Biologicals最新文献

{"title":"Conference report WHO informal consultation on the draft WHO Guideline on the phasing out of animal tests for the quality control of biological products","authors":"Ian Feavers ,&nbsp;Dianliang Lei ,&nbsp;Catherine Milne ,&nbsp;Ivana Knezevic ,&nbsp;Tiequn Zhou ,&nbsp;Eunkyung Kim","doi":"10.1016/j.biologicals.2025.101862","DOIUrl":"10.1016/j.biologicals.2025.101862","url":null,"abstract":"<div><div>Animal testing has long supported the development and quality control of biotherapeutics and vaccines by ensuring safety and efficacy. However, its variability and time-consuming nature can delay product availability. Advances in non-animal technologies, guided by the 3Rs principles, have led to more efficient and scientifically robust alternatives. Recognizing the limitations of animal assays, WHO encourages their replacement when scientifically justified and has drafted a Guideline on phasing out animal tests in biological product quality control. Following public consultation, an informal meeting at WHO Headquarters brought together regulators, industry representatives, and other stakeholders to review the draft. The Guideline was developed based on ECBS recommendations and a review of existing WHO documents. Participants proposed improvements, including a revised title, to better emphasize the scientific rationale for replacing animal-based tests used in quality control scheme. These updates aim to support finalization of the document for a second public consultation and ECBS adoption.</div></div>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"92 ","pages":"Article 101862"},"PeriodicalIF":1.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new Japanese regulatory perspective regarding the indication extrapolation between approved intravenous immunoglobulins (IVIg) products based on comparability assessments of quality attributes","authors":"Takashi Kameda ,&nbsp;Kazuki Nagashima ,&nbsp;Shun Masuta ,&nbsp;Teruhide Yamaguchi ,&nbsp;Michihiro Ogawa","doi":"10.1016/j.biologicals.2025.101860","DOIUrl":"10.1016/j.biologicals.2025.101860","url":null,"abstract":"<div><div>Intravenous immunoglobulin (IVIg) product is a pooled human plasma-derived IgG medicinal product indicated for various immunodeficiency and autoimmune diseases. These indications have essentially been approved in Japan based on clinical evaluations of each product, but a harmonization or standardization of IVIg products would be helpful. We introduce a new Japanese regulatory perspective on the extrapolation of indications for approved IVIg products from a reference product composed of intact IgG (chemically unmodified full-length IgG) based on the consideration of the mode of action (MOA), a quality-comparability analysis, and the post-marketing clinical track record's re-examination regarding the products' efficacy and safety.</div></div>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"92 ","pages":"Article 101860"},"PeriodicalIF":1.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of the fourth conference on next-generation sequencing (NGS) for adventitious virus detection in biologics for humans and animals: Validation and implementation of NGS","authors":"Arifa S. Khan ,&nbsp;Laurent Mallet ,&nbsp;Johannes Blümel ,&nbsp;Noémie Deneyer ,&nbsp;Sigrid De C.J. Keersmaecker ,&nbsp;Blandine de Saint-Vis ,&nbsp;Ivana Knezevic ,&nbsp;Carine Logvinoff ,&nbsp;Marie Murphy ,&nbsp;Siemon H.S. Ng ,&nbsp;Yoji Sato ,&nbsp;Michael Wall ,&nbsp;Ana Goios ,&nbsp;Pieter Neels","doi":"10.1016/j.biologicals.2025.101859","DOIUrl":"10.1016/j.biologicals.2025.101859","url":null,"abstract":"<div><div>This report is a summary of the 4th Conference on NGS for Adventitious Virus Detection, which took place on December 4–5, 2024, in Frankfurt, Germany, and was sponsored by the International Alliance for Biological Standardization (IABS), and co-chaired by the U.S. Food and Drug Administration (FDA) and the European Directorate for the Quality of Medicines &amp; HealthCare (EDQM). The increased interest in using NGS for adventitious virus detection follows its recent introduction in the ICH Q5A (R2) guideline and the new EDQM/European Pharmacopoeia general chapter 2.6.41. Key conference objectives included evaluating NGS validation and implementation, addressing regional challenges, and discussing regulatory acceptance as an alternative method to the conventional assays. The conference fostered networking between early and established NGS users and emphasized the Advanced Virus Detection Technologies Working Group as a key learning hub for NGS applications. Discussions focused on method validation requirements and the need for defining a specific limit of detection. Participants shared updates on scientific developments and regulatory submissions. A general consensus was reached on the readiness of NGS to replace the <em>in vivo</em> adventitious virus detection assays and PCR assays, and to supplement or replace the <em>in vitro</em> cell-based assays, based on a suitable validation package.</div></div>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"92 ","pages":"Article 101859"},"PeriodicalIF":1.