The importance of World Health Organization international reference standards in the product life cycle of biosimilars.

Technological advances in analytics, as well as scientific and regulatory knowledge and experience gained from biosimilar development/approvals over the last decade, enabled the World Health Organization (WHO) in 2022 to revise its guidelines on the evaluation of biosimilars. Among the revisions, there is more reliance on analytical and functional aspects to prove similarity (and likely fewer clinical requirements). WHO international reference standards for biosimilars provide additional confidence to regulators looking for evidence- and data-based regulatory convergence in scientific and technical measures of quality attributes.

Disparities in donor heart acceptance between the USA and Europe: clinical implications.

Background And Aims: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes.

Incorporating digitally derived endpoints within clinical development programs by leveraging prior work.

Digital health technologies (DHTs) enable remote data collection, support a patient-centric approach to drug development, and provide real-time data in real-world settings. With increasing use of DHTs in clinical care and development, we expect a growing body of evidence supporting use of DHTs to capture endpoint data in clinical trials. As the body of evidence grows, it will be critical to ensure that available prior work can be leveraged.

Report of the third conference on next-generation sequencing for adventitious virus detection in biologics for humans and animals.

Next-generation sequencing (NGS) has been proven to address some of the limitations of the current testing methods for adventitious virus detection in biologics. The International Alliance for Biological Standardization (IABS), the U.S.

Availability and use of Standards in vaccine development.

Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines' responses. Equally important are the standards needed to control the vaccine manufacturing processes.

An Analysis of the Influence of Surface Roughness and Clearance on the Dynamic Behavior of Deep Groove Ball Bearings Using Artificial Neural Networks.

The deep groove ball bearing is one of the most important components of the rotary motion system and is the research subject in this paper. After factory assembly, new ball bearings need to pass quality control. The conventional approach relies on measuring the vibration amplitudes for each unit and sorting them into classes according to the vibration level.

Recurrent HeartMate 3 Right Ventricular Assist Device Stoppages in a Biventricular Assist Device Carrier.

A 44-year-old female patient with chemotherapy-induced cardiomyopathy presented with acute cardiogenic shock requiring ECMO support. Multiple failed weaning trials from temporary mechanical circulatory assistance prompted a transition to staged durable biventricular support. Her course was complicated with recurrent RVAD stoppages.

Three-month outcomes after the implantation of two HeartMate 3 devices in total artificial heart configuration.

Background: Total artificial heart (TAH) implantation is a rarely performed procedure. Contrarily, left ventricular assist device (VAD) implantation is rather common in many centers. As transplantation is quantitatively limited cardiac replacement with artificial hearts is a viable alternative in the treatment of severe biventricular heart failure.

WHO guidelines on biosimilars: Toward improved access to safe and effective products.

The World Health Assembly resolution on access to biotherapeutics in 2014 urges WHO and Member States to facilitate access to biotherapeutics while ensuring their quality, safety, and efficacy. While efforts to date have contributed to increased availability and better access to biotherapeutics, including biosimilars, huge gaps still remain, with lack of product access identified as a problem in many countries. A thorough review of the WHO guidelines on biosimilars issued in 2009 in view of technical developments, accumulated and emerging scientific evidence as well as experience in biosimilar evaluation since the release of the guidelines provided an opportunity to introduce greater flexibility and to reduce regulatory requirements in biosimilar development where possible.

Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project): protocol for an observational study.

Introduction: The growing worldwide prevalence of Alzheimer's disease (AD) and the lack of effective treatments pose a dire medical challenge. Sleep disruption is also prevalent in the ageing population and is increasingly recognised as a risk factor and an early sign of AD. The ALFASleep project aims to characterise sleep with subjective and objective measurements in cognitively unimpaired middle/late middle-aged adults at increased risk of AD who are phenotyped with fluid and neuroimaging AD biomarkers.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

On the use of wearable sensors as mobility biomarkers in the marketing authorization of new drugs: A regulatory perspective.

The loss of mobility is a common trait in multiple health conditions (e.g., Parkinson's disease) and is associated with reduced quality of life.

Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience.

The World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the ECBS considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence. The goal of this publication is to review the current clinical experience and scientific evidence and to provide an expert perspective for updating the WHO guidelines to provide more flexibility and clarity.

WHO informal consultation on revision of guidelines on evaluation of similar biotherapeutic products, virtual meeting, 30 June - 2 July 2021.

The WHO informal consultation was held to promote the revision of WHO guidelines on evaluation of similar biotherapeutic products (SBPs) adopted by the Expert Committee on Biological Standardization (ECBS) in 2009. It was agreed in the past consultations that the evaluation principles in the guidelines are still valid, but a review was recommended to provide more clarity and case-by-case flexibility. The opportunity was therefore taken to review the experience and identify areas where the current guidance could be more permissive without compromising its basic principles, and where additional explanation could be provided regarding the possibility of reducing the amount of data needed for regulatory approval.

