In-Use Stability of SB12 (Eculizumab, Soliris Biosimilar) Diluted in Saline and Dextrose Infusion Solution after an Extended Storage Period.

INTRODUCTION: SB12 is a biosimilar to eculizumab reference product [SolirisTM (Soliris is a trademark of Alexion Pharmaceuticals, Inc.)] that acts as a C5 complement protein inhibitor. The infusion stability of in-use (diluted) SB12 outside the conditions stated in the reference product's label is unknown. OBJECTIVE: The objective of this study was to assess the stability of SB12 after extended storage in conditions not claimed in the originator label. METHODS: Infusion stability was assessed in SB12 samples (diluted in 0.9% NaCl, 0.45% NaCl, and 5% dextrose, final concentration of 5 mg/mL per clinical trial protocol and the reference product's label) kept at 5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% relative humidity (RH) for 72 h. The product was stored in different containers [polyolefin (PO) bags, glass bottles and syringes], and the protocol followed International Conference on Harmonisation (ICH) and European Medicines Agency (EMA) requirements for stability evaluation of biological products. Stability was evaluated using complementary assays, including pH, protein concentration (A280), purity (size exclusion-high-performance liquid chromatography, capillary electrophoresis-sodium dodecyl sulfate, and imaged capillary isoelectric focusing), biological activity (C5 binding and inhibition), and safety (subvisible particles). RESULTS: Except for charge variants in SB12 diluted in 5% dextrose, all results met the stability acceptance criteria. There were no major changes in terms of physicochemical stability, biological activity, and subvisible particles. CONCLUSIONS: The infusion stability of SB12 after extended storage (5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% RH for 72 h) was demonstrated for longer periods and at higher temperatures than what is stated in the EU and US labels of the reference product. The physicochemical properties, biological activity, and subvisible particles of in-use SB12 diluted in 0.9% NaCl and 0.45% NaCl were maintained under the described conditions and for all tested containers. However, instability was observed for the diluted SB12 in 5% dextrose. These results may reduce the workload of clinical staff and minimize drug waste from treatment delays without any loss in product quality and biological activity.

Combining Model-Agnostic Meta-Learning and Transfer Learning for Regression.

For cases in which a machine learning model needs to be adapted to a new task, various approaches have been developed, including model-agnostic meta-learning (MAML) and transfer learning. In this paper, we investigate how the differences in the data distributions between the old tasks and the new target task impact performance in regression problems. By performing experiments, we discover that these differences greatly affect the relative performance of different adaptation methods. Based on this observation, we develop ensemble schemes combining multiple adaptation methods that can handle a wide range of data distribution differences between the old and new tasks, thus offering more stable performance for a wide range of tasks. For evaluation, we consider three regression problems of sinusoidal fitting, virtual reality motion prediction, and temperature forecasting. The evaluation results demonstrate that the proposed ensemble schemes achieve the best performance among the considered methods in most cases.

Physicochemical and Biological Stability Assessment of SB11 (Ranibizumab Biosimilar) Under Ambient and In-Use Storage for Intravitreal Administration.

INTRODUCTION: SB11 (Byooviz™) is a ranibizumab biosimilar that acts as a vascular endothelial growth factor (VEGF)-A inhibitor. Stability data for unopened SB11 vials at room temperature are limited and no data are available for SB11 withdrawn into syringes (in-use) for intravitreal administration. METHODS: SB11 stability was assessed in two different settings: unopened vials stored at 30 ± 2 °C/65 ± 5% relative humidity (RH) for 2 months, and in-use SB11 withdrawn into syringes stored at 5 ± 3 °C for 98 days and then 25 ± 2 °C/60 ± 5% RH for 24 h. The product was stored in the absence of light, and the experimental design followed International Conference on Harmonization and European Medicines Agency requirements for stability evaluation of biological products. Analysis included visual appearance (color, clarity, and presence of visible particles), pH, protein concentration (A280) and purity (size-exclusion high-pressure liquid chromatography, capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity (VEGF binding and neutralization), and safety (sub-visible particulates). RESULTS: Except for charge variants in unopened vials at room temperature after 1 month by US standards, all results met the stability acceptance criteria (US and EU) for both unopened vials and for in-use SB11. There were no major changes in terms of physicochemical stability, biological activity and sub-visible particulates. CONCLUSION: SB11 was stable for longer periods and at higher temperatures than what is stated in the labels of the reference product (Lucentis) and SB11. The physicochemical properties, biological activity, and sub-visible particulates of SB11 in both tested settings (unopened vials at room temperature and in-use product withdrawn into syringes) were maintained under the described storage periods. This information can help to avoid unnecessary delays in patient treatment without any loss in quality and biological activity, lower the workload of health care providers and reduce costs associated with drug waste.

