact on morbidity and mortality, they may also be important drivers of antimicrobial resistance. Despite such concerns, our understanding of this relationship remains rudimentary. Substandard and falsified medicines have the potential to either increase or decrease levels of resistance, and here we discuss a range of mechanisms that could drive these changes. Understanding these effects and their relative importance will require an improved understanding of how different drug exposures affect the emergence and spread of resistance and of how the percentage of active pharmaceutical ingredients in substandard and falsified medicines is temporally and spatially distributed.

The role of pharmacists in eliminating counterfeit medicines in Nigeria.

Introduction: Over the years, counterfeit pharmaceuticals have posed immense concerns for global health and patient safety. This menace encompasses various classes of medications. Given the criticality of pharmacists' interventions in drug distribution and supply, this study aimed at exploring their role in the prevention and control of counterfeit pharmaceutical products in Nigeria. Methods: A cross-sectional study was undertaken, using questionnaires to collect data from pharmacists across various sectors of pharmacy practice in Nigeria. Face and content validity was undertaken on the study tool prior to data collection. Ethical approval was obtained from the National Institute for Pharmaceutical Research and Development Health Research Ethics Committee, and confidentiality was strictly maintained during data collection process. Data were analyzed using Statistical Package for Social Sciences. Descriptive statistical analysis was undertaken and chi square was used to determine association between socio-demographic characteristics and variables. Results: The responses comprised 205 (52.6%) female and 185 (47.4%) male participants. Almost all the participants (98.4%) agreed that strict enforcement of drug laws can contribute to adequate control of counterfeit medicines in Nigeria, and majority of the study sample (64.7%) indicated that the poor implementation of these laws was a major factor influencing the preponderance of counterfeit medicines in the country. Two-thirds (63.5%) of the participants supported the need for pharmacists to provide adequate education to patients on strategies to identify counterfeit medicines, and a similar proportion (68.0%) were of the opinion that it was the responsibility of pharmacists to ensure that drugs are purchased from credible sources. Conclusion: Findings from this study, in addition to confirming pharmacists' instrumentality in the fight against counterfeit medicines, identified certain context specific factors that can strengthen the regulation, policy and the entire healthcare system. Government and relevant stakeholders can therefore begin to articulate strategic reforms for contextual policy intervention that address medicines' counterfeiting, whilst prioritising pharmacists' role in other critical areas in the healthcare system.

Model verification for population detection of counterfeits.

The quality of counterfeit items has increased dramatically, with modern global manufacturing being able to duplicate the materials, construction, and visual features of items. Detection of fraudulent coinage can parallel authentication of food, beverages, and manufactured goods by studying product-inherent features. Counterfeit detection is performed by comparing an Example group with a Questioned group. A model is developed for both groups using standard tests on individual pieces. Coin weight is used here as an illustration. The model should also follow the natural science of the system. In this case, the manufacturing process variation is known and steady, and the underlying distribution is known or can be determined from authentic pieces. The proposed detection method uses testing of many individual pieces, then using reverse-quality-engineering methods to identify possible sources. This strategy looks at the variation between individual pieces to determine the process capability of a machine, assembly line, or plant to create product consistency for a manufacturer. Fraudulent items may be manufactured within specification, but demonstrate a manufacturing process capability different than that of the authentic manufacturer. In this report, we examine the model previously reported and use reconstruction techniques to re-create the evidence set to validate the model, increase model accuracy, and confirm the conclusion previously reached, showing that the Questioned set is likely over 37% non-conforming by weight. In this case, the decision outcome of the analysis was improved by using additional methods not included in the modeling software package originally used.

Assessing the self-reported honesty threshold in adolescent epidemiological research: comparing supervised machine learning and inferential statistical techniques.

BACKGROUND: Epidemiological surveys offer essential data on adolescent substance use. Nevertheless, the precision of these self-report-based surveys often faces mistrust from researchers and the public. We evaluate the efficacy of a direct method to assess data quality by asking adolescents if they were honest. The main goal of our study was to assess the accuracy of a self-report honesty item and designate an optimal threshold for it, allowing us to better account for its impact on point estimates. METHODS: The participants were from the 2020 Illinois Youth Survey, a self-report school-based survey. We divided the primary dataset into subsets based on responses to an honesty item. Then, for each dataset, we examined two distinct data analysis methodologies: supervised machine learning, using the random forest algorithm, and a conventional inferential statistical method, logistic regression. We evaluated item thresholds from both analyses, investigating probable relationships with reported fake drug use, social desirability biases, and missingness in the datasets. RESULTS: The study results corroborate the appropriateness and reliability of the honesty item and its corresponding threshold. These contain the agreeing honesty thresholds determined in both data analyses, the identified association between reported fake drug use and lower honesty scores, increased missingness and lower honesty, and the determined link between the social desirability bias and honesty threshold. CONCLUSIONS: Confirming the honesty threshold via missing data analysis also strengthens these collective findings, emphasizing our methodology's and findings' robustness. Researchers are encouraged to use self-report honesty items in epidemiological research. This will permit the modeling of accurate point estimates by addressing questionable reporting.

Recent developments in electromigration techniques related to pharmaceutical and biomedical analysis - A review.

The analysis of pharmaceutical compounds is an important research topic as the use of different drugs affects people's daily life for the treatment of diseases. In addition to the widespread use of the internet, counterfeit drugs have appeared in the market. The development of modern analytical techniques, reliable, precise, sensitive, and rapid methods, has provided powerful means of analysis used in various fields such as drug production, quality control, determination of impurities and/or metabolites, biochemistry, pharmacokinetics, etc. Analytical techniques so far used in the pharmaceutical analysis include high-performance liquid chromatography (HPLC), gas chromatography (GC), super/sub-critical fluid chromatography (SFC), and capillary electromigration techniques such as capillary electrophoresis (CE) and rather rarely capillary electrochromatography (CEC). CE has some advantages over other techniques, e.g., very high efficiency, reduced costs (use of minute volumes of solvents and samples), the possibility to use different separation mechanisms, etc. In this review paper, the main features and limitations of the capillary electromigration techniques (especially CE) are discussed. Some selected applications of CE to the analysis of pharmaceutical compounds published in the period 2021-2023 (May) are reported.

