Edible unclonable functions.

Counterfeit medicines are a fundamental security problem. Counterfeiting medication poses a tremendous threat to patient safety, public health, and the economy in developed and less developed countries. Current solutions are often vulnerable due to the limited security levels. We propose that the highest protection against counterfeit medicines would be a combination of a physically unclonable function (PUF) with on-dose authentication. A PUF can provide a digital fingerprint with multiple pairs of input challenges and output responses. On-dose authentication can verify every individual pill without removing the identification tag. Here, we report on-dose PUFs that can be directly attached onto the surface of medicines, be swallowed, and digested. Fluorescent proteins and silk proteins serve as edible photonic biomaterials and the photoluminescent properties provide parametric support of challenge-response pairs. Such edible cryptographic primitives can play an important role in pharmaceutical anti-counterfeiting and other security applications requiring immediate destruction or vanishing features.

Iatrogenic Botulism Outbreak in Egypt due to a Counterfeit Botulinum Toxin A Preparation - A Descriptive Series of Patient Features and Outcome.

Iatrogenic botulism resulting from the substantial increase in use of botulinum neurotoxin type A (BoNT-A) treatment is rarely reported. We aimed to describe a large iatrogenic botulism outbreak in Egypt in June-July 2017. Nine patients developed botulism after receiving intramuscular injections of BoNT-A (dose: 200-300 IU) to treat cerebral palsy (N = 7), spastic dystonia (N = 1) and hyperhidrosis (N = 1). Detailed findings were available in five of nine cases. Patients were admitted to the hospital 5-10 days after the BoNT-A injection. Complaints included muscle weakness in the upper and lower limbs (N = 5), dysphagia (N = 5), dizziness (N = 2), dyspnoea (N = 2), dysphonia (N = 2), dysarthria (N = 2), fatigue (N = 1), diplopia (N = 1) and blurred vision (N = 1). Physical examination showed bilateral ptosis (N = 5), diminished gag reflex (N = 2), ophthalmoparesis (N = 1), facial paresis (N = 1) and tongue weakness (N = 1). Diagnosis was based on the patients' history and presentation and did not require any confirmatory test. On hospital admission, patients received supportive care and trivalent botulism type A/B/E antitoxin (250-500 IU) was started. No patient required mechanical ventilation. Immediate reversal of the most severe features was observed while varying degrees of peripheral muscular weakness persisted. Full recovery required 6-12 weeks. Cases were promptly reported to the Egyptian health authorities, and epidemiological investigations revealed that the outbreak was related to a recently imported highly concentrated unlicensed BoNT-A preparation sold as Neuroxin® . Immediate withdrawal from the market was ordered. In conclusion, iatrogenic botulism outbreak due to counterfeit botulism toxin may result in life-threatening features. The early administration of botulism antitoxin in addition to supportive care is life-saving. Clinicians should remain mindful of the risk of systemic botulism with BoNT-A therapy.

Rapid identification of oral solid dosage forms of counterfeit pharmaceuticals by discrimination using near-infrared spectroscopy.

BACKGROUND: Since it can take an enormous amount of time and cost to discriminate counterfeit medicines by using conventional methods, counterfeit medicines has been spread in the world markets. OBJECTIVE: The purpose of this study was to develop a rapid and simple analytical method to discriminate counterfeit drugs using near infrared (NIR) spectroscopy. METHODS: Seven types of brand name tablet and generic tablets containing atorvastatin calcium sesquihydrate (AT) preparations were used as simulated counterfeit medicines. NIR spectra of 35 AT tablet products were measured using a diffuse reflection method. RESULTS: The NIR spectral data were analyzed by principal component analysis (PCA). The PCA results suggested that the model had sufficient accuracy to discriminate the 7 types for AT tablets. The NIR spectral data were also analyzed using a soft independent modeling of class analogy (SIMCA) method. Predicting the classification of the AT tablet samples was performed based on all the validated AT tablet data using the SIMCA model, and the probability of classification of 7 types was 100%. The discrimination power spectrum of the SIMCA model indicated significant patterns based on diluents. CONCLUSIONS: The PCA and SIMCA classification of the AT tablets were depended on the major excipient combinations.

Cosmetic Practitioners Take Huge Risks Purchasing and Administering Illegal Botulinum Toxin Drug Products.

In their article "Importing Injectables" in the September 2014 issue of the Journal of Drugs in Dermatology, Dr. Kenneth Beer and Karen Rothschild highlighted the possible harm to patients and practitioners from the use of unapproved botulinum toxin products - eg, Botox, Dysport, Xeomin, and Myobloc - and other cosmetic prescription drug products purchased from foreign or unlicensed suppliers.1 In the intervening years, the accuracy of their critique has been repeatedly demonstrated, as the dangers to patients' health, as well as to cosmetic practitioners' liberty, has only increased.