Multilink Operation in IEEE 802.11be Wireless LANs: Backoff Overflow Problem and Solutions.

The next-generation wireless LAN standard named IEEE 802.11be supports a multilink operation to cost-efficiently boost throughput performance, for which an efficient multilink channel scheme is essential. The synchronous channel access scheme with an enhancement allowing multilink transmission before backoff completion greatly enhances the performance of multilink devices with no simultaneous transmit and receive capability, for which, however, backoff count compensation is necessary for coexistence with legacy and other multilink devices. In this paper, we identify the backoff count overflow problem of the enhanced synchronous channel access scheme with backoff compensation, which becomes aggravated once triggered due to repeated compensations. Then, we propose four solutions to mitigate this problem: limiting consecutive free-riding transmissions, limiting a compensated backoff value, using the contention window value of a main link, and balancing transmissions between links. Through comparative evaluation and analyses for dense single-spot and indoor random deployment scenarios, we demonstrate in terms of throughput and latency that the proposed solutions successfully mitigate the problem while preserving the coexistence performance.

Power Resource Optimization for Backscatter-Aided Symbiotic Full-Duplex Secondary Transmission with Hardware Impairments in a Cognitive Radio Framework.

This paper investigates the power resource optimization problem for a new cognitive radio framework with a symbiotic backscatter-aided full-duplex secondary link under imperfect interference cancellation and other hardware impairments. The problem is formulated using two approaches, namely, maximization of the sum rate and maximization of the primary link rate, subject to rate constraints on the secondary link, and the solution for each approach is derived. The problem of a half-duplex secondary link is also solved. Simulation results show that the sum rate and exploitation of the full-duplex capability of the secondary link are strongly affected by both the problem objective and hardware impairments.

Multi-Link Operation with Enhanced Synchronous Channel Access in IEEE 802.11be Wireless LANs: Coexistence Issue and Solutions.

Multi-link operation is a new feature of IEEE 802.11be Extremely High Throughput (EHT) that enables the utilization of multiple links using individual frequency channels to transmit and receive between EHT devices. This paper aims to illustrate enhanced multi-link channel access schemes, identify the associated coexistence challenge, and propose solutions. First, we describe the multi-link operation of IEEE 802.11be and how the asynchronous and synchronous channel access schemes facilitate multi-link utilization. Next, we describe the design variants of the synchronous channel access scheme and demonstrate the associated coexistence challenge. Subsequently, we propose four features to address this challenge by assigning penalties to multi-link devices (repicking a backoff count, doubling the contention window size, switching to another contention window set, and compensating the backoff count) as well as five coexistence solutions derived from combinations of these features. Comparative simulation results are provided and analyzed for dense single-spot and indoor random deployment scenarios, demonstrating that the throughput and latency gains of multi-link operation differ between schemes. At the same time, we investigate the coexistence performance of multi-link operation with and without the capability of simultaneous transmission and reception and demonstrate that the proposed solutions mitigate the coexistence problem. In particular, compensating the backoff count achieves the highest coexistence performance among the proposed solutions, with a marginal throughput decrease of multi-link devices. A metric for evaluating both the throughput and latency gains and the coexistence performance of a multi-link channel access scheme using a single value is also proposed.

Multi-Filter Decoding in WiFi Backscatter Communication.

WiFi backscatter communication has emerged as a promising enabler of ultralow-power connectivity for Internet of things, wireless sensor network and smart energy. In this paper, we propose a multi-filter design for effective decoding of WiFi backscattered signals. Backscattered signals are relatively weak compared to carrier WiFi signals and therefore require algorithms that filter out original WiFi signals without affecting the backscattered signals. Two multi-filter designs for WiFi backscatter decoding are presented: the summation and delimiter approaches. Both implementations employ the use of additional filters with different window sizes to efficiently cut off undesired noise/interference, thus enhancing frame detection and decoding performance, and can be coupled with a wide range of decoding algorithms. The designs are particularly productive in the frequency-shift WiFi backscatter communication. We demonstrate via prototyping and testbed experiments that the proposed design enhances the performance of various decoding algorithms in real environments.

