GCC Consolidated Feedback to ICH on the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline.

The 13th GCC Closed Forum for Bioanalysis was held in New Orleans, Louisiana, USA on April 5th, 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants from eight countries representing 44 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the ICH M10 Bioanalytical Method Validation Draft Guideline and to build unified comments to be provided to the ICH.

2018 White Paper on Recent Issues in Bioanalysis: 'A global bioanalytical community perspective on last decade of incurred samples reanalysis (ISR)' (Part 1 - small molecule regulated bioanalysis, small molecule biomarkers, peptides & oligonucleotide bioanalysis).

The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) 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 LC-MS, hybrid ligand binding assay (LBA)/LC-MS 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 1) covers the recommendations for LC-MS for small molecules, peptides, oligonucleotides and small molecule biomarkers. Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays) are published in volume 10 of Bioanalysis, issues 23 and 24 (2018), respectively.

The current skills gaps in analytical sciences are failing industry: debate at the 21st International Reid Bioanalytical Forum.

21st International Reid Bioanalytical Forum, University of Surrey, Guildford, UK, 7-10 September 2015 The 21st International Reid Bioanalytical Forum held between 7 and 10 September 2015, brought together over 100 scientists from around the world, representing industry, academia and vendors, for 4 days of engaging science at the University of Surrey in Guildford, UK. The scientific program consisted of 43 podium and 23 poster presentations from key opinion leaders and those just setting out on their scientific career. The latter being the focus of the meeting. One of the highlights of the forum was the debate. An expert panel helped spark off an active discussion among a passionate audience on the topic of 'The Current Skills Gaps in Analytical Sciences are Failing Industry.'

European Bioanalysis Forum: recommendation for dealing with internal standard variability.

Adequate monitoring of internal standard (IS) response across an analytical run and identification of anomalies is now a common expectation. However, the means to conduct this assessment in an appropriate manner is unclear and differs widely between laboratories. A European Bioanalysis Forum (EBF) topic team was formed to survey current practices within European Bioanalysis Forum member companies and to recommend a best practice approach for dealing with IS response variability.

Ask the experts: increasing and maintaining productivity in the bioanalytical laboratory.

Bioanalysis invited a selection of leading researchers to express their views on increasing and maintaining productivity in the bioanalytical laboratory. The topics discussed include the challenges of maintaining productivity when integrating new innovations into existing processes, the impact of automation on productivity, and how they effectively manage productivity in their own bioanalytical laboratories. Their enlightening responses provide a valuable insight into current methods of increasing productivity and the future of the constantly evolving bioanalytical laboratory.

Recommendations on biomarker bioanalytical method validation by GCC.

The 5th GCC in Barcelona (Spain) and 6th GCC in San Antonio (TX, USA) events provided a unique opportunity for CRO leaders to openly share opinions and perspectives, and to agree upon recommendations on biomarker bioanalytical method validation.

Interview: challenges faced by the modern bioanalytical laboratory.

Timothy Sangster (Charles River Laboratories) and Mike Oliver (Thermo Fisher Scientific) speak to Thomas Payne at Bioanalysis in September 2012 about the challenges faced by the modern bioanalytical laboratory. Timothy Sangster has been with Charles River Laboratories since September 2009. Having worked for Quintiles, Pharmacia, Astrazeneca and Huntingdon Life Sciences, he has gained experience over 17 years in both CRO and pharmaceutical environments, and also in both Europe and the USA. Specific areas of interest over the past years have been microchromatography, sample preparation and matrix effects, to name a few. Mike Oliver has held the position of Global Product Manager for sample preparation at Thermo Fisher Scientific since 2010, being responsible for the development and introduction of new innovative technologies such as SOLA™ to the market place. Prior to this role, Mike has worked for two leading MS vendors over a 9­year period, being responsible for biotechnology sales within the UK and providing application solutions for proteomic and metabolic workflows based on high-resolution LC-MS platforms, respectively. Mike holds a PhD in MS and Biochemistry from the MS Research Unit, University of Wales, Swansea, UK.

