Feedback from the Science Café roundtables at the ninth European Bioanalysis Forum Young Scientist Symposium: optimizing the work-life balance in a bioanalytical laboratory.

As part of the European Bioanalysis Forum's continued commitment to develop young scientists beyond their scientific skills, we also focus on soft skills and a community responsibility during the Young Scientist Symposia, with the Science Café. In previous years, we have focused on topics such as sustainability (green lab) or the impact of the COVID-19 pandemic on career development. At the ninth Young Scientist Symposium, the Science Café roundtables focused on the work-life balance and how caring for it can be beneficial for both the individual and the company. Feedback from a premeeting survey and from the discussions during the roundtables can be an important addition to personal and professional development. If organizations are not already focusing on the importance of a healthy work-life balance, they can be inspired to include some aspects of the outcome of the Science Café discussions when developing their staff toward future (scientific) leadership.

The challenges for implementing Good Clinical Practices in the bioanalytical laboratory: a discussion paper from the European Bioanalysis Forum.

This manuscript reports back from the discussion in the European Bioanalysis Forum community on the challenges observed when implementing Good Clinical Practices in the bioanalytical laboratory. It is not intended to challenge any regulatory requirements but to open a discussion on where the bioanalytical community sees ambiguities on implementing Good Clinical Practices or areas where expectations are either felt not being owned by Bioanalysis or where Good Clinical Practices requirements are at risk of getting contaminated with requirements originating from Good Laboratory Practices. In addition to this, the discussions focused on three additional main challenges: the informed consent withdrawal, expedited reporting of unexpected results and the risk-based approach to quality management, The European Bioanalysis Forum community is continuing discussions, but already this manuscript should help to appreciate the challenges and to try and resolve them, involving all stakeholders.

Recommendations and feedback from the European Bioanalysis Forum Workshop: 1 year into ICH M10 - keeping our finger on the pulse.

The ICH M10 guideline on bioanalytical method validation and sample analysis is being adopted since 2023. However, and inevitably, some paragraphs or requirements remain ambiguous and are open for different interpretations. In support of a harmonized interpretation by the industry and health authorities, the European Bioanalysis Forum organized a workshop on 14 November 2023 in Barcelona, Spain, to discuss unclear and/or ambiguous paragraphs which were identified by the European Bioanalysis Forum community and delegates of the workshop prior to the workshop. This manuscript reports back from the workshop with recommendations and aims at continuing an open scientific discussion within the industry and with regulators in support of a science-driven guideline for the bioanalytical community and in line with the ICH mission - that is, achieve greater harmonization worldwide to ensure that safe, effective and high-quality medicines are developed and registered in the most resource-efficient manner.

Immunocapture LC-MS(/MS) assays for biotherapeutic and biomarker proteins: the European Bioanalysis Forum continuing discussions on scientific and regulatory challenges.

The use of LC-MS(/MS) assays to quantify (biotherapeutic or biomarker) proteins is commonplace and well accepted across industry. There is a good understanding on the added value over conventional analytical technologies (i.e., ligand-binding assays). In fact, the impact of combining small- and large-molecule technologies for large-molecule analysis has played a significant part in bringing the bioanalytical communities closer together and building a mutual respect and understanding between scientists. This paper from the European Bioanalysis Forum presents a history of the journey and future perspectives for hybrid assays, with focus on the unanswered scientific questions, including regulatory discussions to be had. Hybrid assays are essentially a combination of ligand-binding assays and MS, and the ICH M10 guideline does not address this approach directly. Decision-based acceptance criteria are still being discussed, and the industry should continue to do so.

Quantitative polymerase chain reaction in the bioanalytical laboratory and technical and scientific considerations for nonclinical and clinical assay characterization, validation and sample analysis.

In this manuscript, the European Bioanalysis Forum reports back on their discussions on practical and scientific considerations related to bioanalytical applications of quantitative polymerase chain reaction. This publication follows an earlier publication in which the European Bioanalysis Forum recommends to consider principles of context of use when defining assay acceptance criteria for method validation criteria and sample analysis.

Biomarker context-of-use: how organizational design can impact the implementation of the appropriate biomarker assay strategy.

Since 2011, the European Bioanalysis Forum has been discussing the topic of context-of-use for biomarker assays, in support of a cross-industry implementation of its principles. The discussions have led to the acknowledgement of the challenges that we face as an industry in implementing these principles. In addition to scientific recommendations, the European Bioanalysis Forum has addressed these challenges by providing recommendations on organizational design, and what works in both sponsor and contract research organizations, to support and enable context-of-use across biomarker strategies. Here, we highlight the key considerations for organizational design to help ensure that biomarker assays are characterized and validated according to the right context-of-use, to ensure that the right decisions based on the biomarker data can be made during drug development.

Feedback from the 8th European Bioanalysis Forum Young Scientist Symposium.

