In-line prediction of viability and viable cell density through machine learning-based soft sensor modeling and an integrated systems approach: An industrially relevant PAT case study.

The biopharmaceutical industry is shifting toward employing digital analytical tools for improved understanding of systems biology data and production of quality products. The implementation of these technologies can streamline the manufacturing process by enabling faster responses, reducing manual measurements, and building continuous and automated capabilities. This study discusses the use of soft sensor models for prediction of viability and viable cell density (VCD) in CHO cell culture processes by using in-line optical density and permittivity sensors.

Enhancing the therapeutic activity of hyperimmune IgG against chikungunya virus using FcγRIIIa affinity chromatography.

Introduction: Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown.

Automated Real-Time Eddy Current Array Inspection of Nuclear Assets.

Inspection of components with surface discontinuities is an area that volumetric Non-Destructive Testing (NDT) methods, such as ultrasonic and radiographic, struggle in detection and characterisation. This coupled with the industrial desire to detect surface-breaking defects of components at the point of manufacture and/or maintenance, to increase design lifetime and further embed sustainability in their business models, is driving the increased adoption of Eddy Current Testing (ECT). Moreover, as businesses move toward Industry 4.

HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme.

Background: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy.

Virus filtration: A review of current and future practices in bioprocessing.

For drug products manufactured in mammalian cells, safety assurance practices are needed during production to assure that the final medicinal product is safe from the potential risk of viral contamination. Virus filters provide viral retention for a range of viruses through robust, largely size-based retention mechanism. Therefore, a virus filtration step is commonly utilized in a well-designed recombinant therapeutic protein purification process and is a key component in an overall strategy to minimize the risks of adventitious and endogenous viral particles during the manufacturing of biotechnology products.

Proceedings of the 2019 Viral Clearance Symposium, Session 8. Conference Summary: Key Discussion and Outcomes, Pending Questions, and Proposed Experiments and Actions.

This report provides a high-level summary of the key outcomes and gaps based on the research presented at the 2019 Viral Clearance Symposium and identifies new areas for future study and improvements. The 2019 conference structure extended the framework from the preceding conferences, focusing on the key gaps and associated developments and including the additional focus areas of facility risk mitigation, modular viral clearance claims, depth filter viral clearance, retrospective analysis of viral clearance and continuous processing, quantitation and analysis of viral clearance, viral inactivation by detergents and low pH, viral filtration mechanisms, viral filtration of media, viral detection by next-generation sequencing, and ways to improve the efficiency of the overall adventitious agent strategy.

Proceedings of the 2019 Viral Clearance Symposium, Session 6: Virus-Retentive Filtration.

Manufactures of therapeutic biological products are required to incorporate downstream unit operations that can inactivate or remove potential viral contaminants from the manufacturing process. The viral filtration unit operation is one of the most robust virus removal steps incorporated into downstream manufacturing processes. The primary virus removal mechanism is size exclusion by a network of nanopores in the viral filter membrane.

Comparison of clinical outcomes between nurse practitioner and registrar-led medical emergency teams: a propensity-matched analysis.

Objective: Medical emergency teams (MET) are mostly led by physicians. Some hospitals are currently using nurse practitioners (NP) to lead MET calls. These are no studies comparing clinical outcomes between these two care models.

Atrial Fibrillation in Indigenous Australians: A Multisite Screening Study Using a Single-Lead ECG Device in Aboriginal Primary Health Settings.

Background: Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.

Analytical and Functional Similarity Assessment of ABP 710, a Biosimilar to Infliximab Reference Product.

Purpose: ABP 710 has been developed as a biosimilar to infliximab reference product (RP). The objective of this study was to assess analytical similarity (structural and functional) between ABP 710 and infliximab RP licensed by the United States Food and Drug Administration (infliximab [US]) and the European Union (infliximab [EU]), using sensitive, state-of-the-art analytical methods capable of detecting minor differences in product quality attributes.

Methods: Comprehensive analytical characterization utilizing orthogonal techniques was performed with 14 to 28 unique lots of ABP 710 or infliximab RP, depending on the assay.

Feasibility and acceptability of opportunistic screening to detect atrial fibrillation in Aboriginal adults.

Objective: Examine the feasibility and acceptability of an electrocardiogram (ECG) attached to a mobile phone (iECG) screening device for atrial fibrillation (AF) in Aboriginal Controlled Community Health Services (ACCHS) and other community settings.

Methods: Semi-structured interviews were conducted with ACCHS staff in urban, rural and remote communities in three Australian states/territories. Quantitative and qualitative questions identified the enabling factors and barriers for staff and Aboriginal patients' receptiveness to the device.

Validation and optimization of viral clearance in a downstream continuous chromatography setting.

