I (Don't) want to consume counterfeit medicines: exploratory study on the antecedents of consumer attitudes toward counterfeit medicines.

BACKGROUND: Substandard and falsified medicine (SFM) sales (an estimated > $200 billion) has become one of the worlds' fastest growing criminal enterprises. It presents an enormous public health and safety challenge. While the developed world is not precluded from this challenge, studies focus on low-income countries. They emphasize supply chain processes, technological, and legal mechanisms, paying less attention to consumer judgment and decision-making aspects. METHODS: With attention to the demand side of the counterfeit medicines challenge, this survey of U.S. consumers (n = 427) sheds light on some of the social, psychological, and normative factors that underlie consumers' attitudes, risk perceptions, and purchase intentions. RESULTS: Consumers who (a) self-report that they know about the problem, (b) are older, (c) view counterfeit medicine consumption as ethical, and (d) think their significant others would approve of them using such products are more inclined to perceive lower risks and have favorable purchase intentions. Risk averseness is also inversely related to the predicted outcomes. Perceived benefit of SFMs is a factor but has no effect when risk perception and aversion, attitudes, and subjective norms are factored into the model that predicts purchase intentions. CONCLUSION: The results of this study indicate that consumer knowledge (albeit in an unexpected direction), people's expectations about what will impress their significant others, their ethical judgments about selling and consuming counterfeits, and their risk-aversion are associated with their decision-making about counterfeit medicines. The study offers insights into a demand-side approach to addressing SFM consumption in the U.S. Implications for public health, consumer safety, and brand advocacy education are discussed.

Implementation of digital technologies in human rights to healthcare.

OBJECTIVE: The aim: The aim of the study is to examine the blockchain technology in the field of healthcare, to analyze the principles of the European Convention on Human Rights regarding respect for private and family life, home and correspondence, to analyze the key positions of the European Court of Human Rights (hereinafter - ECHR) in the field of human rights to privacy, to analyze the European Union (hereinafter - EU) secondary legislation regarding the supply of medicines, prospects for the blockchain usage in order to protect human rights to privacy and improve the quality of medicines. PATIENTS AND METHODS: Materials and methods:Scientific works that are devoted to the outspread of digital technologies in healthcare, the provisions of the European Convention on Human Rights, the ECHR's practice on the protection of human rights to privacy, the provisions of the EU secondary legislation that regulate the supply of medicines are studied. The methodology of this article is based on comparative and legal analysis techniques and includes system-structural method, method of generalization, method of analysis and synthesis as well. CONCLUSION: Conclusions:The blockchain technology in medicine and pharmacology will increase the level of protection of human rights to healthcare quality.

The development and appraisal of a tool designed to find patients harmed by falsely labelled, falsified (counterfeit) medicines.

BACKGROUND: Falsely labelled, falsified (counterfeit) medicines (FFCm's) are produced or distributed illegally and can harm patients. Although the occurrence of FFCm's is increasing in Europe, harm is rarely reported. The European Directorate for the Quality of Medicines & Health-Care (EDQM) has therefore coordinated the development and validation of a screening tool. METHODS: The tool consists of a questionnaire referring to a watch-list of FFCm's identified in Europe, including symptoms of their use and individual risk factors, and a scoring form. To refine the questionnaire and reference method, a pilot-study was performed in 105 self-reported users of watch-list medicines. Subsequently, the tool was validated under "real-life conditions" in 371 patients in 5 ambulatory and in-patient care sites ("sub-studies"). The physicians participating in the study scored the patients and classified their risk of harm as "unlikely" or "probable" (cut-off level: presence of ≥2 of 5 risk factors). They assessed all medical records retrospectively (independent reference method) to validate the risk classification and documented their perception of the tool's value. RESULTS: In 3 ambulatory care sites (180 patients), the tool correctly classified 5 patients as harmed by FFCm's. The positive and negative likelihood ratios (LR+/LR-) and the discrimination power were calculated for two cut-off levels: a) 1 site (50 patients): presence of two risk factors (at 10% estimated health care system contamination with FFCm's): LR + 4.9/LR-0, post-test probability: 35%; b) 2 sites (130 patients): presence of three risk factors (at 5% estimated prevalence of use of non-prescribed medicines (FFCm's) by certain risk groups): LR + 9.7/LR-0, post-test probability: 33%. In 2 in-patient care sites (191 patients), no patient was confirmed as harmed by FFCm's. The physicians perceived the tool as valuable for finding harm, and as an information source regarding risk factors. CONCLUSIONS: This "decision aid" is a systematic tool which helps find in medical practice patients harmed by FFCm's. This study supports its value in ambulatory care in regions with health care system contamination and in certain risk groups. The establishment of systematic communication between authorities and the medical community concerning FFCm's, current patterns of use and case reports may sustain positive public health impacts.

