Japan Bioanalysis Forum Research Articles

Highlights of the 15th Japan Bioanalysis Forum Symposium.

The 15th Japan Bioanalysis Forum (JBF) Symposium was held in Kyoto, Japan, between 5 and 7 February 2024. The conference theme, 'Toward the new world - Science as a universal endeavor' indicated that universal discussion based on science is making a basis of regulatory and analytical sciences, now internationally harmonized. The symposium discussed a wide range of topics, including ICH M10, quantitative PCR, immunogenicity, peptide LC-MS, e-notebooks, artificial intelligence, reliability standards, carrier development, inviting domestic and overseas experts. Approximately 360 attendees from various fields, including pharmaceutical companies, contract research organizations, academia and regulators, gathered in person or online.

Highlights of the 14th Japan Bioanalysis Forum Symposium.

The 14th Japan Bioanalysis Forum Symposium was held at Tower Hall Funabori, Japan from 1-3 March 2023. The conference theme, 'Bringing Together - the Expertise of Bioanalysis', aimed to enable people from various fields to gather, learn and collaborate together for the common goal of delivering medicines to patients faster. Approximately 360 participants from various fields, including pharmaceutical industries, contractors, academia and regulatory authorities, gathered at an in-person symposium which had an online participation option, for the first time in 4 years. The symposium offered a wide range of topics including ICH M10, new modalities, biomarkers, immunogenicity, electronization and patient-centric sampling. The latest research results were provided from domestic and overseas scientists. This report summarizes the major topics.

Understanding quantitative polymerase chain reaction bioanalysis issues before validation planning: Japan Bioanalysis Forum discussion group.

Investigating the biodistribution of cell and gene therapy products may play an important role in evaluating their safety and pharmacology. As quantitative polymerase chain reaction (qPCR) is often used for these analyses, it is essential to improve the reliability of bioanalysis performed using qPCR. In this report, the authors discuss the use of qPCR in nonclinical studies, as it can be used to detect target DNA/RNA and it is quantitative and applicable for long-term analysis. The authors also discuss points to consider during bioanalysis using qPCR and present appropriate validation items and their criteria. The authors anticipate the discussion provided herein to contribute to the development of validation and sample analysis for pharmaceuticals analyzed using qPCR.

Highlights of the 13th Japan Bioanalysis Forum Symposium.

Approximately 280 people from pharmaceutical industries, contractors, academic institutionsand regulatory authorities attended the 13th Japan Bioanalysis Forum Symposium. The symposium was held via web to prevent the spread of COVID-19 from the28February to 2March2022. The theme of the symposium was 'All for One Goal', and the event has provided an opportunity for open discussion among researchers with different backgrounds but who share a common goal: "to deliver more effective and safe pharmaceuticals to patients as quickly as possible". The speakers focused on hot topics in bioanalysis, including chromatography, biomarker analysis, cell and gene therapy, COVID-19 and antidrug antibody. This symposium provided a great opportunity for the participants to have meaningful discussions, even though 'on the web'was a limited space.

Handling unstable analytes: literature review and expert panel survey by the Japan Bioanalysis Forum Discussion Group.

Analyzing unstable small molecule drugs and metabolites in blood continues to be challenging for bioanalysis. Although scientific countermeasures such as immediate cooling, immediate freezing, addition of enzyme inhibitors, pH adjustment, dried blood spot or derivatization have been developed, selecting the best practices has become an issue in the pharmaceutical industry as the number of drugs with such problems is increasing, even for generic drugs. In this study, we conducted a comprehensive literature review and a questionnaire survey to determine a suitable practice for evaluating instability and implementing countermeasures. Three areas of focus, matrix selection, effect of hemolysis and selection of esterase inhibitors, are discussed.

Highlights of the 12th Japan Bioanalysis Forum Symposium.

Approximately 300 people associated with pharmaceutical industries, contractors, academic institutionsand regulatory authorities attended the 12th Japan Bioanalysis Forum Symposium. The webinar was conducted from9to 11March 2021. The theme of the symposium was 'for the next generation', and the event provided 'an opportunity for young researchers in bioanalysis (including students)'and 'an opportunity to discuss new frontiers of bioanalysis'. The speakers focused on hot topics of bioanalysis, including biomarker analysis, patient centric sampling, virtual clinical trials, gene therapy, cancer genome medicineand therapeutic middle molecules. The symposium presented a platform for the discussion of the prospects and challenges facing bioanalysts working in the field of pharmacokinetics. This report presents the key issues discussed.

The 10th Japan Bioanalysis Forum Symposium conference: a report.

The Japan Bioanalysis Forum Symposium was held on 12-14 February 2019 (Yokohama, Japan), in celebration of its 10th anniversary, and over 370 participants from pharmaceutical industries, contractors, academia and regulatory authorities from home and abroad came together in Yokohama. The 3-day symposium particularly aimed to foster collaboration with the scientists surrounding bioanalysts, according to the theme 'Open to the Public.' The symposium also included a broad range of pioneering programs, such as lectures by speakers from DMPK/metabolomics fields, discussions of future bioanalysis and poster presentations by publicly offered presenters as well as the regular ones we had organized. This report summarizes the major topics as a conference report.

