Harmonization of Vaccine Ligand Binding Assays Validation.

The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA, USA on April 1-5, 2019 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event - a full immersion week of bioanalysis, biomarkers, immunogenicity and gene therapy. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LCMS, hybrid LBA/LCMS, LBA cell-based/flow cytometry assays and qPCR approaches. This 2019 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2019 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers New Insights in Biomarker Assay Validation, Current & Effective Strategies for Critical Reagent Management, Flow Cytometry Validation in Drug Discovery & Development & CLSI H62, Interpretation of the 2019 FDA Immunogenicity Guidance and Gene Therapy Bioanalytical Challenges. Part 1 (Innovation in Small Molecules and Oligonucleotides & Mass Spectrometry Method Development Strategies for Large Molecule Bioanalysis) and Part 2 (Recommendations on the 2018 FDA BMV Guidance, 2019 ICH M10 BMV Draft Guideline and regulatory agencies' input on bioanalysis, biomarkers, immunogenicity and gene therapy) are published in volume 11of Bioanalysis, issues 22 and 23 (2019), respectively.

The 19th Workshop on Recent Issues in Bioanalysis (19th WRIB) took place in New Orleans, LA, USA on April 7-11, 2025. Over 1200 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 19th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on "Implementation Practice for the Newest ELN/LIMS Systems" and on "Vaccine Cell-Based/Functional & Molecular Assays as part of the harmonization of vaccine clinical assays global initiative" were the special features of the 19th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and Regulatory Agency experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2025 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2025 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers in the Part 1A the recommendations on Mass Spectrometry Assays and Regulated Bioanalysis/BMV and in Part 1B the Regulatory Inputs on these topics. Part 2 (Biomarkers/BAV, IVD/CDx, Ligand-Binding Assays and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 18 of Bioanalysis, issues 1 and 2 (2026), respectively.

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on 19-23June2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication (Part 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 2) discusses the recommendations for Hybrid LBA/LCMS and regulatory inputs from major global health authorities. Parts 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) have been published in the Bioanalysis journal, issues 22 and 23, respectively.

Background Over the last year, the bioanalytical community strongly expressed their need for international harmonization of bioanalytical guidances through numerous international meetings and publications, and this need was acknowledged by several regulatory agencies [1–5]. Following the 4th Calibration and Validation Group (CVG) Workshop on Regulated Bioana lysis hosted in Montreal (April 2010), a unanimous consensus was reached for the global bioanalytical community to identify non-prescriptive, s ciencebased language that could form the basis of a proposed guidance document on bioana lysis [6]. Ideally, such guidance language would describe the rationale behind each bioanalytical requirement and would be presented for consideration by agencies and industry worldwide. A recent concrete action taken towards such global harmonization of bioanalytical guidances was the creation of the Global Bioana lysis Consortium (GBC). Drawing from representatives of scientific associations with involvement in regulated bioana lysis across the globe, the objective of the GBC is to merge existing or emerging bioanalytical guidances and create a unified document that can be presented to the regulatory authorities in various countries and regions. The development of the GBC is currently in process, with the intention to present plans and updates at upcoming bioanalytical meetings and to seek input from the scientists conducting bioana lysis [7]. At the 4th CVG Bioana lysis Workshop in Montreal, Canada, several Contract Research Organizations (CROs) highlighted the importance of having a strong and cohesive CRO contribution to the global harmonization process. Having CROs, academic laboratories and pharma ceutical industries appropriately represented was viewed as critical to identifying optimum language. Consequently, the proposal to build a Global CRO Council (GCC) arose, designed to be a distinct group consisting exclusively of bioanalytical CRO members conducting r egulated bioana lysis business. To initiate creation of the GCC, a special closed forum was held in Montreal on 14 September 2010, where 41 executive representatives from 32 bioanalytical CROs were present to discuss scientific harmonization issues and the institution of the GCC. This first CRO Formation of a Global Contract Research Organization Council for Bioana lysis

Biomarker measurements: how far have we come and where are we heading?