Testing of complementarity of PDA and MS detectors using chromatographic fingerprinting of genuine and counterfeit samples containing sildenafil citrate.

Counterfeit medicines are a global threat to public health. High amounts enter the European market, which is why characterization of these products is a very important issue. In this study, a high-performance liquid chromatography-photodiode array (HPLC-PDA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) method were developed for the analysis of genuine Viagra®, generic products of Viagra®, and counterfeit samples in order to obtain different types of fingerprints. These data were included in the chemometric data analysis, aiming to test whether PDA and MS are complementary detection techniques. The MS data comprise both MS1 and MS2 fingerprints; the PDA data consist of fingerprints measured at three different wavelengths, i.e., 254, 270, and 290 nm, and all possible combinations of these wavelengths. First, it was verified if both groups of fingerprints can discriminate between genuine, generic, and counterfeit medicines separately; next, it was studied if the obtained results could be ameliorated by combining both fingerprint types. This data analysis showed that MS1 does not provide suitable classification models since several genuines and generics are classified as counterfeits and vice versa. However, when analyzing the MS1_MS2 data in combination with partial least squares-discriminant analysis (PLS-DA), a perfect discrimination was obtained. When only using data measured at 254 nm, good classification models can be obtained by k nearest neighbors (kNN) and soft independent modelling of class analogy (SIMCA), which might be interesting for the characterization of counterfeit drugs in developing countries. However, in general, the combination of PDA and MS data (254 nm_MS1) is preferred due to less classification errors between the genuines/generics and counterfeits compared to PDA and MS data separately.

[Contemporary aspects of using sildenafil].

Sildenafil has been thoroughly studied in 74 registered double-blind, placebo-controlled clinical trials assessing the efficacy and safety of the drug in a total of more than 16 000 men with erectile dysfunction (ED). However, practicing urologists have some questions regarding administering the drug in patients with multiple comorbidities. In this review, on a par with the now "classic" research, we outline the latest updates of meta-analyzes and comparative studies relating to the use of sildenafil in different groups of patients. We also discuss the problem of self-discontinuation of sildenafil therapy and the possible risks of using counterfeit phosphodiesterase type 5 inhibitors (PDE-5i).

Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs.

The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed-phase high-performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C(18) (100 mm × 2.1 mm inside diameter, 2.6 µm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries.

Rapid discrimination of slimming capsules based on illegal additives by electronic nose and flash gas chromatography.

The discrimination of counterfeit and/or illegally manufactured medicines is an important task in the pharmaceutical industry for pharmaceutical safety. In this study, 22 slimming capsule samples with illegally added sibutramine and phenolphthalein were analyzed by electronic nose and flash gas chromatography. To reveal the difference among the different classes of samples, principal component analysis and linear discriminant analysis were employed to analyze the data acquired from electronic nose and flash gas chromatography, respectively. The samples without illegal additives can be discriminated from the ones with illegal additives by using electronic nose or flash gas chromatography data individually. To improve the performance of classification, a data fusion strategy was applied to integrate the data from electronic nose and flash gas chromatography data into a single model. The results show that the samples with phenolphthalein, sibutramine and both can be classified well by using fused data.

Design and testing of a low impedance transceiver circuit for nitrogen-14 nuclear quadrupole resonance.

A low impedance transceiver circuit consisting of a transmit-receive switch circuit, a class-D amplifier and a transimpedance amplifier (TIA) was newly designed and tested for a nitrogen-14 NQR. An NQR signal at 1.37MHz from imidazole was successfully observed with the dead time of ~85µs under the high Q transmission (Q~120) and reception (Q~140). The noise performance of the low impedance TIA with an NQR probe was comparable with a commercial low noise 50Ω amplifier (voltage input noise: 0.25 nV/Hz) which was also connected to the probe. The protection voltage for the pre-amplifier using the low impedance transceiver was ~10 times smaller than that for the pre-amplifier using a 50Ω conventional transceiver, which is suitable for NQR remote sensing applications.