The Japan Bioanalysis Forum (JBF): the past 8 years and future perspective.

The Japan Bioanalysis Forum (JBF): the past 8 years and future perspective.

Proposed selection strategy of surrogate matrix to quantify endogenous substances by Japan Bioanalysis Forum DG2015-15.

It is important to select an appropriate surrogate matrix for preparing calibration standards and quality control samples while quantitatively assaying for endogenous substances, because a blank matrix that does not contain the endogenous substance cannot be derived from the species from which the target study samples are collected. This is because the assay results might be affected, depending on the characteristics of the analyte in the surrogate matrix. Our discussion group that participated in the Japan Bioanalysis Forum discussed the recommended selection strategies, focusing on large and small molecules in ligand binding assays and LC-MS, respectively. We established an efficient selection strategy for a surrogate matrix, with simple compositions as the first candidates stated in this article.

The ninth Japan Bioanalysis Forum symposium.

The ninth Japan Bioanalysis Forum symposium took place at tower hall Funabori, Tokyo, Japan, between 6 and 8 February, 2018. Bioanalytical scientists from the pharmaceutical industry, CROs, academia and regulatory bodies had many meaningful and relevant discussions on current topics of interest in bioanalysis. The 3-day symposium featured updated perspectives and experiences on regulated bioanalysis of small and large molecules, biomarker measurement and assessment of immunogenicity, as well as new areas of bioanalytical validation such as quantitative polymerase chain reaction(qPCR) and flow cytometry. There were over 260 participants from six countries, with 23 oral and 11 poster presentations, including the outcomes of Japan Bioanalysis Forum discussion groups. This report summarizes the major discussion topics from the conference.

Analytical convergence in surrogate control matrices.

Analytical convergence in surrogate control matrices.

Proposal for risk-based scientific approach on full and partial validation for general changes in bioanalytical method.

The guidance and several guidelines on bioanalytical method validation, which were issued by the US FDA, EMA and Ministry of Health, Labour and Welfare, list the 'full' validation parameters; however, none of these provide any details for 'partial' validation. Japan Bioanalysis Forum approved a total of three annual discussion groups from 2012 to 2014. In the discussion groups, members from pharmaceutical companies and contract research organizations discussed the details of partial validation from a risk assessment viewpoint based on surveys focusing on bioanalysis of small molecules using LC-MS/MS in Japan. This manuscript presents perspectives and recommendations for most conceivable changes that can be made to full and partial validations by members of the discussion groups based on their experiences and discussions at the Japan Bioanalysis Forum Symposium.

マイクロサンプリングに関わるトキシコキネティクス評価の分析技術における課題（JBF DG2017-29研究活動結果報告より）

マイクロサンプリングに関わるトキシコキネティクス評価の分析技術における課題（JBF DG2017-29研究活動結果報告より）

The 8th Japan Bioanalysis Forum symposium.

The 8th Japan Bioanalysis Forum symposium, the Tower Hall Funabori, Tokyo, Japan, 8-9 February 2017 The 8th Japan Bioanalysis Forum (JBF) symposium was successfully held between 8 and9 February 2017 at the Tower Hall Funabori, Tokyo, Japan. In total, 24 speakers from Japan, USA and Europe gave presentations regarding the immunogenicity of biopharmaceuticals, ICH S3A Q&A microsampling, ICH M10 bioanalytical method validation, large molecule analysis through LC-MS, auditing activities for bioanalysis and biomarker bioanalysis. Achievements regarding eight diverse themes were also shared by Japan Bioanalysis Forum discussion groups. Over 300 scientists from regulatory agencies, industry and academia actively took part in discussions during the symposium. This article provides the highlights of all the topics discussed in this symposium.

Giving Consideration to Scientific Validation in Japanese Drug Application by Japan Bioanalysis Forum Discussion Group

Giving Consideration to Scientific Validation in Japanese Drug Application by Japan Bioanalysis Forum Discussion Group

7th Japan Bioanalysis Forum Symposium: Regulated Bioanalysis, to A New Stage

Tower Hall Funabori, Tokyo, Japan, 9-10 March 2016 At the 7th Japan Bioanalysis Forum symposium, bioanalytical methods and processes were discussed with authorities after the issuing of bioanalytical method validation guidelines (EMA and Japanese Ministry of Health, Labour and Welfare) and draft guidance (US FDA). Method establishment and bioanalysis of biomarkers were discussed with a focus on scientific validation. Bioanalytical methods for antibody-drug conjugates, the potential of MS imaging and microsampling activity in drug development were introduced. Discussion groups presented and openly discussed their results with about 300 attendees. This manuscript provides an overview of the highlights of the symposium.

