Suicide-related over-the-counter analgesic exposures reported to United States poison control centers, 2000-2018.

PURPOSE: To investigate suicide-related over-the-counter (OTC) analgesic medication exposures among individuals ≥6 years old reported to United States (US) poison control centers. METHODS: Data from the National Poison Data System for the years 2000-2018 were retrospectively analyzed. RESULTS: From 2000 to 2018, US poison control centers recorded 549 807 suicide-related cases involving OTC analgesics, including 327 781 cases (59.6%) admitted to the hospital and 1745 deaths (0.3%). Most cases involved a single substance (67.5%) and occurred among females (72.7%) and individuals 6-19 years old (49.7%). Overall, the rate of exposures increased significantly by 33.5% from 2000 to 2018, primarily driven by the increasing exposure rate among 6- to 19-year-old females. From 2000 to 2018, exposure rates for acetaminophen and ibuprofen increased, while that for acetylsalicylic acid decreased. Additionally, the proportion of cases resulting in a serious medical outcome or healthcare facility admission increased for all types of OTC analgesics. Acetaminophen and acetylsalicylic acid accounted for 48.0% and 18.5% of cases, respectively, and 64.5% and 32.6% of deaths, respectively. Both acetaminophen and acetylsalicylic acid had greater odds of healthcare facility admission (ORs 2.56 and 2.63, respectively) and serious medical outcomes (ORs 2.54 and 4.90, respectively) compared with ibuprofen. CONCLUSIONS: The rate of suicide-related OTC analgesic cases is increasing. Acetaminophen and acetylsalicylic acid cases are associated with greater morbidity and mortality. Prevention efforts should include implementing unit-dose packaging requirements and restrictions on package sizes and purchase quantities for acetaminophen and acetylsalicylic acid products to reduce access to large quantities of these analgesics.

Changes in roll-your-own tobacco and cigarette sales volume and prices before, during and after plain packaging legislation in the UK.

BACKGROUND: Plain packaging and minimum pack size legislation for tobacco products was introduced in the UK in May 2016, with a 1-year sell-off period until May 2017, during which both fully branded and plain packs of various sizes were legally available. This study investigates trends in prices of roll-your-own tobacco (RYO) before, during and after implementation of this legislation, and compares trends with those observed in the cigarette market. METHODS: We used Nielsen Scantrack data for the period from March 2013 to June 2018 to describe trends in UK inflation-adjusted prices and volumes of both RYO and cigarettes, and linear regression to estimate changes in prices associated with the introduction of plain packaging and the minimum pack sizes of 30 g RYO and 20 cigarettes. RESULTS: In contrast to a downward trend in cigarette sales volumes, RYO volumes rose throughout the study period. By the time plain packs accounted for 75% or more of sales, the average price of products sold in equivalent pack sizes had increased, relative to average prices in the year before implementation and with adjustment for tax changes, from 34.9 to 38.8 pence per gram for RYO (mean difference 4.26, 95% CI 3.99 to 4.53 pence, 12% increase), and from 38.6 to 41.13 pence for cigarettes (mean difference 2.53, 95% CI 2.24 to 2.83 pence, 7% increase) per cigarette. CONCLUSIONS: New legislation resulted in higher prices for RYO and manufactured cigarettes. However, sales volumes of RYO continued to increase throughout the study period, perhaps because RYO remains a less expensive means of smoking tobacco.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

PURPOSE: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. METHOD: Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. RESULTS: Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p < 0.0001) but not an immediate jump in the incidence (p = 0.5991) following the increased availability. Adjusting for trends in hospital episodes for self-harm, suicides, and the sales volume of paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. CONCLUSIONS: The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

Labelling of electronic cigarettes: regulations and current practice.

BACKGROUND: Over the past decade e-cigarettes have established themselves in the global market. E-cigarettes triggered much interest in relation to their content and efficacy as smoking cessation tools, but less attention has been paid to users and environmental safety warnings and guidance. Several regulations have been introduced to promote their safe handling and disposal. From May 2016, liquids and cartridges will be regulated by European Community Directives (ECDs) 2001/83/EC and 93/42/EEC, or 2014/40/EU if marketed as tobacco-related products. Currently, manufacturers and distributors must abide by the Chemical (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP) or Classification, Labelling and Packaging Regulations (CLP), the latter replacing CHIP in June 2015. OBJECTIVE: In this work, the compliance of marketed e-liquids and e-cigarettes with current European Union and UK legislations is assessed. RESULTS: E-liquids and e-cigarettes (21 and 9 brands, respectively) were evaluated. Evidence of non-compliance was found in relation to the CHIP/CLP toxic (13%) and environmental (37%) pictograms, tactile warning (23%), nominal amount of solution (30%), supplier contact telephone number and address (40%). None of the evaluated e-cigarettes displayed information on the correct disposal/recycling of batteries in line with the ECD 2006/66/EC. CONCLUSIONS: More stringent enforcement of regulations is needed to ensure not only the user's safety and awareness, but also the safeguarding of the environment.

