Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars.

BACKGROUND: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). METHODS: SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. RESULTS: The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. CONCLUSIONS: Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies.

An intelligent remote monitoring system for artificial heart.

A web-based database system for intelligent remote monitoring of an artificial heart has been developed. It is important for patients with an artificial heart implant to be discharged from the hospital after an appropriate stabilization period for better recovery and quality of life. Reliable continuous remote monitoring systems for these patients with life support devices are gaining practical meaning. The authors have developed a remote monitoring system for this purpose that consists of a portable/desktop monitoring terminal, a database for continuous recording of patient and device status, a web-based data access system with which clinicians can access real-time patient and device status data and past history data, and an intelligent diagnosis algorithm module that noninvasively estimates blood pump output and makes automatic classification of the device status. The system has been tested with data generation emulators installed on remote sites for simulation study, and in two cases of animal experiments conducted at remote facilities. The system showed acceptable functionality and reliability. The intelligence algorithm also showed acceptable practicality in an application to animal experiment data.

Assessment and improvement of the system efficiency for the moving-actuator type biventricular assist device.

This is a test report on the efficiency of a moving-actuator type biventricular assist device (AnyHeart, Seoul National University). From the viewpoint of the various system mechanisms, the device can be subdivided into three separate parts: the motor and its associated controller, the actuator and motor assembly, and the blood sac and its associated components (including valves). The motor was operated under various conditions, including different torque, angular speed, and voltage pulses. The total system efficiency of 8% has been reported before, with subpart efficiencies of 50%, 85%, and 19%, respectively, for the motor and its associated controller, the actuator and motor assembly, and the blood sac and its associated components (including valves), under normal operating conditions (4 L/min pump output, 100 mm Hg aortic pressure [AoP]). This article focuses on the method of analyzing and improving the system efficiency. The applied input voltage under the normal operating conditions of the pump was determined using the analyzed results. Also, a speed profile that takes into consideration the filling state of the blood sac was provided. On the basis of tests performed involving in vitro mock circulation, experimental results are provided to demonstrate the effectiveness of the approach presented in this article.

Hydrodynamic and static performance evaluation of the moving-actuator type biventricular assist device, AnyHeart.

This study evaluated the hydrodynamic characteristics and efficiency of the moving-actuator type implantable biventricular assist device (BVAD), AnyHeart. A blood analog made of 52% glycerin and 48% water was used to simulate the density and viscosity of blood. The maximum pump flow was 9 L/min with 28.8 watts of power input, and the maximum electrical-to-hydraulic power conversion efficiency was approximately 11% at a pump flow of 3.5 L/min. The pump was able to generate 4 L/min output against 100 mm Hg afterload with less than 9 watts of power input. In addition to the overall system efficiency, the inner subpart power conversion efficiency was also evaluated. The system was subdivided according to system mechanism into three major parts: motor part, actuator part, and blood sac part. In normal working conditions (4 L/min, 100 mm Hg) with the AnyHeart, the total system efficiency was 8%, with subpart efficiencies of 50%, 85%, and 19% for motor part, actuator part, and blood sac part, respectively. The pump performance assessed in the in vitro Donovan-type mock circulation loop test was acceptable as a BVAD in terms of flow and pressure.