Usefulness of medicine screening tools in the frame of pharmaceutical post-marketing surveillance.

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance.

Controlling malaria in a population accessing counterfeit antimalarial drugs.

A mathematical model is developed for describing malaria transmission in a population consisting of infants and adults and in which there are users of counterfeit antimalarial drugs. Three distinct control mechanisms, namely, effective malarial drugs for treatment and insecticide-treated bednets (ITNs) and indoor residual spraying (IRS) for prevention, are incorporated in the model which is then analyzed to gain an understanding of the disease dynamics in the population and to identify the optimal control strategy. We show that the basic reproduction number, $ R_{0} $, is a decreasing function of all three controls and that a locally asymptotically stable disease-free equilibrium exists when $ R_{0} < 1 $. Moreover, under certain circumstances, the model exhibits backward bifurcation. The results we establish support a multi-control strategy in which either a combination of ITNs, IRS and highly effective drugs or a combination of IRS and highly effective drugs is used as the optimal strategy for controlling and eliminating malaria. In addition, our analysis indicates that the control strategies primarily benefit the infant population and further reveals that a high use of counterfeit drugs and low recrudescence can compromise the optimal strategy.

CRIMINAL OFFENCES RELATED TO ILLICIT TRAFFICKING IN FALSIFIED MEDICINES: INVESTIGATION PROBLEMS.

OBJECTIVE: The aim: Formulate recommendations for improving the efficiency of detection and investigation of trafficking in falsified medicines, application of criminal¬istics knowledge. To analise the contemporary condition and the latest trends in combating this type of crimes and to justify the need for creation of a complex criminalistic methodic investigation. PATIENTS AND METHODS: Materials and methods: Аnalysis of the applicable laws governing trade in medical products in Ukraine; judgments of courts of Ukraine for the period from 2013 to 2022; results of generalization of 128 criminal proceedings; active employee survey results (205 respondents) etc. Over the course of the present research, we have used general scientific and specialised research methods. RESULTS: Results and Conclusions: Increasing the effectiveness of combating the illegal circulation of falsified falsified medicines is a complex problem that encompasses a whole system of directions, requiring the combined efforts of international bodies and organizations, various scientists. One of the priority directions for the introduction of an effective mechanism for combating the distribution of falsified medicines is the development of a complex criminalistic methodic investigation.

SALE OF FALSIFIED MEDICINES VIA THE INTERNET IN UKRAINE: PROBLEMS OF DETECTION AND COUNTERACTION.

OBJECTIVE: The aim: The purpose of the article is to identify and analyze problematic theoretical and practical aspects related to the sale of counterfeit medicines via the Internet and measures to counteract the spread of their counterfeit products, as well as to search for evidence-based ways to improve the regulatory and legal mechanism that regulates the activities of the pharmaceutical business in Ukraine. PATIENTS AND METHODS: Materials and methods: The research based by the analysis of international acts, conventions and national legislation of Ukraine in the sphere of trade medi¬cines via the Internet, scientific achievements in this area. Methodologically, this work is based on the system of methods, scientific approaches, techniques and principles with the help of which the realization of the research aim is carried out. There have been applied universal, general scientific and special legal methods. CONCLUSION: Conclusions: Analyzed the legal regulation of online sales of medicines. Made the conclusion about necessity implementation of projects to create forensic records which have shown their effectiveness in the fight against counterfeit medicines in European countries.

Health, Economic, and Social Impacts of Substandard and Falsified Medicines in Low- and Middle-Income Countries: A Systematic Review of Methodological Approaches.

Little is known about the adverse health, economic, and social impacts of substandard and falsified medicines (SFMs). This systematic review aimed to identify the methods used in studies to measure the impact of SFMs in low- and middle-income countries (LMICs), summarize their findings, and identify gaps in the reviewed literature. A search of eight databases for published papers, and a manual search of references in the relevant literature were conducted using synonyms of SFMs and LMICs. Studies in the English language that estimated the health, social, or economic impacts of SFMs in LMICs published before June 17, 2022 were considered eligible. Search results generated 1,078 articles, and 11 studies were included after screening and quality assessment. All included studies focused on countries in sub-Saharan Africa. Six studies used the Substandard and Falsified Antimalarials Research Impact model to estimate the impact of SFMs. This model is an important contribution. However, it is technically challenging and data demanding, which poses challenges to its adoption by national academics and policymakers alike. The included studies estimate that substandard and falsified antimalarial medicines can account from 10% to ∼40% of total annual malaria costs, and SFMs affect rural and poor populations disproportionately. Evidence on the impact of SFMs is limited in general and nonexistent regarding social outcomes. Further research needs to focus on practical methods that can serve local authorities without major investments in terms of technical capacity and data collection.

Insights from a qualitative study of the procurement and manufacture of active pharmaceutical ingredients in India.

Medicine supply systems are a crucial part of health systems and access to effective essential medicines is a key pillar of Universal Health Coverage. However, efforts to expand access are compromised by the proliferation of substandard and falsified medicines. The vast majority of research to date on medicine supply chains has focused on the formulation and distribution of the finished product, overlooking the crucial steps of Active Pharmaceutical Ingredient production that precede this. In this paper, we draw on qualitative interviews with manufacturers and regulators in India to take a 'deep dive' into these understudied parts of medicine supply chains.