[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.

[The Herceptin® case : A case of falsification of medicinal products to a greater extent]. / Der Herceptin®-Fall : Ein Fälschungsfall von Arzneimitteln größeren Ausmaßes.

Falsified medicines are a raising problem for the German drug market. The complex distribution channels across the European market facilitates the introduction of falsified and stolen medicines into the legal supply chain and may pose a risk for patients. The "Herceptin® case" from 2014 of falsified medicines of Italian origin demonstrates how complex distribution systems have been misused by criminal organizations in order to introduce stolen and thus falsified medicines via the parallel trade into the market, and which measures the authorities and the parallel-traders in the national and European network have taken to ensure patient safety. Falsified medicines will continue to be a problem in the future, so new monitoring systems have to be established and effectively used for prevention. The introduction of the EU-wide serialisation system in February 2019 is therefore intended to identify falsified drugs and to prevent the further trade as well as the expenditure to the patient. Furthermore, the maintenance and intensification of the cooperation between all EU authorities involved remains indispensable to close gateways in the distribution system for falsified medicines and to minimise the risk to the population.

Development of the risk-based, phased-in approach for the international harmonization of the regulation of container closure systems for drugs in Taiwan.

The main concern for container closure systems of drugs is to ensure suitability for the intended use which is associated with issues regarding protection, compatibility, safety, and performance. Among various concerns, leachables may pose a safety hazard to patients, while risks might vary depending on the dosage form and the administration route. Stringent regulatory authorities such as the European Medicines Agency and the United States Food and Drug Administration have established risk-based regulatory requirements and published corresponding guidelines to facilitate implementation. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes every effort to harmonize with international regulations and to strengthen protection of public health through regulatory controls. The aim of the present study was to investigate the regulatory framework and policies set by stringent regulatory authorities. The strategy proposed for the development of an eventual guideline was sent to the Taiwan Food and Drug Administration for decision. A risk-based, phased-in approach which was extensively discussed in the expert committee was proposed. The approach proposed herein could also serve as a starting point which is worth considered by other countries in which international harmonization is in process.

[A fine line between legal and illegal oral drug repackaging]. / La delgada línea entre lo legal e ilegal en el reenvasado de los medicamentos orales.

In 2009, with the implementation of the National Hospital Pharmacy Model, Mexico began regulating single-dose drugs. The repackaging of oral drugs is fundamental and critical and should be standardized by Mexican health legislation to enable quality drugs to be dispensed. Data is required on stability, compatibility, drug interactions, containers, and repackaging methods, in order to establish a new expiration date. The literature on health regulations applicable to repackaging was analyzed, revealing major conceptual imprecisions since there is no legislation in Mexico that regulates repackaging; rather, everything is carried out according to pharmacists' recommendations and criteria. The conclusion is that the regulations need to be rewritten to establish minimum single-dose oral drug criteria for dispensing hospitals-regulations that cover infrastructure, equipment, and professionals complying with good practices in oral drug repackaging. A proposal is offered to implement an official Mexican standard that regulates single-dose repackaging and unifies concepts, criteria, and means of verification, while the pharmaceutical industry would be responsible for the technology and resources for single-dose drug packaging designed for the health sector.

Revision of Import and Export Requirements for Controlled Substances, Listed Chemicals, and Tableting and Encapsulating Machines, Including Changes To Implement the International Trade Data System (ITDS); Revision of Reporting Requirements for Domestic Transactions in Listed Chemicals and Tableting and Encapsulating Machines; and Technical Amendments. Final rule.

The Drug Enforcement Administration is updating its regulations for the import and export of tableting and encapsulating machines, controlled substances, and listed chemicals, and its regulations relating to reports required for domestic transactions in listed chemicals, gamma-hydroxybutyric acid, and tableting and encapsulating machines. In accordance with Executive Order 13563, the Drug Enforcement Administration has reviewed its import and export regulations and reporting requirements for domestic transactions in listed chemicals (and gamma-hydroxybutyric acid) and tableting and encapsulating machines, and evaluated them for clarity, consistency, continued accuracy, and effectiveness. The amendments clarify certain policies and reflect current procedures and technological advancements. The amendments also allow for the implementation, as applicable to tableting and encapsulating machines, controlled substances, and listed chemicals, of the President's Executive Order 13659 on streamlining the export/import process and requiring the government-wide utilization of the International Trade Data System (ITDS). This rule additionally contains amendments that implement recent changes to the Controlled Substances Import and Export Act (CSIEA) for reexportation of controlled substances among members of the European Economic Area made by the Improving Regulatory Transparency for New Medical Therapies Act. The rule also includes additional substantive and technical and stylistic amendments.

Imaging of body packing: errors and medico-legal issues.

