Criminal Action Against Drug Counterfeiters: Assessment of the FDA Office of Criminal Investigation Database 2016 Through 2021.

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.

Experiences With Counterfeit Aesthetic Medical Devices and Injectables: A National Survey.

BACKGROUND: Counterfeit medical devices and injectables have recently garnered interest in the field of aesthetics. Unlike their original counterparts, these counterfeit products have neither been tested nor verified using certified quality control measures. OBJECTIVE: Our study investigated the pervasiveness of counterfeit products in the field as well as the experiences and attitudes of practitioners. MATERIALS AND METHODS: An online survey was distributed to current members of the American Society for Dermatologic Surgery (ASDS) and the American Society for Laser Medicine and Surgery (ASLMS). RESULTS: For medical devices, 37.4% have encountered counterfeits and 20.1% have experienced patients with adverse events from them. For injectables, 41.1% have encountered counterfeits and 39.7% have experienced patients with adverse events from them. Compared with their original, most respondents believe that counterfeits are worse in terms of reliability, safety, and effectiveness. The majority also believe that counterfeits are either very or extremely endangering to patient safety. CONCLUSION: Counterfeit medical devices and injectables are not uncommonly encountered. Overall, practitioners believe counterfeits are endangering patient safety and result in adverse events and think that either stricter rules and regulations or better enforcement of existing regulations is necessary.

Veterinary pharmacovigilance in sub-Sahara Africa context: a pilot study of adverse reactions to veterinary medicine in Cameroon.

BACKGROUND: Sub-Saharan African market is highly affected by counterfeit veterinary drugs. Though these counterfeit and non-compliance of drugs can induce adverse effects during their utilization, there is no monitoring system of veterinary medicines. The present pilot study was carried out in Cameroon to identify and describe suspected cases of adverse reactions to veterinary drugs in animals and / or humans as well as inefficacy of veterinary drugs. The methodology involved a descriptive cross-sectional survey of 67 actors in the veterinary medicine sector in Cameroon. RESULTS: A total of 74/120 (62%) cases of suspected adverse effects and or lack of efficacy of veterinary drugs in animals and 46 (38%) cases of adverse reactions in humans were identified. Antiparasitics were the most incriminated therapeutic class in animals (61%) and human (56%). Adverse reactions were reported in dogs (44%) and poultry (24%) while drug inefficacy was most observed in poultry (47%). According to animal health professionals, levamisole (24%) and ivermectin (16%) were identified to be responsible for the adverse effects and that the highest level of inefficacy was most frequently reported for oxytetracycline (29%). The main adverse reactions were systemic (22%), gastrointestinal (20%) and neurological (13%) disorders. CONCLUSION: The results of this study showed that misuse and circulation of poor quality as well as lack of efficacy of veterinary drugs is very common in Cameroon. Adverse reactions were observed in animals and humans. Therefore, the establishment of a national veterinary pharmacovigilance system based on solid legal bases is essential for a continuous assessment of the risks-benefits effects of veterinary drugs marketed in Cameroon.

Global scenario of counterfeit antimalarials: A potential threat.

Malaria, a parasitic infectious disease causes approximately >1 million deaths annually worldwide. Treatment with effective antimalarials is one of the major strategies to combat malaria-related mortalities. However, there is a continuous threat of counterfeit antimalarials in the community. Counterfeit antimalarial drugs not only result in an economic loss but also decrease the efficacy of treatment resulting in the loss of faith in the health system and increases the the chances of drug resistance in the parasites. Counterfeit drugs hamper the intellectual property-based innovation paradigms as well. Awareness about these counterfeit drugs not only helps in avoiding drug resistance but may also enhance the drug therapeutic value. This review discusses the prevalence of counterfeit drugs in different geographic areas across the globe, the methods deployed for its detection and possible anticounterfeiting strategies. Literature search was conducted through PubMed, Google and International Pharmaceutical Abstracts using the terms 'counterfeit antimalarials', 'substandard', 'falsified', and 'drug resistance'. Free searches in other search engines included the terms 'antimalarial counterfeit drugs' and 'drug resistance'. Analysis of the literature survey indicated that majority of such studies were conducted in Southeast Asia and Africa region. The prevalence of substandard antimalarials was reported as high as 88.4% in Africa region and 53 % in Southeast Asia region. There is a need to follow a multifaceted approach to prevent the entry of falsified drugs with pre- and post-marketing surveillance. The samples need to be examined by regulatory bodies and strict legislation should be envisaged in order to maintain the quality of medicines.

Oncology drugs in the crosshairs of pharmaceutical crime.

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

The health consequences of falsified medicines- A study of the published literature.

