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The globalization of drug trade has led to the increased production of falsified medicines. In addition, poor medication adherence increases the costs of healthcare. The need to manage medication has given rise to marketing of highly functional networked digital medicine. Therefore, a growing need has emerged to ensure the traceability of pharmaceutical products from shipment to patient distribution. Microtaggant technologies that can encode individual numbers on pharmaceutical products are expected to serve achieving this goal. Taggants are a class of materials that can be applied to an object to make it identifiable, like barcodes and holograms. Since the smaller size of microtaggant make it invisible to naked eyes, it is more difficult to reverse-engineer than conventional taggants. The U.S. Food and Drug Administration (FDA) has established guidelines for the use of microtaggants. Many studies have explored the use of various analytical technologies and materials as the microtaggants. However, the advantages and disadvantages of each method have not been established yet. In this review, recent research on the use of microtaggants for anti-counterfeiting is summarized and compared to current anti-counterfeiting technologies with spectrographic methods, distribution management systems with barcodes, and medication management systems with sensor devices. We also discuss the microtaggants implementation costs and security level.

Near-infrared (NIR) spectroscopy is a promising technique for field identification of substandard and falsified drugs because it is portable, rapid, nondestructive, and can differentiate many formulated pharmaceutical products. Portable NIR spectrometers rely heavily on chemometric analyses based on libraries of NIR spectra from authentic pharmaceutical samples. However, it is difficult to build comprehensive product libraries in many low- and middle-income countries due to the large numbers of manufacturers who supply these markets, frequent unreported changes in materials sourcing and product formulation by the manufacturers, and general lack of cooperation in providing authentic samples. In this work, we show that a simple library of lab-formulated binary mixtures of an active pharmaceutical ingredient (API) with two diluents gave good performance on field screening tasks, such as discriminating substandard and falsified formulations of the API. Six data analysis models, including principal component analysis and support-vector machine classification and regression methods and convolutional neural networks, were trained on binary mixtures of acetaminophen with either lactose or ascorbic acid. While the models all performed strongly in cross-validation (on formulations similar to their training set), they individually showed poor robustness for formulations outside the training set. However, a predictive algorithm based on the six models, trained only on binary samples, accurately predicts whether the correct amount of acetaminophen is present in ternary mixtures, genuine acetaminophen formulations, adulterated acetaminophen formulations, and falsified formulations containing substitute APIs. This data analytics approach may extend the utility of NIR spectrometers for analysis of pharmaceuticals in low-resource settings.

Substandard and falsified medicines are an enormous threat to global health. Poor quality antibiotic preparations contribute to the development of antimicrobial resistance. In surgery, where the occurrence of healthcare-associated infections is high, healthcare teams need to rely on the quality of antibiotic prophylaxis to prevent infections. We assessed the quality of antibiotics used for surgical infection prophylaxis in Benin. Thirty-three samples were collected from six hospitals located in various departments in Benin. The antibiotics (powders for injection: amoxicillin + clavulanic acid, ampicillin, ceftriaxone; solutions for injection: ciprofloxacin, gentamicin, metronidazole) were assessed using visual inspection, pharmacotechnical tests (including uniformity of mass, pH measure, sterility test, and active pharmaceutical ingredient identification), and assay tests (including a simple analytical method thin layer chromatography) and complex analytical techniques (ultraviolet-visible spectrophotometry, high-performance liquid chromatography—diode-array detection, conductometry). Because the material needed for the methods recommended by the pharmacopeias to assess the dosage of gentamicin was not available, we developed and validated a conductometry method. Results showed that 97% (n = 32) of the samples passed visual inspection; 100% (n = 33) of the samples passed the pharmacotechnical tests, identification of active ingredients, and sterility test; 88% (n = 29) passed the test for percentage of active pharmaceutical ingredients. Overall, 15% of the samples did not pass the quality test (3% on visual inspection and 12% for excess active ingredients). Although most of the samples passed the quality tests, it appears important to perform routine quality control for intravenous medicines.

Substandard and falsified medicines are harmful to patients, causing prolonged illness, side effects, and preventable deaths. Moreover, they have an impact on the health system and society more broadly by leading to additional care, higher disease burden, productivity losses and loss of trust in health care. Models that estimate the health and economic impacts of substandard and falsified medicines can be useful for regulators to contextualize the problem and to make an economic case for solutions. Yet these models have not been systematically catalogued to date. We reviewed existing models that estimate the health and economic impact of substandard and falsified medicines to describe the varying modeling approaches and gaps in knowledge. We compared model characteristics, data sources, assumptions, and limitations. Seven models were identified. The models assessed the impact of antimalarial (n = 5) or antibiotic (n = 2) quality at a national (n = 4), regional (n = 2), or global (n = 1) level. Most models conducted uncertainty analysis and provided ranges around potential outcomes. We found that models are lacking for other medicines, few countries’ data have been analyzed, and capturing population heterogeneity remains a challenge. Providing the best estimates of the impact of substandard and falsified medicines on a level that is actionable for decision-makers is important. To enable this, research on the impact of substandard and falsified medicines should be expanded to more medicine types and classes and tailored to more countries that are affected, with greater specificity.

Falsified medicines are a major threat to global health. Antimalarial drugs have been particularly targeted by criminals. As DNA analysis has revolutionized forensic criminology, we hypothesized that these techniques could also be used to investigate the origins of falsified medicines. Medicines may contain diverse adventitious biological contamination, and the sealed nature of blister-packages may capture and preserve genetic signals from the manufacturing processes allowing identification of production source(s). We conducted a blinded pilot study to determine if such environmental DNA (eDNA) could be detected in eleven samples of falsified and genuine artesunate antimalarial tablets, collected in SE Asia, which could be indicative of origin. Massively Parallel Sequencing (MPS) was used to characterize microbial and eukaryote diversity. Two mitochondrial DNA analysis approaches were explored to detect the presence of human DNA. Trace eDNA from these low biomass samples demonstrated sample specific signals using two target markers. Significant differences in bacterial and eukaryote DNA community structures were observed between genuine and falsified tablets and between different packaging types of falsified artesunate. Human DNA, which was indicative of likely east Asian ancestry, was found in falsified tablets. This pilot study of the ‘pharmabiome’ shows the potential of environmental DNA as a powerful forensic tool to assist with the identification of the environments, and hence location and timing, of the source and manufacture of falsified medicines, establish links between seizures and complement existing tools to build a more complete picture of criminal trade routes. The finding of human DNA in tablets raises important ethical issues that need to be addressed.

ObjectiveSubstandard and falsified (SF) veterinary medicines affect animal health, agricultural production and food security and will influence antimicrobial resistance (AMR) in both animals and humans. Yet, our understanding of their extent and impact is poor. We assess the available public domain evidence on the epidemiology of SF veterinary medicines, to better understand their prevalence and distribution and their public health impact on animals and humans.MethodsSearches were conducted in Embase, PubMed, MEDLINE, Global Health, Web of Science, CAB Abstracts, Scopus, Google Scholar, Google and websites with interest in veterinary medicines quality up to 28 February 2021. Identified articles in English and French were screened for eligibility. The Medicine Quality Assessment Reporting Guidelines were used to assess the quality of prevalence surveys.ResultsThree hundred and fourteen publications were included with a failure frequency (the percentage of samples that failed at least one quality test) of 6.5% (2335/35 733). The majority of samples were from post-marketing surveillance by medicines regulatory authorities of the Republic of Korea and China. A small proportion (3.5%) of samples, all anti-infectives, were from 20 prevalence surveys, with more than half (53.1%, 662/1246) collected in low-income and lower middle-income countries in Africa and Asia. The prevalence survey sample size ranged from 4 to 310 samples (median (Q1–Q3): 50 (27–80)); 55.0% of surveys used convenience outlet sampling methods. In 20 prevalence surveys more than half of the samples (52.0%, 648/1246) failed at least one quality test. The most common defects reported were out-of-specification active pharmaceutical ingredient(s) (API) content, failure of uniformity of units and disintegration tests. Almost half of samples (49.7%, 239/481) that failed API content tests contained at least one of the stated APIs below pharmacopoeial limits. Fifty-two samples (4.2% of all samples) contained one or more incorrect API. One hundred and twenty-three publications described incidents (recalls/seizures/case reports) of SF veterinary medicines in 29 countries.ConclusionThe data suggest that SF veterinary products are likely to be a serious animal and public health problem that has received limited attention. However, few studies of SF veterinary medicines are available and are geographically restricted. Lower API content and disintegration/dissolution than recommended by pharmacopoeial standards risks treatment failure, animal suffering and contribute to AMR. Our findings highlight the need of more research, with robust methodology, to better inform policy and implement measures to assure the quality of veterinary medicines within supply chains. The mechanism and impact of SF veterinary products on animal and human health, agricultural production, their economy and AMR need more transdisciplinary research.