Comparison of arthroscopy versus percutaneous radiofrequency thermal ablation for the management of intra- and juxta-articular elbow osteoid osteoma: case series and a literature review.

Background: Today, intra-articular and juxta-articular osteoid osteomas are treated with arthroscopy and radiofrequency thermal ablation. However, for the case of an elbow joint, arguments are made for the use of a minimally invasive technique to be the optimal choice. This study aims to analyse our experiences of arthroscopically treated elbow osteoid osteomas and to compare it with the published results of both techniques.

Transendocardial CD34 Cell Therapy Improves Local Mechanical Dyssynchrony in Patients With Nonischemic Dilated Cardiomyopathy.

We investigated the effects of cell therapy on local mechanical dyssynchrony (LMD) in patients with nonischemic dilated cardiomyopathy (NICM). We analyzed electromechanical data of 30 NICM patients undergoing CD34 cell transplantation. All patients underwent bone marrow stimulation; CD34 cells were collected by apheresis and injected transendocardially.

WHO informal consultation on regulatory considerations for evaluation of the quality, safety and efficacy of RNA-based prophylactic vaccines for infectious diseases, 20-22 April 2021.

This paper presents the key outcomes of the above WHO informal consultation with global stakeholders including regulatory authorities, vaccine developers and manufacturers, academia and other international health organizations and institutions involved in the development, evaluation and use of messenger RNA (mRNA) vaccines. The aim of the consultation was to further clarify the main principles to be presented in an upcoming WHO guidance document on the regulatory considerations in evaluating the quality, safety and efficacy of mRNA prophylactic vaccines for infectious diseases. This WHO guidance document is intended to facilitate global mRNA vaccine development and regulatory convergence in the assessment of such vaccines.

WHO International Standard for evaluation of the antibody response to COVID-19 vaccines: call for urgent action by the scientific community.

The first WHO International Standard and International Reference Panel for anti-SARS-CoV-2 immunoglobulin were established by the WHO Expert Committee on Biological Standardization in December, 2020. The WHO International Antibody Standards are intended to serve as global reference reagents, against which national reference preparations or secondary standards can be calibrated. Calibration will facilitate comparison of results of assays (eg, of the neutralising antibody response to candidate COVID-19 vaccines) conducted in different countries.

Soundtrack of life: An fMRI study.

Most people have a soundtrack of life, a set of special musical pieces closely linked to certain biographical experiences. Autobiographical memories (AM) and music listening (ML) involve complex mental processes ruled by differentiate brain networks. The aim of the paper was to determine the way both networks interact in linked occurrences.

Exploring food shopping behaviours through a study of Ottawa social media.

This study explored the important attributes of the local food retail environments that residents from Ottawa, Ontario, Canada, used in recommending where to purchase fresh produce, including fruits and vegetables, in the Ottawa area. Drawing upon an approach originating in marketing and consumer research, qualitative thematic analysis was used to analyze 79 discussions from three social media platforms that occurred between 2015 and 2018. We identified three patterns of conversations about food shopping, characterized by participants describing important factors of their local retail food environments that shaped their recommendations for different retail food establishments: 1) Pleasant represented discussions where having a pleasurable food shopping experience was the main discussion point.

Left Ventricular Pseudoaneurysm: Unexpected Finding in a Patient Who Presented With Bacterial Endophthalmitis.

A large left ventricular pseudoaneurysm was discovered in a patient who presented with bacterial endophthalmitis 1 year after medically treated mitral valve endocarditis. After medical therapy, the patient underwent cardiac surgery uneventfully. We present a rare finding of a pseudoaneurysm complicated with a very late ocular septic event.

First Metatarsophalangeal Joint Arthroscopy of 36 Consecutive Cases.

PURPOSE OF THE STUDY In this study, we retrospectively reviewed a consecutive case series of first metatarsophalangeal (MTP) joint arthroscopies performed in our department over a span of six years. This study aimed to evaluate the efficacy and safety of arthroscopic treatment for various first MTP joint pathologies. MATERIAL AND METHODS A total of 36 patients that underwent first MTP joint arthroscopy between January 2014 and December 2019 were reviewed.

A cautionary perspective regarding the isolation and serial propagation of SARS-CoV-2 in Vero cells.

An array of SARS-CoV-2 virus variants have been isolated, propagated and used in in vitro assays, in vivo animal studies and human clinical trials. Observations of working stocks of SARS-CoV-2 suggest that sequential propagation in Vero cells leads to critical changes in the region of the furin cleavage site, which significantly reduce the value of the working stock for critical research studies. Serially propagating SARS-CoV-2 in Vero E6 cells leads to rapid increases in genetic variants while propagation in other cell lines (e.