OBJECTIVES: To analyse and present the literature describing the health consequences of falsified medicines, focusing on mortality and morbidity, as well as the scale of the issue, the geographic extent, the medicines affected, and the harm caused at both the individual and population levels. METHODS: We searched for articles in PubMed, using pre-optimized keywords '(counterfeit OR fake OR bogus OR falsified OR spurious) AND (medicine OR drug)'. Searches up to February 2017 yielded 2006 hits, of which 1791 were full-length articles in English. Among them, we found 81 papers that qualitatively or quantitatively described 48 incidents in which falsified medicines caused patients to suffer serious adverse effects, injury, symptoms or death. RESULTS: The distribution of incidents was examined according to the economic status of the countries involved, regional location in the world, therapeutic category of the medicines, number of incidents and victims by year, and characteristics of the falsified medicines. Among the 48 reported incidents, 27 (56.3%) occurred in developing countries and 21 (43.7%) in developed countries. These incidents involved a total of approximately 7200 casualties including 3604 deaths. CONCLUSIONS: Despite the poor quality of much of the reported data, the results of this study indicate that all types of medications have been targeted for falsification, and falsified medicines have had a serious impact on the health of both adults and children worldwide, with similar numbers of incidents in developing and developed countries.

An insight into the deep web; why it matters for addiction psychiatry?

OBJECTIVE: Nowadays, the web is rapidly spreading, playing a significant role in the marketing or sale or distribution of "quasi" legal drugs, hence facilitating continuous changes in drug scenarios. The easily renewable and anarchic online drug-market is gradually transforming indeed the drug market itself, from a "street" to a "virtual" one, with customers being able to shop with a relative anonymity in a 24-hr marketplace. The hidden "deep web" is facilitating this phenomenon. The paper aims at providing an overview to mental health's and addiction's professionals on current knowledge about prodrug activities on the deep web. METHODS: A nonparticipant netnographic qualitative study of a list of prodrug websites (blogs, fora, and drug marketplaces) located into the surface web was here carried out. A systematic Internet search was conducted on Duckduckgo® and Google® whilst including the following keywords: "drugs" or "legal highs" or "Novel Psychoactive Substances" or "NPS" combined with the word deep web. RESULTS: Four themes (e.g., "How to access into the deepweb"; "Darknet and the online drug trading sites"; "Grams-search engine for the deep web"; and "Cryptocurrencies") and 14 categories were here generated and properly discussed. CONCLUSIONS: This paper represents a complete or systematical guideline about the deep web, specifically focusing on practical information on online drug marketplaces, useful for addiction's professionals.

Captagon: use and trade in the Middle East.

BACKGROUND: Fenetheylline, a psychostimulant drug, often branded as Captagon, is a combination of amphetamine and theophylline. Since the cessation of its legal production in 1986, counterfeited products have been produced illicitly in south-east Europe and far-east Asia. Its profitable trade has been linked to terrorist organizations, including Islamic State of Iraq and the Levant. This study aims to reach up-to-date data, concerning the Captagon e-commerce and use in the Middle East. METHODS: A multi-staged and multi-lingual literature search was carried out. A list of prespecified keywords was applied across medical and paramedical databases, web and Dark web, search engines, social communication media, electronic commerce websites, media networks, and the Global Public Health Intelligence Network database. RESULTS: The use of Captagon as a stimulant in terrorist settings has been marginally covered in the literature. Data can widely be retrieved from Google and AOL search engines, YouTube, and Amazon e-commerce websites, and to a lesser extent from Alibaba and eBay. On the contrary, Middle Eastern e-commerce websites yielded almost no results. Interestingly, the Dark web generated original data for Captagon e-commerce in the Middle East. CONCLUSION: Further investigations are needed on the role that psychoactive drugs play in terrorist attacks and civil war zones. Unless a comprehensive methodological strategy, inclusive of unconventional methods of research, is implemented, it will not be feasible to face such a threat to humanity.

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.

Substandard/counterfeit antimicrobial drugs.

Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue.

[Falsified pharmaceutical products : Legislative measures in the European Union and in Germany]. / Arzneimittelfälschungen : Maßnahmen der Gesetzgeber in der Europäischen Union und in Deutschland.

Falsified pharmaceutical products are multi-faceted and driven by great criminal power. The health risks for patients who are frequently very seriously ill are high. The problem in Europe has been recognised. The European Union has created statutory requirements that considerably improve and tighten the system of manufacturing, distribution and documentation, and of pharmaceutical product authorisations. The traceability of each package via safety features is strengthened and made binding by detailed delegated legislation. Implementation is in progress. An publicly accessible database on good manufacturing and distribution practice (GMDP) is intended to optimise control not only by the authorities but also by concerned groups. The distance selling of medicinal products by mail order pharmacies has been tightened and unified (harmonized). Uniform logos throughout Europe are intended to make it easier for consumers to distinguish between legal and illegal sources. The transformation is in full swing. The European Commission will be documenting the success of the measures in a report.

[Current cases of falsified medicinal products within the competence of the Federal Institute for Drugs and Medical Devices (BfArM) : Case studies and extent]. / Aktuelle Fälschungsfälle bei Arzneimitteln in der Zuständigkeit des Bundesinstituts für Arzneimittel und Medizinprodukte (BfArM) : Fallbeispiele und Ausmaß.