マイクロサンプリングの実施状況に関するアンケート結果（バイオアナリシス・フォーラム，DG2015-17による調査）

マイクロサンプリングの実施状況に関するアンケート結果（バイオアナリシス・フォーラム，DG2015-17による調査）

Survey on the tiered approach for Japanese bioanalysts operated by Japan bioanalysis forum DG2014-09.

Background The tiered approach is a strategy to limitedly characterize an analytical method initially and expand the range of characterization gradually to a full validation as the drug development process proceeds [1–3]. This approach has been discussed in European Bioanalysis Forum (EBF) [1,3] and Global Bioanalysis Consortium (GBC) [4,5] and is considered so beneficial that it enables the flexible use of analytical methods in dayto-day laboratory works [6,7]. In principle, it complies with the Japanese bioanalytical method validation (BMV) guideline [2], but the description in the guideline is not sufficient to put this approach into practice. In Japan, the importance of building a bioanalytical community was recognized in recent years, and the Japan Bioanalysis Forum (JBF) was established in 2011 [8]. As one of its activities, voluntary discussion groups (DGs) were organized in 2013. Under this circumstance, ‘tiered approach to the metabolite quantification’ was adopted as one of the DG topics in 2013 (named DG2013-03). In DG2013-03, analytical tiers raised by GBC were put into a typical workflow of drug discovery and development with consideration of regional practices as reported previously [9,10]. As a subsequent activity, a further survey on the tiered approach for Japanese bioanalysts was performed in a follow-up DG (DG2014-09) in the fiscal year 2014 [11]. Survey on the tiered approach A survey and discussion on following items were performed to facilitate the use of tiered approach in metabolite quantification. Initially, general opinions on tiered approach were collected:

Tiered approach to metabolite quantification: regional practices reviewed by Japan Bioanalysis Forum discussion group.

2015 Tiered approach; familiarization is essential A tiered approach [1–3] is an idea of step-bystep characterization of analytical methods in coordination with the stage of drug development and the importance of the analytical results obtained. It is thought that this approach contributes to the optimization of the framework of bioanalytical laboratories by adding flexibility to the analytical methods [4]. Nevertheless, it appears that bioanalysts are not ready to use this tiered approach in their day-to-day work because bioanalytical method validation guidances or guidelines, which are in force in the USA, Europe, Brazil and Japan, do not provide a framework for this approach (although the Japanese guidelines do outline the concept of a tiered approach). In addition, bioanalytical experts in industry or regulatory authorities have not provided detailed scientific requirements for different assay types or stages of drug development [4]. The tiered approach is often accompanied with the idea of case-by-case consideration. This makes it hard for those who are not familiar with this concept to understand the whole picture. The common question is how to implement the tiered approach practically (timing and characterization details of the analytical methods). This question seems to show that detailed models of works for the tiered approach are necessary in drug discovery and development stages. Though one of the ultimate goals for the tiered approach is to add flexibility to the bioanalytical works, we considered that it is useful to be familiarized with the approach at first through the typical workflow model. Complete understanding would contribute to more flexible usage of the methods. This activity may help remove certain hurdles toward general acceptance of the tiered approach in laboratory works [4]. Accordingly, a voluntary discussion group (named DG2013–03) of Japan Bioanalysis Forum (JBF), consisting of eight Japanese researchers from pharmaceutical companies and a contract research organization, tried to get the birds-eye-view of the tiered approach in accordance with drug discovery and development stages with emphasis on metabolite research [5]. This activity was intended to provide detailed scientific requirements in assay type or stage of drug development as described above. As an outcome of JBF DG2013–03, this report outlines tiered characterization of the analytical methods in metabolite quantification in relation to actual regional practices in Japan.

Discussion on Partial Validation in Small Molecule Regulated Bioanalysis: Change in Analytical Instruments

In recent years, the necessity of a bioanalytical method validation has been discussed and guidance/guidelines have been released from regulatory agencies. However, none of these provides any details for partial validation (PV) in case of a partial change in the validated analytical method. Therefore eleven scientists have launched a discussion group (DG) with the approval of Japan Bioanalysis Forum (JBF), and have been discussing PV for chromatographic methods based on survey results of Japanese bioanalysts. This document reports the results of discussion on PV for a change of analytical instruments such as: 1) full system (limited to same manufacturer and model); 2) pump; 3) autosampler; and 4) mass spectrometer. The DG members agreed on an outline that validation items required for PV are as follows: calibration curve and reproducibility in case 1); calibration curve, reproducibility, and selectivity in case 2); calibration curve, reproducibility, and carryover in case 3); and nearly full validation items without recovery, dilution integrity, and stability in case 4), in consideration of instrument specification and characteristics of each analytical method. Note that this report does not represent a consensus of all the members of JBF, but is a recommendation from the DG members at this stage. Thus further thought is recommended for future discussions.