The 2016 10th Workshop on Recent Issues in Bioanalysis (10 WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 2) discusses the recommendations for Hybrid LBA/LCMS and regulatory inputs from major global health authorities. Parts 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) have been published in the Bioanalysis journal, issues 22 and 23, respectively.

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity. This 2015 White Paper encompasses recommendations that emerged from the extensive discussions held during the workshop, and is aimed at providing the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to advance scientific excellence, improve quality and deliver better regulatory compliance. Due to its length, the 2015 edition of this comprehensive White Paper has been divided into three parts. Part 2 covers the recommendations for hybrid LBA/LCMS and regulatory agencies' inputs. Part 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in volume 7 of Bioanalysis, issues 22 and 24, respectively.

Therapeutic proteins and peptides have potential to elicit immune responses resulting in anti-drug antibodies that can pose problems for both patient safety and product efficacy. During drug development immunogenicity is usually examined by risk-based approach along with specific strategies for developing “fit-for-purpose” bioanalytical approaches. Enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays are the most widely used platform for ADA detection due to their high sensitivity and throughput. During the past decade, LC/MS has emerged as a promising technology for quantitation of biotherapeutics and protein biomarkers in biological matrices, mainly owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we describe here an immunocapture-LC/MS methodology for simultaneous isotyping and semiquantitation of ADA in human plasma. Briefly, ADA and/or drug-ADA complex is captured by biotinylated drug or anti-drug Ab, immobilized on streptavidin magnetic beads, and separated from human plasma by a magnet. ADA is then released from the beads and subjected to trypsin digestion followed by LC/MS detection of specific universal peptides for each ADA isotype. The LC/MS data are analyzed using cut-point and calibration curve. The proof-of-concept of this methodology is demonstrated by detecting preexisting ADA in human plasma.

There is an increasing demand for quantitative data on metabolite exposure triggered by regulatory guidances. This contribution describes the accuracy of nanoelectrospray ionization mass spectrometry response of drug compounds and their metabolites from biological matrices compared with radiometric quantification. This is a comprehensive investigation of a set of real-life pharmaceutical compounds in relevant matrices such as urine, bile, feces and plasma. The data suggest that nanoelectrospray mass spectrometry can be used for semi-quantitation of metabolites in the absence of reference standards. Therefore, this approach is suitable to screen out non-relevant metabolites early in development as long as an adequate analytical error margin is applied thus balancing risks and resources.

The past decades have witnessed a fl ourish of novel high-rise structures throughout the world under the requirement of a ceaselessly progressing architectural aesthetics, resulting in a complex plan and elevation of a building. Shanghai International Design Center is such a high-rise building with two towers of different heights connected by trusses, and the structural system is composed of steel frame, reinforced concrete (RC) core wall and shear walls. The great irregularity in plan and elevation, according to Chinese code, necessitates a detailed study, which usually includes refi ned structural analysis, scaled structural model test and large size member or joint test. As recommended by the peer review committee, the shaking table tests of the 1:15-scale structural model were performed. Based on the analysis and shaking table model testing, it was found that the stiffness of the connecting trusses is capable of coordinating the two towers to resist lateral forces jointly even under strong earthquakes. As a result of stiffening action brought by the connecting trusses, whipping-lash effect in longitudinal direction develops sharply on top storeys. Structural responses at storeys around the connecting trusses vary remarkably due to sudden change in lateral stiffness. Through comparison between tests and numerical analysis, weak positions of the structure are identifi ed, and some corresponding measures for improving the design of this structure are also put forward.generalized. It is reported that the application of such system in Japan must be evaluated by the Building Center so as to obtain special permission from the Minister of Construction (Morino, 1998). In spite of the relatively more application of this system in China since the 1980s, its seismic behaviour or performance has not yet been investigated systematically, and experimental study on the hybrid structural system is not suffi cient so far compared with that on composite members or joints.This paper investigates the seismic response of an irregular steel perimeter frame-RC core high-rise building with two towers of different heights connected with steel trusses, when subjected to a series of simulated earthquake ground motions. Presented below are the design and construction of the model, the experimental set-up, test results, summary and conclusions. DESCRIPTION OF THE PROTOTYPE STRUCTUREShanghai International Design Center (SIDC) will be built in Yangpu District, Shanghai, China. The main building consists of two towers of different structural heights, connected by a truss system at the middle of the higher tower. The main elevation and typical fl oor layouts of the prototype structure are shown in Figure 1. Tower A is a steel frame-RC core structure with a total structural height of 96 m, and tower B is 48 m high and a steel frame-RC shear wall structure.The main characteristics of this building can be summarized as follows: 767 Figure 1. Prototype building (unit: mm in plan size, m in elevation): (a) south elevation; (b) typical fl oor plans...