Pharmaceutical Crime, Fakeshare

A recent study, "Medicrime vs Volcano: a practical case study on how the Council of Europe Convention could improve the fight against pharmaceutical crime", carried out within the framework of the Council of Europe MEDICRIME Convention has highlighted shortcomings of current legislative approaches in relation to the protection of patients against falsified medicines in Europe. The study, authored by Domenico Di Giorgio of the Italian Medicines Agency (AIFA), and Diana Russo, Public Prosecutor of Naples, Italy, with the support of the EDQM, focused on a real case from the 2014 “Operation Volcano”, which saw anti-cancer medicines stolen from Italian hospitals and reintroduced in distribution chains to be sold throughout Europe. The study shows how the MEDICRIME Convention would have supported the prosecution of the case and led to effective sanctions against perpetrators, making a case for the appropriate implementation of the convention. Based on a survey of regulators and prosecutors in participating countries (Armenia, Belgium, Germany, Italy, Serbia and the United Kingdom), the study outcome highlighted the inadequacy of existing legislation on pharmaceutical crimes in light of their serious potential repercussions on public health. The study highlighted in particular shortcomings in traceability systems, the fragmentation of proceedings related to pharmaceutical crimes and insufficient options for accessory sanctions. The survey showed that applicable criminal charges remained mostly generic and were not fit for the specific implications for public health that derive from falsifying medicines. From theft of goods or handling of stolen goods to criminal association – which can currently only be punished under provisions for mafia associations (Italy) or for conspiracy (UK) – most regulatory frameworks do not take into consideration the fact that reintroducing stolen medicines to markets represents a far greater risk for patients than ordinary thefts. Medicines that are not stored correctly or are tampered with may deprive unwitting patients of the care needed and negatively affect their health. Similarly, sanctions for manufacturing illegal medicinal products or for manipulating authentic medicines, although covered in most criminal codes, are often subordinate to proof of damage to patients or considered as a breach of trademark, contrary to the provisions in the MEDICRIME Convention, which foresees direct charges thanks to its focus on the potential risk for patients. Other types of offences were also analysed in the study and compared with the legal framework provided by the MEDICRIME Convention. The very concept of “illegal possession of medicines” is not addressed by the legal systems of most countries concerned, which only prohibit the possession of illegal substances such as narcotics or psychoactive drugs. Moreover, the illegal export of goods can only be fined in European Union (EU) countries under provisions in EU directives requiring proper licences for trading medicines. For these reasons, sanctions have mostly resulted in simple suspensions of licences or similar administrative penalties. On the contrary, the framework provided by the MEDICRIME Convention specifically addresses the mere detention of falsified medicines, as well as the falsification of related documents, which is defined beyond simple fraud as a specific criminal act, with aggravating circumstances in cases where health professionals misuse their positions to support pharmaceutical crimes. The study concluded that overall, applicable sanctions were not a sufficiently strong deterrent when weighed against the potential profits of falsifying medicines. Co-ordination and information were also seen as important aspects in need of improvement, due to the involvement of many different judicial authorities in cross-border investigations and often also within the same country. The study also pointed out that raising awareness of pharmaceutical crime within the judicial sector would pave the way for implementing good practices related to information sharing between prosecution officers. https://www.edqm.eu/en/news/council-europe-study-highlights-inadequacy-legislation-pharmaceutical-crime

Availability of human medicines is affected by problems associated with both manufacturing and distribution-related issues. The lack of definition of “shortages” or “unavailability” of medicines in European regulation represents an obstacle to the set up of proper preventive and counteracting measures. In this review, we describe how, within this framework, Italy started a program of shared activities, involving central and local authorities, police forces, and private stakeholders’ associations through an “ad hoc technical forum,” that reduced the extent of the problem, at least in the short term, as demonstrated through some indicators defined by considering the key medicines affected by unavailability due to distribution-related issues. These measures should be strengthened and complemented with others so as to ensure their effectiveness in the long term.

In recent years, medicine thefts have become a European challenge. In Italy, the number of thefts, from hospitals, has increased exponentially since 2011. The major drivers were the introduction of life-saving expensive medicines, the price differentials between countries and the different reimbursement regimes adopted in the European Union. This situation resulted in the AIFA (Italian Medicines Agency) Counterfeiting Prevention Unit setting up a number of preventive strategies that have minimized and in some cases eradicated the problem. In this review, we briefly describe trends and impacts of medicine thefts in Italy, the ‘Herceptin Case’, a major criminal effort that has been dismantled, and some of the preliminary results of PADLOck (Progetto di Adeguamento Dei Livelli di sicurezza delle farmacie Ospedaliere contro il rischio di furti e definizione di standard tecnici), a study aimed at evaluating the safety of hospital pharmacists and made sure that preventive and corrective measures against medicine thefts are put in place. The implementation of some of the tools developed by AIFA is under evaluation and/or implementation by other European Authorities, leading to a more effective approach in tackling one of the most relevant challenges in access to medicines in the European Union.

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.

Summary of the biggest investigation on pharmaceutical crime held in Europe in recent years: stolen and falsified medicines, sourced from Italian hospitals and from other illegal chains, were recycled in the EU distribution network. This White Paper was submitted to the EC and published by AIFA.