Body packing is the ingestion or insertion in the human body of packed illicit substances. Over the last 20 years, drug smuggling has increased global and new means of transport of narcotics have emerged. Among these, the most frequent one is the gastrointestinal tract: from mouth to anus, vagina, and ears. Cocaine is one of the most traded drugs, followed by heroin. Condoms, latex gloves, and balloons are typically used as drug packets for retention in the body. There are different radiologic modalities to detect illicit drugs in body packing: Plain radiography, computed tomography (CT), ultrasound, and magnetic resonance. Current protocols recommend the use of radiography to confirm packet retention and, in case of doubt, the use of abdominal CT scan with reduced mAs. In case of packet rupture, catastrophic effects can occur. Management of patients carrying packets of drugs is a recurrent medico-legal problem. To improve diagnostic accuracy and prevent hazardous complications, radiologists and emergency physicians should be familiar with radiologic features of body packing. The radiologist plays both a social and a medico-legal role in their assessment, and it should not be limited only to the identification of the packages but must also provide accurate information about their number and their exact location. In this review, we focus on diagnostic errors and medico-legal issues related to the radiological assessment of body packers.

Analysing compliance of cigarette packaging with the FCTC and national legislation in eight former Soviet countries.

AIM: To analyse compliance of cigarette packets with the Framework Convention on Tobacco Control (FCTC) and national legislation and the policy actions that are required in eight former Soviet Union countries. METHODS: We obtained cigarette packets of each of the 10 most smoked cigarette brands in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Moldova, Russia and Ukraine. The packets were then analysed using a standardised data collection instrument. The analysis included the placing, size and content of health warning labels and deceptive labels (eg, 'Lights'). Findings were assessed for compliance with the FCTC and national legislation. RESULTS: Health warnings were on all packets from all countries and met the FCTC minimum recommendations on size and position except Azerbaijan and Georgia. All countries used a variety of warnings except Azerbaijan. No country had pictorial health warnings, despite them being mandatory in Georgia and Moldova. All of the countries had deceptive labels despite being banned in all countries except Russia and Azerbaijan where still no such legislation exists. CONCLUSIONS: Despite progress in the use of health warning messages, gaps still remain-particularly with the use of deceptive labels. Stronger surveillance and enforcement mechanisms are required to improve compliance with the FCTC and national legislation.

Classification of two steroids, prostanozol and methasterone, as Schedule III anabolic steroids under the Controlled Substance Act. Final rule.

With the issuance of this Final Rule, the Administrator of the DEA classifies the following two steroids as "anabolic steroids'' under the Controlled Substances Act (CSA): prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone (2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one). These steroids and their salts, esters, and ethers are Schedule III controlled substances subject to the regulatory control provisions of the CSA.

Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

Experience of reviewing the follow-on biologics including Somatropin and erythropoietin in Japan.

To share the experience of reviewing clinical data required for the licensing of follow-on biologic products (biosimilar products and similar biotherapeutical products as EU and WHO terminology, respectively) in Japan, the data packages of two follow-on biologics, "Somatropin BS s.c. [Sandoz] (Omnitrope®)" and "Epoetin alfa BS [JCR]", which have been recently approved in Japan according to the "Guidelines for the Quality, Safety and Efficacy Assurance of Follow-on Biologics" published on March 4th 2009, are described. The clinical data package and indication of Somatropin BS/Omnitrope(®) were different in each country. In case of Epoetin alfa BS [JCR], non-clinical and clinical data-package was different from those of erythropoietin biosimilar products approved in EU. Submission of post-marketing surveillance plans for both products was required. Even though there seem to be differences in data requirements by each national regulatory authority, the accumulation of experience will provide the rationale and consensus on how to design the clinical trials for follow-on biologics.

Self-certification and employee training of mail-order distributors of scheduled listed chemical products. Interim final rule with request for comment.

On October 12, 2010, the President signed the Combat Methamphetamine Enhancement Act of 2010 (MEA). It establishes new requirements for mail-order distributors of scheduled listed chemical products. Mail-order distributors must now self-certify to DEA in order to sell scheduled listed chemical products at retail. Sales at retail are those sales intended for personal use; mail-order distributors that sell scheduled listed chemical products not intended for personal use, e.g., sale to a university, are not affected by the new law. This self-certification must include a statement that the mail-order distributor understands each of the requirements that apply under part 1314 and agrees to comply with these requirements. Additionally, mail-order distributors are now required to train their employees prior to self certification. DEA is promulgating this rule to incorporate the statutory provisions and make its regulations consistent with the new requirements and other existing regulations related to self-certification.

Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Final Order.

The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily schedule three synthetic cathinones under the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). The substances are 4-methyl-N-methylcathinone (mephedrone), 3,4-methylenedioxy-N-methylcathinone (methylone), and 3,4-methylenedioxypyrovalerone (MDPV). This action is based on a finding by the Administrator that the placement of these synthetic cathinones and their salts, isomers, and salts of isomers into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety. As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil and administrative penalties, sanctions and regulatory controls of Schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cathinones.