Counterfeit medicines: relevance, consequences and strategies to combat the global crisis

Abstract Counterfeiting of medicines, also known as "falsification" or "adulteration", is the process in which the identity, origin, or history of genuine medicines are intentionally modified. Currently, counterfeit medicines are a global crisis that affects and is mostly caused by developing countries in Asia, Africa and Latin America. These countries lack strict law enforcement against this practice and have low-income populations with medicinal needs. Lately, the crisis has escalated, impacting developed countries as well, e.g., the US and the EU, mainly via the Internet. Despite this extension, some current laws aim to control and minimize the crisis' magnitude. Falsification of medicines maintains an illegitimate supply chain that is connected to the legitimate one, both of which are extremely complex, making such falsification difficult to control. Furthermore, political and economic causes are related to the crisis' hasty growth, causing serious consequences for individuals and public health, as well as for the economy of different countries. Recently, organizations, technologies and initiatives have been created to overcome the situation. Nevertheless, the development of more effective measures that could aggregate all the existing strategies into a large functioning network could help prevent the acquisition of counterfeit medicines and create awareness among the general population.

The Supreme Court Decision on Federal Prescribing Rules for Controlled Substances.

This Viewpoint explains how a recent Supreme Court decision clarifies rules for prescribing controlled substances so that patients are not denied appropriate care and physicians are not unjustly prosecuted.

Too Important for the Bureaucrats: Rethinking Risk and Regulatory Presumptions in Times of Crisis.

The posture of American regulation of medicine is negative-we assume that a new drug is unsafe and ineffective until it is proven safe and effective.1 This regulatory posture is a heuristic normative principle, a specific instance of the so-called precautionary principle in public health law.2 It is defensible, if debatable, in many ordinary circumstances.3 But like many normative heuristics, this negative posture may compel suboptimal decision-making in emergencies, where context-specific decisions must be made and a range of unique values may apply.

Challenges in clinical trials for children and young people.

There is a well-known knowledge gap regarding the efficacy and safety of medicines in children of all ages and children are often treated with medicines off-label. Children are thus deprived of treatment based on the same quality of information that guides treatment in adults. The knowledge gap regarding efficacy and safety of medicines in children has been acknowledged by authorities and is reflected in legislation both in North America and in the European Union. Recent reports on the effects of legislation indicates that paediatric clinical trials remain a challenge.Paediatric clinical trials are needed in the entire developmental age spectrum and are especially needed in certain therapy areas. Paediatric clinical trials have special features compared with trials in adults, and these need to be taken into account. These special features include scientific issues related to small samples and heterogeneity, the consent/assent procedure, the need for age-appropriate study information, specific outcomes and safety issues related to development and maturation. Competence in paediatric clinical trials is required in both designing, planning, co-ordinating and organising paediatric clinical trials, as well as research infrastructure and networks to increase power and disseminate information and expert advice. Strengthening of paediatric clinical research is essential to facilitate generating the data that will let children enjoy new medical advances in a similar manner as adults.

Loose Regulatory Standards Portend a New Era of Imprecision Oncology.

Precision oncology has revolutionized the therapeutic landscape of oncology and is a goal for cancer drug development. However, lenient drug approvals by the United States Food and Drug Administration under the auspices of precision oncology are setting up this therapeutic approach to fail. In this commentary, I review two recent FDA drug approvals (pembrolizumab for tumor mutation burden-high solid tumors and olaparib for castration-resistant prostate cancer with deleterious homologous recombination repair mutations) where the FDA indication is broader than the studied population. I explain how these broad approvals stray from principles of precision oncology and can cause harm to patients.

Probiotics and the Microbiome-How Can We Help Patients Make Sense of Probiotics?

The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs. No probiotic product has been able to satisfy the regulatory requirements to be categorized as a drug, a substance intended to cure, mitigate, or prevent disease. However, patients take probiotic products in the belief that they will help to treat their intestinal or systemic diseases. Thus far, the regulators have failed to create policies that would assist to inform the public in this area. In fact, the existing regulatory regime actually creates formidable barriers to research that could provide evidence for clinical efficacy of probiotic products. We propose a potential solution to this vexing problem, where a committee created through a partnership of academia, professional organizations, and industry, but free of potential conflicts of interest, would be charged with rigorous evaluation of specific probiotic products and the evidence in support of their different claims. Companies that would submit to this process would earn the trust of consumers and healthcare providers, as well as a distinction in the marketplace.

The Best Pharmaceuticals for Children Act and Pediatric Research Equity Act reach the age of majority-An oncology perspective.