Selecting relevant Fourier transform infrared spectroscopy wavenumbers for clustering authentic and counterfeit drug samples.

This paper proposes a novel method for selecting subsets of wavenumbers provided by attenuated total reflectance by Fourier transform infrared (ATR-FTIR) spectroscopy able to improve the clustering of medicine samples into two groups; i.e., authentic or fraudulent. For that matter, we apply principal components analysis (PCA) to ATR-FTIR data, and derive two variable importance indices from the PCA parameters. Next, an iterative variable (i.e. wavenumbers) elimination procedure and sample clustering through k-means and Fuzzy C-means techniques are carried out; clustering performance is assessed by the Silhouette Index (SI). The performance of the proposed method is compared with a greedy variable selection method, the "leave one variable out at a time" approach, in terms of clustering quality, percent of retained variables, and computational time. When applied to Viagra ATR-FTIR data, our propositions increased the average SI from 0.5307 to 0.8603 using 0.61% of the original 661 wavenumbers; as for Cialis ATR-FTIR data, clustering quality increased from 0.7548 to 0.8681 when 1.21% of the original wavenumbers were retained in the procedure. The retained wavenumbers, located in the 1091-1046cm(-1) region, comprise the lactose typically hailed as key substance to discriminate between authentic and counterfeit samples.

The impact of global falsified medicines regulation on healthcare stakeholders in the legitimate pharmaceutical supply chain: a systematic review.

Background: Falsified medicines and their international regulation impacts all healthcare sectors and their actors. These regulations aim to strengthen and protect the global pharmaceutical supply chain against falsified medicines. However, an evaluation of the impacts of these regulations on key stakeholders within the legitimate supply chain have not been explored. Objective: This research aimed to evaluate both the positive and negative impacts of falsified medicines regulation on key stakeholders within the global pharmacy sector including including manufacturers, wholesalers, hospital pharmacies, community pharmacy and patients. Design: This research consists of a systematic review and thematic analysis concerning falsified medicines regulation and the subsequent impacts of existing global regulations on healthcare. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and checklist were utilized for reporting in this systematic review. Data sources and methods: A search of three databases, Embase, ProQuest and PubMed, was undertaken to determine studies applicable to the research question. The Mixed Methods Appraisal Tool (MMAT) was used to assess methodological quality and risk of bias for all included studies. Results: From the initial 657 studies, a final set of 13 relevant studies were identified. The most frequently reported falsified medicines regulation was the Falsified Medicines Directive (FMD) [n = 11]. The impact of falsified medicines regulation in the literature related to four areas: (1) Financial, (2) Social, (3) Organizational, and (4) Pharmacy Practice. These common themes across the included studies frequently relate to challenges and/or concerns associated with falsified medicines regulation implementation as well as both the logistics and practicality of incorporating falsified medicines regulations into daily operations. Conclusion: Implementation and enforcement of falsified medicines regulation does not yet appear to categorically fulfill the primary aim of the regulations, to strengthen the drug supply chain. However, in recent years, such regulations have challenged the legitimate pharmaceutical supply change actors as they attempt to successfully implement these regulations. Studies mainly detail the negative impacts of regulation during the implementation phase but with the overall benefit pertaining to the prioritization and enhancement of patient care and safety within the healthcare sector.

Evaluating aspects of online medication safety in long-term follow-up of 136 Internet pharmacies: illegal rogue online pharmacies flourish and are long-lived.

