123 research outputs found
Critical project management success factors analysis for the construction industry of Bangladesh
Purpose â This paper aims to identify the critical project management success factors and analyze those factors to achieve a sustainable construction industry in Bangladesh.
Design/methodology/approach â This study identified 41 major problematic factors from the related literature. In this research, a detailed questionnaire survey was conducted among the experts and stakeholders of the construction industry of Bangladesh. The survey was carried out on a Likert scale and ranked the critical factors using the relative importance index (RII). The 41 problematic factors were divided into five group factors and ranked by the RII index to prioritize the factors. Finally, stakeholdersâ opinions were analyzed with the critical assessed factors, which was a very effective technique to eliminate the risks and uncertain occurrences in the construction industry of Bangladesh. Findings â The factors analysis revealed that cost overrun, traffic jam, low wedges, slow payment for
completed works and financial issues of the owner were leading critical factors in construction projects.
Moreover, the critical factors are divided into five-factor groups, namely, financial management, monitoring
and feedback, competency management, communication and coordination management, and risk management, which exhibit 0.767, 0.720, 0.711, 0.710 and 0.658 RII values. After all, the stakeholdersâ opinion suggested that implementing modern tools and techniques can help to avoid the critical situation in the construction industry of Bangladesh.
Practical implications â The construction industry of Bangladesh is moving away from stable construction
work day by day. Previously, the potential CSFs were discussed unstructured way. Hence, detecting early
warning signals in a structured way has become necessary for the building firmâs survival. Originality/value â Though some scattered critical issues are discussed in different literature, the critical issues of the Bangladeshi construction industry were not investigated extensively. Therefore, this study finds out the potential critical issues of the construction industry of Bangladesh to accumulate such harmful construction issues in a single platform so that the construction industry can have an overview of them with the help of innovative technologies
FcRn Affinity-Pharmacokinetic Relationship of Five Human IgG4 Antibodies Engineered for Improved In Vitro FcRn Binding Properties in Cynomolgus Monkeys
ABSTRACT: Th
Minireview Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper
ABSTRACT An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs
Engineered FcRn Binding Fusion Peptides Significantly Enhance the Half-Life of a Fab Domain in Cynomolgus Monkeys
FcRn affinity-pharmacokinetic relationship of five human IgG4 antibodies engineered for improved in vitro FcRn binding properties in cynomolgus monkeys. Drug Metab Dispos 2012; 40:1545-55; PMID:22584253; http://dx
equilibrium dissociation constant; ELISA, enzyme linked immunosorbent assay; pH 50 , pH at which 50% of the FcRn-antibody complexes dissociate; HRP, horseradish peroxidase; IV, intravenous; LLOQ, lower limit of quantitation; pI, isoelectric point; cIEF, capillary isoelectric focusing; T m , thermal stability; DSC, differential scanning calorimetry; AUC 0-â , area under the plasma concentration curve from zero to infinity; CL, clearance; C max , maximal observed plasma concentration; t 1/2 , elimination half-life; k off , Our results suggest that there is likely not a single in vitro parameter that readily predicts in vivo pharmacokinetics, but that the relative contribution and interplay of several factors along with the FcRn binding affinity are important determinants of mAb pharmacokinetic properties
An Organic Intravesical Foreign Body Caused by Penetrating Trauma that was Missed during Initial Management
Pharmacokinetic Developability and Disposition Profiles of Bispecific Antibodies: A Case Study with Two Molecules
Bispecific antibodies (BsAb) that engage multiple pathways are a promising therapeutic strategy to improve and prolong the efficacy of biologics in complex diseases. In the early stages of discovery, BsAbs often exhibit a broad range of pharmacokinetic (PK) behavior. Optimization of the neonatal Fc receptor (FcRn) interactions and removal of undesirable physiochemical properties have been used to improve the âpharmacokinetic developabilityâ for various monoclonal antibody (mAb) therapeutics, yet there is a sparsity of such information for BsAbs. The present work evaluated the influence of FcRn interactions and inherent physiochemical properties on the PK of two related single chain variable fragment (scFv)-based BsAbs. Despite their close relation, the two BsAbs exhibit disparate PK in cynomolgus monkeys with BsAb-1 having an aberrant clearance of ~2 mL/h/kg and BsAb-2 displaying a an ~10-fold slower clearance (~0.2 mL/h/kg). Evaluation of the physiochemical characteristics of the molecules, including charge, non-specific binding, thermal stability, and hydrophobic properties, as well as FcRn interactions showed some differences. In-depth drug disposition results revealed that a substantial disparity in the complete release from FcRn at a neutral pH is a primary factor contributing to the rapid clearance of the BsAb-1 while other biophysical characteristics were largely comparable between molecules
Antibody Conjugates-Recent Advances and Future Innovations
Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Clinical success rates of antibodies have exceeded expectations, resulting in heavy investment in biologics discovery and development in addition to traditional small molecules across the industry. However, protein therapeutics cannot drug targets intracellularly and are limited to soluble and cell-surface antigens. Tremendous strides have been made in antibody discovery, protein engineering, formulation, and delivery devices. These advances continue to push the boundaries of biologics to enable antibody conjugates to take advantage of the target specificity and long half-life from an antibody, while delivering highly potent small molecule drugs. While the âmagic bulletâ concept produced the first wave of antibody conjugates, these entities were met with limited clinical success. This review summarizes the advances and challenges in the field to date with emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, absorption, distribution, metabolism, and excretion (ADME), and product developability. We discuss lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications
Influence of improved FcRn binding on the subcutaneous bioavailability of monoclonal antibodies in cynomolgus monkeys
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