The occurrence of non-anatomical therapeutic chemical-international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study.

The General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies on specific categories of suspected illegal or illegally traded products. These studies are generally based on a combination of retrospective and prospective data collection over a defined period of time. This paper reports the results of the most recent study in this context with the focus on health products containing non-Anatomical Therapeutic Chemical-International Nonproprietary Name (ATC-INN) molecules. In total 1104 cases were reported by 16 countries for the period between January 2017 and the end of September 2019. The vast majority of these samples (83%) were collected from the illegal market, while only 3% originated from a legal source. For the rest of the samples, categorisation was not possible. Moreover, 69% of all the reported samples were presented as medicines, including sexual performance enhancers, sports performance enhancers, physical performance enhancers and cognitive enhancers or nootropic molecules that act on the central nervous system (CNS). Although the popularity of anabolics, PDE-5 inhibitors and CNS drugs in illegal products has already been reported, the study showed some new trends and challenges. Indeed, 11% of the samples contained molecules of biological origin, that is, research peptides, representing the second most reported category in this study. Furthermore, the study also clearly shows the increasing popularity of Selective Androgen Receptor Modulators and nootropics, two categories that need attention and should be further monitored.

Microbiological contamination in counterfeit and unapproved drugs.

BACKGROUND: Counterfeit and unapproved medicines are inherently dangerous and can cause patient injury due to ineffectiveness, chemical or biological contamination, or wrong dosage. Growth of the counterfeit medical market in developed countries is mainly attributable to life-style drugs, which are used in the treatment of non-life-threatening and non-painful conditions, such as slimming pills, cosmetic-related pharmaceuticals, and drugs for sexual enhancement. One of the main tasks of health authorities is to identify the exact active pharmaceutical ingredients (APIs) in confiscated drugs, because wrong API compounds, wrong concentrations, and/or the presence of chemical contaminants are the main risks associated with counterfeit medicines. Serious danger may also arise from microbiological contamination. We therefore performed a market surveillance study focused on the microbial burden in counterfeit and unapproved medicines. METHODS: Counterfeit and unapproved medicines confiscated in Canada and Austria and controls from the legal market were examined for microbial contaminations according to the US and European pharmacopoeia guidelines. The microbiological load of illegal and legitimate samples was statistically compared with the Wilcoxon rank-sum test. RESULTS: Microbial cultivable contaminations in counterfeit and unapproved phosphodiesterase type 5 inhibitors were significantly higher than in products from the legal medicines market (p < 0.0001). Contamination levels exceeding the USP and EP limits were seen in 23% of the tested illegal samples in Canada. Additionally, microbiological contaminations above the pharmacopoeial limits were detected in an anabolic steroid and an herbal medicinal product in Austria (6% of illegal products tested). CONCLUSIONS: Our results show that counterfeit and unapproved pharmaceuticals are not manufactured under the same hygienic conditions as legitimate products. The microbiological contamination of illegal medicinal products often exceeds USP and EP limits, representing a potential threat to consumer health.

Zeeman-driven Lifshitz transition: a model for the experimentally observed Fermi-surface reconstruction in YbRh2Si2.

The heavy-fermion metal YbRh(2)Si(2) displays a field-driven quantum phase transition where signatures of a Fermi-surface reconstruction have been identified, often interpreted as a breakdown of the Kondo effect. We argue that instead many properties of the material can be consistently described by assuming a Zeeman-driven Lifshitz transition of narrow heavy-fermion bands. Using a suitable quasiparticle model, we find a smeared jump in the Hall constant and lines of maxima in susceptibility and specific heat, very similar to experimental data. An intermediate non-Fermi-liquid regime emerges due to the small effective Fermi energy near the transition. Further experiments to discriminate the different scenarios are proposed.

Nonequilibrium spin dynamics in the ferromagnetic Kondo model.

Motivated by recent experiments on molecular quantum dots we investigate the relaxation of pure spin states when coupled to metallic leads. Under suitable conditions these systems are well described by a ferromagnetic Kondo model. Using two recently developed theoretical approaches, the time-dependent numerical renormalization group and an extended flow equation method, we calculate the real-time evolution of a Kondo spin into its partially screened steady state. We obtain exact analytical results which agree well with numerical implementations of both methods. Analytical expressions for the steady state magnetization and the dependence of the long-time relaxation on microscopic parameters are established. We find the long-time relaxation process to be much faster in the regime of anisotropic Kondo couplings. The steady state magnetization is found to deviate significantly from its thermal equilibrium value.