The scarcity of adequate pediatric drug labeling information has long been problematic in the pediatric population, which may place children at risk for adverse drug effects. The ontogeny of infants, children, and adolescents over the course of the first two decades of life pose complex pharmacokinetic, dosing, administration, effectiveness, and toxicity-related questions that require specific investigation. Here, we review the history that led to the passage of the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA), and provide commentary on issues relevant to pediatric oncology now and in the future.

La Regulación de los medicamentos veterinarios en España / The regulation of veterinary drugs in Spain

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Regulación y terminología dermocosmética: los orígenes de las normas INCI en España / Dermocosmetic's regulation and terminology: the origins of the INCI norms in Spain

INTRODUCCIÓN: el uso de normas concretas para identificar correctamente los ingredientes que componían los cosméticos resultó fundamental para su control. En este trabajo se analiza el costoso proceso requerido para la adopción de la terminología INCI en España realizado entre las décadas de 1960 y 1990. MÉTODOS: se ha realizado un análisis de la legislación publicada en España sobre el control de los productos cosméticos entre las décadas de 1940 y 1990. Se ha recuperado de forma sistemática aquellas cuestiones relacionadas con el registro de los productos cosméticos y las terminologías y nomenclaturas utilizadas para identificar los ingredientes con los que se fabricaban. También se han consultado fuentes primarias impresas, así como prensa periódica. Estas fuentes primarias se han discutido y contextualizado con la ayuda de publicaciones especializadas en historia de la ciencia más recientes. Resultados y CONCLUSIONES: la adopción de una nomenclatura o terminología cosmética precisa era necesaria tanto para su registro ante las administraciones sanitarias, como para los consumidores que eran informados en el etiquetado. La regulación sanitaria de los productos cosméticos era muy laxa hasta que, en la década de 1960, se desarrolló esta industria y su mercado en España. La consolidación del sector dermofarmacéutico se produjo en la década de 1970, en parte debido a los esfuerzos de diversos sectores farmacéuticos. La progresiva introducción de nomenclaturas cosméticas internacionales culminó en la década de 1990 con la adopción oficial de la terminología INCI en España

INTRODUCTION: the use of specific rules to correctly identify ingredients used in cosmetics was essential for their control. This paper analyses the complex process to adapt the INCI terminology between the 1960s and the 1990s. METHOD: analysis of the legislation published in Spain on the control of cosmetic products between the 1940s and the 1990s, focusing on cosmetic's registers and terminologies and nomenclatures used to identify their ingredients. Printed Primary sources, and periodical press have also been consulted. Primary sources have been discussed and contextualized with the help of more recent history of science publications. Results and CONCLUSIONS: The adoption of precise cosmetic nomenclature or terminology was required by health authorities registering these products, as well as for the labelling to inform consumer. The sanitary regulation of cosmetic products was very lax until the development of this industry and its market in Spain in the 1960s. The consolidation of the dermopharmaceutical sector occurred in the 1970s, in part due to the efforts of various pharmaceutical sectors. The gradual introduction of international cosmetic nomenclatures culminated in the 1990s with the official introduction of the INCI terminology in Spain

[How does a new medicine reach the patient?] / Hoe bereikt een nieuw geneesmiddel de patiënt?

The Medicines Evaluation Board (MEB) grants market authorisation for medicinal products in the Netherlands. The European Medicines Agency (EMA) coordinates the evaluation and safeguarding of medicinal products in the European Union. The core task of the MEB is to evaluate the quality of every medicinal product for which marketing authorisation is applied for by the manufacturer, and to assess the risk - efficacy balance of the product concerned. There are three different procedures that a manufacturer can follow: (a) the national procedure; (b) the decentralised procedure or mutual recognition procedure; (c) the centralised procedure. After marketing authorisation has been granted, the MEB ensures pharmacovigilance in cooperation with partners such as the Netherlands Pharmacovigilance Centre (Lareb). The MEB determines the text of the package leaflet, the packaging and the Summary of Product Characteristics (SmPC). The MEB checks the warnings that are sent out by manufacturers if important new information about a medicinal product becomes available.

Knowledge and practices of community pharmacists towards non-prescription dispensing of antibiotics in Northern Nigeria.