Continuous bioprocessing holds the potential to improve product consistency, accelerate productivity, and lower cost of production. However, switching a bioprocess from traditional batch to continuous mode requires surmounting business and regulatory challenges. A key regulatory requirement for all biopharmaceuticals is virus safety, which is assured through a combination of testing and virus clearance through purification unit operations.

Inverse resource allocation between vision and olfaction across the genus Drosophila.

Divergent populations across different environments are exposed to critical sensory information related to locating a host or mate, as well as avoiding predators and pathogens. These sensory signals generate evolutionary changes in neuroanatomy and behavior; however, few studies have investigated patterns of neural architecture that occur between sensory systems, or that occur within large groups of closely-related organisms. Here we examine 62 species within the genus Drosophila and describe an inverse resource allocation between vision and olfaction, which we consistently observe at the periphery, within the brain, as well as during larval development.

Personnel flux and workplace anxiety: Personal and interpersonal consequences of understaffing in UK ultrasound departments.

Introduction: By 2013, the UK government's Migration Advisory Committee had determined sonography to be a formal shortage speciality, and understaffing remains a key concern for research in the domain. This paper, emergent of a qualitative study funded by Health Education North West, explores unit managers' perspectives on the present state of UK ultrasound. The focus herein falls upon the personal and interpersonal consequences of this circumstance for individuals working in specific understaffed departments.

Charting the practical dimensions of understaffing from a managerial perspective: The everyday shape of the UK's sonographer shortage.

Introduction: Across the last two decades, ultrasound services in many healthcare sectors have become increasingly pressurised as a consequence of upsurging demand and difficulties in recruiting viable clinicians. Indeed by 2013, the UK government's Migration Advisory Committee had listed sonography as an official 'shortage specialty'. Comparatively little research has to date, however, explored the impacts of this situation upon the departments themselves, and the individuals working therein.

Women's experiences of cancer-related cognitive impairment, its impact on daily life and care received for it following treatment for breast cancer.

Several women who undergo treatment for breast cancer experience cancer-related cognitive impairment [CRCI] commonly known as 'Chemobrain' or 'Chemofog'. However, many oncologists and other cancer clinicians are unaware of the high prevalence and severity of these symptoms. Few qualitative studies on the topic provide a comprehensive description of this phenomenon.

Proceedings of the 2017 Viral Clearance Symposium, Session 1.2: Upstream Mitigation, Part 2-Virus Barrier Filter and HTST.

Various mammalian cell lines are used as substrates for drug production without safety issues concerning viral contamination. However, viral contamination events in good manufacturing practice (GMP) cell culture processes, while rare, do sometimes occur. When contamination happens, it can result in serious consequences, including supply risk of life-saving drugs and substantial financial loss.

Proceedings of the 2017 Viral Clearance Symposium, Session 1.1: Upstream Mitigation, Part 1-Cell Bank and Bulk Harvest Testing.

Monoclonal antibodies (mAbs) are typically produced using mammalian cell lines, which are known to express endogenous retrovirus-like particles (RVLPs) and also have the potential to be infected by viruses. This session focused on the detection and measurement of these viruses and RVLPs. In the first session, it was shown that next-generation sequencing (NGS) can detect, with a similar sensitivity as polymerase chain reaction (PCR), viruses in cells without a priori knowledge of the specific virus and more importantly that a specific NGS approach can decipher whether the signal corresponds to a replicating virus.

Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome.

Background: Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n.

Mechanistic modeling of the loss of protein sieving due to internal and external fouling of microfilters.

Fed-batch and perfusion cell culture processes used to produce therapeutic proteins can use microfilters for product harvest. In this study, new explicit mathematical models of sieving loss due to internal membrane fouling, external membrane fouling, or a combination of the two were generated. The models accounted for membrane and cake structures and hindered solute transport.

Improved Lysosomal Trafficking Can Modulate the Potency of Antibody Drug Conjugates.

Antibody drug conjugates (ADCs) provide an efficacious and relatively safe means by which chemotherapeutic agents can be specifically targeted to cancer cells. In addition to the selection of antibody targets, ADCs offer a modular design that allows selection of ADC characteristics through the choice of linker chemistries, toxins, and conjugation sites. Many studies have indicated that release of toxins bound to antibodies via noncleavable linker chemistries relies on the internalization and intracellular trafficking of the ADC.

The role of more than 40 years of improvement in protein A chromatography in the growth of the therapeutic antibody industry.

Protein A chromatography has been used as the mAb capture step in the majority of FDA submissions. In this study, the performance of protein A chromatography, as indicated by capacity, operational flow rate, and productivity (rate of mAb production per liter of resin) was examined over its full history to gain insights into the reasons for its consistent use. Protein A productivity and capacity have increased 4.