Counterfeiting is a worldwide issue affecting many industrial sectors, ranging from specialized technologies to retail market, such as fashion brands, pharmaceutical products, and consumer electronics. Counterfeiting is not only a huge economic burden ($ 1 trillion losses/year), but it also represents a serious risk to human health, for example, due to the exponential increase of fake drugs and food products invading the market. Considering such a global problem, numerous anticounterfeit technologies have been recently proposed, mostly based on tags. The most advanced category, based on encryption and cryptography, is represented by physically unclonable functions (PUFs). A PUF tag is based on a unique physical object generated through chemical methods with virtually endless possible combinations, providing remarkable encoding capability. However, most methods adopted nowadays are based on expensive and complex technologies, relying on instrumental readouts, which make them not effective in real-world applications. To achieve a simple yet cryptography-based anticounterfeit method, herein we exploit a combination of nanotechnology, chemistry, and artificial intelligence (AI). Notably, we developed platinum nanocatalyst-enabled visual tags, exhibiting the properties of PUFs (encoding capability10

Objective The objective of this study was to describe law enforcement oversight of counterfeit drugs by the Food and Drug Administration (FDA) in the United States from 2016 through 2021. Methods The FDA Office of Criminal Investigation database with hyperlinked press releases of enforcement actions was used to identify legal action against drug counterfeiters. Incidences of counterfeit drugs sold via Internet, how often they were obtained without a prescription, the most prevalent counterfeit drugs, the countries where counterfeit operations occurred, and the scale of counterfeit operations were assessed. Results There were 130 unique enforcement actions against counterfeiting organizations and individuals. Overall, 64.6% of enforcement actions involved counterfeit products sold over the Internet, in 84.6% of actions counterfeit medications could be obtained without a prescription, and in 33.1% of actions the products were sold as dietary supplements. Sexual dysfunction, opioid, stimulant, anabolic muscle building, benzodiazepine, and dermatologic drugs were most counterfeited. China was the most prevalent country to produce counterfeit drugs followed by India, Turkey, Pakistan, and Russia. Counterfeiting operations were large with tens of millions of pills and hundreds of millions of dollars in sales. Health outcomes for counterfeit drugs were rarely discussed in the press releases and not all press releases had data for each parameter of interest. Conclusion and Relevance This is the first report assessing enforcement actions against drug counterfeiters from the FDA Office of Criminal Investigation. The FDA is actively involved in identifying and prosecuting counterfeit drug rings, but the number of enforcement actions is smaller than the size of the problem.

This article explores dermatologic consequences of substandard, spurious, falsely labeled, falsified, and counterfeit (SSFFC) pharmaceutical products. Many of these SSFFC products are neither safe nor effective, and are more likely to cause adverse events than the proper preparations. These products also affect the health of populations by generating drug-resistant pathogens and failing to control the spread of disease. This article reviews classification systems for fraudulent medications, provides a general overview of medical and public health problems associated with substandard medications, provides examples of dermatologic consequences of each category, and presents recommended steps to take when clinicians encounter suspected SSFFC products.

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities - nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

Counterfeit or substandard drugs are pharmaceutical formulations in which the active pharmaceutical ingredients (APIs) have been replaced or ingredients do not comply with the drug leaflet. With the outbreak of the COVID-19 pandemic, fraud associated with the preparation of substandard or counterfeit drugs is expected to grow, undermining health systems already weakened by the state of emergency. Analytical chemistry plays a key role in tackling this problem, and in implementing strategies that permit the recognition of uncompliant drugs. In light of this, the present work represents a feasibility study for the development of a NIR-based tool for the quantification of dexamethasone in mixtures of excipients (starch and lactose). Two different regression strategies were tested. The first, based on the coupling of NIR spectra and Partial Least Squares (PLS) provided good results (root mean square error in prediction (RMSEP) of 720 mg/kg), but the most accurate was the second, a strategy exploiting sequential preprocessing through orthogonalization (SPORT), which led (on the external set of mixtures) to an R2pred of 0.9044, and an RMSEP of 450 mg/kg. Eventually, Variable Importance in Projection (VIP) was applied to interpret the obtained results and determine which spectral regions contribute most to the SPORT model.

The aim:comparative analysis of the results of a questionnaire survey of pharmaceutical and medical professionals and consumers, conducted by the authors during 2019-2021 to identify opinions on which there are coincidences and differences, as well as an assessment of the problem of drug counterfeiting in Ukraine to develop approaches to prevent their spread. Materials and methods.The study used scientific publications, as well as the results of a survey of specialists of the State Service of Ukraine for Medicines and Drug Control (State Medical Service) and its territorial bodies, pharmaceutical and medical professionals of health care institutions and consumers on the fight against drug falsification. The research was conducted using the methods of questionnaires, systematization and generalization. Results.According to the results of a comprehensive questionnaire during 2019-2021, it was found that the share of CM in the Ukrainian pharmaceutical market is estimated at 5 % by a majority of respondents on average 58.5 %, including 59.7 % of experts of the State Medical Service, 42.3 % of pharmacy specialists, 11.4 % by doctors and 73.5 % by consumers. Respondents' answers about the signs of drug falsification differ significantly, so most experts believe that this is a change in the usual signs (taste, smell, color), while pharmacy specialists - labelling in a foreign language, doctors - no therapeutic effect, for consumers it is a change in packaging design (labels) and a significantly lower price. The main sales channels of CM for experts and pharmacy specialists are e-commerce (68.7 % and 75.7 %, respectively), while the majority of consumers could not determine. Many experts and pharmacy specialists pointed to the need to introduce special security features of packaging in the form of 2d barcodes as the main method for protection and detection of CM (79.1 % and 39.6 %, respectively). Most of the surveyed pharmacy workers and consumers believe that the risk of purchasing counterfeit drugs is higher in the pharmacies of individual entrepreneurs or small pharmacy chains.The main problem that hinders the effective fight against drug counterfeiting was the imperfect legislation (68.7 %). Regarding effective tools in the fight against counterfeit drugs, experts called a significant strengthening of the powers of the regulatory body - following the example of the FDA (70.1 %). Conclusions.It is established that the most important priorities of the state policy for combating CM in Ukraine are the improvement of the system of state control and quality assurance of medicines, in particular 2d coding, as well as the need to strengthen the responsibility for drug falsification. The results of research on the problem of drug falsification indicate the feasibility of introducing a systematic survey for a wider range of respondents - professionals and consumers

Technology has always emerged to embolden the existing working process. On the one hand, it encourages transparency, accessibility and robustness in the system and on the other hand, it begets mitigation of the risks and allows us to detect, evaluate and eliminate vulnerability in the system. The most prominent technologies in todays’ world like Artificial Intelligence, Virtual/Augmented Reality, Automation, Cloud Computing are thriving to solve society’s problems and ensure the expedition in the process from its previous generation. Blockchain technology is no exception in providing the solution to eliminate the counterfeit markets across the globe and building trust among parties to do business without the fear of indulging or facing any unscrupulous business. Blockchain technology can ensure data privacy while improving supply chain transparency and reducing fraud. It can provide all stakeholders within a certain supply chain with access to the same information, potentially reducing errors. A decentralised application can pave the way to promulgate online pharmaceutical business where health information and each stakeholders’ data is not compromised. Against this backdrop the research conducted throws light on the challenges in the online medical drug and devices’ distribution and proposes a solution, an architectural design for blockchain technology in an online pharmaceutical platform to mitigate the counterfeit market while bringing efficiency to the ecosystem.