Background Non-prescription dispensing of antibiotics is common in Nigeria and this could contribute to the emergence of microbial resistance. Objectives To evaluate knowledge, perception and practices of community pharmacists towards dispensing antibiotics without prescription. Setting Community pharmacies in two cities in Northern Nigeria. Methods A prospective cross-sectional study was conducted among community pharmacists in two cities in Northern Nigeria, using a validated and pilot-tested questionnaire. The questionnaire was self-administered and data was collected between 06th April and 31st May 2019. The data was analyzed using descriptive and inferential analyses. Main outcome measure Knowledge, perception and practices towards dispensing antibiotics without prescription. Results A total of 98 out of 130 community pharmacists completed and returned the questionnaire (response rate: 75.3%). About two-third (64.3%) of the community pharmacists were aware that dispensing antibiotics without prescription is illegal. However, this malpractice was common as 39.7% of the respondents indicated that they dispensed antibiotics without prescription five times or more in a day. Antibiotics dispensed without prescription were used for the treatment of urinary tract infections (83.7%), typhoid fever (83.7%) and sexually transmitted infections (66.3%). Pharmacist's confidence in knowledge of antibiotic therapy was the most common reason for non-prescription dispensing of antibiotics. Respondents with less than 5 years of working experience (66.7%) were significantly more likely to dispense antibiotics without prescription 5 times or more in a day compared to those with more than 5 years community pharmacy experience (33.3%), P = 0.031. Conclusion Non-prescription dispensing of antibiotics was common among community pharmacists despite awareness about its prohibition and implications. The malpractice was associated with number of years of community pharmacy experience. Confidence in knowledge of antibiotic therapy was the main reason community pharmacists dispensed antibiotics without prescription. Continuous pharmacy education and training on handling of antibiotics may help to reduce inappropriate practices among community pharmacists.

Nuevo marco legal para la erradicación de los medicamentos falsificados: los nuevos dispositivos de seguridad / New legal framework for the eradication of falsified medicines: the new safety devices

INTRODUCCIÓN: Los medicamentos falsificados son un problema emergente en la sociedad actual. Una de las principales estrategias para poder combatirlos es el empleo del Derecho. Por ello se promulgó, por parte de las instituciones europeas legalmente competentes para ello, el Reglamento Delegado de la Unión Europea 2016/161 de la Comisión de 2 de octubre de 2015, que completa la Directiva 2001/83/CE del Parlamento Europeo y del Consejo estableciendo disposiciones detalladas relativas a los dispositivos de seguridad que figuran en el envase de los medicamentos de uso humano (de fabricación industrial). MÉTODO: Se realizó una revisión bibliográfica de esta nueva normativa, promulgada por diversas instituciones comunitarias, con el objetivo de analizar las novedades existentes en el ámbito del medicamento. RESULTADOS: La norma comunitaria, objeto de nuestro estudio, establece las directrices para verificar aquellos medicamentos con mayor riesgo de falsificación, mediante unos dispositivos de seguridad compuestos de dos partes. Un dispositivo anti-manipulación que permite visualizar que el envase no ha sido alterado y un código identificador único, que será reconocido en todos los países comunitarios y que posee información sobre el medicamento. Desde las oficinas de farmacia se autentifica cada medicamento mediante la verificación y desactivación del código identificador en el momento de la dispensación del mismo. CONCLUSIONES: Esta nueva normativa pretende evitar la posible entrada de medicamentos falsificados en la cadena de suministro legal de medicamentos. Sus principales ventajas son, garantizar al paciente la veracidad del medicamento dispensado en las oficinas de farmacia y mejorar la trazabilidad de los mismos

INTRODUCTION: Falsified medicines are an emerging problem in today's society. One of the main strategies to combat them is the use of law. That is why the Commission Delegated Regulation (EU) 2016/161 of 2 October 2015 was enacted by the relevant European institutions, which supplements Directive 2001/83/ EC of the European Parliament and of the Council by laying down detailed provisions relating to safety features appearing on the external packaging of medicinal products for human use (industrial manufacturing). METHOD: A literature review of this new legislation enacted by various Community institutions has been carried out with the aim of analyzing developments in the scope of the medicinal product. RESULTS: The Community regulation sets out the guidelines for verifying those medicinal products which have an increased risk of been falsified, using safety features consist of two parts: an anti-tampering device that allows to view that the packaging has not been altered, and a unique identifier code, which will be recognized in all Community countries and it has information on the medicinal product. Each drug is authenticated from the Pharmacies by verifying and deactivating the identifier code at the time of dispensing it. CONCLUSIONS: This new regulation aims to avoid the possible entry of falsified medicines into the legal supply chain of medicinal products. Its main advantages are ensuring to the patient the veracity of the drugs dispensed in the Pharmacy and improving the traceability of them

Cannabis labelling and consumer understanding of THC levels and serving sizes.

