Q2 Solutions (United States)

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.

Presented on Wednesday 17 May: Session 21 Upstream Production Solutions Eastern business has completed 12 months maintaining a Total Recordable Injury Frequency Rate (TRIFR) of zero. This does not result from running an inherently safe operation. Maintaining performance has required significant effort in the right areas: Training and competence, and verifying competencies are adequately developed; Setting clear expectations for behaviours, and providing visible management support; Providing the right HSE (Health, Safety and Environment) support in the right areas (with a focus on effort where the risk is); Strong reporting culture, with information captured and communicated positively throughout our organisation, avoiding a culture of blame; Practical risk assessment, with robust risk mitigations put in place and tested; Deployment of the right tools (including Step Back 5 × 5 and Job Hazard Analysis) to support conscious review at the work site, with review and feedback provided to teams; Developing leading indicators and visible reporting; and Management review and continuous improvement building our learning of what works. We have continued to face challenges over the past 12 months of operation and we will present examples of issues identified and corrective actions undertaken, including: Training delivered, but competence not achieved prior to starting work on site; Change in work practises not identified and assessed through management of change process – business is exposed to new risks without robust mitigation in place; and Some of our corporate HSE management practises were not delivering real benefits and had to be changed to support delivery of safe operations. Upstream PS will share practical learnings and examples from the last 12 months of this journey. To access the Oral Presentation click the link on the right. To read the full paper click here

Aim: Dried blood spot (DBS) is a sampling approach that offers several advantages over plasma and whole blood (WB) sampling, but several factors, such as hematocrit and temperature, can adversely affect quantitation. Methodology & results: In an open-label, three-way crossover study in healthy subjects, we explored the correlation between DBS, WB and plasma samples, and between DBS samples from finger-prick and venipuncture blood for measuring edoxaban and its metabolite M-4 using LC-MS/MS. The methods were validated comprehensively. The incurred sample reanalysis experiments demonstrated quantitation reproducibility in all three matrices. Overall, there was a good correlation (near perfect concordance for edoxaban) among plasma, WB and DBS measurements. M-4 concentrations in DBS and WB were lower than in plasma. Conclusion: These results indicate using DBS may be used as an alternative methodology to measure edoxaban pharmacokinetics.

As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: (i) to determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large studies, are applicable to blood pressure control in subjects from a rural population; (ii) to measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and (iii) to identify other SNPs that may help understand patient-specific responses to an intervention. We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) and Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. In conclusion, the identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

The international MAQC Society launches to enhance reproducibility of high-throughput technologies

Steve Lowes from Q2 Solutions speaks to Sankeetha Nadarajah, Managing Commissioning Editor: about outsourcing strategy implementation. Steve started his industrial career at VG Biotech in the UK that became the LC-MS instrument entity of Waters Corporation. Since joining the CRO group that became Advion and then Q2 Solutions, his career has focused on regulated bioanalysis with particular emphasis on LC-MS. He is a founding member of the Global Bioanalysis Consortium and a past-chair of the AAPS Bioanalytical Focus Group. At Q2Solutions, Steve leads the scientific disciplines around LC-MS bioanalysis for both small molecule and biomolecule applications including biomarker assays. Steve has over 40 peer-reviewed publications on bioanalysis and is a frequent speaker at national and international conferences.

As the building blocks of proteins, amino acids support the diversity of life. They also exist in the body as individual molecules and individually play critical roles in many biochemical pathways. This chapter briefly discusses how the general structures of amino acids make them important to various biochemistries. It presents some examples where measurement of amino acids gives insight into the function of a biochemical pathway and may provide an indication of disease. Ultimately, the chapter examines analytical approaches to measure these molecules and offer guidance to ensure optimum assay characteristics such as accuracy, precision, and selectivity using methodologies involving LC-MS. Amino acids can also be funneled into metabolic pathways to be used as an energy source. Tyrosine is a precursor for dopamine, norepinephrine, and epinephrine; decarboxylation of glutamate and histidine results in gamma-aminobutyric acid (GABA) and hista-mine, respectively; and tryptophan can be metabolized to serotonin.