Objective Substandard and falsified (SF) medical products are a global public health threat. The presence and spread of SF drugs negatively affect (1) patients’ safety and health outcomes, (2) national economy, (3) public trust in the healthcare system, and (4) the international fight against serious health challenges such as malaria and antimicrobial resistance. The objective of the current study was to investigate and provide a snapshot analysis of the evolution and developmental patterns of global research publications on SF products. Methods A bibliometric approach was adopted using terms such as fake, falsified, counterfeit, substandard, and others. No language restriction was made. The study period was from 1900 up to 2020. The search strategy was validated and implemented using Scopus database. Results The search strategy retrieved 978 documents authored by 2861 researchers from 100 different countries and published in 421 different journals. The retrieved documents received 11,237 citations (11.5 citations per document) with an H-index of 53. The 978 documents retrieved from Scopus were published from 1961 to 2020, giving an average of 16.6 publications per year. The present study indicated that research on SF medical products: (a) has experienced a steep growth from 2001 to 2012 followed by a steady-state growth; (b) was disseminated in a wide range of journals, mainly in the fields of the pharmaceutical industry, analytical chemistry, public health, infectious diseases, and internal medicine; (c) was published by scholars with diverse and distant geographical backgrounds; (d) was mainly produced in the United States, United Kingdom, and Germany; (d) has fragmented research networks and a limited number of researchers per network; (e) has limited cross-country collaboration except for that between the US and the UK in one hand and countries in the Mekong region in the other hand; (f) emphasized on medications related to malaria and sexual stimulants; and (g) received relatively inadequate funding. Conclusions Research on SF medical products is important and should remain a priority to ensure good quality of medications. Research activity in the field needs to be encouraged in world regions such as Africa and the Middle East where drug regulations are unsatisfactory and cross-border trade of illegal medications is common.

BackgroundThe World Health Organization (WHO) has warned that substandard and falsified medicines threaten health, especially in low- and middle-income countries (LMIC). However, the magnitude of that threat for many medicines in different regions is not well described, and high-quality studies remain rare. Recent reviews of studies of cardiovascular and diabetes medicine quality recorded that 15.4 % of cardiovascular and 6.8% of diabetes samples failed at least one quality test. Review authors warn that study quality was mixed. Because they did not record medicine volume, no study reflected the risk posed to patients.Methods and FindingsWe investigated the quality of five medicines for cardiovascular disease and diabetes in Malang district, East Java, Indonesia. Our sample frame, based on dispensing volumes by outlet and price category, included sampling from public and private providers and pharmacies, and reflected the potential risk posed to patients. The content of active ingredient was determined by High Performance Liquid Chromatography, and compared with the labelled content. Dissolution testing was also performed.We collected a total of 204 samples: amlodipine (88); captopril (22); furosemide (21); glibenclamide (21); and simvastatin (52), comprising 83 different brands/products. All were manufactured in Indonesia, and all samples met specifications for both assay and dissolution. None was suspected of being falsified.ConclusionsWhile we cannot conclude that the prevalence of poor-quality medicines in Malang district is zero, our sampling method, which reflects likely exposure to specific brands and outlets, suggests that the risk to patients is very low; certainly nothing like the rates found in recent reviews of surveys in LMICs. Our study demonstrates the feasibility of sampling medicines based on likely exposure to specific products, and underlines the dangers of extrapolating results across countries.What is already known on this topicThe World Health Organisation suggests that as many as one in 10 medicines in low- and middle-income countries are of poor quality, but studies of the prevalence of substandard and falsified rarely take into account patient exposure.Medicines for non-communicable diseases and studies from large middle-income countries are under-represented in existing studies.What this study addsWe showed that it is feasible to sample medicines based on patient exposure. Our exposure-based study of cardiovascular and diabetes medicines in Indonesia, a lower-middle income country that is the world’s fourth most populous, found that all met quality standards.How this study might affect research, practice or policyAdopting exposure-based methods for sampling and/or calculating the prevalence of substandard and falsified medicines would improve our understanding of the potential public health impact of poor-quality products globally.

Background Drug counterfeiting is a rising problem due to difficulties with identifying counterfeit drugs and the lack of regulations and legislation in developing countries. Objective This study aims to develop a robust and economic reversed phase high performance liquid chromatography (LC) method for simultaneously determining metformin HCl, vildagliptin, saxagliptin, alogliptin benzoate, sitagliptin phosphate monohydrate, and linagliptin to target counterfeiting. Methods Plackett-Burman (PB) and Box-Behnken (BB) designs were used to screen and optimize the mobile phase composition. Chromatographic separation was carried out on an Inertsil® ODS-3 C18 column with isocratic elution mode and the mobile phase was a mixture of acetonitrile–methanol–ammonium formate buffer, pH 3.5 (25:10:65, v/v/v). This method was applied to analyze synthetic drugs in three traditional Chinese and Indian herbal medicines. To identify the adulterants, thin-layer chromatography (TLC), nuclear magnetic resonance (NMR), and mass spectrometry (MS) were used on counterfeit herbal medicines. Results The developed method is sensitive, simple, rapid, economical, accurate, and highly robust. Student's t-test and variance ratio (F-test at P Conclusion The study found that the analyzed herbal medicines were adulterated with metformin and the quantification of anti-diabetic counterfeits was therefore applied. Highlights This study determined counterfeited anti-diabetic drugs in Indian and Chinese traditional herbal medicines(THMs). Design-of-experiment, PB, and BB designs were used. Method validation was also performed in accordance with the International Conference on Harmonization guidelines.

Since ancient times, fake drugs have been on the market in Chinese society. However, during the Ming-Qing Dynasty, this problem intensified as the size of the pharmaceutical market grew, the collection and distribution structure of pharmaceutical products became increasingly complex, and the phenomenon of separation between the prescription and distribution of drugs advanced. Additionally, the government did not manage the manufacturing or quality of drugs and there was no law or institution designed to solve the problem of fake drugs. Furthermore, social opinion also criticized the widespread problem of fake drugs, and patients and doctors had to rely on various pharmacognostic books and medical knowledge to find reliable drugs in the drug market. Meanwhile, as merchants participated and invested commercial capital in the pharmaceutical industry, large reputable pharmacies began to emerge in large cities and produced drugs. With the commercialization of the pharmaceutical market, the public gained interest in drugs and consumed drugs produced by these pharmacies. Moreover, there were frequent problems in the market as fake drugs imitating popular drugs were distributed and the names of famous pharmacies were stolen. Although fake drugs were a universal social problem, the Qing government was reluctant to strictly control them tried to solve this issue by enforcing banning and punishment through local governments. Prominent pharmacies filed several lawsuits against the government over the theft of fake drugs and drug names. They also advertised the legitimacy and authenticity of drugstore to the public and customers. Doctors and merchants responded to the problem of fake drugs by following occupational morality, developing drug discrimination, cracking down on organizational discipline, filing complaints with government offices, and advertising their authenticity. However, the fake medicines did not easily disappear despite such a response, as there was no state control or legislation. Evidently, the pharmaceutical market was already highly commercialized and its structure were complex. Moreover, the financial benefits of fake drugs, competition in the pharmaceutical market, and public demand for drugs with similar effects at low prices also affected the popularity of fake drugs. Hence, the distribution of fake medicine in the Qing society can be seen as a phenomenon of separation between the prescription and distribution of drugs, commercialization and consumption of drugs, and competition on the medical market.

The excessive prescription of benzodiazepines is putting more people at risk of dependence on these drugs and is exacerbating the fatal overdose toll of opioids. A rapid and sensitive SERS method has been developed for trace detection of select benzodiazepines in low-dosage suspect counterfeit tablets, capsules, and injectable solutions using two different portable handheld Raman spectrometers equipped with either a 785-nm laser or a 1064-nm laser. A total of 169 samples and blanks were examined using five handheld Raman spectrometers, which provided data set of 729 examinations. The extraction/SERS procedures yielded true positive rates above 90% for alprazolam, diazepam, and midazolam using the 1064-nm device and yielded true positive rates above 95% for alprazolam, clonazepam, diazepam, estazolam, midazolam, and temazepam using the 785-nm device; however, the extraction/SERS procedures yielded true positive rates below 60% for lorazepam and triazolam. The minimum concentration (Cmin ) of the benzodiazepine standards that reproducibly yielded a positive match ranged from 1 to 10 μg/ml using the 1064-nm laser device and from 0.5 to 50 μg/ml using the 785-nm laser device. For the analysis of authentic and suspect counterfeit tablets containing these benzodiazepines, the measured Cmin ranged between 10 and 15 µg per tablet or capsule for 1064-nm laser device and 1-100 µg per tablet or capsule for 785-nm laser device. The developed methods are simple, rapid, and ideal for screening suspect benzodiazepine-containing pharmaceutical products at satellite laboratories located within or near international mail facilities and express courier hubs.