BACKGROUND: A growing number of online pharmacies have been established worldwide. Among them are numerous illegal websites selling medicine without valid medical prescriptions or distributing substandard or counterfeit drugs. Only a limited number of studies have been published on Internet pharmacies with regard to patient safety, professionalism, long-term follow-up, and pharmaceutical legitimacy verification. OBJECTIVE: In this study, we selected, evaluated, and followed 136 Internet pharmacy websites aiming to identify indicators of professional online pharmacy service and online medication safety. METHODS: An Internet search was performed by simulating the needs of potential customers of online pharmacies. A total of 136 Internet pharmacy websites were assessed and followed for four years. According to the LegitScript database, relevant characteristics such as longevity, time of continuous operation, geographical location, displayed contact information, prescription requirement, medical information exchange, and pharmaceutical legitimacy verification were recorded and evaluated. RESULTS: The number of active Internet pharmacy websites decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months and only 67 monitored websites (49.3%) were accessible at the end of the four-year observation period. However, not all operated continuously, as about one-fifth (31/136) of all observed online pharmacy websites were inaccessible provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any contact details, while only 59 (43.4%) displayed all necessary contact information on the website. We found that the declared physical location claims did not correspond to the area of domain registration (according to IP address) for most websites. Although the majority (120/136, 88.2%) of the examined Internet pharmacies distributed various prescription-only medicines, only 9 (6.6%) requested prior medical prescriptions before purchase. Medical information exchange was generally ineffective as 52 sites (38.2%) did not require any medical information from patients. The product information about the medicines was generally (126/136, 92.6%) not displayed adequately, and the contents of the patient information leaflet were incomplete in most cases (104/136, 76.5%). Numerous online operators (60/136, 44.1%) were defined as rogue Internet pharmacies, but no legitimate Internet-based pharmacies were among them. One site (0.7%) was yet unverified, 23 (16.9%) were unapproved, while the remaining (52/136, 38.2%) websites were not available in the LegitScript database. Contrary to our prior assumptions, prescription or medical information requirement, or the indication of contact information on the website, does not seem to correlate with "rogue pharmacy" status using the LegitScript online pharmacy verification standards. Instead, long-term continuous operation strongly correlated (P<.001) with explicit illegal activity. CONCLUSIONS: Most Internet pharmacies in our study sample were illegal sites within the definition of "rogue" Internet pharmacy. These websites violate professional, legal, and ethical standards and endanger patient safety. This work shows evidence that online pharmacies that act illegally appear to have greater longevity than others, presumably because there is no compelling reason for frequent change in order to survive. We also found that one in five websites revived (closed down and reopened again within four years) and no-prescription sites with limited medicine and patient information are flourishing.

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

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

Market violence through destructive entrepreneurship: Assessing institutional responses to the proliferation of counterfeit traditional and alternative medicines in Ghana.

Purpose: This multidisciplinary study seeks to determine the nature and structure of the informal markets for counterfeit medicines, the co-factors underpinning the demand and supply of counterfeit Western allopathic medicines (WAM), traditional and alternative medicines (TAM), and potential institutional responses in Ghana. Method: This study is based on an interpretive research approach. It deploys a synthesis of a longitudinal ethnographic fieldwork, with multiple repeated visits for observations, analysis of documents, interviews, and focus group discussions. Findings: The study identifies five major inter-related discoveries that point to the need for urgent institutional responses: Approaches to global health governance pay little attention to the complex economic gamut of TAM, including herbal medicines. The rise in necessity entrepreneurship and the availability of easy-to-use packaging and advertising technologies have made TAM a major competitor of WAM. The informal markets for WAM and TAM are structured in ways that allow them to evade formalized interventions and regulations. Standardization allows destructive entrepreneurs to derive advantage from economies of scale and reduce production costs, allowing the sector to flourish with little economic risk while inflicting violence on consumers. Personalization and co-creation of medicine with consumers has the added psychological effect of increasing consumer confidence. This, however, enlists consumers in the market violence against themselves. Social implications: Destructive entrepreneurship, whether inadvertent or criminal creates benefits for groups and individuals but negatively affects public health on various levels. Originality: Mitigation and interventions that ignore the informal TAM market of destructive entrepreneurship only answer a part of the big question of how to guarantee patient/consumer safety from the threats of all counterfeits.

Challenges Associated with Addressing Counterfeit Medicines in Nigeria: An Exploration of Pharmacists' Knowledge, Practices, and Perceptions.