The alarming presence of such a phenomenon and the importance of spreading information have prompted UNICRI to complete a report on Counterfeit Medicines and Organized Crime. The findings were thoroughly examined and elaborated with a critical approach. UNICRI made this work comprehensive and accessible for the general public. Various dimensions of the issue were taken into consideration: The production and distribution routes of counterfeit medicines; the peculiarities of the national, regional and international markets; the chain of perpetrators implicated in this crime and the involvement of organized criminals; The extent and the geographical magnitude of the phenomenon, with a distinction between developed countries and countries with developing economies.

Open minds, free minds: no easy prey for counterfeit medicines aims to inform, provide a concept for development and use of interactive storytelling for training and education at school: using a cartoon format, teachers can discuss risks and encourage behaviour that avoids known routes for exposure to counterfeit and similarly dangerous medical products. The main risk areas covered are mental and physical capacity-enhancers, and slimming products or medicines from illegal distribution channels. Target audiences include teachers, trainers, and social workers who will address this topic directly with children/adolescents. The cartoons are developed by professionals to enable children and adolescents to have fun and learn relevant preventative behaviours by gaming. To obtain a printed version, please contact the EDQM.

In Europe, the use of falsified medical products (Medicrime products) is increasing. The unreliable quality of these products is expected to cause health damage. The nature and extent of this damage is difficult to determine because the expected symptoms are not sufficiently specific to be recognized in everyday practice. It is also unclear to health care professionals where and how they can report their suspicions about usage. This is shown in an exploratory study by RIVM. Medicrime products are rarely found at (family) doctors and official pharmacies. However, consumers receive these products when they purchase medical products from unreliable suppliers, mainly over the internet. Through this source they are increasingly exposed to Medicrime products. This study assesses Medicrime products that are seized throughout Europe and the associated health complaints expected. Six categories of Medicrime products are seized most: erectile dysfunction agents, psychoactive drugs (such as stimulants, and designer drugs), drugs (especially steroids), slimming agents, strong painkillers and medicines for heart disease. These categories represent about 40 per cent of the seized Medicrime products. The remaining 60 per cent comprises a large variety of drugs, including anti-cancer agents, antibiotics, and anti-retroviral drugs. Even though these are seized in smaller numbers, the health threat is not to be underestimated due to their nature. With respect to epidemics and the development of resistance, it is undesirable that unreliable anti-infective medicines are used. It is recommended to raise awareness among physicians of the phenomenon of Medicrime products through, for example publications in medical journals. It is also recommended to create an information exchange platform on suspect products and complaints. Finally, it is important to devise a simple registration procedure for suspected medical products to set, for example, by adding a tickbox to the international adverse events reporting form by WHO. The recommendations have been incorporated into a pilot study in several European countries that is currently being tested.

This publication is a part of a more widespread project - developed by AIFA and EDQM with the help of experts from various institutions who daily confront the problem, in the framework of the EDQM/Council of Europe “Committee of Experts on Minimising Public Health Risks posed by Counterfeiting of Medical Products and Related Crimes” (CD-P-PH/CMED) activities - which is aimed at increasing knowledge and awareness about a phenomenon which is often the object of unreliable information and data. This book is a good example of the international collaboration which has been established with the deep conviction that communication with both the public and health workers represents an indispensable aspect in the fight against counterfeit medicine. The book examines, through real case studies, the various aspects of pharmaceutical counterfeiting: the root causes of the phenomenon, the types of counterfeit products, their distribution through uncontrolled channels such as the Internet, current legislation, the role of national and international institutions and their initiatives.

Identification of pharmaceutical active ingredients sildenafil and tadalafil and the characterization of a dimethylated thio-derivative of sildenafil, called thioaildenafil or thiodimethylsildenafil, in illicit dietary supplements were described. A multi-residual ultra-performance liquid chromatography–time of flight mass spectrometry (UPLC–TOF/MS) method was developed to screen for the presence of the phosphodiesterase-5 (PDE-5) inhibitors sildenafil, tadalafil, and vardenafil and their analogues thioaildenafil and thiohomosildenafil in powders and pharmaceutical dosage forms. The study was developed in connection with an operation supervised by the Italian Medicines Agency (A.I.F.A.), aimed to monitor dietary supplements in the Italian market. In two of the eleven specimens under investigation, high-resolution mass spectrometry (HR-MS) allowed the identification of the PDE-5 inhibitors sildenafil and tadalafil, while another specimen proved to contain a unapproved dimethylated thioderivative of sildenafil, thioaildenafil or thiodimethylsildenafil, identified for the first time in Italy as adulterant in food supplements.

Trend of the phenomenon of pharmaceutical thefts in Italy over the years 2013-2016: discussion of the positive results of the "Operation Volcano" and of the related tools that were developed in the framework of the Fakeshare project, and of the forthcoming development of this kind of pharmaceutical crime.

In the framework of the EC supported Fakeshare project (www.fakeshare.eu), a comprehensive summary of the general features and of the recent developments in tackling pharmaceutical crime (IE counterfeiting, diversion, falsification of medicines) was developed, as an instrument for the Italian police forces. This English, updated version of the e-book was developed as a Fakeshare deliverable, with the goal of sharing the research in the field with all EU health authorities, police forces and scientists.