There is a paucity of evidence-based information regarding healthcare professionals’ awareness and views toward counterfeit medicines in developing countries. Therefore; this is aimed to assess health care providers’ knowledge, attitude, and practice toward counterfeit medicines in Mizan-Tepi University Teaching Hospital, South West Ethiopia. A cross-sectional study was conducted among health care providers working in Mizan-Tepi University Teaching Hospital from December 2020 to January 2021. A total of 171 health care providers participated in the study. Data were collected through self-administered structured questionnaires developed by reviewing similar surveys with some modifications. The data analyzed using a Statistical Package for Social Sciences (SPSS, version 21). Variables with P value

Due to COVID-19 restrictions, purchasing goods and services through the internet has become commonplace. As they begin to develop, buying medication online has become one of the top concerns for public health. This research aims to assess and evaluate the perspective and professional fulfillment of community pharmacists regarding the online selling of OTCs and prescription drugs during COVID-19 in Metro Manila. Self-administered online surveys were used as the primary tool for quantitative data collection to gain information from the respondents based on their knowledge and experiences. The results were gathered and analyzed using descriptive statistics, Fisher test, Chi-square, and R version 4.2.0. to summarize and establish associations between responses. The research concluded that the adaptation of online selling of over-the-counter and prescription drugs during COVID-19 has a significant relationship between the community pharmacist’s perspective and professional fulfillment. However, it may cause a disadvantage for purchasing medicines online due to the possibility of counterfeit drugs and utilizing fake prescriptions.&nbsp

A world-wide crisis to public and the consumers with high risks can be drug counterfeiting. The standardization of drug safety has become difficult and is a major concern due to the rise in the number of internet pharmacies. Since the drugs pass through difficult and complex distribution networks, it becomes difficult to detect counterfeits. Thus increasing the opportunities for falsified medicines to enter the actual supply chain. In this particular paper, we are using blockchain technology to mention data immutability to chop back the cost of operation within the pharmaceutical supply-chain hence making it safer. This is often implemented through blockchain technology which might be an allegedly immutable cryptographic ledger which has repeated sequential hashing and is fault-tolerant using a consensus algorithm by adding an alert system thus notifying when there's any fault.

Chemometrics applied to spectroscopic measurements such as near-infrared are gaining more and more importance for quality control of pharmaceutical products. Handheld near-infrared devices show great promise as a medicines quality screening technique for post-marketing surveillance. These devices are able to detect substandard and falsified medicines in pharmaceutical supply chains and enable rapid action before these medicines reach patients. The instrumental and environmental changes, expected or not, can adversely affect the analytical performances of prediction models developed for routine applications. Based on a previous study, PLS prediction models were developed and validated on three similar handheld NIR transmission spectrophotometers of the same model and from same company. These models have shown to be effective in analyzing metformin tablet samples, but significant spectral differences between handheld systems complicated their deployment for routine analysis. In this study, different strategies have been applied and compared to correct the instrumental variations, including global modelling (GM) and calibration transfer methods (Direct Standardization, DS; Spectral Space Transformation, SST and Slope/Bias correction, SBC), considering the RMSEP and the accuracy profile as assessment criteria. The transfer methods showed good capabilities to maintain the predictive performances comparable to that of the global modelling approach, except for a remaining slight bias. This approach is interesting since very few standardization samples are required to develop an adequate transfer model. GM, SST and SBC were able to correct/handle drifts in the spectral responses of different handheld instruments and thus may help to avoid the need for a long, laborious, and costly full recalibration process due to inter-instrument variations.

There are many reports of falsified medicines that may cause harm to patients. A rapid and simple method of identifying falsified medicines that could be used in the field is required. Although Raman scattering spectroscopy has become popular as a non-destructive analysis, few validation experiments on falsified medicines that are actually distributed on the market have been conducted. In this study, we validated a discriminant analysis using an ultra-compact, portable, and low-cost Raman scattering spectrometer combined with multivariate analysis. The medicines were three types of erectile dysfunction therapeutic tablet and one type of antifungal tablet: tadalafil (Cialis), vardenafil hydrochloride (Levitra), sildenafil citrate (Viagra), and fluconazole (Diflucan), which is sometimes advertised as female Viagra. For each medicine, the authentic standard product and products obtained by personal import via the internet (genuine or falsified) were used. Discriminant analyses were performed on the Raman spectra combined with soft independent modeling of class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA). It was possible to identify all falsified samples by SIMCA using the standard product model for all four products. Using the PLS-DA using the PLS models of the four standard products, falsified Levitra and Diflucan samples were classified correctly, although some falsified Cialis and all Viagra samples also belonged to the standard class. In this study, SIMCA might be more suitable than PLS-DA for identifying falsified medicines. A spectroscopic module that combines the low-cost Raman scattering spectroscopy with SIMCA might contribute to the rapid identification of falsified medicines in the field.

La falsificación de medicamentos afecta a todos los países del mundo sin importar su ubicación geográfica o su grado de desarrollo económico. En Costa Rica, se han decomisado importantes cantidades de medicamentos y otros productos de interés sanitario, lo cual evidencia el nivel de la problemática, así como la existencia de un mercado que demanda este tipo de productos. El objetivo de este estudio es realizar una revisión de los conceptos más importantes relacionados con medicamentos falsificados y subestándar, además de presentar una revisión de las alertas emitidas por el Ministerio de Salud, desde enero del 2009 y hasta diciembre del 2019. En total, en el país se han publicado un total de 64 alertas con información relevante respecto a la presencia o posible circulación de medicamentos falsificados (n=20) y productos sin registro sanitario aprobado por el Ministerio de Salud de Costa Rica (n=44). Se detallan los casos de medicamentos como vitaminas del complejo B, ceftriaxona y anticonceptivos orales. Además, se resaltan situaciones de robo de productos de interés sanitario de contenedores. Dentro de la sociedad muchos actores pueden jugar un rol importante en la prevención de la falsificación de medicamentos. La autoridad sanitaria debe acompañarse por la industria farmacéutica, los cuerpos policiales, los profesionales de la salud y sus representantes, y toda aquella organización que busque la protección del paciente. Este usuario final, debe también empoderarse de sus tratamientos y conocer los medios más seguros para la obtención y uso racional de sus medicamentos. The counterfeiting of medicines affects all countries around the world regardless of their geographical location or their economic development. In Costa Rica, large quantities of medicines, and other health-related products, have been confiscated by authorities. This shows how problematic the situation is, and the existence of a market that demands these products. The aim of this study is review of the most important concepts related to counterfeit and substandard medicines. In addition, a review of the alerts issued by the Ministry of Health from January 2009 to December 2019, is presented. In Costa Rica, a total of 64 alerts have been published with relevant information regarding the presence or possible circulation of counterfeit drugs (n = 20) and products without a sanitary registry approved by the Costa Rican Ministry of Health (n = 44). As examples, we present details of the alerts issued for intramuscular vitamin B complex, ceftriaxone, and oral contraceptives. Within this society, many actors can play an important role in the prevention of counterfeiting medicines. The health authority must be accompanied by the pharmaceutical industry, police forces, health professionals and their representatives, and any organization that seeks the safety of the patient. This end user must also be empowered to understand its treatment and the safest ways for obtaining and rationally use medications. Universidad de Costa Rica/[]/UCR/Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones Farmacéuticas (INIFAR)

An alleviation of patient wellness and safety, the pharmaceutical ecotechnology play crucial role by eliminating the threat of counterfeit drugs, medicines and drug adulteration. The numerous issue of supply chain such as production of inferior copy of branded product with label of the original brand name, the risk of putting wrong product into distribution, unauthorized distribution of branded product and lack of consistency across countries are now a days creating challenges for pharmaceutical manufacturers worldwide. The regulatory authorities of countries and pharmaceutical industries believe that serialization and product tracking could be the ultimate solution for these worldwide issues. Serialization system has the capacity to find out current and past locations of the product through entire supply chain. Hence, due to urgent necessity in today’s competitive environment, the implementation of this technology has found to be more effective to enhance counterfeit prevention, pilferage reduction and targeted recalls as well as improve security, visibility, synchronization and supply chain efficiency. Keywords: Serialization, Pharmaceutical.