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Effect of biomolecules derived from human platelet-rich plasma on the ex vivo expansion of human adipose-derived mesenchymal stem cells for clinical applications\" [Biologicals 75 (2022) 37-48].","authors":"Silvia M Becerra-Bayona, Víctor Alfonso Solarte, Juan Dario Alviar Rueda, Claudia L Sossa, Martha L Arango-Rodríguez","doi":"10.1016/j.biologicals.2025.101861","DOIUrl":"https://doi.org/10.1016/j.biologicals.2025.101861","url":null,"abstract":"","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":" ","pages":"101861"},"PeriodicalIF":1.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Vaccination and surveillance for high pathogenicity avian influenza in poultry-current situation and perspectives\" [Biologicals 91 (2025) 101840].","authors":"Nancy C Sajjadi, Celia Abolnik, Francesca Baldinelli, Ian Brown, Angus Cameron, J J de Wit, Madhur Dhingra, Olivier Espeisse, Jean Luc Guerrin, Timm Harder, Jeremy Ho, Tze-Hoong Chua, Khaled Hussein, Nicholas Lyons, Isabella Monne, Yukitake Okamuro, Damian Tago Pacheco, Gounalan Pavade, Nicolas Poncon, Teguh Yodiantara Prajitno, Jose Gonzales Rojas, Gonzalo Simone, David Swayne, Arjan Stegeman","doi":"10.1016/j.biologicals.2025.101858","DOIUrl":"https://doi.org/10.1016/j.biologicals.2025.101858","url":null,"abstract":"","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":" ","pages":"101858"},"PeriodicalIF":1.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pharmacokinetics and safety comparison of Zamerovimab and Mazorelvimab monoclonal antibodies vs. HRIG in category III rabies post-exposure prophylaxis: a stratified analysis by wound characteristics","authors":"Xiaoqiang Liu ,&nbsp;Yongxian Zha ,&nbsp;Zhengxiong Wang ,&nbsp;Ya Jiang ,&nbsp;Xiangyu Zhang ,&nbsp;Jiangshu Guo ,&nbsp;Jingyu Li ,&nbsp;Qingchao Zhang ,&nbsp;Eric Tsao","doi":"10.1016/j.biologicals.2025.101852","DOIUrl":"10.1016/j.biologicals.2025.101852","url":null,"abstract":"<div><h3>Objective</h3><div>To compare rabies virus neutralizing antibody (RVNA) kinetics and safety profiles of Zamerovimab and Mazorelvimab monoclonal antibodies (mAbs) versus human rabies immunoglobulin (HRIG) in Category III rabies-exposed patients with heterogeneous wound characteristics.</div></div><div><h3>Methods</h3><div>In this randomized, double-blind, phase III trial, 1000 participants with Category III exposure were stratified into single-wound (n = 735) and multi-wound (n = 265) subgroups. Subjects received either 0.3 mg/kg mAbs (n = 750) or 20 IU/kg HRIG (n = 250) on Day 0, followed by Essen regimen vaccination. RVNA levels were quantified by Rapid Fluorescent Foci Inhibition Test (RFFIT) at 0, 3, 7, 14, and 42 days. Primary endpoints included RVNA geometric mean concentration (GMC), seroconversion rate (RVNA ≥0.5 IU/mL) and incidence of adverse events (AEs).</div></div><div><h3>Results</h3><div>The mAbs-treated subgroups exhibited significantly higher RVNA GMCs than HRIG at early timepoints (e.g., Day 3, single-wound subgroups: 4.552 vs. 0.297 IU/mL; multi-wound subgroups: 4.06 vs. 0.305 IU/mL), achieving over 99.8 % seroconversion by Day 3. The mAbs showed similar or higher RVNA seroconversion rates in multi-wound subgroup compared to single-wound subgroup, while HRIG exhibited lower serum positivity rates. AEs were more common in HRIG recipients across both single-wound and multi-wound subgroups (mAbs: 41.9 %, 42.4 %; HRIG: 55.3 %, 54.8 %). Treatment-related AEs were also higher in HRIG groups (mAbs: 26.3 %, 27.1 %; HRIG: 39.9 %, 48.4 %), particularly in multi-wound subgroups. Most local and systemic AEs were mild to moderate in severity. No suspected rabies cases or deaths occurred through the 365-day study period, and no participants withdrew due to AEs.</div></div><div><h3>Conclusion</h3><div>Zamerovimab and Mazorelvimab achieves earlier and higher RVNA titers than HRIG across diverse wound types, with comparable safety. In multi-wound exposures, mAbs therapy demonstrates superior RVNA seroconversion rate and reduced reactogenicity compared to HRIG, providing robust evidence for its preferential use in high-risk rabies exposures.</div></div><div><h3>Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> #NCT04644484.</div></div>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"92 ","pages":"Article 101852"},"PeriodicalIF":1.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of 1^st WHO anti-malaria reference reagent for competition ELISA harmonisation and development of ADAMSEL analytical platform.","authors":"Bhagwati Khatri, Peggy Riese, Hanna Shkarlet, Daniella Mortier, Helen McShane, Paul W Bowyer, Edmond Remarque","doi":"10.1016/j.biologicals.2025.101850","DOIUrl":"https://doi.org/10.1016/j.biologicals.2025.101850","url":null,"abstract":"<p><p>This study focuses on harmonising the competition ELISA (cELISA) assay for Plasmodium falciparum (P. falciparum), using the 1st WHO reference reagent for anti-malaria (P. falciparum) human reference serum (10/198). Antibody-mediated immune responses against the Apical Membrane Antigen 1 (AMA1) play a significant role in protection against malaria. However, the sequence diversity of AMA1 and cross-reactivity among variants pose