Finger printing of counterfeit bevacizumab and identifying it before clinical use.

BACKGROUND: Bevacizumab is widely used for ophthalmic purposes. Recently, counterfeit bevacizumab has become a matter of concern. We analysed samples of suspected counterfeit formulations of bevacizumab and assessed the possibility of using simple tests in the clinic by ophthalmologists to prevent the use of counterfeit preparations in patients. METHODS: We did a protein analysis using Bradford assay and SDS-PAGE to confirm the presence of bevacizumab in 16 samples - 6 suspected and 10 others. The samples were also subjected to physicochemical analysis such as osmolarity, chloride content and pH. The samples tested negative for protein were analysed by mass spectrometry to detect drugs used in place of bevacizumab. We standardized the method of frothing and precipitation analysis for identifying authentic samples of bevacizumab before their clinical use. RESULTS: Five of the 16 samples tested were negative for the presence of bevacizumab. The physicochemical parameters also supported the protein analysis test. However, no ionizable organic compound (other drug[s]) was detected by mass spectrometry. CONCLUSION: Ophthalmic use of counterfeit bevacizumab can be prevented by simple methods such as the frothing and precipitation tests. These can identify the absence of an active drug.

Los medicamentos falsificados en internet y el proyecto europeo Fakeshare: experiencias y actuaciones en España / Counterfeit medicines in internet and the Fakeshare european project: experiences and activities in Spain

El tráfico ilícito de medicamentos a través de Internet es un problema en auge que afecta a la salud pública. Desde el año 2013, la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) participa en el proyecto europeo Fakeshare, cofinanciado por la Comisión Europea y coordinado por la Agenzia Italiana del Farmaco (AIFA). Este proyecto tiene el propósito de coordinar iniciativas desarrolladas contra el suministro ilegal de medicamentos, incluyendo la compraventa a través de sitios web que realizan una actividad ilegal a los robos y otros desvíos de medicamentos al tráfico ilícito. Este artículo presenta las actividades desarrolladas en este ámbito a nivel nacional así como las estrategias y materiales elaborados. Las claves para combatir o hacer frente a la venta ilegal de medicamentos a través de Internet son la colaboración coordinada con todos los agentes implicados, a difusión de campañas de comunicación para concienciar y sensibilizar a consumidores, profesionales sanitarios y organizaciones del sector sobre los riesgos que supone la compra de medicamentos en sitios web ilegales, la creación de bases de datos para compartir la información sobre robos y otros desvíos al mercado ilícito, así como la difusión de las prácticas nacionales a nivel europeo e internacional (AU)

The illicit trafficking of medicines over the Internet is a growing problem that affects public health. Since 2013, the Spanish Agency of Medicines and Medical Devices (AEMPS) participates in the European project Fakeshare, co-funded by the European Commission and coordinated by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). This project aims to coordinate initiatives against the illegal supply of medicines, including from purchases through websites engaged in illegal activity, to thefts and other diversions of medicines to the illicit trafficking. This paper presents the activities in that area as well as strategies and elaborated materials at the national level. The keys to fight or face the illegal sale of medicines over the internet are coordinated cooperation with all the stakeholders, development of communication campaigns to raise awareness and sensitize consumers, health professionals and industry organizations about the risks of buying medicines on illegal websites, creating databases to share information on thefts and other deviations to the illegal market and disseminate national practices to combat illicit medicines trafficking at European and international levels (AU)

Resultados de una metodología para la identificación de distribución inversa de medicamentos en oficinas de farmacia / Methodology for identification of inverse drug distribution, Spain

FUNDAMENTOS: El fenómeno del tráfico inverso en la cadena legal de suministro de medicamentos es una práctica ilícita con graves riesgos para la Salud Pública. El objetivo de este trabajo fue identificar de forma proactiva, oficinas de farmacia que realizan estas conductas ilegales. MÉTODOS: Se cruzaron los datos de facturación al SAS de 52 millones de envases de medicamentos con los de las 496 farmacias de la provincia en un periodo de 29 meses (abril de 2012 a agosto de 2014). Junto con la aplicación del indicador específico definido denominado "porcentaje de sobrecompra", permitió identificar los establecimientos farmacéuticos con alto riesgo de estar implicados en el comercio ilícito. RESULTADOS: Se comprobó que hubo desvío en dos oficinas de farmacia, una rural (de 5.130 envases de medicamentos y beneficio ilícito obtenido de 9.591,78 €) y otra urbana (9.982 envases y 26.885,11 €), los cuales habían pasado desapercibidos en anteriores actuaciones inspectoras. CONCLUSIONES: La metodología implantada permite definir un perfil de oficina de farmacia infractora de alto riesgo en estas prácticas ilícitas, identificarlas, ponderar los fármacos destinados a este comercio ilegal y determinar nuevos medicamentos objeto de desvío. Ayuda a ajustar de forma precisa el cálculo del beneficio ilícito obtenido