Aim: Critically investigating the possibility of adopting blockchain technology within the Nigerian pharmaceutical supply chain to curb the supply of counterfeit drugs. Study Design: The study is qualitative in nature and the primary data were fetched through interviews. Place and Duration of the Study: Conducted within Nigeria for a period of 3 months. Methodology: A qualitative method of data collection was adopted in the study, where some stakeholders were interviewed. The interviews were conducted with employees from different pharmaceutical companies and some drug regulatory agencies in Nigeria. Result: Firstly, this study has ascertained the current prevalence of counterfeit drugs and the reasons for that. The study discovers a very high level of counterfeit drugs and some reasons behind that. Secondly, this study has also found some barriers to blockchain adoption, including the fact that the level of awareness of blockchain technology among stakeholders within the Nigerian pharmaceutical supply chain and the regulatory agencies is very low. Conclusion: It was concluded that the efforts put in developing a viable COVID-19 vaccine could be undermined due to the current nature of the Nigerian pharmaceutical supply chain, the nature of porous borders in place, absence of an apparent drug distribution system, among others. This study also concludes that the supply chain's current structure needs more regulatory and structural interventions by the Nigerian government than blockchain technology. In other words, with the current nature of the supply chain, blockchain technology adoption would not be effective in delivering the said benefits reported by scholars because the atmosphere is not conducive for successful blockchain adoption.

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.

The problem of medicines counterfeiting is relevant for all countries of the world, without exception. At the same time, the effectiveness of combating the spread of counterfeit medicines (CM) in different countries, as well as the volume of counterfeited medical products, varies. Any state that aimed to ensure highly effective control over the circulation of medicines has to elaborate a comprehensive solution to this problem, primarily to adopt high-quality national legislation. The executive authorities should not only pay attention to neutralizing CM problem, but also take the most active part in this process. The primary role here should be played by law enforcement authorities. There is a need for coordinated work by law enforcement authorities to investigate the cases of falsified medicines and clandestine production, as well as by regulatory bodies to identify such products. It is also necessary to systematize the investigative and judicial practice on this issue, create an unified system for recording the facts of identifying the counterfeit drugs. The need for systematic monitoring and analysis of regulatory legal acts regarding the counteraction to the circulation of the CM in order to assess their effectiveness, as well as the adoption of appropriate measures by the authorized bodies, determine the relevance of the study. The aim of the work was to analyze the laws and regulations of CM adopted in Ukraine after the Declaration of Independence had been signed (1991), to assess their effectiveness in terms of bringing perpetrators to justice for pharmaceutical counterfeiting. Materials and methods. Scientific publications on the problem of CM, as well as the Laws of Ukraine and legal acts adopted by various authorities to combat the spread of falsified medicines, reports of law enforcement agencies, the General Prosecutor’s Office, the State Judicial Administration, court decisions included in the Unified State Register of Court Decisions (USRCD) under Article 321-1 of the Criminal Code of Ukraine. The analysis of the respective norms of the legislation adopted during 1991–2020 is carried out. Results. Having analyzed the reports of law enforcement agencies, the State Statistical Office, and the Prosecutor General’s Office, the authors established that none of the people who had been convicted under Article 321-1 of the Criminal Code of Ukraine, after the entry of the guilty verdict into force, was in places of deprivation of liberty. There are many information sources that provide various forms of statistics, but understanding them is quite a challenge. A large number of criminal proceedings have been investigated for a long time, and since the USRCD is inaccessible, and is available only for the pre-trial investigation bodies and the prosecutor’s office, it is impossible for a private person to get information regarding the end of the pre-trial investigation in certain cases. Conclusions. Despite the large quantity of regulatory legal acts adopted in Ukraine to prevent the spread of counterfeit medicines, the severity of the sanctions of Article 321-1 of the Criminal Code, which criminalizes the falsification and circulation of medicines, as well as the importance of medicines’ counterfeiting for public health, the effectiveness of measures to combat this phenomenon is dramatically low.

Near-infrared spectrometry (NIRS) is a new pharmacopoeial method. It is widely used in the pharmaceutical industry for quality control of medicinal products at various production stages (control of raw materials and finished products), and for detection of substandard and counterfeit drugs.The aim of the study was to assess the feasibility of using NIRS as an identification test for active ingredients during pre-marketing quality control of medicinal products.Materials and methods: 327 drugs samples represented as solid and semisolid dosage forms were tested by NIRS following their examination by well-established pharmacopoeial Identification methods during pre-marketing laboratory evaluation. The NIR spectra of the test samples were compared with the spectral library classification models.Results: NIRS confirmed the identity of 3.1% of the tested medicinal products. It was demonstrated that library classification models could be used for identification of only those medicines that were produced by a specific manufacturer, i.e. for confirmation of medicine identity.Conclusions: the NIRS method is unpractical as an Identification test for active ingredients in medicinal products during the pre-marketing laboratory evaluation stage. The main limitations of NIRS are lack of complete sets of library classification models for all medicinal products available in the market and non-reproducibility of spectral library data obtained with a different instrument.

The use of falsified and unregistered drugs is a worldwide public health problem. Because these global market products usually do not follow the Good Manufacturing Practices required by health legislation, its composition may be completely different from the original or may contain relevant concentrations of impurities and toxic contaminants. Since anabolic steroids are among the main irregular therapeutic classes seized in Brazil, here we propose a new methodology for analyzing these products, in tablets form, using Attenuated Total Reflection Fourier Transform Infrared Microspectroscopy (µATR-FTIR) mapping. Spectra were acquired from solid tablets by attenuated total reflection, through point mapping methodology. In data processing, a characteristic absorption band for each Active Pharmaceutical Ingredient (API) was integrated and plotted to create its distribution map. This technique was applied in an unprecedented way for the forensic analysis of anabolic steroids and proved to be effective in distinguishing falsified products based on the detection of their APIs. It was possible to detect APIs in 26 out of 30 samples, five of which were classified as falsified only through µATR-FTIR analysis. We were able to create distribution maps of the detected substances associating the microspectroscopic results with characteristic band integration method, which can be used to detect substances and to study samples' homogeneity. We concluded that this methodology is promising for the analysis of anabolic steroid tablets, and can be used in a complementary way with techniques already consolidated in forensic laboratory routine for a better classification of questioned samples between authentic and falsified ones.

This paper provides a detailed overview of the block chain technology and how it can be used to build a foolproof system in eliminating counterfeit products in pharmaceutical industries. From the last decade, pharmaceutical companies are facing difficulties in tracking their products during the supply chain process, allowing the counterfeiters to add their fake medicines into the market. Counterfeit drugs are analysed as a very big challenge for the pharmaceutical industry worldwide. As indicated by the statistics, yearly business loss of around $200 billion is reported by US pharmaceutical companies due to these counterfeit drugs. These drugs may not help the patients to recover the disease but have many other dangerous side effects. According to the World Health Organization (WHO) survey report, in under-developed countries every 10th drug use by the consumers is counterfeit and has low quality. Hence, a system that can trace and track drug delivery at every phase is needed to solve the counterfeiting problem. The block chain has the full potential to handle and track the supply chain process very efficiently. In this paper, we have proposed and implemented a block chain based drug supply chain management. Our proposed system block chain-based drug supply chain management for consumers. In this drug supply chain management the system is deployed using Hyper ledger fabrics which is capable of continuously monitor and track the drug delivery process in the smart pharmaceutical industry. Finally, we also perform several tests to check the efficiency and usability of our proposed system.

