Properties Of Medium Research Articles

A 3D computational model for ground motion simulation in Peninsular India

Due to the gradual and constant accumulation of seismic energy, Peninsular India (PI) is typically considered seismically stable with low to moderate seismicity. The seismic studies in Peninsular India always resorted to synthetic ground motion simulations, because of the limited instrumentation and hence lack of recorded data. In the absence of a well-defined medium model for PI, the usual practice is to use simple site proxies or one-dimensional velocity structures for ground motion simulations. However, the region consists of multi-scale geometric complexities, significant topography, and sedimentary basins and is surrounded by deep oceans. Thus, the radiated seismic wave field in the region is influenced by the medium properties and in the absence of a well-defined tomography model the reliable estimation of seismic hazard is a challenging problem in PI. Therefore, the seismic wave propagation in PI can be investigated using numerical simulation with reliable 3D computational model for PI, incorporating the knowledge of the underlying Earth structure. Hence, the present study attempts to develop a sophisticated three-dimensional (3D) medium model of Peninsular India for physics-based ground motion simulations for regional earthquakes. This is aided by the availability of one-dimensional (1D) velocity models and the crustal structure from the receiver function analysis which provides valuable insight into the variation of material properties in the region. In the present study, >100 s of 1D velocity profiles are collected from various literature, which is then grouped under 23 different geological regions identified in PI (as per GSI (2000)). The averaged material properties are assigned per each geological region and the information on sediment depths, basin geometry, topography, and bathymetry are incorporated. We use the spectral element method (SEM) to calibrate our 3D computational model by simulating synthetic seismograms and comparing them to recorded ground motions for two past earthquakes: the 2001 Mw 7.6 Bhuj earthquake and the 1997 Mw 5.8 Jabalpur earthquake. Further, the seismic waveforms at the near field of 2001 Mw 7.6 Bhuj event are simulated using a refined regional model. The spatial variability of associated seismic intensities and peak ground velocity (PGV) amplification are investigated. In addition, a study of the impact of model depth truncation and sphericity on ground motion is also conducted. The implemented medium model is the first of its kind for Peninsular India and can reliably be used in seismic wave propagation studies in the region. The simulated outcomes from the model are of engineering importance as these results can be used for seismic hazard assessment of the region.

The hot circumgalactic media of massive cluster satellites in the TNG-Cluster simulation: Existence and detectability

The most massive galaxy clusters in the Universe host tens to hundreds of massive satellite galaxies M⋆ ∼ 1010 − 12.5 M⊙, but it is unclear if these satellites are able to retain their own gaseous atmospheres. We analyze the evolution of ≈90 000 satellites of stellar mass ∼109 − 12.5 M⊙ around 352 galaxy clusters of mass M200c ∼ 1014.3 − 15.4 M⊙ at z = 0 from the new TNG-Cluster suite of cosmological magneto-hydrodynamical galaxy cluster simulations. The number of massive satellites per host increases with host mass, and the mass–richness relation broadly agrees with observations. A halo of mass M200chost ∼ 1014.5(1015) M⊙ hosts ∼100 (300) satellites today. Only a minority of satellites retain some gas, hot or cold, and this fraction increases with stellar mass. lower-mass satellites ∼109 − 10 M⊙ are more likely to retain part of their cold interstellar medium, consistent with ram pressure preferentially removing hot extended gas first. At higher stellar masses ∼1010.5 − 12.5 M⊙, the fraction of gas-rich satellites increases to unity, and nearly all satellites retain a sizeable portion of their hot, spatially extended circumgalactic medium (CGM), despite the ejective activity of their supermassive black holes. According to TNG-Cluster, the CGM of these gaseous satellites can be seen in soft X-ray emission (0.5−2.0 keV) that is, ≳10 times brighter than the local background. This X-ray surface brightness excess around satellites extends to ≈30 − 100 kpc, and is strongest for galaxies with higher stellar masses and larger host-centric distances. Approximately 10% of the soft X-ray emission in cluster outskirts ≈0.75 − 1.5 R200c originates from satellites. The CGM of member galaxies reflects the dynamics of cluster-satellite interactions and contributes to the observationally inferred properties of the intracluster medium.

