Report of the European Medicines Agency Conference on RNA-Based Medicines.

RNA-based medicines have potential to treat a large variety of diseases, and research in the field is very dynamic. Proactively, The European Medicines Agency (EMA) organized a virtual conference on February 2, 2023 to promote the development of RNA-based medicines. The initiative addresses the goal of the EMA Regulatory Science Strategy to 2025 to "catalyse the integration of science and technology in medicines development." The conference focused on RNA technologies (excluding RNA vaccines) and involved different stakeholders, including representatives from academia, industry, regulatory authorities, and patient organizations. The conference comprised presentations and discussion sessions conducted by panels of subject matter experts. In this meeting report, we summarize the presentations and recap the main themes of the panel discussions.

Advanced Complex Analysis of the Thermal Softening of Nitrided Layers in Tools during Hot Die Forging.

This article is devoted to the issues of thermal softening of materials in the surface layer of forging tools. The research covers numerical modeling of the forging process, laboratory tests of tempering of nitrided layers, and the analysis of tempering of the surface layer of tools in the actual forging process. Numerical modeling was supported by measuring the temperature inside the tools with a thermocouple inserted into the tool to measure the temperature as close to the surface as possible. The modeling results confirmed the possibility of tempering the die material. The results of laboratory tests made it possible to determine the influence of temperature on tempering at different surface layer depths. Numerical analysis and measurement of surface layer microhardness of tools revealed the destructive effect of temperature during forging on the tempering of the nitrided layer and on the material layers located deeper below the nitrided layer. The results have shown that in the hot forging processes carried out in accordance with the adopted technology, the surface layer of working tools is overheated locally to a temperature above 600 °C and tempering occurs. Moreover, overheating effects are visible, because the surface layer is tempered to a depth of 0.3 mm. Finally, such tempering processes lead to a decrease in the die hardness, which causes accelerated wear because of the abrasion and plastic deformation. The nitriding does not protect against the tempering phenomenon, but only delays the material softening process, because tempering occurs in the nitrided layer and in the layers deeper under the nitrided layer. Below the nitrided layer, tempering occurs relatively quickly and a soft layer is formed with a hardness below 400 HV.

Case Study of the Effect of Precoating on the Decarburization of the Surface Layer of Forged Parts during the Hot Die Forging Process.

This paper aims to evaluate the effect of pre-coating of forged parts on decarburization in the die forging process. The studies consisted of three stages. In the first instance, different coatings were tested under laboratory conditions by heating steel samples to the temperature of 1200 °C for over five minutes to model the preheating conditions of the induction. Next, testing continued in a commercial forging stand where we tested the effects of different coatings on the rods decarburization during the induction heating process, usually performed before forging. Once completed testing, the measurements and observations of the decarbonized layer were made. The third stage involved analysis of the decarburization of the forged parts after forging. The forged parts were made using precoating of pre-forging elements; pieces cut off a metal rod. Based on tests results, the possibility of using this solution in the technique of industrial hot forging was evaluated. The results of laboratory tests have confirmed that lubrication of metal pieces is sufficient, as well as proved it to be effective in reducing decarburization of the surface layer. Research works conducted in an induction heater showed differences in decarburization depending on a substance and concentration of lubricants that were used. These differences become more apparent when observing the surface layer of the forged parts. Results indicate that decarburization may be reduced to a minimum when we use Bonderite product in a concentration of 66% and 50%. Another lubricant, Berulit 913, may also be used. However, due to burning graphite in high temperatures, reduction of decarburization goes only as far as half of the thickness of the decarbonized layer. Condursal has no significant effect; nevertheless, it protects over the induction heating stage.

Characterization of Low-Molecular-Weight Heparins by Strong Anion-Exchange Chromatography.

Currently, detailed structural characterization of low-molecular-weight heparin (LMWH) products is an analytical subject of great interest. In this work, we carried out a comprehensive structural analysis of LMWHs and applied a modified pharmacopeial method, as well as methods developed by other researchers, to the analysis of novel biosimilar LMWH products; and, for the first time, compared the qualitative and quantitative composition of commercially available drugs (enoxaparin, nadroparin, and dalteparin). For this purpose, we used strong anion-exchange (SAX) chromatography with spectrophotometric detection because this method is more helpful, easier, and faster than other separation techniques for the detailed disaccharide analysis of new LMWH drugs. In addition, we subjected the obtained results to statistical analysis (factor analysis, t-test, and Newman-Keuls post hoc test).