ABSTRACT
The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. 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 1 week 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 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.
Subject(s)
Biological Assay , Technology , Biological Assay/methods , Biomarkers/analysis , Cell- and Tissue-Based Therapy , Immunotherapy, ActiveABSTRACT
The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. 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 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th 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 2022 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 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1 (Mass Spectrometry and ICH M10) and Part 2 (LBA, Biomarkers/CDx and Cytometry) are published in volume 15 of Bioanalysis, issues 16 and 15 (2023), respectively.
Subject(s)
Prescription Drugs , Technology , Biological Assay/methods , Biomarkers/analysis , Cell- and Tissue-Based TherapyABSTRACT
Interest and efforts to use recombinant adeno-associated viruses (AAV) as gene therapy delivery tools to treat disease have grown exponentially. However, gaps in understanding of the pharmacokinetics/pharmacodynamics (PK/PD) and disposition of this modality exist. This position paper comes from the Novel Modalities Working Group (WG), part of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). The pan-industry WG effort focuses on the nonclinical PK and clinical pharmacology aspects of AAV gene therapy and related bioanalytical considerations.Traditional PK concepts are generally not applicable to AAV-based therapies due to the inherent complexity of a transgene-carrying viral vector, and the multiple steps and analytes involved in cell transduction and transgene-derived protein expression. Therefore, we explain PK concepts of biodistribution of AAV-based therapies and place key terminologies related to drug exposure and PD in the proper context. Factors affecting biodistribution are presented in detail, and guidelines are provided to design nonclinical studies to enable a stage-gated progression to Phase 1 testing. The nonclinical and clinical utility of transgene DNA, mRNA, and protein analytes are discussed with bioanalytical strategies to measure these analytes. The pros and cons of qPCR vs. ddPCR technologies for DNA/RNA measurement and qualitative vs. quantitative methods for transgene-derived protein are also presented. Last, best practices and recommendations for use of clinical and nonclinical data to project human dose and response are discussed. Together, the manuscript provides a holistic framework to discuss evolving concepts of PK/PD modeling, bioanalytical technologies, and clinical dose selection in gene therapy.
Subject(s)
Dependovirus , Genetic Therapy , Humans , Dependovirus/genetics , Tissue Distribution , Drug Development , Polymerase Chain ReactionABSTRACT
Immunogenicity has imposed a challenge to efficacy and safety evaluation of adeno-associated virus (AAV) vector-based gene therapies. Mild to severe adverse events observed in clinical development have been implicated with host immune responses against AAV gene therapies, resulting in comprehensive evaluation of immunogenicity during nonclinical and clinical studies mandated by health authorities. Immunogenicity of AAV gene therapies is complex due to the number of risk factors associated with product components and pre-existing immunity in human subjects. Different clinical mitigation strategies have been employed to alleviate treatment-induced or -boosted immunogenicity in order to achieve desired efficacy, reduce toxicity, or treat more patients who are seropositive to AAV vectors. In this review, the immunogenicity risk assessment, manifestation of immunogenicity and its impact in nonclinical and clinical studies, and various clinical mitigation strategies are summarized. Last, we present bioanalytical strategies, methodologies, and assay validation applied to appropriately monitor immunogenicity in AAV gene therapy-treated subjects.
ABSTRACT
Background: Monitoring appearance of neutralizing antibodies (NAbs) to multidomain large molecule drugs is a challenging task. Materials & methods: Here, we report development of a competitive ligand-binding assay for detection of NAbs to a bispecific candidate drug using a multiplex Meso Scale Discovery platform, which allows for detection of NAbs to both drug arms in the same sample. Results: The assay has sensitivity better than 250 ng/ml and is tolerant to the presence of drug at concentration >600 µg/ml and to the level of soluble target(s) >400 ng/ml. Conclusion: Our data suggest that multiplex approach can be successfully used for development of NAb assays in competitive ligand-binding assay format.