OBJECTIVE: As part of cannabis legalization in Canada and several US states, regulations specify how THC levels should be labelled on products; however, there is little evidence on the extent to which consumers understand and use THC labelling to inform consumption amounts. The current study was designed to assess comprehension of cannabis-related information including communication of dose and strength of product on different labelling designs among young Canadians. METHODS: Two experiments were conducted in October 2017 among Canadian youth and young adults aged 16-30 years as part of an online cross-sectional survey (N = 870). Experiment 1 randomized respondents to one of three labelling conditions (1=No Label, 2=mgTHC, 3=Doses). Respondents interpreted a recommended serving and number of servings contained in the package. Experiment 2 randomized respondents to one of four labelling conditions communicating THC level (1=No Label, 2=%THC, 3=mgTHC, 4=Traffic Light System). Respondents determined level of THC in the product. RESULTS: Labelling the number of doses per package was associated with the greatest proportion of correct responses (54.1 %) when respondents had to determine a recommended serving compared with the no-label control condition (7.4 %) and THC mg condition (13.4 %). When cannabis products were labelled using a traffic light system, participants were more likely to identify THC level: low THC (85.1 %) or high THC (86.4 %) than the control condition (2.0 % and 5.2 % respectively). CONCLUSION: Few consumers can understand and apply quantitative THC labelling; in contrast, THC labels that provide 'interpretive' information, such as descriptors, symbols, or references to servings have greater efficacy.

The Dobson-Rawlins pact and the National Institute for Health and Care Excellence: impact of political independence on scientific and legal accountability.

This analysis considers whether the independence of the National Institute for Health and Care Excellence (NICE), while safeguarding guidelines from commercial lobbying, may render NICE legally and scientifically unaccountable. The analysis examines the role of judicial reviews and stakeholder consultations in place of peer review in light of current debates concerning the depression guideline.

Treatment versus Punishment: Understanding Racial Inequalities in Drug Policy.

CONTEXT: Many observers believe that the policy response to the opioid crisis is less punitive than the crack scare and that the reason is that victims are (stereotypically) white. METHODS: To assess this conjecture, we compile new longitudinal data on district-level drug-related deaths and (co)sponsorship of legislation on drug abuse in the House of Representatives over the past four decades. Using legislator fixed effects models, we then test how changes in drug-related death rates in legislators' districts predict changes in (co)sponsorship of treatment-oriented or punitive legislation in the subsequent year and assess whether these relationships vary by race of victim or drug type. FINDINGS: Policy makers were more likely to introduce punitive drug-related bills during the crack scare and are more likely to introduce treatment-oriented bills during the current opioid crisis. The relationship between district-level drug deaths and subsequent sponsorship of treatment-oriented legislation is greater for opioid deaths than for cocaine-related deaths and for white victims than for black victims. By contrast, district-level drug deaths are not significantly related to sponsorship of punishment-oriented bills. CONCLUSIONS: These results suggest that the racial inequalities and double standards of drug policy still persist but in different forms.

Mutual recognition in the European system: A blueprint for increasing access to medicines?

The European regulatory system for approval of medicinal products is globally recognised as a unique platform for regulatory work-sharing and mutual recognition. As such, it potentially serves as a role model for regulatory capacity building worldwide. While focusing on mutual recognition and decentralised procedures, this paper illustrates key success factors and structures allowing for the reliance-based authorisation of medicines in the European Economic Area from the perspective of a national regulatory authority (NRA). This paper presents major challenges in fulfilling the requirements for joining the European Medicines Regulatory Network (EMRN) and the strategies regarding how those challenges could be successfully addressed based on the example of the Agency for Medicinal Products and Medical Devices of Croatia, the most recent NRA in the EMRN. It also discusses the hallmarks of successful implementation of the European system of reliance as a blueprint for increasing access to safe and efficacious medicines from the perspective of a NRA.

Phage Therapy Regulation: From Night to Dawn.

After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, the resulting regulatory framework is hardly reconcilable with the concept of sustainable phage therapy, involving tailor-made medicinal products in the global perspective of both evolutionary and personalized medicine. The repeated appeal for a dedicated regulatory framework has not been heard by the European legislature, which, in this matter, features a strong resistance to change despite the precedent of the unhindered implementation of advanced therapy medicinal product (ATMPs) regulation. It is acknowledged that in many aspects, phage therapy medicinal products are quite unconventional pharmaceuticals and likely this lack of conformity to the canonical model hampered the development of a suitable regulatory pathway. However, the regulatory approaches of countries where phage therapy traditions and practice have never been abandoned are now being revisited by some Western countries, opening new avenues for phage therapy regulation. As a next step, supranational and international organizations are urged to take over the initiatives originally launched by national regulatory authorities.