Introduction: Counterfeit medicines are substandard pharmaceutical products that are produced and sold with the intent to deceptively represent their authenticity, origin, or effectiveness. The risk of the existence of such products in healthcare provision remains a significant threat to public health. Pharmacists represent the most critical stakeholders in the supply, manufacture, purchase, and dispensing of pharmaceutical products, and as such can play critical roles in detecting and reducing the circulation of fake medicines. This study aimed to assess the knowledge and practices of pharmacists in Nigeria in relation to counterfeit medicines as well as the challenges associated with preventing and mitigating this menace in the country. Methods: A cross-sectional study was undertaken to administer questionnaires to pharmacists across various sectors of practice in Nigeria. Data were analysed using Statistical Package for Social Sciences. Results: A total of 390 valid responses were received. The respondents indicated that online drug commerce (72.68%), inadequate inspection (90.93%), inadequate legislation (88.83%), poor collaboration (89.94%), and poor cross-border enforcement (90.43%) were primary challenges to the mitigation of fake medicines circulation in the country. Whilst pharmacists were knowledgeable about counterfeit drugs, gaps were observed in their practices towards detection of these products, as about one-third (30.7%) of the sample indicated that their current knowledge and skills were inadequate to detect counterfeit medicines. Age, years of practice, and area of practice significantly influenced the abilities of the participants to detect counterfeit medicines. Conclusion: Evidence from the study revealed that pharmacists had good knowledge of medicine counterfeiting in Nigeria. However, factors such as poor collaboration among regulatory agencies, inadequate inspection and legislation on the regulation of the pharmaceutical sector and online sales of medicines have contributed to the circulation of counterfeit medicines, and this has in turn affected healthcare services in the country.

The era of fake medicines: Investigating counterfeit medicinal products for erectile dysfunction disguised asherbal supplements.

Sales of substandard and falsified medical products (SF) are rising rapidly everywhere around the globe. The wide and easy access to these products is an alarming issue to the global health systems and undermined the health of patients, especially with the thrive of online commerce. To tackle this threat to public health, new ways to access these products should be identified and detection technologies should be strengthened. The overarching aim of this study was to investigate if herbal supplements sold online claiming to be natural alternatives to Viagra® were amongst these SF medical products and how effective different analytical techniques are in providing information about these products. 3 products which claimed to be herbal supplements for men sexual performance were purchased from an e-commerce platform. Two products were received as unregistered generic sildenafil citrate tablets manufactured in India (and thus different to the products information on the website) while one product was received in the same packaging as shown on the website, claiming to be an herbal product. Nevertheless, all products were proven to contain sildenafil citrate, the active pharmaceutical ingredients in Viagra® after the comprehensive analytical tests. The results elucidated that the quality standards for the unregistered generic sildenafil citrate tablets were fulfilled according to the British Pharmacopeia, but the falsified product failed the quality tests and contained approximately 200 mg sildenafil citrate, which is equivalent to 2-fold of the daily maximum dose. Furthermore, physical characterisations, including powder x-ray diffraction and thermal analysis were performed and revealed that the polymorphic forms of sildenafil citrate were different, demonstrating the importance of employing thermal analysis in addition to the conventional analysis techniques for the substandard and falsified medical products. These techniques provided valuable insights into the physical form of the active ingredient in these products. What is more, the ease with which these SF products were obtained and confirmed to be misleading consumers emphasises the need for tighter regulation for e-commerce websites in line with those enforced on online pharmacies.

Health Care Providers' Knowledge, Attitude and Practice Toward Counterfeit Medicines in Mizan-Tepi University Teaching Hospital, South West Ethiopia: A Cross-Sectional Study.

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 <.05 were considered as statistically significant. Large proportions of the study participants (84.2%) have information on counterfeit drugs and 15.8% of them described counterfeit medicine as product with toxic impurities. 50.3% of them were able to distinguish a counterfeit drug from the genuine drug. 8.2% of the participants demonstrated that counterfeit medicine can be identified by physical observation of labeling, color appearance and packaging. 61.4% of the study respondents revealed that strong legal action can prevent circulation of counterfeit medicine. Professional distribution was significantly associated with the attitude of health care providers toward counterfeit medicines (P < .05). Accordingly, public health officers and midwifery health care providers were more likely to have poor attitude toward counterfeit medicines (AOR = 6.09, CI (1.798-20.69) and (AOR = 3.98(1.54-10.25)) respectively as compared to nurses. This study demonstrated the importance of awareness creation to all health care providers. Drug regulatory bodies and concerning bodies must play an active role in designing appropriate program and policy to enhance health professionals' knowledge and attitude toward CFM. There is also a need of empowering the practitioners in identifying counterfeit drugs by simple observations.

