BIOLOGICALS 为人类和兽医学中使用的生物制品各个方面的新闻、辩论和原创研究提供了一个现代和多学科的国际论坛。该杂志发表与源自新颖和成熟生物技术的生物的开发、生产、质量控制和标准化相关的原始论文、评论和信件。制作特刊以反映国际上特别感兴趣和关注的主题。欢迎三种类型的论文：原创研究报告、短论文和评论文章。该杂志还将发表评论和致编辑的信件、书评、会议报告和监管问题信息。

Biologicals is a modern international forum that covers all aspects of biological products used in human and veterinary medicine, including news, debates, and original research. The journal publishes original papers, reviews, and letters related to the development, production, quality control, and standardization of biologics derived from both novel and established biotechnologies. Special issues are produced to reflect topics of particular interest and concern internationally. We welcome three types of submissions: original research articles, short papers, and review articles. The journal also includes commentaries, letters to the editor, book reviews, conference reports, and information on regulatory issues.

《Biologicals》是一个现代化的国际论坛，涵盖人类和兽医学中使用的生物制品的各个方面，包括新闻、辩论和原创研究。该杂志发表与新兴和成熟生物技术相关的生物的开发、生产、质量控制和标准化的原创论文、评论和信件。我们还会制作特刊，反映国际上特别感兴趣和关注的主题。欢迎提交三种类型的论文：原创研究报告、短论文和评论文章。此外，杂志还会刊登评论、致编辑的信件、书评、会议报告以及监管问题的信息。

Biologicals

This study focuses on the detection of chicken anemia virus (CAV) and avian gyrovirus 2 (AGV2) genomes in commercially available poultry vaccines. A duplex quantitative real-time PCR (dqPCR), capable of identifying genomes of both viruses in a single assay, was employed to determine the viral loads of these agents in commercially available vaccines. Thirty five vaccines from eight manufacturers (32 prepared with live and 3 with inactivated microorganisms) were examined. Genomes of CAV were detected as contaminants in 6/32 live vaccines and in 1/3 inactivated vaccines. The CAV genome loads ranged from 6.4 to 173.4 per 50 ng of vaccine DNA (equivalent to 0.07 to 0.69 genome copies per dose of vaccine). Likewise, AGV2 genomes were detected in 9/32 live vaccines, with viral loads ranging from 93 to 156,187 per 50 ng of vaccine DNA (equivalent to 0.28-9176 genome copies per dose of vaccine). These findings provide evidence for the possibility of contamination of poultry vaccines with CAV and AGV2 and they also emphasize the need of searching for these agents in vaccines in order to ensure the absence of such potential contaminants.

Ana Paula Muterle Varela

Helton Fernandes Dos Santos

Samuel Paulo Cibulski

Camila Mengue Scheffer

Candice Schmidt

Francisco Esmaile Sales Lima

Alessandra D'Avila Silva

Paulo Augusto Esteves

Ana Cláudia Franco

Paulo Michel Roehe

Biologicals : journal of the International Association of Biological Standardization

Chicken anemia virus and avian gyrovirus 2 as contaminants in poultry vaccines.

禽疫苗中的污染源：鸡贫血病毒与禽圆环病毒2型。

Quality by design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody (MAb). This chapter describes the tools used for the characterization and validation of MAb manufacturing process under the QbD paradigm. This comprises risk assessments for the identification of potential Critical Process Parameters (pCPPs), statistically designed experimental studies as well as studies assessing the linkage of the unit operations. Outcome of the studies is the classification of process parameters according to their criticality and the definition of appropriate acceptable ranges of operation. The process and product knowledge gained in these studies can lead to the approval of a Design Space. Additionally, the information gained in these studies are used to define the 'impact' which the manufacturing process can have on the variability of the CQAs, which is used to define the testing and monitoring strategy.

Christian Hakemeyer

Nathan McKnight

Rick St John

Steven Meier

Melody Trexler-Schmidt

Brian Kelley

Frank Zettl

Robert Puskeiler

Annika Kleinjans

Fred Lim

Christine Wurth

Process characterization and Design Space definition.

过程表征与设计空间定义。

Replacement of the potency tests for diphtheria vaccines is a high priority for the international initiative to reduce, refine, and replace animal use in vaccine testing. Diphtheria toxoid containing vaccine products marketed in the US currently require potency testing by the United States Public Health Service (USPHS) test, which includes an in vivo passive protection test with a diphtheria toxin challenge. Here we describe an in vitro Diphtheria Vero Cell (DVC) assay which combines the immunization approach from the USPHS test and the use of a cell based neutralization assay for serological testing of vaccine potency. The DVC assay reduces the overall number of animals used compared to other serological potency tests and eliminates the in vivo toxin challenge used in the US test. The DVC assay can be used to test vaccine products with a low or high diphtheria toxoid dose. It has been optimized and validated for use in a quality control testing environment. Results demonstrate similar sera antibody unitage as well as agreement between the serum neutralization values determined using the USPHS test and the DVC assay and thus support the use of the DVC assay for routine and stability testing for diphtheria toxoid containing vaccine products.

Marin Ming

Judy Caterini

Luciano Ettorre

Mei Tang

Martha Schreiber

Danielle Salha

Lucy Gisonni-Lex

Replacing the in vivo toxin challenge test with an in vitro assay for assessment of potency for diphtheria toxoid containing vaccines.