Valley edge states with opposite chirality in temperature dependent acoustic media

The valley degree of freedom in phononic crystals and metamaterials holds immense promise for manipulating acoustic and elastic waves. However, the impact of acoustic medium properties on valley edge state frequencies and their robustness to one-way propagation in valley topological phononic crystals remains unexplored. While significant attention has been devoted to scatterer design embedded in honeycomb lattices within acoustic and elastic media to achieve valley edge states and topologically protected nontrivial bandgaps, the influence of variations in acoustic medium properties, such as wave velocity and density affected by environmental temperature, has been overlooked. In this study, we investigate the effect of valley edge states and topological phases exhibited by topological phononic lattices in a temperature-dependent acoustic medium. We observe that a decrease in wave velocity and density, influenced by changing environmental temperature, shifts the topological valley edge states to lower frequencies. Therefore, alongside phononic lattice design, it is crucial to consider the impact of acoustic medium properties on the practical application of acoustic topological insulators. This issue becomes particularly significant when a topological phononic crystal is placed in a wave medium that transitions from incompressible to compressible, where wave velocity and density are no longer constant. Our findings offer a novel perspective on investigating topological insulators in variable acoustic media affected by changing thermodynamic and fluid properties.

Dynamic changes in dissolved organic matter during transport of landfill leachate in porous medium.

The dynamic changes in dissolved organic matter (DOM) during the transport of landfill leachate (LL) in porous medium should be explored, considering the high levels of DOM in the LL of municipal solid waste. Column experiments were carried out at 25°C at a Darcy's flux of 0.29cm/h for 2722h to compare the transport of Cl-, ultraviolet absorbance at 254nm (UV254), chemical oxygen demand (COD), and dissolved organic carbon (DOC) in the simulated porous medium by using the CXTFIT2.1 code. Results showed that the convection-dispersion equation (CDE) could describe Cl- transport well. The high levels of λ and D could be highly correlated with the physicochemical properties of the porous medium. The transport of the studied DOM with evident aromatic character could be described appropriately by the CDE model with the first-order reaction assumption, considering the similar variation trends of UV254, COD, and DOC in the effluent during experiments. Specifically, the values of retardation factor (R) were in the following order: DOC > UV254 > COD, whereas the low values of the first-order decay coefficient (k1) for DOC and COD were still higher than that for UV254. High contents of humic-like substances in the DOM with complex toxic components resulted in the natural low removal efficiencies of COD, DOC, and UV254 (≤ 23%), which could be confirmed by the variations of fluorescence index (FI) and humification index (HIX) in the effluent. The results should be helpful in evaluating the environmental risk induced by the LL leakage in a landfill site.

GA-NIFS: The core of an extremely massive protocluster at the epoch of reionisation probed with JWST/NIRSpec