The 2014 8th Workshop on Recent Issues in Bioanalysis (8thWRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three partsfor editorial reasons. This publication (Part 3) covers the recommendations for Large molecules bioanalysis using LBA and Immunogenicity. Part 1 (Small molecules bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input) were published in the Bioanalysis issues 6(22) and 6(23), respectively.

Consensus guidelines for the validation of qRT-PCR assays in clinical research by the CardioRNA consortium

Validation of a Sensitive Flow Cytometry Assay to Assess Minimal Residual Disease of Multiple Myeloma Cells in Apheresis Product

This chapter describes the process of validating in-house molecular assays although the principles described are equally relevant to all diagnostic assays. The best practice principles described below are based on the In Vitro Diagnostic Medical Devices Directive (IVDD) and associated documentation. Although compliance with these regulations is not required for diagnostic reagents used on animals, the principles are equally relevant to validation of all diagnostic assays, whatever their purpose.

To assess the correlation between the clinical and molecular assays in identify early and robust prostate cancer detection. Early detection, management of cancer and decision about the disease are important for beneficial treatment of prostate cancer. We used a computerized search of the Medline/ PubMed databases with the key words prostate cancer, biomarker, and early detection. Clinical management of cancer is facilitated by a conventional test such as prostate-specific antigen and digital rectal exam for application in clinical practice. Although these tests have significantly reduced the mortality with prostate cancer, but have some drawbacks and false positive rate. Fortunately, there are strong correlations between the clinical and molecular assays in identifying early and robust cancer detection, because molecular assays are less invasive and reliable. The use of genetic markers has the potential to providing useful prognostic or predictive information into clinically useful diagnostic tests to improve clinical decision-making and enhance therapeutic success. Different clinical and molecular assays are for detecting prostate cancer and use the biomarkers as potential tumor markers could be a useful predictor in the screening and monitoring to avoid over treatment prostate cancer.

Next-generation sequencing (NGS) provides a powerful high-throughput approach to identify and track B-cell immunoglobulin (IG) heavy chain clonality and to assess somatic hypermutation status in a massively parallel manner. The NGS-based clonality/SHM testing demonstrated superior performance over the conventional capillary electrophoresis (CE) methods in characterization of B-cell neoplasms. However, its broad utilization in clinical diagnostics requires extensive validation of assays as well as standardization of data interpretation. We present here an NGS assay designed and validated specifically for IG clonality/SHM characterization of B-cell malignancies. The assay was designed to simultaneously target the Leader, FR1, FR2, and FR3 regions of the IGH gene to identify clonal IGH VH-JH rearrangement as well as the IGK gene to identify clonal IGK VK-JK, VK-Kde, and INTR-Kde rearrangement. The validation was performed to assess assay accuracy, specificity, sensitivity, repeatability, and reproducibility, with both pre-characterized reference controls and prospectively collected clinic peripheral blood and bone marrow aspirate specimen included. Triplicates were included and testing was performed at different times and by different operators to assess the assay precision. Over 60 clinic peripheral blood and bone marrow aspirate specimens were collected, including patients with B-cell malignancies such as CLL, B-ALL, and DLBCL as well as heathy donors, processed within 7 days for DNA extraction, and assessed by the NGS assay for IGH clonality and SHM assessment. Assay sensitivity as low as 2.5% for baseline clonality and as low as 0.001% for tracking MRD were observed. Near-perfect assay specificity and precision were observed at these sensitivity levels. The validated NGS assay was further qualified by ERIC (the European Research Initiative on CLL) with a certificate granted to standardize the data interpretation of this assay for testing in chronic lymphocytic leukemia. In conclusion, a NGS IG clonality/SHM assay was analytically and clinically validated under medical oversight, with a demonstrated rigor of the test by its high sensitivity/specificity and robust reproducibility. The clinical diagnostic testing results with this assay is interpreted in accordance with ERIC standards for reliable clinical reporting. Citation Format: Xin-Xing Tan, Tricia Peters, Meredith Berry, Kristyn Jeter, Brigitte Lovell, Victor Venegas, Yanglong Mou, Brad Thomas, Vincent Funari, Josette William. Validation of a next generation sequencing clinical assay for detection of immunoglobulin heavy chain clonality and somatic hypermutation in chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2778.