Subject(s)
Antibodies, Neutralizing/blood , Immunoassay/methods , Ligands , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Binding, Competitive , Cytokines/immunology , Female , Humans , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/pathology , Limit of Detection , Male , Reproducibility of Results , Solid Phase ExtractionABSTRACT
Aim: To investigate the feasibility of singlicate analysis in anti-drug antibody (ADA) assay by comparing performance characteristics for assays qualified in duplicate and singlicate formats. Materials & methods: We employed modeling to assess and quantify the impact of singlicate to cut point factor (CPF) in scenarios with the duplicate precision from 1-20% and the proportion of well-to-well variance to overall assay variance from 0.01-0.90. The impact to CPF by singlicate is marginal if the well-to-well coefficient of variation is <10% and represents <25% of the overall variability. Results & conclusion: The assay parameters including sensitivity, precision, selectivity, drug and target tolerance were comparable between singlicate and duplicate based assays. Our results suggested the minimal impact of singlicate analysis on ADA assay with good duplicate precision. The study provided additional supportive evidence that the singlicate-based analysis is feasible in ADA ligand binding assays.
Subject(s)
Biological Products/immunology , Luminescent Measurements/methods , Feasibility Studies , Humans , Models, Statistical , Sensitivity and Specificity , SerumABSTRACT
The 14th edition of the Workshop on Recent Issues in Bioanalysis (14th WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14th WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the Global 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 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity). Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 2A (BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation) and Part 2B (Regulatory Input) are published in volume 13 of Bioanalysis, issues 4 and 5 (2020), respectively.
Subject(s)
Cell- and Tissue-Based Therapy , Flow Cytometry , Genetic Therapy , Real-Time Polymerase Chain Reaction , Vaccines/analysis , Humans , Quality Control , Receptors, Chimeric Antigen/analysis , United States , United States Food and Drug AdministrationABSTRACT
Aim: Drug interference poses great analytical challenges for cell-based neutralizing antidrug antibodies (NAb) assay. The work aimed to improve assay drug tolerance through biotin-drug extraction with acid dissociation method optimization and developing new approach. Results: The NAb extraction with biotin-drug extraction with acid dissociation approach has been optimized by reducing biotinylated drug leaching and improving NAb elution efficiency, resulting in drug tolerance of up to 160 µg/ml. To circumvent the low acid elution efficiency of NAb from drug, a novel drug depletion approach was developed, which combined acid dissociation and drug targeted crosslinked capture, achieved drug tolerance up to 400 µg/ml. At last, a strategy workflow for sample pretreatment approach selection and optimization was established for improving drug tolerance of NAb assay. Conclusion: We demonstrated that reduced biotinylated drug leaching and the high NAb elution efficiency was critical for improving assay drug tolerance. Drug depletion offers an alternative approach to overcome low NAb elution efficiency.
Subject(s)
Antibodies, Neutralizing/immunology , Biological Assay/methods , Drug Tolerance/immunology , HumansABSTRACT
After tier 1 and 2 cut points for anti-drug antibody (ADA) assays are derived during pre-study assay validation in a population, there is a need to verify the continued appropriateness of the previously derived cut points during sample analysis in the same or different populations, per FDA guidance (US HHS, FDA, CDER, CBER, 2019). Proper sample size-dependent criteria with statistical underpinning were derived and presented in this technical note to aid in assessing the appropriateness of tier 1 and tier 2 cut points, respectively.
Subject(s)
Antibodies/analysis , Immunologic Tests/standards , Proteins/immunology , Research Design , Data Interpretation, Statistical , False Positive Reactions , Humans , Predictive Value of Tests , Proteins/therapeutic use , Reproducibility of Results , Sample SizeABSTRACT
The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA on 1-5 April 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 2) covers the recommendations on the 2018 FDA BMV guidance, 2019 ICH M10 BMV draft guideline and regulatory agencies' input on bioanalysis, biomarkers, immunogenicity and gene therapy. Part 1 (Innovation in small molecules and oligonucleotides and mass spectrometry method development strategies for large molecules bioanalysis) and Part 3 (New insights in biomarker assay validation, current and effective strategies for critical reagent management, flow cytometry validation in drug discovery and development and CLSI H62, interpretation of the 2019 FDA immunogenicity guidance and gene therapy bioanalytical challenges) are published in volume 10 of Bioanalysis, issues 22 and 24 (2019), respectively.