Identifying the most relevant tablet regions in the image detection of counterfeit medicines.

This paper proposes a novel image-based approach to detect counterfeit medicines and identify the most relevant regions of the tablet in the task of classification. Images of medicine tablets undergo an initial pre-processing step which (i) removes the background to find the region of interest, (ii) clusters individual pixels into super-pixels, and (iii) extracts features containing color and texture information. The classification relying on Support Vector Machine (SVM) defines the class the respective image will be inserted into. The task of identifying the relevant regions of the tablets for counterfeiting detection is performed using the concept of support vectors, generating a heat map that indicates the regions that contribute the most to the classification purpose. Two datasets containing images of authentic and counterfeit tablets of Cialis and Viagra were used to validate our propositions, achieving correct classification rates of 100% on both datasets. Regarding the task of identifying the most relevant regions, our proposition outperformed the traditional LIME (Local Interpretable Model-agnostic Explanations) method by yielding more robust explanations.

Current challenges in the detection and analysis of falsified medicines.

Falsified medicines affect public health all around the globe. Complex distribution routes, illegal online webshops and reuse of packaging materials make them hard to detect. In order to tackle this problem, detection methods for the recognition of suspicious medicines and subsequent confirmation of falsification by analytical techniques is required. In this review, we focus on the developments and challenges that existed in the last five years (2015-2020) in the detection and analysis of falsified medicines. These challenges might have not been solved yet or arisen with new types of falsifications, new analytical techniques or detection strategies. Detection of suspicious medicines starts with visual inspection of packaging materials. However, re-use of packaging materials and high-quality imitations complicate visual inspection. Recent developments in the analysis of packaging by microscopic and spectroscopic techniques such as optical microscopy, X-ray fluorescence, infrared spectroscopy and Raman spectroscopy or microscopy, in combination with multivariate analysis show promising results in the detection of falsified medicines. An ongoing big challenge in the analysis of falsified medicines is the affordability of analytical devices. Yet, recent reports showed that lower cost devices, such as Counterfeit Drug Indicator or Counterfeit Detection device version 3 show promising use in the detection of falsified medicines. Furthermore, combining the outcomes of different low-cost analytical techniques, such as Minilab, colorimetry and Counterfeit Drug Indicator significantly increased selectivity and sensitivity in the detection of falsified medicines. Also, recent developments make it possible to link a low-cost technique, such as TLC, to mobile phones. Proper training of personnel has shown room for improvement and remains a challenge, even for relatively simple techniques. With an increased use of analytical fingerprints, an upcoming challenge is the accessibility of the growing pool of data. There is also the need of validated reference libraries on both national and international levels. Developments of the last few years bring us a step closer in the fight against falsified medicines, however challenges remain in the worldwide accessibility of affordable, easily operable and sensitive techniques.

Authentication of Antibiotics Using Portable Near-Infrared Spectroscopy and Multivariate Data Analysis.

Counterfeit medicines represent a global public health threat warranting the development of accurate, rapid, and nondestructive methods for their identification. Portable near-infrared (NIR) spectroscopy offers this advantage. This work sheds light on the potential of combining NIR spectroscopy with principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) for authenticating branded and generic antibiotics. A total of 23 antibiotics were measured "nondestructively" using a portable NIR spectrometer. The antibiotics corresponded to six different active pharmaceutical ingredients being: amoxicillin trihydrate and clavulanic acid, azithromycin dihydrate, ciprofloxacin hydrochloride, doxycycline hydrochloride, and ofloxacin. NIR spectra were exported into Matlab R2018b where data analysis was applied. The results showed that the NIR spectra of the medicines showed characteristic features that corresponded to the main excipient(s). When combined with PCA, NIR spectroscopy could distinguish between branded and generic medicines and could classify medicines according to their manufacturing sources. The PCA scores showed the distinct clusters corresponding to each group of antibiotics, whereas the loadings indicated which spectral features were significant. SIMCA provided more accurate classification over PCA for all antibiotics except ciprofloxacin which products shared many overlapping excipients. In summary, the findings of the study demonstrated the feasibility of portable NIR as an initial method for screening antibiotics.