The SPT0311-58 system resides in a massive dark-matter halo at z sim 6.9. It hosts two dusty galaxies (E and W) with a combined star formation rate (SFR) of sim 3500 mostly obscured and identified by the rest-frame IR emission. The surrounding field exhibits an overdensity of submillimetre sources, making it a candidate protocluster. Our main goal is to characterise the environment and the properties of the interstellar medium (ISM) within this unique system. We used spatially resolved low-resolution ($R$=100) and high-resolution ($R$=2700) spectroscopy provided by the JWST/NIRSpec Integral Field Unit to probe a field of sim 17 times 17 kpc$^2$ around this object, with a spatial resolution of sim 0.5 kpc. These observations reveal ten new galaxies at zsim 6.9 characterised by dynamical masses spanning from sim 109 to 1010 and a range in radial velocity of sim 1500 in addition to the already known E and W galaxies. The implied large number density (phi sim $) and the wide spread in velocities confirm that is at the core of a protocluster immersed in a very massive dark-matter halo of sim (5 pm 3) times 1012 and therefore represents the most massive protocluster ever found at the epoch of reionisation (EoR). We also studied the dynamical stage of its core and find that it is likely not fully virialised. The galaxies in the system exhibit a wide range of properties and evolutionary stages. The contribution of the ongoing Halpha -based unobscured SFR to the total star formation (SF) varies significantly across the galaxies in the system. Their ionisation conditions range from those typical of the field galaxies at similar redshift recently studied with JWST to those found in more evolved objects at lower redshift, with OIII varying from sim 0.25 to 1. The metallicity spans more than 0.8 dex across the FoV, reaching nearly solar values in some cases. The detailed spatially resolved spectroscopy of the E galaxy reveals that it is actively assembling its stellar mass, showing inhomogeneities in the ISM properties at subkiloparsec scales, and a metallicity gradient (sim 0.1 dex/kpc) that can be explained by accretion of low metallicity gas from the intergalactic medium. The kinematic maps also depict an unsettled disc characterised by deviations from regular rotation, elevated turbulence, and indications of a possible precollision minor merger. These JWST/NIRSpec IFS observations confirm that is at the core of an extraordinary protocluster, and reveal details of its dynamical properties. They also unveil and provide insights into the diverse properties and evolutionary stages of the galaxies residing in this unique environment.

Sloshing cold fronts in galaxy cluster Abell 2566

This paper presents properties of the intracluster medium (ICM) in the environment of a cool core cluster Abell 2566 (redshift z= 0.08247) based on the analysis of 20 ks Chandra X-ray data. 2D imaging analysis of the Chandra data from this cluster revealed spiral structures in the morphology of X-ray emission from within the central 109 kpc formed due to gas sloshing. This analysis also witness sharp edges in the surface brightness distribution along the south-east and north-west of the X-ray peaks at 41.6 kpc and 77.4 kpc, respectively. Spectral analysis of 0.5 – 7 keV X-ray photons along these discontinuities exhibited sharp temperature jumps from 2.3 to 3.1 keV and 1.8 to 2.8 keV, respectively, with consistency in the pressure profiles, implying their association with cold fronts due to gas sloshing of the gas. Further confirmation for such an association was provided by the deprojected broken power-law density function fit to the surface brightness distribution along these wedge shaped sectorial regions. This study also witness an offset of 4.6′′(6.8 kpc) between the BCG and the X-ray peak, and interaction of the BCG with a sub-system in the central region, pointing towards the origin of the spiral structure due to a minor merger.

Evolution of grain size distribution in the circumgalactic medium

Abstract In order to theoretically understand dust properties in the circumgalactic medium (CGM), we construct a dust evolution model that incorporates the evolution of grain size distribution. We treat the galaxy and the CGM as separate one-zone objects, and consider the mass exchange between them. We take into account dust production and interstellar dust processing for the galaxy based on our previous models, and newly incorporate sputtering in the hot phase and shattering in the cool phase for the CGM. We find that shattering increases the dust destruction (sputtering) efficiency in the CGM. The functional shape of the grain size distribution in the CGM evolves following that in the galaxy, but it is sensitive to the balance between sputtering and shattering in the CGM. For an observational test, we discuss the wavelength dependence of the reddening in the CGM traced by background quasar colors, arguing that, in order to explain the observed reddening level, a rapid inflow from the CGM to the galaxy is favored because of quick dust/metal enrichment. Small grain production by shattering in the CGM also helps to explain the rise of dust extinction toward short wavelengths.

