13 research outputs found
Repeat Analysis and Incurred Sample Reanalysis: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team
The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis. With international representation from Europe, Latin America, North America and the Asia Pacific region, the team first collated common practices and guidance recommendations and assessed their suitability from both a scientific and logistical perspective. Subsequently, team members developed best practice recommendations and refined them through discussions and presentations with industry experts at scientific meetings. This review summarizes the team findings and best practice recommendations. The few topics where no consensus could be reached are also discussed. The A7 HT recommendations, together with those from the other GBC teams, provide the basis for future international harmonization of regulated bioanalytical practices
Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group
The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) Metabolite Bioanalysis Working Group (WG) on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from IND enabling studies, and Phase I, Phase II, and Phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development
Sensitive, High-Throughput, and Robust Trapping-Micro-LC-MS Strategy for the Quantification of Biomarkers and Antibody Biotherapeutics
For
LC-MS-based targeted quantification of biotherapeutics and
biomarkers in clinical and pharmaceutical environments, high sensitivity,
high throughput, and excellent robustness are all essential but remain
challenging. For example, though nano-LC-MS has been employed to enhance
analytical sensitivity, it falls short because of its low loading
capacity, poor throughput, and low operational robustness. Furthermore,
high chemical noise in protein bioanalysis typically limits the sensitivity.
Here we describe a novel trapping-micro-LC-MS (T-μLC-MS) strategy
for targeted protein bioanalysis, which achieves high sensitivity
with exceptional robustness and high throughput. A rapid, high-capacity
trapping of biological samples is followed by μLC-MS analysis;
dynamic sample trapping and cleanup are performed using pH, column
chemistry, and fluid mechanics separate from the μLC-MS analysis,
enabling orthogonality, which contributes to the reduction of chemical
noise and thus results in improved sensitivity. Typically, the selective-trapping
and -delivery approach strategically removes >85% of the matrix
peptides
and detrimental components, markedly enhancing sensitivity, throughput,
and operational robustness, and narrow-window-isolation selected-reaction
monitoring further improves the signal-to-noise ratio. In addition,
unique LC-hardware setups and flow approaches eliminate gradient shock
and achieve effective peak compression, enabling highly sensitive
analyses of plasma or tissue samples without band broadening. In this
study, the quantification of 10 biotherapeutics and biomarkers in
plasma and tissues was employed for method development. As observed,
a significant sensitivity gain (up to 25-fold) compared with that
of conventional LC-MS was achieved, although the average run time
was only 8 min/sample. No appreciable peak deterioration or loss of
sensitivity was observed after >1500 injections of tissue and plasma
samples. The developed method enabled, for the first time, ultrasensitive
LC-MS quantification of low levels of a monoclonal antibody and antigen
in a tumor and cardiac troponin I in plasma after brief cardiac ischemia.
This strategy is valuable when highly sensitive protein quantification
in large sample sets is required, as is often the case in typical
biomarker validation and pharmaceutical investigations of antibody
therapeutics