Subject(s)
Biological Assay/standards , Biomarkers/analysis , Guidelines as Topic , Immunogenetic Phenomena , Research Report , United States Food and Drug Administration/legislation & jurisprudence , Humans , United StatesABSTRACT
Anti-drug antibody (ADA) assay selectivity is evaluated during assay validation to assess the potential for individual matrices to interfere with detection of ADA. While current EMA and FDA guideline documents suggest comparative analysis with and without matrix, they do not provide specific recommendations on the acceptance criteria such as an acceptable percent positive control (PC) recovery range or positive rate. Industry has adopted an approach where recovery of PC spiked sample is expected to fall within ± 20% (80 to 120%) vs. that for the PC material spiked in negative control matrix or assay buffer. Here, it is proposed that ADA assay selectivity evaluated using a qualitative assessment of PC recovery vs. a PK-like quantitative method may be more appropriate. The PC recovery test should focus on the reliability of the method to detect the low PC level in individual samples and avoid false-negative ADA reporting. Therefore, it is proposed that assessment of high PC level as well as the assessment of quantitative percent recovery (within ± 20%) should not be included in the test. The recovery test may be viewed as acceptable should a pre-selected number of individual samples (for example at least 8 or 9 out of 10) prepared at the low PC concentration of the assay score as ADA positive.
Subject(s)
Antibodies, Monoclonal/immunology , Antibodies/immunology , Humans , Immunoassay/methods , Reproducibility of ResultsABSTRACT
Assays for the detection and confirmation of anti-drug antibodies (ADA) are commonly used tools for assessing the immunogenicity of drug candidates in both clinical and nonclinical studies. During the development of such assays, it is typical to optimize the assay conditions based on factors such as sensitivity or signal/noise ratio (S/N) and is commonly done using an assay positive control (PC). However, even carefully optimized methods often suffer with problems due to low cut-point factors and failure to distinguish assay "noise" from a true biological response. In this paper, we describe an approach to assay development in which the impacts of assay conditions on the response and variability, both analytical and biological, of drug-naïve samples are tested by way of PC-independent assay condition optimization. Using two ADA methods as model systems, we examine the impact of minimum required dilution, assay reagent (labeled drug) concentrations, incubation time, assay, and wash buffer composition. We find that the choice of assay conditions, particularly the labeled drug concentration, can greatly affect the distribution of naïve sample responses and thus impact screening and confirmatory assay cut-points. In two case studies presented, screening assay cut-point (SCP) varied from 1.38 to 2.20 and 1.04 to 1.20 while the confirmatory assay cut-point (CCP) varied from 58.5 to 95.6% and 26.2 to 16.2% depending on the conditions tested. Some of the conditions produced unacceptably high CCP values. It is proposed that the degree of the observed impact of the assay conditions on SCP and CCP values depends on the compound nature and assay matrix composition and is likely connected with the diversity of interactions between drug protein and matrix components. Because it was also observed that higher assay SCP can associate with a loss of the PC-based assay sensitivity, additional assessment of the assay conditions would be required to determine an overall assay performance acceptability, including assay PC-based sensitivity, drug, and target tolerance characteristics. In conclusion, it is suggested that by assessing performance of treatment-naïve samples at various assay conditions, one can identify potential assay protocols that allow to avoid undesirably low screening (e.g., < 1.2) and confirmatory (e.g., < 25%) cut-points.
Subject(s)
Antibodies/blood , Biological Products/immunology , Drug-Related Side Effects and Adverse Reactions/immunology , Immunoassay/methods , Drug-Related Side Effects and Adverse Reactions/blood , Humans , Immunoassay/standards , Sensitivity and Specificity , Signal-To-Noise RatioABSTRACT
The 2018 12th Workshop on Recent Issues in Bioanalysis took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. 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 and LBA/cell-based assays approaches. This 2018 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 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays. Part 1 (LCMS for small molecules, peptides, oligonucleotides and small molecule biomarkers) and Part 2 (hybrid LBA/LCMS for biotherapeutics and regulatory agencies' inputs) are published in volume 10 of Bioanalysis, issues 22 and 23 (2018), respectively.