Impact of Surrounding Environment on Hot‐Exciton Based Organic Emitters for TADF Applications

AbstractUnderstanding thermally activated delayed fluorescence (TADF) in solid‐state environments is crucial for practical applications. However, limited research focuses on how the medium affects TADF properties of hot‐exciton‐based emitters. In our study, we calculated and compared reverse intersystem crossing, radiative, and non‐radiative decay rates of TADF emitters in gas, solvent, and solid phases. The designed emitters have a donor‐acceptor‐donor (D‐A‐D) structure, with donors such as triphenylamine (TPA) and diphenylamine thiophene (ThPA), combined with acceptors such as benzothiadiazole (BT), pyridine thiadiazole (PT) and thiadiazolobenzopyridine (NPT). We model the solvent and solid phases with the polarizable continuum model (PCM) and quantum mechanical/molecular mechanics (QM/MM) methods, respectively. Using density functional theory (DFT) and time‐dependent DFT, we analyze how TADF emitters′ geometrical, electronic, and excited‐state properties vary in these phases. Our results show that the solid‐state environment significantly influences the geometry and TADF properties of emitters. In the presence of solid medium, our study indicates that non‐radiative decay rates tend to be slower. On the other hand, radiative emission rates were found to be less influenced by the properties of the surrounding medium. Overall, our study connects emitter chemical structure and the surrounding environment‘s impact on excited‐state characteristics and photochemical properties.

Nanobubble transport in porous media: Towards agro- and environmental applications

Nanobubbles have been increasingly used in various applications involving porous media, such as groundwater remediation and irrigation. However, the fundamental scientific knowledge regarding the interactions between nanobubbles and the media is still limited. The interactions can be repulsive, attractive, or inert, and can involve reversible or irreversible attachment as well as destructive mechanisms. Specifically, the stability and mobility of nanobubbles in porous media is expected to be dependent on the dynamic conditions and the physicochemical properties of the porous media, solutions, and nanobubbles themselves. In this study, we investigated how changes in solution chemistry (pH, ionic strength, and valence) and media characteristics (size and wettability) affect the size and concentration of nanobubbles under dynamic conditions using column experiments. Quartz crystal microbalance with dissipation monitoring provided a deeper understanding of irreversible and elastic nanobubbles’ interactions with silica-coated surfaces. Our findings suggest that nanobubbles are less mobile in solutions of higher ionic strength and valence, acidic pH and smaller porous media sizes, while the wettability of porous media has a negligible influence on the retention of nanobubbles. Overall, our findings provide insights into the underlying mechanisms of nanobubble interactions and suggest potential strategies to optimize their delivery in various applications.

Auswirkungen der visuellen Flussgeschwindigkeit auf das Radfahrerlebnis in der virtuellen Realität

AbstractApplying virtual reality to exercise has revealed mood- and performance-enhancing properties of immersive media. Social–cognitive theory and the Proteus effect suggest that avatar appearance contributes to this relation by eliciting behavioral changes. Attempting to influence exercise parameters without modifying the virtual avatar, the present study investigated the effects of differing visual flow speeds on physiological and perceived effort during aerobic exercise. Eighty-two university students participated in three separate experimental trials. During each trial, a virtual cycling track was presented at one of three velocities (16, 20, 24 km/h) in counterbalanced order, while participants cycled at a moderate intensity for 20 min. Objective and subjective measures of effort and affective states were recorded every five minutes. With increasing visual flow speed, a linear decrease of heart rate, perceived effort, and arousal and a linear increase of valence were expected. Mixed linear model analyses revealed no significant main effect of visual flow speed on any dependent variable. A nonlinear relation between visual flow speed and heart rate was identified through pairwise comparisons between visual flow conditions.

Flow-Independent Thermal Conductivity and Volumetric Heat Capacity Measurement of Pure Gases and Binary Gas Mixtures Using a Single Heated Wire.

Among the different techniques for monitoring the flow rate of various fluids, thermal flow sensors stand out for their straightforward measurement technique. However, the main drawback of these types of sensors is their dependency on the thermal properties of the medium, i.e., thermal conductivity (k), and volumetric heat capacity (ρcp). They require calibration whenever the fluid in the system changes. In this paper, we present a single hot wire suspended above a V-groove cavity that is used to measure k and ρcp through DC and AC excitation for both pure gases and binary gas mixtures, respectively. The unique characteristic of the proposed sensor is its independence of the flow velocity, which makes it possible to detect the medium properties while the fluid flows over the sensor chip. The measured error due to fluctuations in flow velocity is less than ±0.5% for all test gases except for He, where it is ±6% due to the limitations of the measurement setup. The working principle and measurement results are discussed.