The nature of a falsification of a medicinal product can vary a lot. Therefore the means to detect them and the potential risk to patient safety can also be very different. The whole range of falsification will be described using observed cases from the Federal Institute for Drugs and Medical Devices (BfArM).Based on the relatively low number of detected cases of falsified medicines, the legal supply chain can still be regarded as safe. It has to be assumed that in the illegal supply chain, e. g. illegal internet trade, the majority of the offered medicinal products are not only falsifications due to illegal trade but because they are completely falsified. Therefore there is an especially high risk for the consumer to be harmed by medicinal products that do not fulfil the required specifications.The trend indicates that increased efforts will be necessary to keep the legal supply chain safe and to contain illegal trade with falsifications. The higher federal authorities BfArM, PEI and BVL are involved in this task by coordinating and ensuring the flow of information to the concerned authorities and stakeholders as well as informing the public. Increased efforts are also necessary due to the rising involvement of organised crime in the falsification of medicinal products. A package of measures was enacted with the Falsified Medicines Directive 2011/62/EU to protect the legal supply chain from falsified medicinal products.

[Falsified dietary food supplements for men: expertise difficulties and medical problems].

Falsified dietary food supplements for men: expertise difficulties and medical problems. According to numerous chemical-toxicological and forensic researches it have been sildenafil and tadalafil in a variety of dietary food supplements. Falsified dietary food supplements, are essentially a substitute for drugs - phosphodiesterase type 5 inhibitor, but are produced with unknown composition and in unknown dose of synthetic pharmaceutical substances. This can cause consumers unpredictable nezative conseauences. including death.

[Counterfeit and Falsified Drugs: an Overview]. / Trafic de faux médicaments : panorama 2014.

If the traffic of fake medicines may represent an economic threat for the pharmaceutical industry, it can also be responsible of safety concerns for patients. Despite fake drugs represent a real threat for public health, the intended punishments are until now only based on intellectual property rights. Estimated to generate more than 55 billion euros per year, the traffic of falsified drugs varies from a country to another one. Indeed, the proportion of falsified drugs ranges from 1% in industrialized countries with a regulated and controlled distribution system to 60% of medicines in some developing countries. Currently, the measures developed to limit this traffic concern five main areas: legislation / regulation, cooperation, enforcement, technology and communication. Communication actions should be performed to inform health professionals as the populations about the risks of using drugs purchased outside the legal drug market.

Autonomy and paternalism in medical e-commerce.

One of the overriding interests of the literature on health care economics is to discover where personal choice in market economies end and corrective government intervention should begin. Our study addresses this question in the context of John Stuart Mill's utilitarian principle of harm. Our primary objective is to determine whether public policy interventions concerning more than 35,000 online pharmacies worldwide are necessary and efficient compared to traditional market-oriented approaches. Secondly, we seek to determine whether government interference could enhance personal  utility maximization, despite its direct and indirect (unintended) costs on medical e-commerce. This study finds that containing the negative externalities of medical e-commerce provides the most compelling raison d'etre of government interference. It asserts that autonomy and paternalism need not be mutually exclusive, despite their direct and indirect consequences on individual choice and decision-making processes. Valuable insights derived from Mill's principle should enrich theory-building in health care economics and policy.

Acute intraocular inflammation caused by endotoxin after intravitreal injection of counterfeit bevacizumab in Shanghai, China.

PURPOSE: To describe an outbreak of intraocular inflammation caused by endotoxin-contaminated counterfeit bevacizumab in China. DESIGN: Retrospective, observational case series. PARTICIPANTS: Patients undergoing intravitreal injection at a public hospital in September 2010. METHODS: The medical records and microbiology results of patients who presented with intraocular inflammation after injection with intravitreal counterfeit bevacizumab were reviewed. MAIN OUTCOME MEASURES: The incidence of intraocular inflammation, results of pathogen cultures, and clinical features of inflammation. RESULTS: A total of 116 patients (70 men and 46 women) were injected from 3 vials of counterfeit bevacizumab. Intraocular inflammation developed in 80 patients. The estimated median incubation period was 12 hours (range, 2-24 hours), and the median duration of symptoms was 6 days (range, 3-22 days). All patients were treated initially with topical corticosteroid and antibiotics. Vitreous tap and intravitreal injection were performed on 43 patients. Twenty-one patients with hypopyon and significant vitreous inflammation underwent vitrectomy. Microscopic evaluations and microbiologic cultures of all ocular specimens were negative for bacterial and fungal contamination. The presence of endotoxin in specimens was confirmed by laboratory testing. We refer to this new clinical syndrome as "endotoxin-induced ocular toxic syndrome" (EOTS). The inflammation regressed rapidly after treatment, and 63 patients (78.8%) recovered their pre-injection vision. CONCLUSIONS: This study implicates endotoxin as the cause of intraocular inflammation after the intravitreal injection of counterfeit bevacizumab. The EOTS appeared clinically distinct from typical infectious endophthalmitis.

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.