Subject(s)
Antigens/analysis , Biological Assay/standards , Flow Cytometry/standards , Genetic Therapy/standards , Pharmacokinetics , Antigens/immunology , Biological Assay/methods , Biomarkers/analysis , Biotechnology , Flow Cytometry/methods , Government Agencies , Humans , Reference ValuesABSTRACT
Insufficient drug tolerance presents a major challenge in the development of neutralizing antibody (NAb) assays for biotherapeutics. Sample pre-treatment using solid-phase extraction with acid dissociation (SPEAD) is widely reported to improve drug tolerance. In this paper, a case study is presented in which SPEAD was used in conjunction with a competitive ligand binding NAb assay format. A significant degree of biotin-drug conjugate leaching was observed resulting in the reporting of both false positive and false negative results in NAb assay. Mitigation steps have been evaluated to address drug/biotin-drug conjugate leaching. These steps included assessment of the streptavidin-coated plate in conjunction with biotin-drug conjugates at various biotin molar challenge ratios (MCR). In addition, an alternative method based on covalent capture of the drug on an aldehyde-activated plate was assessed. Both approaches were compared for the degree of drug/biotin-drug conjugate leaching during the second elution step of the SPEAD procedure. Moreover, the impact of various conditions on the assay performance was assessed, including elution pH, sample incubation time, and biotin MCR. For the covalent drug capture method, capture conditions were evaluated. Optimized conditions in both streptavidin capture and covalent capture methods enabled a significant reduction of drug/biotin-drug conjugate leaching. A streptavidin high binding capacity approach using biotin-drug conjugate with a MCR of 50:1 was chosen as the optimal method yielding a NAb assay with a fit for purpose sensitivity (153 ng/mL) and a drug tolerance of up to 50 µg/mL with 500 ng/mL PC.
Subject(s)
Antibodies, Neutralizing/isolation & purification , Indicators and Reagents/chemistry , Neutralization Tests/methods , Solid Phase Extraction/methods , Antibodies, Monoclonal, Humanized/chemistry , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Neutralizing/immunology , Biological Products/chemistry , Biological Products/immunology , Biological Products/pharmacology , Biotin/analogs & derivatives , Biotin/chemistry , Chemistry, Pharmaceutical , Chromatography, Affinity/methods , Drug Tolerance , False Negative Reactions , False Positive Reactions , Humans , Streptavidin/chemistry , Succinimides/chemistryABSTRACT
In ligand binding assays (LBA), the concentration to response data is a nonlinear relationship driven by the law of mass action. Four parameter logistic (4PL) and five parameter logistic (5PL) curve fitting models are two widely accepted and validated models for LBA calibration curve data. Selection of the appropriate regression model and weighting function are key components of LBA development. Assessment of selected model and weighting function should be performed during assay development and confirmed later during validation. There has been limited published work on practical approaches to determining an appropriate weighting function and selection of a regression model for ligand binding assays. Herein, a structured scheme is presented to determine both. By applying commonly available software, assay performance data were analyzed to determine weighting functions and associated choice of a curve fitting model in three presented case studies. As a result, assay ranges of quantification were improved by reducing lower limit of quantification (from 1.00 to 0.317 ng/mL in one case study and from 2.06 to 1.37 ng/mL in another) or extending both low and upper limits of quantification(e.g., 1.04 to 48.3 ng/mL improved to 0.602 to 145 ng/mL). In addition, assay calibration curve performance demonstrated improved assay accuracy (%RE) and precision (%CV). Recommendations on decision flow when determining appropriate weighting function and curve fit model are presented.