Singular solutions for complex second order elliptic equations and their application to time-harmonic diffuse optical tomography

We construct singular solutions of a complex elliptic equation of second order, having an isolated singularity of any order. In particular, we extend results obtained for the real partial differential equation in divergence form by Alessandrini in 1990. Our solutions can be applied to the determination of the optical properties of an anisotropic medium in time-harmonic Diffuse Optical Tomography (DOT).

The influence of doping with different surface modified SiO2 nanoparticles on the dielectric properties of natural ester insulating oil

Nanoparticles are presently considered to be high-potential filler materials in insulation medium. Surface-modified nanoparticles can not only improve the compatibility between nanoparticles and insulation liquid but also enhance the dielectric properties. Herein, models of soybean oil-based natural ester insulation oil doped with two silane coupling agents (A151, KH550) modified SiO2 were established, respectively. Molecular dynamics and DFT first principles were applied to explore the effect of two nanoparticles on the dielectric properties of liquid-insulation medium. The results showed that two types of nanoparticles can restrict the diffusion of water molecules by forming hydrogen bonds, while the number of hydrogen bonds in KH550–SiO2 is one-third more than that in A151-SiO2, and the interaction energy is lower, demonstrating a stronger adsorption effect on water molecules. Moreover, surface electrostatic potential and frontier molecular orbitals showed that KH550–SiO2 have a higher adsorption on charged particles in natural ester insulation oil, which can further inhibit the development of streamer discharge in the liquid insulation medium, improve its dielectric property and delay the aging and deterioration of natural ester insulation oil. This study extends our knowledge into the influence of silane coupling agents modified SiO2 nanoparticles on the dielectric performance of liquid insulation materials from a microscopic perspective.

Formation of convective roll patterns over a longitudinal throughflow in an active inhomogeneous porous medium with weak clogging

The convective stability of a plane-parallel longitudinal throughflow in a system consisting of two porous sublayers with distinct permeability is studied taking into account the weak pore clogging effect and given a finite difference in concentration between the upper and lower boundaries of the system. A system of differential equations for convection is derived within the framework of the continuum approach and the nonlinear MIM model. A linear stability analysis of the basic longitudinal flow is carried out. The boundary value problem is solved using the numerical technique for constructing a fundamental system of solutions. The neutral stability curves of the basic flow with respect to the disturbances in the form of rolls with different wavelength are obtained. For the absence of pore clogging, the convective stability maps of the critical solutal Rayleigh-Darcy number versus the permeability ratio for the initial uncontaminated sublayers, as well as the plots of the critical disturbance frequency and wave number versus the permeability ratio for some values of the Peclet number, are constructed. It is shown that these results have symmetry with respect to the solution for equal initial permeability of sublayers. The clogging effect associated with the solute adsorption and desorption in a porous medium is studied in the two-layered systems with the values 0.1 and 10 of the ratio of initial permeabilities of the sublayers; convection localization occurs in distinct sublayers. It was found that clogging increases the stability of the longitudinal basic flow relative to solutal inhomogeneity and breaks the symmetry of solutions with respect to the case when the two-layered system is reduced to a single layer with the same filtration properties of the porous medium throughout its volume. The influence of sorption effects on the critical parameters of oscillatory convection is investigated by plotting the critical solutal Rayleigh-Darcy number, disturbance frequency and wave number against the adsorption coefficient at fixed values of the desorption coefficient. The isolines of the stream function are constructed to analyze convective flow patterns. It was established that there is a weak relationship between the typical size of local convective roll patterns and the clogging parameters. It is shown that the sorption processes, which can lead to clogging, have a significant impact on the velocity of convective rolls moving along the two-layered system at a slight variation in their sizes.