BACKGROUND: The phenomenon of reverse drug trafficking in the legal supply chain is an unlawful practice to serious risks to public health. The aims was to identify proactively pharmacies that carry out these illegal activities. METHODS: An analysis was performed through the crossing billing data to SAS of 52 million packs of medicines for the 496 pharmacies in the province over a period of 29 months with the drug packaging data supplied by the distribution entities of the provincewith the implementation of specific indicator defined called 'percentage overbought' allows us to detect those pharmacies at high risk of being involved in this illicit trade. RESULTS: It was tested in two pharmacies one rural and other urban a detour of 5.130 medicine containers and an illicit profit obtained from € 9,591.78 for the first and 9.982 packaging and € 26,885.11 for the second; they had gone unnoticed in previous inspections. CONCLUSIONS: The methodology implemented to define a profile of infringing pharmacies high risk in these illicit practices, identify new ones that had not been sanctioned, weigh the drugs for illegal trade and to identify new drugs subject to diversion; also added as a challenge, it helps to adjust accurately and effectively calculate the illicit profit obtained

Desoxipipradrol. Fármacos antiguos, problemas nuevos / Desoxypipradrol. Old drugs, new problems

A través de Internet recientemente se han comercializado algunas sustancias estimulantes estructuralmente parecidas a neurotransmisores derivadas de medicamentos ya retirados, que potencialmente pueden causar cuadros clínicos de diversa gravedad. Su efecto estimulante y el hecho de que aparecen antes de prohibirse su consumo explican la denominación genérica de legal highs. La exposición a estas sustancias se manifiesta como cuadros parecidos a los del consumo de productos como fenciclidina, anfetaminas o cocaína, ya que muy probablemente compartan mecanismos de acción sobre la recaptación de dopamina en los núcleos cerebrales implicados en el comportamiento de gratificación. La escasez de información médica contrastada, y las dificultades para disponer de material de calibración constituyen un reto diagnóstico. El desoxipipradol, sintetizado hace más de 6 décadas para el tratamiento del trastorno hipercinético, fue relegado por el metilfenidato, un compuesto análogo. En 2009 reapareció como droga recreativa responsable de algunos cuadros clínicos de intoxicación (AU)

Stimulant substances previously used for therapeutic purposes, and are currently banned, have recently been marketed through the Internet. These drugs, structurally similar to neurotransmitters, can potentially cause severe clinical conditions. Exposure to these 'legal highs' results in symptoms similar to those of well-known substances such as phencyclidine, amphetamines or cocaine, probably because they share mechanisms of action related to dopamine reuptake in brain nuclei involved in the regulation of reward behavior. The limitations of medical evidence, as well as difficulties in obtaining calibration material, constitute an analytical challenge. Desoxypipradol was synthesized more than six decades ago for the treatment of hyperkinetic disorder, but was surpassed by methylphenidate, a similar compound with a better pharmacokinetic performance. In 2009 desoxypipradol appeared as a recreational drug involved in several cases of clinical intoxication (AU)

A survey on illegal and counterfeit medicines for the treatment of erectile dysfunctions in Italy.

INTRODUCTION: In developed countries the phenomenon of pharmaceutical counterfeiting is steadily increasing through the illegal and the Internet market. Medicines for the treatment of erectile dysfunctions containing phosphodiesterase type 5 inhibitors (PDE5) are especially prone to falsification. AIMS: To obtain evidence of the health risks for patients taking these products and to provide useful information to general practitioners and specialists in sexual medicine. METHODS: First the samples were visually inspected and then analyzed to get information about their identity and quality. MAIN OUTCOME MEASURES: A survey on the PDE5 medicines analyzed by the Italian official medicines control laboratory between 2005 and 2011 was performed. All the analyzed medicines were gathered from the Italian illegal market (seizures by police forces) or were bought from illegal online pharmacies. Results. The study revealed that 24% of the analyzed samples were counterfeit and 54% were illegal medicines. In 12% of the cases an intermediate classification (illegal/counterfeit) was assigned. Only 7% of the samples were original. Moreover, the examination of the packaging evidenced potential risks: outer and immediate packaging missing; inconsistency between the carton box and the blister as regards the expiry date and/or the batch number; expiry date or manufacturer's name or country missing. CONCLUSIONS: In 19% of the samples a potential health risk for patients was identified due to either the presence in the sample of more than one undeclared PDE5(s) or an amount of the active ingredient higher than that declared (up to 190% of the maximum dose) or to the presence of potentially dangerous excipients of non-pharmaceutical origin or quality (e.g., gypsum or non-purified talc).