Near-infrared spectroscopy (NIR) has become one of the most important methods for counterfeit drugs identification for its low cost, non-destructive, and on-site detection. However, it is often invalid for unknown samples beyond the scope of modeling samples, as well as it is not efficient in conditions of insufficient samples (insufficient number of samples within the class), unbalanced samples (large difference in the number of samples between classes), and sensitivity of identification results (different tolerance for different errors in application scenarios). To solve these problems, this paper proposes a general method for on-site identification of counterfeit drugs based on Siamese-network modeling with near-infrared spectroscopy, which especially constructs the train set and test set, learning the general knowledge of spectral differences to identify the different drugs by a costumed one-dimensional convolution neural network (1D-CNN), and finally answered the question of whether the on-site two spectra are pointed to the same drug. Based on experimental modeling samples of 1314 spectra, which are involved 9 drugs produced by 25 manufacturers, this paper has constructed and fully trained its model. Then, not known at the time of modeling, 4 drugs produced by 9 manufacturers are used for testing in the on-site application, and the accuracy rate amounts to 97.3%. For generalizing consideration, randomly divided into training and testing categories, the 32015 spectra of 135 drugs produced by 391 manufacturers in the spectral library are handled by the same processing. The generalization model is equally applicable, and the accuracy is above 97%. Compared with traditional binary classification identification methods such as SVM, PLS-DA, Auto-encoding, and one class (OC) threshold identification algorithms such as SVM-OC, SIMCA, conformity test (CT), the proposed method has the best identification ability for unknown samples in modeling.

There has been a recent surge in the amount of substandard and falsified clopidogrel. Pharmacopeial based assays using high performance liquid chromatography and mass spectroscopy are widely used for the measurement of clopidogrel but are not accessible in low to middle income countries. Therefore, our study explored four different techniques (mid-infrared spectroscopy, thin layer chromatography, ultraviolet visible spectroscopy, and differential pulse voltammetry), which could be used in low to middle income countries. Differential pulse voltammetry showed the best performance for accurate and precise determination of clopidogrel in the presence of excipients. Clopidogrel tablets were fully crushed and sonicated in buffer for 30 seconds prior to differential pulse voltammetry measurements using a 3 mm glassy carbon electrode. Measurements were made without removing the excipients and the limit of detection was 0.08 mg ml−1 and the sensitivity was 15.7 μA mg ml−1. When conducting a blinded study, differential pulse voltammetry was able to identify varying types of substandard and falsified samples. Our findings highlight that voltammetry could be a vital analytical technique for the determination of substandard and falsified medicines in low- and middle-income countries.

Purpose This paper examines the scope of anorectics in counterfeit weight-reducing formulations and provides insight into the present state of research in determining such adulterants. Analytical techniques utilised in profiling adulterants found in slimming products, including limitations and mitigation steps of these conventional methods are also discussed. The current legal status of the anorectics and analogues routinely encountered in non-prescription slimming formulations is also explored. Methods All reviewed literature was extracted from Scopus, Web of Science, PubMed, and Google Scholar databases using relevant search terms, such as, ‘counterfeit drugs’, ‘weight loss drugs’, ‘weight-reducing drugs’, ‘slimming drugs’, ‘anorectic agents’, and ‘counterfeit anorexics’. Legislation related to anorectics was obtained from the portals of various government and international agencies. Results Anorectics frequently profiled in counterfeit slimming formulations are mostly amphetamine derivatives or its analogues. Five routinely reported pharmacological classes of adulterants, namely anxiolytics, diuretics, antidepressants, laxatives, and stimulants, are mainly utilised as coadjuvants in fake weigh-reducing formulations to increase bioavailability or to minimise anticipated side effects. Liquid and gas chromatography coupled with mass spectrometric detectors are predominantly used techniques for anorectic analysis due to the possibility of obtaining detailed information of adulterants. However, interference from the complex sample matrices of these fake products limits the accuracy of these methods and requires robust sample preparation methods for enhanced sensitivity and selectivity. The most common anorectics found in counterfeit slimming medicines are either completely banned or available by prescription only, in many countries. Conclusions Slimming formulations doped with anorectic cocktails to boost their weight-reducing efficacy are not uncommon. Liquid chromatography combined with mass spectrometry remains the gold standard for counterfeit drug analysis, and requires improved preconcentration methods for rapid and quantitative identification of specific chemical constituents. Extensive method development and validation, targeted at refining existing techniques while developing new ones, is expected to improve the analytical profiling of counterfeit anorectics significantly.

Instruct clinicians on counterfeit drugs and their implications for patient health. Counterfeit drugs imperil patients around the globe, and their penetration into the United States, Canada, and Western Europe is only increasing over time. In addition to inserting counterfeit drugs in the legitimate drug supply, rogue Internet pharmacies and consumer purchases while traveling abroad allow counterfeit drugs to endanger patients. Pharmacists need to understand the nature and severity of the issue and directly counter it through personal actions to secure a legitimate drug supply, such as by using verified distributors and examining the shipment packaging, product packaging, the bottle, and the label for evidence to determine if it is counterfeit or has been tampered with. They can also indirectly counter it through patient education and by working with other key stakeholders in the health care system. Given the risk to patients, pharmacists have an important role to play in limiting patient use of counterfeit drugs.

Poor quality medicines include substandard and falsified (i.e. counterfeited) medicines. WHO report of 2017 estimates that the rates of substandard and falsified medical products in low- and middle-income countries is approximately 10.5% with an estimated spend of US$ 30.5 billion

Background and Objectives: The drug distribution network is one of the most important pillars of the Iranian pharmaceutical system which plays a vital role in rapid and easy access to drugs. The purpose of this article is to evaluate drug distribution system in Iran and also to provide the suggestions for improvement. Material and Methods: In terms of purpose, the present study is among the applied researches and in terms of data collection method, it is a multi-method study that has used a quantitative and qualitative approach. Data collection tools were structured questionnaire and semi-structured interviews and also data evaluation was performed by thematic analysis. The study population includes pharmaceutical industry activists. To select the sample among industry players, snowball sampling method was used. Initially, existing drug distribution system was documented, current potentialities and flows in the network were identified and they were drawn by Bizagi Modeler. Then, distribution network evaluation indicators were extracted from relevant literature. Also, status of these indicators was evaluated by using a questionnaire. By using factor relationship technique (FARE), the priorities of these indicators were determined. Finally, existing bottlenecks were diagnosed by thematic analysis. Ultimately, guidelines to tackle such bottlenecks were provided. Results: In this study, 11 complications were identified for the drug distribution network. Drug unavailability or shortage, supply of near-expiration drugs, supply of counterfeit drugs, improper sale of over-the-counter drugs, black market activity and drug trafficking, sharp price fluctuations, insufficient interaction with consumption pharmacist, high distribution costs, low distribution network performance in emergency deliveries, long time to search and find drugs (in case of certain drugs) and low quality of response and consumer complaints seem to be some of the complications identified in this study. Conclusion: Investments on measuring patients' needs correctly, supporting drug retailing competitive brands development, improving drug distribution system information comprehensive system throughout the country within needs measurement loops, network inventory, production and importation, improving the utilization of modern tools and technologies such as internet–based sales, seller-free shops, establishing electronic files for patients and similar ones, utilizing direct sale methods and fostering the roles of potentialities such as insurance in planning, decision making and monitoring drug distribution system countrywide are some of the solutions obtained from this research that are used to improve the drug distribution system in the country.

The need for reliable communications in industrial systems becomes more evident as industries strive to increase reliance on automation. This trend has sustained the adoption of WirelessHART communications as a key enabling technology and its operational integrity must be ensured. This paper focuses on demonstrating pre-deployment counterfeit detection using active 2D Distinct Native Attribute (2D-DNA) fingerprinting. Counterfeit detection is demonstrated using experimentally collected signals from eight commercial WirelessHART adapters. Adapter fingerprints are used to train 56 Multiple Discriminant Analysis (MDA) models with each representing five authentic network devices. The three non-modeled devices are introduced as counterfeits and a total of 840 individual authentic (modeled) versus counterfeit (non-modeled) ID verification assessments performed. Counterfeit detection is performed on a fingerprint-by-fingerprint basis with best case per-device Counterfeit Detection Rate (%CDR) estimates including 87.6% < %CDR < 99.9% and yielding an average cross-device %CDR ≈ 92.5%. This full-dimensional feature set performance was echoed by dimensionally reduced feature set performance that included per-device 87.0% < %CDR < 99.7% and average cross-device %CDR ≈ 91.4% using only 18-of-291 features—the demonstrated %CDR > 90% with an approximate 92% reduction in the number of fingerprint features is sufficiently promising for small-scale network applications and warrants further consideration.