After 2 years of COVID-19 restrictions, the 8th Young Scientist Symposium was organized again as a face-to-face meeting covering a broad array of scientific presentations. As in the previous editions, the meeting was organized by young scientists for young scientists under the umbrella of the European Bioanalysis Forum and in collaboration with academia. The traditional Science Café was again included as an interactive round table session. This year, the main focus was on the challenges of communication. New for the 8th edition was a session connecting the young scientists with more seasoned experts in an effort to bridge talent and experience. In this article, we share the feedback of the scientific sessions and the Science Café held at the symposium.

Conference Report from the European Bioanalysis Forum Workshop: toward harmonized implementation of the ICH M10 guideline.

In this report, the European Bioanalysis Forum shares the proposals for harmonized implementation of the ICH M10 guideline on bioanalytical method validation and study sample analysis from the ICH M10 workshop. The focus of the discussions was to understand new, changed or still ambiguous regulatory expectations in the guideline, as identified in feedback from the pre-workshop surveys or during the workshop. The proposals from the workshop aim at stimulating and helping a harmonized implementation of the guideline, and using our community as a sounding board during and after implementation to highlight areas of misalignment and to create a platform for continued sharing with the regulatory authorities in an effort to contribute to industry and regulators developing similar interpretations on guideline expectations.

Recommendations and discussion points on immunogenicity, biomarkers, automation/technology and protein-MS from the 2021 European Bioanalysis Forum Focus Workshops.

During the first half of 2021, and due to the SARS-CoV-2 pandemic preventing in-person meetings, the European Bioanalysis Forum organized four workshops as live interactive online meetings. The themes discussed at the workshops were carefully selected to match the cyberspace dynamics of the meeting format. The first workshop was a training day on challenges related to immunogenicity. The second one focused on biomarkers and continued the important discussion on integrating the principles of Context of Use (CoU) in biomarker research. The third workshop was dedicated to technology, that is, cutting-edge development in cell-based and ligand-binding assays and automation strategies. The fourth was on progress and the continued scientific and regulatory challenges related to peptide and protein analysis with MS. In all four workshops, the European Bioanalysis Forum included a mixture of scientific and regulatory themes, while reminding the audience of important strategic aspects and our responsibility toward the patient.

Applying context of use to quantitative polymerase chain reaction method validation and analysis: a recommendation from the European Bioanalysis Forum.

Polymerase chain reaction (PCR) is widely used in various fields of laboratory testing, ranging from forensic, molecular biology, medical and diagnostic applications to a wide array of basic research purposes. COVID-19 infection testing has brought the three-letter PCR abbreviation into the vocabulary of billions of people, making it likely the most well-known laboratory test worldwide. With new modalities and translational medicine gaining importance in pharmaceutical research and development, PCR or more specifically, quantitative PCR (qPCR) is now becoming a standard tool in the (regulated) bioanalytical laboratory, driving the bioanalytical community to define best practices for method development, characterization and validation. In absence of specific guidance from health authorities, qPCR may be vulnerable to scope creep from pharmacokinetics (PK) assay validation as defined in bioanalytical method validation guidance/guidelines. In this manuscript, the European Bioanalysis Forum builds a rationale for applying context of use principles when defining requirements for qPCR assay performance and validation criteria.

Feedback from the Science Café at the 7th European Bioanalysis Forum Young Scientist Symposium.

The 7th Young Scientist Symposium, a meeting again organized as a hybrid online event by young scientists for young scientists under the umbrella of the European Bioanalysis Forum and in collaboration with the Universities of Bologna and Ghent, included a variety of interesting presentations on cutting-edge bioanalytical science and processes. On the morning of day 2, the meeting hosted their traditional Science Café around the theme: 'How has COVID-19 changed our future?' in which the Young Scientist Symposium organizing committee engaged with the delegates on how the COVID-19 pandemic has impacted the careers of young scientists working in a bioanalytical (industry or academic) laboratory, that is, things they lost, for good or for bad - things they gained, wanted or unwanted, things they learned about themselves and their industry. This manuscript provides feedback from those discussions.

Feedback from the Sixth European Bioanalysis Forum Young Scientist Symposium.

As part of the European Bioanalysis Forum mission to provide development opportunities for scientists, a Young Scientist Symposium has been organized every year since 2014. The meetings, organized by and for young scientists, aim at immersing talent from industry and academia in the scientific and process challenges important for their (future) professional environment. In an ideal world, the setting of an interactive symposium in stimulating auditorium sets the foundation for long lasting peer scientific relationship. This year, a pandemic has descended across all continents, changing the dynamics of the meeting. This manuscript summarizes the discussions at the Sixth EBF Young Scientist Symposium, originally planned as a face-to face event in March 2020 in Bologna, Italy but finally executed as a hybrid meeting in Cyberspace and on location in a few regions across Europe between 24-25 September 2020.

A strategic approach to nonclinical immunogenicity assessment: a recommendation from the European Bioanalysis Forum.