Here we describe reference materials for measurable residual disease (MRD) assay design and validation as well as initial data from testing. The analytical validation of liquid biopsy-based assays that attempt to monitor for the disappearance and reemergence of cancer can be challenging due to the need for reference materials that allow for the assessment of sensitivity and specificity at variant allele frequencies (VAFs) that can be over an order of magnitude below those that can be detected reliably by typical circulating tumor DNA (ctDNA) assays. At such low VAFs, a given plasma sample may only contain limited somatic variants - and only at a few copies - which is why some MRD assays focus on monitoring only patient-specific somatic variants and do not analyze other parts of the genome. However, this also means that validation should include the steps needed to monitor patient-specific somatic variants. Therefore, we designed our reference materials for a tumor/normal workflow as a set of three components. First, one cell line is a source of normal DNA that can be used to assess specificity. Second, a germline SNP-matched cell line provides hundreds to thousands of additional somatic variants. Third, blends of fragmented and sized DNA are used to mimic circulating cell-free DNA (ccfDNA) and serve as the input for MRD assays at VAFs from 0.1% to 0.01% (one mutant copy per 3.5 to 35 ng of ccfDNA) and at 0%. As a proof of concept, we analyzed three cell lines for somatic variants by Whole Exome Sequencing (WES). Using the resulting data, digital PCR assays were designed and two different error corrected NGS assays were customized to measure some of the identified variants. Based on past experiments, A>G (T>C) and C>T (G>A) changes had the highest background in NGS data, so these were generally avoided. The tumor and normal samples were used to assess the performance of a given customized assay to measure a variant. Digital PCR was used to verify VAFs in the ccfDNA format, which proved challenging for 0.01% given the expectation of approximately one positive droplet per assay well. NGS was then used to look for the variants using around 50 ng of input per reaction. While the detection of 0.1% VAFs appeared to be feasible with customized off-the-shelf assays, 0.01% was difficult given the need to measure a variant-containing region over 10,000 times to observe a somatic variant - if it was included in the library - and to measure each starting molecule around 10 times for error correction, which required a depth of greater than 100,000 for 20 of several hundred identified candidate variants. While we did not evaluate the reference materials with emerging clinical MRD assays and focused our initial testing on customized off-the-shelf assays, these reference materials should enable the design, validation, and evaluation of MRD assays. Citation Format: Yves Konigshofer, Matthew G. Butler, Jessica Dickens, Omoshile Clement, Andrew Anfora, Dan Brudzewsky, Bharathi Anekella, Russell K. Garlick. Reference materials for measurable residual disease (MRD) monitoring [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1978.

The Building Strong Library and Information Science Education (BSLISE) Working Group of the International Federation of Library Associations and Institutions (IFLA) was formed in 2016 to develop an international quality assurance (QA) framework that will guide and promote international educational standards in LIS. The first phase of its efforts has been to conduct an international survey (by means of questionnaires) of qualifications for LIS professional practice inclusive of regional and national contexts. Key findings of the study along with recommendations appear in the Building Strong Library and Information Science Education: a Call to Global and Local Action White Paper published in August 2018. This review briefly outlines the White Paper’s content and comments on its main points. Based on the analysis, the BSLISE Working Group identified six key findings with recommended actions and change agents, and prioritized three actions for its next steps: to develop an international resource that identifies local structures; to develop an international framework for the assessment of quality standards in LIS education; to identify core and other competencies for transferability and reciprocity. The article concludes that there has been a longstanding need for comprehensive documentation of LIS education globally.

BackgroundEligibility for afami-cel is determined by germline HLA-A*02 genotype and expression of MAGE-A4 in tumor cells as determined by immuno-histochemistry (IHC). Biomarker-based patient selection in a single arm clinical trial...