Substandard and falsified medicines present a serious threat to public health. Simple, low-cost screening tools are important in the identification of such products in low- and middle-income countries. In the present study, a smartphone-based imaging software was developed for the quantification of thin-layer chromatographic (TLC) analyses. A performance evaluation of this tool in the TLC analysis of 14 active pharmaceutical ingredients according to the procedures of the Global Pharma Health Fund (GPHF) Minilab was carried out, following international guidelines and assessing accuracy, repeatability, intermediate precision, specificity, linearity, range and robustness of the method. Relative standard deviations of 2.79% and 4.46% between individual measurements were observed in the assessments of repeatability and intermediate precision, respectively. Small deliberate variations of the conditions hardly affected the results. A locally producible wooden box was designed which ensures TLC photography under standardized conditions and shielding from ambient light. Photography and image analysis were carried out with a low-cost Android-based smartphone. The app allows to share TLC photos and quantification results using messaging apps, e-mail, cable or Bluetooth connections, or to upload them to a cloud. The app is available free of charge as General Public License (GPL) open-source software, and interested individuals or organizations are welcome to use and/or to further improve this software.

This study evaluates the use of the Global Pharma Health Fund (GPHF) Minilab for medicine quality screening by 16 faith-based drug supply organizations located in 13 low- and middle-income countries. The study period included the year before the COVID-19 pandemic (2019) and the first year of the pandemic (2020). In total 1,919 medicine samples were screened using the GPHF Minilab, and samples showing serious quality deficiencies were subjected to compendial analysis in fully equipped laboratories. Thirty-four (1.8%) of the samples were found not to contain the declared active pharmaceutical ingredient (API), or less than 50% of the declared API, or undeclared APIs, and probably represented falsified products. Fifty-four (2.8%) of the samples were reported as substandard, although the true number of substandard medicines may have been higher due to the limited sensitivity of the GPHF Minilab. The number of probably falsified products increased during the COVID-19 pandemic, especially due to falsified preparations of chloroquine; chloroquine had been incorrectly advocated as treatment for COVID-19. The reports from this project resulted in four international WHO Medical Product Alerts and several national alerts. Within this project, the costs for GPHF Minilab analysis resulted as 25.85 € per sample. Medicine quality screening with the GPHF Minilab is a cost-effective way to contribute to the global surveillance for substandard and falsified medical products.

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.

To assess all the incidents of substandard, falsified and unregistered medicines in 2017 and 2018 in Latin America, determining the types of products affected, stages of the supply chain in which incidents were detected, quality deviations identified in tested samples, and regulatory measures taken by authorities.A comprehensive search of the websites of the Latin American national regulatory authorities was conducted, identifying all eligible incidents during 2017-2018. Standardized values were collected from each incident for pre-determined variables: country, year, type of incident, therapeutic group, supply chain, regulatory measures and laboratory data.A total of 596 incidents in 13 countries were included (236 substandard, 239 falsified, 116 unregistered and 5 stolen). The therapeutic categories with the highest incidents were: anti-infectives, medicines for pain/palliative care, hormones/contraceptives, medicines for the respiratory tract, and medicines for mental/behavioural disorders. The most common places where incidents were detected were commercial establishments, pharmacies, health services and manufacturers. The most recurrent quality deviations were failure in parameters (appearance or physicochemical), incorrect labelling, different quantity of active pharmaceutical ingredient, presence of unknown particles, and microbiological contamination. The most frequent regulatory measures identified were alerts, withdrawals, seizures, and prohibition of marketing/distribution/use.In Latin America, substandard, falsified and unregistered medicines persist as a highly prevalent problem. An advanced degree of regulatory development in countries is associated with higher incident detection/reporting rates and a more comprehensive set of measures. The pharmaceutical supply chain is more vulnerable in its final node. Quality deviations identified in tested samples pose serious risks to public health.Evaluar todos los incidentes de medicamentos de calidad subestándar, falsificados y no registrados en 2017 y 2018 en América Latina, y determinar los tipos de productos afectados, los puntos de la cadena de suministro en los que se detectaron incidentes, las desviaciones de calidad identificadas en las muestras analizadas y las medidas regulatorias adoptadas por las autoridades.Se realizó una búsqueda exhaustiva en los sitios web de las autoridades regulatorias nacionales de América Latina y se identificaron todos los incidentes elegibles publicados durante 2017 y 2018. Se recogieron valores estandarizados de cada incidente conforme a variables predeterminadas: país, año, tipo de incidente, grupo terapéutico, cadena de suministro, medidas regulatorias, y datos de laboratorio.Se incluyeron en total 596 incidentes de 13 países (236 relacionados con calidad subestándar, 239 falsificados, 116 no registrados y 5 robados). Las categorías terapéuticas con mayor número de incidentes fueron los agentes antiinfecciosos, los medicamentos para el dolor/cuidados paliativos, las hormonas/anticonceptivos, los medicamentos para las vías respiratorias y los medicamentos para trastornos mentales/del comportamiento. Los lugares más comunes en los que se detectaron incidentes fueron los establecimientos comerciales, las farmacias, los servicios de salud y los fabricantes. Las fallas de calidad más recurrentes fueron deficiencia de los parámetros (fisicoquímicos, o el aspecto), etiquetado incorrecto, cantidad diferente del principio activo, presencia de partículas desconocidas y contaminación microbiológica. Las medidas regulatorias identificadas con más frecuencia fueron las alertas, los retiros e incautaciones del producto, y la prohibición de su comercialización, distribución o uso.En América Latina, los medicamentos de calidad subestándar, falsificados y no registrados continúan siendo un problema frecuente. Un desarrollo regulatorio avanzado se asocia con tasas más altas de detección y notificación de incidentes, y un conjunto más amplio de medidas en los países. La cadena de suministro farmacéutico es más vulnerable en su último eslabón. Las desviaciones de calidad identificadas en las muestras analizadas plantean graves riesgos para la salud pública.

The phenomenon of counterfeit medicines is common in healthcare systems around the world, making it a global problem. The number of recorded cases of falsified drugs available on the market is increasing every year. The World Health Organization indicates that up to 10% of the drugs in the global market are falsified. In Internet trading, this percentage reaches even 50%. Counterfeit medicines pose a serious threat to human health and life. The Delegated Regulation, which started the implementation of the Falsified Medicines Directive (FMD) published in 2016, was an essential step in the field of patient safety in Europe. Hospital pharmacies in Europe had three years to prepare to start the drug authentication process (the deadline for compliance with the requirements of the European Directive was February 2019). Although the Falsified Medicines Directive affects many groups of healthcare stakeholders, some of them still do not comply with the introduced rules. As a result of FMD, the vast majority of prescription drugs, as well as some over-the-counter (OTC) drugs, will require authentication. The Directive stipulates that each legal medicinal product must have a unique code and a tamper-evident label, which protects the drug against an unauthorized opening, which will enable the authentication of each drug package at the time of its release. The Falsified Medicines Directive offers a real opportunity to reduce this risk and optimize healthcare services, also by optimizing the workflow of pharmacies and supporting patients to comply with medical recommendations. A necessary step to ensure these benefits and achieve compliance with the FMD is the development and regular review of Good Authentication Practice guidelines. The article aims to present the impact of the Falsified Medicines Directive on the operation of a hospital pharmacy, including the additional obligations imposed by this Directive on pharmacists. The main goal of the article is also to present Good Medicine Authentication Practice (GMAP), which will be a practical guide for pharmacy employees in the field of drug authentication.