Immunogenicity assays are required to evaluate anti-drug antibody (ADA) responses that can be generated against biotherapeutic modalities. Regulatory guidelines focus on clinical requirements, yet it has become apparent that industry has applied these clinical recommendations for immunogenicity assessment to nonclinical studies in varying degrees. ADAs are an anticipated outcome of dosing a humanized or fully human biotherapeutic into an animal. However, a nonclinical ADA response is rarely predictive of the immunogenic potential in humans. The addendum to ICH S6 recommends that immunogenicity should be explicitly examined where there is: evidence of altered pharmacodynamic activity; unexpected changes in exposure in the absence of a pharmacodynamic marker or evidence of immuno-mediated reactions. The European Bioanalytical Forum has extensively discussed and reached a consensus on a minimal strategic approach of when and what to include for nonclinical immunogenicity assessments. Additionally, this paper recommends a strategy for ADA assay validation and sample analysis for those cases when it is considered necessary to include an immunogenicity assessment in nonclinical toxicology studies.

Feedback from the Science Café from the Sixth European Bioanalysis Forum Young Scientist Symposium.

The 6th Young Scientist Symposium, a meeting organized by young scientists for young scientists under the umbrella of the European Bioanalysis Forum vzw and in collaboration with the Universities of Bologna and Ghent, included a variety of interesting presentations on cutting edge bioanalytical science and processes. Integrated in the meeting, an interactive round table session, the Science Café, discussed the challenges related to sustainability for bioanalytical lab activities. This manuscript reflects conclusions from these discussions. They can provide our community a compass for future business practices to embrace more sustainable laboratory activities considerate of smarter use of a wide array of resources and laboratory tools, resulting in increased wellbeing for our next generations and our planet.

Update to the European Bioanalysis Forum recommendation on biomarkers assays; bringing context of use into practice.

In 2012, the European Bioanalysis Forum published a recommendation on biomarker method development and the bioanalysis of biomarkers in support of drug development. Since then, there has been significant discussion on how to bring the topic of context of use of biomarker assays to the forefront so that the purpose of the assay, the use of the data and the decisions being made with the data are well defined and clearly understood, not just by the bioanalytical scientist, but across all stakeholders. Therefore, it is imperative that discussions between the bioanalytical laboratory and the end users of the data happen early (and regularly) in the drug development process to enable the right assays to be developed and appropriately validated to generate the correct data and allow suitable decisions to be made. This updated refinement to the previous European Bioanalysis Forum recommendation will highlight the items to consider when discussing context of use for biomarker assay development and validation, thus enabling the correct conversations to occur and the move away from the misapplication of PK assay validation criteria to biomarker assays.

Improving data integrity in regulated bioanalysis: proposal for a generic data transfer process for LC-MS from the European Bioanalysis Forum.

In this paper, the European Bioanalysis Forum reports back from the discussions with software developers, involved in regulated bioanalysis software solutions, on agreeing to data transfer specification in the bioanalytical labs' LC-MS workflows as part of today's Data Integrity (DI) challenges. The proposed specifications aim at identifying what consists of a minimum dataset, that is, which are the pre-identified fields to be included in DI proof bidirectional data transfer between LC-MS and information management systems. The proposal is an attempt from the European Bioanalysis Forum to facilitate new software solutions becoming available to increase compliance related to DI in today's LC-MS workflows. The proposal may also serve as a template and inspiration for new data transfer solutions in other workflows.

European Bioanalysis Forum feedback on draft ICH M10 guideline on bioanalytical method validation during the Step 2b public consultation period.

Once released, the ICH M10 Guideline on bioanalytical method validation will become one of the most important milestones in the history of regulated bioanalysis, closing a chapter on intense discussions among the industry and health authorities started in Crystal City in 2001. In this manuscript, the European Bioanalysis Forum community reports back on their feedback on the ICH M10 draft guideline gathered during the public consultation period. The comments given are intended to contribute to a guideline that combines several decades of experience and current scientific vision. They should provide future generations of bioanalytical scientist a regulatory framework so their bioanalytical work can contribute to safe, effective and high-quality medicines, which can be developed and registered in the most resource-efficient manner.

European Bioanalysis Forum recommendation on singlicate analysis for ligand binding assays: time for a new mindset.

It is well accepted that chromatographic assay methods employ singlicate analysis for toxicokinetic and pharmacokinetic analysis. While conversely, it has been the norm for ligand-binding assays to be run in at least duplicate analyses, stemming mainly from concerns over inherent assay variability and reagent quality. Regulatory guidelines and guidance on bioanalytical method validation has, in the most part, recommended multiple replicates for immunoassays and this has led to the industry being comfortable and familiar with duplicate analysis. Over the last few years, the discussion on whether singlicate analysis is acceptable for ligand-binding assays has grown and the status quo is being challenged for regulated bioanalysis performed using immunoassays. Through interrogation of preclinical and clinical pharmacokinetic assay data from the European Bioanalysis Forum community, the application of a singlicate analysis strategy has shown to have no impact on toxicokinetic and pharmacokinetic parameters when compared with duplicate analysis from the same studies. Therefore, now is the time to adopt a new mindset when it comes to sample analysis for toxicokinetic and pharmacokinetic ligand-binding assays and embrace singlicate analysis in the regulated environment.