Midcrustal moderate-size earthquake occurrence in paleovolcanic structures off Jeju Island, South Korea

A series of midcrustal moderate-size earthquakes occurred in the Korean Peninsula recently. A midcrustal ML4.9 strike-slip earthquake with a fault-plane strike in N-S occurred on December 14, 2021 at the southwestern offshore region of Jeju Island, South Korea. The fault plane orientation and slip sense (faulting mechanism) hardly conform with the regional stress field. The deep focal depth and N-S directional strike-slip motion require transient changes in the medium properties and stress field. Strong ground motions of the midcrustal earthquake induce preferential dynamic stress changes in NE-SW direction, triggering subsequent aftershocks in NE-SW-directional adjacent faults. Both the static and dynamic stress changes caused by the mainshock contribute to the aftershock sequence. The number and focal depths of aftershocks decrease with distance from the mainshock. The different fault-plane orientations between the mainshock and aftershocks suggest earthquake nucleations in independent fault structures. The mainshock occurred in aseismic midcrustal paleovolcanic structure on the outskirt of a high seismicity region. The ML4.9 earthquake suggests possible nucleation of earthquake in seismically-inactive paleotectonic structures, successively incurring aftershocks conforming to the ambient stress. The mainshock and aftershocks suggest that paleotectonic structures may behave as source structures to spawn earthquakes.

Visualization as irritation: producing knowledge about medieval courts through uncertainty.

Visualizations are ubiquitous in data-driven research, serving as both tools for knowledge production and genuine means of knowledge communication. Despite criticisms targeting the alleged objectivity of visualizations in the digital humanities (DH) and reflections on how they may serve as representations of both scholarly perspective and uncertainty within the data analysis pipeline, there remains a notable scarcity of in-depth theoretical grounding for these assumptions in DH discussions. It is our understanding that only through theoretical foundations such as basic semiotic principles and perspectives on media modality one can fully assess the use and potential of visualizations for innovation in scholarly interpretation. We argue that visualizations have the capacity to "productively irritate" existing scholarly knowledge in a given research field. This does not just mean that visualizations depict patterns in datasets that seem not in line with prior research and thus stimulate deeper examination. Complementarily, "irritation" here consists of visualizations producing uncertainty about their own meaning-yet it is precisely this uncertainty in which the potential for greater insight lies. It stimulates questions about what is depicted and what is not. This turns out to be a valuable resource for scholarly interpretation, and one could argue that visualizing big data is particularly prolific in this sense, because due to their complexity researchers cannot interpret the data without visual representations. However, we argue that "productive irritation" can also happen below the level of big data. We see this potential rooted in the genuinely semiotic and semantic properties of visual media, which studies in multimodality and specifically in the field of Bildlinguistik have carved out: a visualization's holistic overview of data patterns is juxtaposed to its semantic vagueness, which gives way to deep interpretations and multiple perspectives on that data. We elucidate this potential using examples from medieval English legal history. Visualizations of data relating to legal functions and social constellations of various people in court offer surprising insights that can lead to new knowledge through "productive irritation."

Learning a general model of single phase flow in complex 3D porous media

Modeling effective transport properties of 3D porous media, such as permeability, at multiple scales is challenging as a result of the combined complexity of the pore structures and fluid physics—in particular, confinement effects which vary across the nanoscale to the microscale. While numerical simulation is possible, the computational cost is prohibitive for realistic domains, which are large and complex. Although machine learning (ML) models have been proposed to circumvent simulation, none so far has simultaneously accounted for heterogeneous 3D structures, fluid confinement effects, and multiple simulation resolutions. By utilizing numerous computer science techniques to improve the scalability of training, we have for the first time developed a general flow model that accounts for the pore-structure and corresponding physical phenomena at scales from Angstrom to the micrometer. Using synthetic computational domains for training, our ML model exhibits strong performance (R 2 = 0.9) when tested on extremely diverse real domains at multiple scales.