Motion-Aware Interplay between WiGig and WiFi for Wireless Virtual Reality.

Wireless virtual reality (VR) is a promising direction for future VR systems that offloads heavy computation to a remote processing entity and wirelessly receives high-quality streams. WiGig and WiFi are representative solutions to implement wireless VR; however, they differ in communication bandwidth and reliability. Our testbed experiments show that the performance of WiGig and VR traffic generation strongly correlates with and consequently can be predicted from a user's motion. Based on this observation, we develop a wireless VR system that exploits the benefits of both links by switching between them and controlling the VR frame encoding for latency regulation and image quality enhancement. The proposed system predicts the performance of the links and selects the one with a higher capacity in an opportunistic manner. It adjusts the encoding rate of the host based on the motion-aware prediction of the frame size and estimated latency of the selected link. By evaluating the testbed data, we demonstrate that the proposed system outperforms a WiGig-only system with a fixed encoding rate in terms of latency regulation and image quality.

Evaluation of the Physico-Chemical and Biological Stability of SB8 (Aybintio), a Proposed Biosimilar to Bevacizumab, Under Ambient and In-Use Conditions.

INTRODUCTION: No stability data of SB8 (proposed biosimilar to bevacizumab) are available for opened vials at 2-8 °C or for unopened vials stored outside of this range. Furthermore, limited stability data are available for dilutions. Stability of unopened vials of SB8 at ambient temperature and in-use stability for opened vials as well as diluted SB8 in infusion bags were evaluated. METHODS: SB8 stability was assessed in three scenarios in the absence of light: unopened 100-mg vials 36 months after manufacture stored at 30 ± 2 °C with 65 ± 5% relative humidity for 1 month, opened 100-mg and 400-mg vials stored at 5 ± 3 °C for 72 h and diluted (1.4 mg/ml or 16.5 mg/ml in 100 ml 0.9% NaCl polyolefin bags) stored for 45 days at 5 ± 3 °C and then 3 days at 30 ± 2 °C; the United Kingdom's National Health Service protocol was used for the study design after dilution. Physicochemical stability (appearance, pH, protein concentration, size-exclusion high-performance liquid chromatography, non-reducing capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity [vascular endothelial growth factor (VEGF) neutralization assay, VEGF binding assay] and potential safety impact properties (subvisible particulates, submicronic aggregation by dynamic light scattering) were determined. RESULTS: All stability-indicating criteria including those for biological activity were met for both unopened vials at ambient condition and for in-use conditions of opened vials as well as both dilutions. No noteworthy changes in terms of physicochemical stability, biological activity and properties with a potential safety impact occurred. CONCLUSION: Under the studied aspetic extreme conditions, SB8 was stable. Our data may support advanced SB8 preparation and may help prevent SB8 wastage because of exceptional temperature excursions or unused product. Sterility assurance is the responsibility of the user and is of utmost importance when opened or diluted SB8 is not immediately used.

Extended Stability of Reconstituted and Diluted SB3 (Trastuzumab Biosimilar) Assessed by Physicochemical and Biological Properties.