Official statistics of the counterfeit medicines circulation significantly reduces the level of patient confidence not only to pharmacy specialists, but also to the healthcare system and even other government institutions. All stakeholders, from academics to politicians, point to the significant implications of this situation for the healthcare system. The relevance and complexity of the problems of combating the falsification of medicines requires an expert assessment of pharmacy specialists.The aim of the work is to evaluate the effectiveness of the anti-counterfeiting of medicines using a questionnaire of specialists of the State Service of Ukraine on Medicines and Drug Control and its territorial bodies.The object of the research was scientific publications, as well as the study of the opinions of specialists of the State Service of Ukraine on Medicines and Drug Control and its territorial bodies on the problems of anti-counterfeiting of medicines. The study was conducted using questionnaire survey methods, systematization and generalization.According to the results of the survey, respondents rated the work of the State Service of Ukraine and its territorial bodies on the prevention of the sale of counterfeit drugs as effective, but there are some problems – 67.16% and 76.12%; in general, as effective – 31.34% and 20.90% respectively. An assessment of the directions of inspection of pharmacies has showed that the majority of respondents to the first place belonged – the cancellation of a note of warning about planned inspection (86.57%), to the second and third – simplification of the inspection procedure in the presence of consumer complaints (without additional approvals), 64.18% and the introduction of the right to conduct «test purchases» of medicines by inspectors (56.72%), respectively. Effective methods that are appropriate to use to identify counterfeit drugs included: scanning 2-d barcodes using special equipment and software – 79.10%, a detailed study of supporting documents – 53.73%, a careful visual inspection of packages – 47,76%.Based on the results of the expert evaluation, the most important tools were established that minimize the problem of counterfeit medicines circulation: a significant increase in the powers of the regulatory body (according to the FDA) – 70.15%, independent serial quality control of imported and manufactured drugs and APIs – 64.18%, strengthening responsibility for admission to the pharmaceutical market of drugs with unproven effectiveness – 59.70%.According to the results of an expert evaluation of the pharmacy specialists, the most important priorities of state policy were established, that allows to increase the effectiveness of the medicines’ anti-counterfeiting, namely improving the system of state quality control and strengthening the responsibility for falsification of medicines.

The illegal market of counterfeit and falsified medicines and supplements containing unlabeled pharmaceuticals is expanding worldwide. They are usually referred to by the term "performance and image enhancing drugs" (PIEDs) and are mainly steroids, stimulants, hormones, and drugs for erectile dysfunction. PIEDs are easily accessible through the online or black markets. We analyzed over 400 such medicines confiscated in Italy in the period 2017-2019, to determine their composition.Confiscated products were analyzed by gas chromatography/mass spectrometry and liquid chromatography/high-resolution mass spectrometry, in order to ascertain their composition and to evaluate the correspondence between what was declared on the label and the actual content, or to identify unknown products.The most commonly found substance was anabolic steroids, found in 64% of products, with 11% containing hormone modulators, 6% stimulants, 6% sexual enhancers (mainly sildenafil) and other drugs, including thyroid hormones, melanin stimulators, and vitamins. These substances were often in mixtures. The products were often mislabeled, containing contaminants in addition to the drug declared, or consisted of a drug completely different from the one reported on the label. Fifteen percent of products had a qualitative composition completely different from that declared, while 10% of products showed cross-contamination with other drugs, mainly testosterone esters, probably due to the presence of residues of other drugs in the production line. In addition, 11% of products were not labeled, so their purported composition was unknown.PIEDs pose a threat to public health. The main risks are related to the intrinsic toxicity of the substances found, especially when taken without a therapeutic indication. Another issue is related to the mislabeling of the fake medicines, and the poor-quality standard of counterfeit product preparation, with additional risks of the presence of other toxic ingredients or microbial contamination.The use of counterfeit products is a public health concern, as it constitutes a high risk for consumer health. It is mainly caused by the uncontrolled use of steroids, stimulants, sexual enhancers, and other medicaments, without medical indication or supervision, with variable and unknown compositions and doses, as well as other contaminants as a result of the absence of good manufacturing practices.

Summary. Falsification of medicines is a global problem in the modern world. The aim of the work is to analyze the problem of falsification of drugs in the Russian pharmaceutical market and measures to counter the creation and distribution of counterfeit drugs. Methods. Collection, systematization and analysis of modern data of scientific literature and the results of their own research on the relevant problem. Results. The share of counterfeit pharmaceutical products in Russia can reach 12%. The most common category of counterfeit drugs on the Russian pharmaceutical market the so-called drugs-copies. Visual distinctive features of counterfeit drugs are presented. According to the survey of pharmacy workers, 22.5% of pharmacists and pharmacists met with counterfeit drugs in their practice. The effectiveness of measures to combat counterfeit drugs in Russia is discussed. Huge hopes in this regard are placed on the track and Trance drug monitoring system. Conclusion. The fight against drug counterfeits must be systematic and involve all stakeholders. It is necessary to identify counterfeits at all stages of promotion of medicines from the manufacturer to the consumer. It is important for drug manufacturers to disseminate information about the distinctive features of their original products. The health Ministry promptly inform the pharmacy network about detected counterfeits. Employees of pharmacies should be familiar with modern methods of detecting counterfeit. Consumers medications needed to use the capabilities of the new system of monitoring medicines Track and Trance.

Background Counterfeit medicines are an increasing scourge that are difficult to identify and they have become industrialized and widespread through highly organized illegal channels. Objective This research aims to develop a robust method to determine four phosphodiesterase type-5 inhibitors in counterfeit drugs based on ultra-performance liquid chromatography. Method Experimental design methodology (DOE) and design space (DS) recommended by ICH Q8 were used side-by-side in the development phase to define the optimal parameters as well as the robustness of the chromatographic method. Moreover, both the uncertainty and risk profile derived from the β-content and γ-confidence tolerance interval were investigated during the validation phase to examine the performance of this method. Results Successful chromatographic results, in a high resolution between the four active ingredients and an optimal analysis time of less than 1.6 min, were achieved at the end of the optimization phase. In addition, validation results show a low risk of future measurements outside acceptance limits set at 5%. Conclusions Our procedure was successfully applied in the routine phase to identify 23 illicit formulations of an erectile dysfunction drug. Highlights An efficient method for the characterization of 4 authorized phosphodiesterase in less than 1.6 min was established. A DS approach was applied to test the performance of this analytical method during analytical development. A risk profile was then carried out to approve the validity of the analytical method through the uncertainty profile approach.

For the past several decades, global health research and policy have raised the alarm about the growing threat of counterfeit and low-quality drugs (henceforth ‘fakes’). These high-profile and regularly-repeated claims about ‘fake drugs’ pepper scholarly publications, grey literature, and popular writing. We reviewed much of this work and found that it shares two characteristics that sit awkwardly alongside one another. First, it asserts that fake drugs constitute an urgent threat to lives. Second, it reports trouble with ‘gaps’ in the evidence on which their claims are based; that data is weaker and less conclusive than anticipated. Given the ubiquity of and urgency with these claims are made, we found this juxtaposition perplexing. To understand this juxtaposition better, we undertook a close reading of the strategies authors employed to negotiate and overcome data and evidence ‘gaps’ and asked questions about the cultures of scholarly publishing in global health research. We argue that a scholarly commitment to studying fakes despite--rather than because of—the evidence functions to support the continuation of similar research. It also works against asking different questions—for instance regarding the lack of easy access to pharmacological data that might make it possible to know fakes differently.

Background: Topical corticosteroids are highly effective compounds that are now widely used in dermatology for the treatment of various autoimmune and inflammatory disorders. Many corticosteroids are misused for diverse indications such as pigmentation, acne, pruritus, fungal or bacterial infections, rashes, and numerous other conditions. These products contain various constituents, most of which have hazards or toxic elements. Objective: The aim is to raise awareness among individuals in the city of Basrah, Iraq about the uses and abuses of applying fake products to the face to inform the consumers about potential harmful adverse effects. Methods: This study was a prospective multi-center clinic questionnaire of a demographic that involved the outpatient dermatology departments at the Al-Basrah teaching hospital and the Abu Al-Khaseeb hospital as well as the private clinics of two dermatology specialists in Basrah. A total of 235 patients with facial dermatoses secondary to the application of topical corticosteroids and counterfeit products or, a mixed formulation, for cosmetic purposes were recruited. Results: Most enrolled patients were female with 10-20 years aged group. The majority applied these products due to friends or pharmacy encouragement. Motivations for the use of these products included: skin fairness, lightening, and general cosmetic. Interestingly, acne and erythema were common whilst, atrophy, dryness, telangiectasia, and hirsutism appear on long- term use only. Conclusion: The abuse of counterfeit cosmetic products and topical corticosteroids is in progress and they have adverse health events. There are many causes behind the abuse but the lack of education, lack of restriction, profitable for sellers and low prices are the main.