用体外试验替代体内毒素挑战试验评估含白喉类毒素疫苗的效力。

The need for an accurate, fast and reliable analysis of carbohydrate test is crucial for numerous biological processes. In that sense, anthrone-sulfuric acid assay is one of the most efficient quantification techniques successfully applied to carbohydrate determination. In this paper, a sensitive and accurate anthrone-sulfuric acid microplate assay was developed and validated for the quantitative estimation of yeast carbohydrates in the production of hepatitis B virus surface antigen, and the main component of the recombinant vaccine HEBERBIOVAC HB. A response surface methodology was applied to design and optimize the assay in order to maximize the differences on the expected effect and to minimize the number of experiments. The proposed method was linear over the concentration range from 10 to 120 microg/mL for glucose, with values for the coefficient of determination >0.99. Intra- and inter-assay variation coefficient ranged between 0.45-4.79% and 2.48-8.94%, respectively. The Student t-test used in the interference study, revealed good parallelism among curves (T(obs)< or =T(0.05)), which indicates the lack of interference in the working range. Yields obtained in accuracy test for two concentration levels varied between 90 and 105%, confirming the assay's reliability. In conclusion, the validated method, which has successfully been used for the process control monitoring of several samples generated from the production of hepatitis B vaccine, allows the quality and purity of the final product.

Alberto Leyva

Anelis Quintana

Meily Sánchez

Elias N Rodríguez

José Cremata

Julio C Sánchez

Rapid and sensitive anthrone-sulfuric acid assay in microplate format to quantify carbohydrate in biopharmaceutical products: method development and validation.

快速灵敏的蒽酮-硫酸微孔板法测定生物制药产品中碳水化合物含量：方法开发与验证。

Spodoptera frugiperda (Sf) cell lines are used to produce several biologicals for human and veterinary use. Recently, it was discovered that all tested Sf cell lines are persistently infected with Sf-rhabdovirus, a novel rhabdovirus. As part of an effort to search for other adventitious viruses, we searched the Sf cell genome and transcriptome for sequences related to Sf-rhabdovirus. To our surprise, we found intact Sf-rhabdovirus N- and P-like ORFs, and partial Sf-rhabdovirus G- and L-like ORFs. The transcribed and genomic sequences matched, indicating the transcripts were derived from the genomic sequences. These appear to be endogenous viral elements (EVEs), which result from the integration of partial viral genetic material into the host cell genome. It is theoretically impossible for the Sf-rhabdovirus-like EVEs to produce infectious virus particles as 1) they are disseminated across 4 genomic loci, 2) the G and L ORFs are incomplete, and 3) the M ORF is missing. Our finding of transcribed virus-like sequences in Sf cells underscores that MPS-based searches for adventitious viruses in cell substrates used to manufacture biologics should take into account both genomic and transcribed sequences to facilitate the identification of transcribed EVE's, and to avoid false positive detection of replication-competent adventitious viruses.

Christoph Geisler

Donald L. Jarvis

Rhabdovirus-like endogenous viral elements in the genome of Spodoptera frugiperda insect cells are actively transcribed: Implications for adventitious virus detection

草地贪夜蛾昆虫细胞基因组中的杆状病毒样内源性病毒元件具有活跃转录活性：对意外病毒检测的启示

Elliot Lilley

Richard Isbrucker

Anthony Holmes

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Reports from a series of NC3Rs stakeholder workshops

将3R方法整合到世卫组织生物制品批量释放检测指南中：来自NC3Rs一系列利益相关者研讨会的报告

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Summary of NC3Rs final report to WHO Expert Committee for Biological Standardisation

将3R方法整合到世界卫生组织生物制品批签发测试指南中：NC3Rs向世界卫生组织生物标准化专家委员会提交的最终报告摘要

Endotoxin masking poses a potential risk to patient safety by rendering endotoxin undetectable. While research often focuses on international endotoxin standards (RSE), the effects of LPS mutants on Low Endotoxin Recovery (LER) are poorly understood. Our study investigated S. minnesota and E. coli mutants with incomplete O-antigen chains (rough LPS) using Limulus amebocyte lysate (LAL), recombinant Factor C (rFC) and the monocyte activation test (MAT). All tested methods detected the mutants, with variations in activity observed. Measurements over time in a common drug formulation (10 mM sodium citrate and 0.05 % (w/v) polysorbate 20) showed different masking kinetics for the mutants using different methods. We were able to show that LAL and rFC have comparable kinetics, whereas MAT showed improved recovery of masked endotoxin. The study showed that the mutation of LPS have an effect on masking, independent of the assay system. We propose that polysaccharide length affects masking susceptibility, with lower hydrophilic/hydrophobic ratios caused by the shortened polysaccharide chain (rough LPS) reducing masking. In addition, the stronger negative charge of the rough mutants increases cation affinity and is suggested to contribute to the stabilisation of supramolecular structures, making the rough mutants less susceptible to masking than the smooth mutants.

Luisa Burgmaier

Stefan Pölt

Meltem Avci-Adali

Johannes Reich

The impact of LPS mutants on endotoxin masking in different detection systems

不同检测系统中LPS突变体对内毒素掩盖作用的影响

Su Kyoung Seong

Hyun-Jung Koh

Hyun Jeong Kim

Yoojung Yi

Chan Woong Choi

In Soo Shin

Youngju Choi

Young Hoon Kim

A collaborative study to establish the second national standard for antithrombin concentrate in Korea

Abbreviation	Biologicals.
Journal Impact	1.42
Quartiles(Global)	PHARMACOLOGY & PHARMACY(Q3)

ISSN	1045-1056, 1095-8320
h-index	66

Publication Information	Publisher: Academic Press，Publishing cycle: Quarterly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1990，Proportion of original research papers: 96.88%，Self Citation Rate:13.30%， Gold OA Rate: 42.52%
Average review cycle	网友分享经验：较慢,6-12周来源Elsevier官网：平均10.2周
Average recruitment ratio	网友分享经验：较易

Biologicals

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