Gauss–Bonnet source of Brans–Dicke scalar field and accelerated expansion of universe

In this work, using a different theoretical approach, we study a homogeneous and isotropic cosmological spacetime filled with a perfect fluid. Using the framework of Brans–Dicke (BD) and Gauss–Bonnet (GB) theories and including a scalar potential, we obtain the analytical solution of the field equations and find the field functions and the relevant expansion parameter of the spacetime. We assume that the BD and GB media can interact with each other, and hence that there is an energy transfer between these two components. Using this approach, we assume that the BD scalar field is related to intrinsic properties of the GB medium. We introduced a power-law scalar field [Formula: see text] and found the appropriate dynamical functions for the different powers p. We found that the expansion rate of spacetime also behaves as a power-law, and the accelerating expansion is always satisfied for this model. We also analyze the stability for physically acceptable critical points for a given scale factor.

Analysis of the Mathematical Models for Identifying the Thickness of the Fouling Layer in Natural Gas Coolers

This article presents an analysis of three different approaches to the identification of the thickness of the fouling layer inside the pipes of natural gas (NG) coolers. At present, there is no existing simple analytical procedure for the identification of the fouling layer thickness. The authors of this article describe in detail the balance method, which required the use of a large number of physical parameters, changes in their sizes depending on the output temperature of the gas, the temperature of the cooling air, the air quantity, as well as the physical properties of both media. The computational model was robust, and its disadvantage was the iterative computation. The second analysed method was a dimensional analysis. It was applied using the Buckingham’s theorem to express the individual similarity criteria. In this method, 10 simplexes and two complexes were created. The fouling layer thickness, expressed using a derived criterial equation, exhibited real results. The third analysed method was based on analysing selected physical parameters with the use of a multiple regression analysis in MinitabX 18 software. The analysis showed that the fouling layer thickness depended on fewer parameters than the number of parameters assumed in the dimensional analysis or the balance method. The standard deviation that was identified in the multiple linear regression for a double crossflow cooler was 0.0667 and the value of reliability (the coefficient of determination of the multiple linear regression) R2 was 0.9985.

Recommendations for the development of sterility testing procedures for biological medicinal products based on pharmacopoeial methods

INTRODUCTION. The distinctive nature and composition of biological medicinal products present certain challenges for the detection of microbial contamination, which affects the reliability of sterility control results. The main challenges associated with testing biologicals include changes in the appearance and physical properties of culture media or samples, an increased risk of contamination or false-positive results in direct inoculation tests, filtration issues, etc. When drafting product specification files and analytical method validation reports in dossiers for biologicals, manufacturers need adequate, reproducible, and pharmacopoeia-based sterility testing procedures for specific medicinal products, including live and inactivated, viral and bacterial, single- and multi-component vaccines, bacteriophages and interferons, sera and immunoglobulins. These challenges can be addressed through providing recommendations for developing analytical procedures based on compendial methods of direct inoculation and membrane filtration.AIM. This study aimed to offer key recommendations for the development of sterility testing procedures for biologicals based on pharmacopoeial methods.DISCUSSION. This article presents a retrospective analysis of the results of reviewing regulatory documentation for biological medicinal products submitted to the testing centre of the Scientific Centre for Expert Evaluation of Medicinal Products in 2021–2023. Having considered major issues with the analytical procedures described in the Sterility section of regulatory submissions, the authors offer the following recommendations for addressing these issues. The authors advise against using low-pH Sabouraud culture media to test blood products by direct inoculation. Biologicals containing mercury preservatives should be tested using a thioglycollate medium at two temperature settings. When testing various biologicals, analysts should refrain from plugging vials with cotton gauze. Instead, they should pour culture media into glass vials with rubber stoppers and crimps. Biologicals in large primary packaging (≥10 mL) should be tested by membrane filtration. Membrane filtration tests for biologicals should use solvents and rinsing agents selected in validation studies. It is also recommended to set the maximum volume of a biological medicinal product that can be filtered through a membrane filter. A reduction in the filtration speed is recommended to minimise foaming when testing blood products.CONCLUSION. The recommendations presented in this article can guide the development of sterility testing procedures for inclusion in the relevant section of regulatory submissions for biologicals. Manufacturers, control laboratories, and regulatory authorities may implement these recommendations to harmonise their approach to sterility testing of biologicals.