INTRODUCTION: Stability information for the trastuzumab biosimilar SB3 is limited to 48 h at 2-8 °C for the reconstituted solution and 24 h at up to 30 °C for diluted solutions. Extended physicochemical stability and biological activity were assessed to evaluate the advanced preparation of reconstituted and diluted SB3. METHODS: Under controlled and aseptic conditions, the stability of reconstituted and diluted SB3 was evaluated using several assessments and according to the UK's National Health Service guidance. Reconstituted SB3 was stored at 25 ± 2 °C with 60 ± 5% relative humidity for 3 days, and subsequently diluted SB3 (0.32-4 mg/mL) was stored in an infusion bag in the absence of light at 25 ± 2 °C with 60 ± 5% relative humidity for 28 days and 5 ± 3 °C for 28 days, respectively. Physicochemical stability (appearance, pH, protein concentration, size exclusion high-performance liquid chromatography, non-reducing capillary electrophoresis-sodium dodecyl sulfate, imaged capillary isoelectric focusing), biological activity (competitive inhibition binding assay to human epidermal growth factor receptor 2 by fluorescence resonance energy transfer, anti-proliferation assay), and properties with a potential safety impact (subvisible particulates, submicronic aggregation by dynamic light scattering) were determined. RESULTS: No physicochemical instability signs or biological activity changes were observed for either reconstituted or diluted SB3 up to 28 days; all stability acceptance criteria were met. No major change was noted in the proportion of molecular weight variants (high molecular weight impurity, total purity) or relative percentages of acidic, main, and basic charge isoforms of the protein. No increases in particulates or aggregates in terms of a potential safety impact were noted. CONCLUSION: The physicochemical stability and biological activity of reconstituted and diluted SB3 are maintained for extended time periods beyond those denoted in the product labeling, which allows for advanced SB3 preparation and may reduce drug wastage and preparation time. FUNDING: Samsung Bioepis Co., Ltd.

Pattern-Based Decoding for Wi-Fi Backscatter Communication of Passive Sensors.

Ambient backscatter communication enables passive sensors to convey sensing data on ambient RF signals in the air at ultralow power consumption. To extract data bits from such signals, threshold-based decoding has generally been considered, but suffers against Wi-Fi signals due to severe fluctuation of OFDM signals. In this paper, we propose a pattern-matching-based decoding algorithm for Wi-Fi backscatter communications. The key idea is the identification of unique patterns of signal samples that arise from the inevitable smoothing of Wi-Fi signals to filter out noisy fluctuation. We provide the mathematical basis of obtaining the pattern of smoothed signal samples as the slope of a line expressed in a closed-form equation. Then, the new decoding algorithm was designed to identify the pattern of received signal samples as a slope rather than classifying their amplitude levels. Thus, it is more robust against signal fluctuation and does not need tricky threshold configuration. Moreover, for even higher reliability, the pattern was identified for a pair of adjacent bits, and the algorithm decodes a bit pair at a time rather than a single bit. We demonstrate via testbed experiments that the proposed algorithm significantly outperforms conventional threshold-based decoding variants in terms of bit error rate for various distances and data rates.

Evaluation of Physicochemical and Biological Stability of 36-Months-Aged SB5 (Adalimumab Biosimilar) for 4 Weeks at Room Temperature.

INTRODUCTION: Tumor necrosis factor (TNF-alpha) inhibitors, such as adalimumab, have shown success in treating autoimmune inflammatory diseases but are associated with substantial financial burdens to the healthcare system. Biosimilars, which are highly similar to biologic agents, offer the potential to reduce the financial burden of treatment. In the case of TNF-alpha inhibitors, they may also offer improved stability and enable prolonged use. SB5, an adalimumab biosimilar, has shown equivalent efficacy and comparable safety to its reference product in clinical trials. Currently, SB5 is approved for storage for 36 months at 2-8 °C and may be stored at room temperature (25 °C) for a maximum period of 14 days. The objective of this study was to evaluate the stability of SB5, aged to its shelf-life of 36 months, at room temperature (25 ± 2 °C) and 60 ± 5% relative humidity (RH) for a period of 4 weeks, which is longer by 14 days than that of SB5 currently approved in the European Union. METHODS: This study evaluated the stability of SB5, aged to its shelf-life of 36 months, at room temperature (25 ± 2 °C) for a period of 4 weeks. Three independent batches of 36 months-aged SB5 were stored at 25 ± 2 °C and 60 ± 5% RH for 4 weeks. Samples were tested at 0, 2, and 4 weeks. RESULTS: Color, clarity, visible particles, pH, protein concentration, and particulate matter were consistent among the batches, and all the test results met the acceptance criteria at each time point. Percent charge variance was maintained over time. Percent of high molecular weight species detected, total purity, relative binding activity by TNF-alpha, and relative potency by TNF-alpha neutralization did not change over time within each batch, and all values were within the acceptance criteria limits. CONCLUSION: SB5 aged for 36 months is physicochemically and biologically stable for 4 weeks at 25 ± 2 °C and 60 ± 5% RH, which is 2 weeks longer than the alternative storage condition as approved by the European Medicines Agency, which is at 25 °C for a period of up to 14 days. FUNDING: Samsung Bioepis Co., Ltd.