Subject(s)
Models, Theoretical , Reference Standards , Blood Proteins/metabolism , Calibration , Chemistry Techniques, Analytical/methods , Chemistry Techniques, Analytical/standards , Humans , Ligands , Limit of Detection , Models, Statistical , Pharmacokinetics , Protein Binding , Reproducibility of Results , SoftwareABSTRACT
The accuracy of reported sample results is contingent upon the quality of the assay calibration curve, and as such, calibration curves are critical components of ligand binding and other quantitative methods. Regulatory guidance and lead publications have defined many of the requirements for calibration curves which encompass design, acceptance criteria, and selection of a regression model. However, other important aspects such as preparation and editing guidelines have not been addressed by health authorities. The goal of this publication is to answer many of the commonly asked questions and to present a consensus and the shared views of members of the ligand binding assay (LBA) community on topics related to calibration curves with focus on providing recommendations for the preparation and editing of calibration curves.
Subject(s)
Ligands , Pharmaceutical Research/standards , Pharmacokinetics , Quality Control , Calibration/standards , Pharmaceutical Research/methods , Reference StandardsABSTRACT
The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los Angeles/Universal City, California, on 3-7 April 2017 with participation of close to 750 professionals 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 and immunogenicity. 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 analysis involving LC-MS, hybrid ligand-binding assay (LBA)/LC-MS and LBA approaches. This 2017 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 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large-molecule bioanalysis, biomarkers and immunogenicity using LBA. Part 1 (LC-MS for small molecules, peptides and small molecule biomarkers) and Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) are published in volume 9 of Bioanalysis, issues 22 and 23 (2017), respectively.
Subject(s)
Biomarkers/analysis , Immunity, Active , Chromatography, Liquid , Consensus Development Conferences as Topic , Drug Tolerance , Guidelines as Topic , Ligands , Mass Spectrometry , PharmacokineticsABSTRACT
The 10th Global CRO Council (GCC) Closed Forum was held in Orlando, FL, USA on 18 April 2016. In attendance were decision makers from international CRO member companies offering bioanalytical services. The objective of this meeting was for GCC members to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at this closed forum included reporting data from failed method validation runs, GCP for clinical sample bioanalysis, extracted sample stability, biomarker assay validation, processed batch acceptance criteria, electronic laboratory notebooks and data integrity, Health Canada's Notice regarding replicates in matrix stability evaluations, critical reagents and regulatory approaches to counteract fraud. In order to obtain the pharma perspectives on some of these topics, the first joint CRO-Pharma Scientific Interchange Meeting was held on 12 November 2016, in Denver, Colorado, USA. The five topics discussed at this Interchange meeting were reporting data from failed method validation runs, GCP for clinical sample bioanalysis, extracted sample stability, processed batch acceptance criteria and electronic laboratory notebooks and data integrity. The conclusions from the discussions of these topics at both meetings are included in this report.
Subject(s)
Biomarkers/analysis , Chemistry Techniques, Analytical/standards , Data Collection/standards , Guidelines as Topic , Pharmaceutical Preparations/analysis , Drug Stability , Government Regulation , Humans , Research ReportABSTRACT
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 weeklong event - A Full Immersion Week of Bioanalysis for PK, 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 PK, 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 3) discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Parts 1 (small molecule bioanalysis using LCMS) and Part 2 (Hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in the Bioanalysis journal, issues 22 and 23, respectively.
Subject(s)
Biomarkers/analysis , Ligands , Antibodies, Monoclonal/analysis , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacokinetics , Chromatography, High Pressure Liquid , Consensus Development Conferences as Topic , Government Agencies , Humans , Macromolecular Substances/analysis , Macromolecular Substances/immunology , Macromolecular Substances/pharmacokinetics , Mass Spectrometry , Validation Studies as TopicABSTRACT
The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5 day, week-long event - A Full Immersion Bioanalytical Week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS and LBA approaches, including the focus on biomarkers and immunogenicity. This 2015 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 2015 edition of this comprehensive White Paper has been divided into three parts. Part 3 discusses the recommendations for large molecule bioanalysis using LBA, biomarkers and immunogenicity. Part 1 (small molecule bioanalysis using LCMS) and Part 2 (hybrid LBA/LCMS and regulatory inputs from major global health authorities) have been published in volume 7, issues 22 and 23 of Bioanalysis, respectively.