Recommendations on bioanalytical method stability implications of co-administered and co-formulated drugs by Global CRO Council for Bioanalysis (GCC).

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years.

Conference report: the 3rd Global CRO Council for Bioanalysis at the International Reid Bioanalytical Forum.

The 3rd Global CRO Council Closed Forum was held on the 3rd and 4th July 2011 in Guildford, United Kingdom, in conjunction with the 19th International Reid Bioanalytical Forum. In attendance were 21 senior-level representatives from 19 CROs on behalf of nine European countries and, for many of the attendees, this occasion was the first time that they had participated in a GCC meeting. Therefore, this closed forum was an opportunity to increase awareness of the aim of the GCC and how it works, share information about bioanalytical regulations and audit findings from different agencies, their policies and procedures and also to discuss some topics of interest and aim to develop ideas and provide recommendations for bioanalytical practices at future GCC meetings in Europe.

Stable-labeled analogues and reliable quantification of nonprotein biomarkers by LC-MS/MS.

BACKGROUND: The aim was to develop, and establish as suitable to begin assessment by full validation, a quantitative LC-MS/MS method for asparagine in human plasma. Therein, to utilize a stable-labeled analogue of asparagine to act as surrogate analyte, producing complete calibration curves and corresponding QC samples and another m/z distinct stable-labeled analogue to act as internal standard. RESULTS: From two candidates, the surrogate analyte was selected through statistical comparisons of concentration-response data and the resultant method employed protein precipitation and LC on an unmodified silica column with multiple reaction monitoring detection mode. The calibration range was 50-10,000 ng/ml. CONCLUSION: This method was successfully proven to meet the accuracy and precision acceptance criteria of current bioanalytical method validation guidelines.

A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis.

Metabonomic/metabolomic studies can involve the analysis of large numbers of samples for the detection of biomarkers and confidence in the analytical data, generated by methods such as GC and HPLC-MS, requires active measures on the part of the analyst. However, quality control for complex multi-component samples such as biofluids, where many of the components of interest in the sample are unknown prior to analysis, poses significant problems. Here the repeat analysis of a pooled sample throughout the run, thereby enabling the analysis to be monitored and controlled using targeted inspection of the data and pattern recognition, is advocated as a pragmatic solution to this problem.

Application of microbore HPLC in combination with tandem MS for the quantification of rosuvastatin in human plasma.

The potential of microbore high-performance liquid chromatography (HPLC) in combination with tandem mass spectrometry (MS/MS) for the sensitive detection of rosuvastatin (Crestor) in human plasma was investigated. Three microbore HPLC columns with internal diameters (i.d.) of 0.5, 1.0 and 2.0 mm were evaluated for column efficiency and mass sensitivity, and compared to a conventional 4.6 mm i.d. column. The 2.0 and 1.0 mm i.d. columns performed very well while the 0.5 mm i.d. column was slightly less efficient, this is probably due to a lower packing density. Good results with respect to gains in mass sensitivity compared to the conventional analytical column were achieved with the 2.0 and 1.0 mm columns. Thus, the 2.0 mm i.d. column had an improved signal-to-noise (S/N) ratio of 16 whilst the 1.0 mm i.d. column had an improved S/N ratio of greater than 70. Experiments with the 1.0 mm i.d. HPLC column were performed to determine the robustness of the microbore method for human plasma extracts after sample preparation using solid-phase extraction (SPE). A number of problems were encountered with extracts including high backgrounds, the blocking of the column and a rapid deterioration in column performance. The blocking of the column by particulates was solved by off-line filtration of the sample extracts. Peak tailing of the analytes and high background, both of which were due to endogenous interferences in the extracts, were eliminated using gradient elution. Using these approaches over 500 injections of plasma extracts were achieved without significant deterioration in assay performance. Quantities of rosuvastatin of 0.3 pg on-column could be detected and cross-validation experiments demonstrated that the conventional and the microbore HPLC-MS/MS methods provided similar information on the concentration of rosuvastatin but with greatly reduced sample consumption using the microbore method.