challenges in assessing antibody responses. To address this, the cELISA assay was selected to examine cross-reactive antibody responses against different variants. The harmonisation process for cELISA was performed in three laboratories. The 10/198 served as an internal standard for the calculation of IgG concentrations in the cELISA using ADAMSEL software. Additionally, a novel semi-automated analytical tool was developed in the R-statistics environment. This tool is freely available for download and streamlines generating results while minimising human error. This study demonstrated the effectiveness of the 1st WHO reference reagent as a standard for cELISA. Additionally, the ADAMSEL software and R-platform tool provide a user-friendly and accessible tool for the analysis of cELISA data. Its automation capabilities improve efficiency and ensure global accessibility at no cost, benefitting laboratories with limited resources.</p>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":" ","pages":"101850"},"PeriodicalIF":1.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aims and Scope/Editorial Board/Publishing Details","authors":"","doi":"10.1016/S1045-1056(25)00045-4","DOIUrl":"10.1016/S1045-1056(25)00045-4","url":null,"abstract":"","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"91 ","pages":"Article 101854"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of the Clostridium perfringens quadruple point mutant epsilon toxin.","authors":"Roopa Anandamurthy Hemanth, Mandrira Ramakrishna Namrutha, Suresh Bindu, Awadhesh Prajapati, Revanaiah Yogisharadhya, Nagappa Karabasanavar, Nihar Nalini Mohanty, Mohammed Mudassar Chanda, Sathish Bhadravati Shivachandra","doi":"10.1016/j.biologicals.2025.101851","DOIUrl":"10.1016/j.biologicals.2025.101851","url":null,"abstract":"<p><p>Epsilon toxin (Etx) is one of the exotoxins (∼18) secreted by the spore-forming bacterium Clostridium perfringens, which plays a major role in the pathogenesis of enterotoxaemia (ET) leading to sudden death in affected small ruminants. A chemically inactivated toxoid of Etx has been used as a vaccine to control ET in animals. Non-toxic Etx-mutant proteins could potentially be used in the development of efficient immuno-assays and alternative subunit vaccine formulations for the control of ET in animals. In this study, a codon-optimized synthetic quadruple point mutant (Y30A, H106P, H149A, Y196A) of the etx gene of Clostridium perfringens was expressed in Escherichia coli to produce a recombinant protein (331 aa, ∼36 kDa). The rEtx-mutant protein was purified under both non-denaturing and denaturing-renatured conditions using a single-step affinity chromatography and was functionally characterized in vivo and in vitro. A quadruple point mutant of Etx was structurally similar to the wildtype Etx. The rEtx protein was activated by trypsin, and had no toxicity when tested using in vitro and in vivo models. Furthermore, the protein elicited antigen-specific antibodies in mice, rabbit, and guinea pigs. In an indirect ELISA, the rEtx-mutant protein was able to detect specific antibodies in sera from ET-vaccinated sheep.</p>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"91 ","pages":"101851"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The past, present and future of blood plasma fractionation","authors":"John Curling ,&nbsp;Albert Farrugia ,&nbsp;Leni von Bonsdorff","doi":"10.1016/j.biologicals.2025.101849","DOIUrl":"10.1016/j.biologicals.2025.101849","url":null,"abstract":"<div><div>Edwin Cohn, appointed to the Harvard Medical School in 1920, was commissioned by the United States military in 1940 to develop a stable albumin solution to treat blood/plasma loss from battlefield injury. Albumin was first produced at the Harvard pilot plant using Cohn's five variable, ethanol precipitation process which was rapidly transferred to private industry for industrial manufacture. For the past decades IgG has been used to treat multiple conditions and has become the industry driver whilst albumin is now a low-price commodity. The development of purification techniques, particularly chromatography, spurred the manufacture of coagulation factors for haemophilia and other proteins from Cohn fractions, leading to the current, unique roster of multiple, essential, plasma-derived medicines. The major cost in fractionation is for plasma, making recombinant and other non-factor alternatives a challenge for the industry. Plasma-derived haemophilia therapies are largely redundant in Western economies, although other products, including prothrombin complex, alpha-1 anti-trypsin, fibrin sealant, provide essential treatments. The established industry is also challenged by potential alternatives to IgG. Despite the plethora of alternative manufacturing technologies, Cohn fractionation in combination with “upstream” harvesting of other proteins through other technologies and “downstream processes” which incorporate unit operations for virus safety is the global industry standard.</div></div>","PeriodicalId":55369,"journal":{"name":"Biologicals","volume":"91 ","pages":"Article 101849"},"PeriodicalIF":1.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}