New Peak Detection Performance Metrics from the MAM Consortium Interlaboratory Study

Abstract

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography–mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.

Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms

“…The method has since been adopted in QC to release testing and MAM consortium has been formed to harmonize best practices and generate methodologies in the facilitation of the widespread integration of the MAM platform in QC labs ( Millán-Martín et al, 2020 ). Recently, industry-wide inter-laboratory study (28 participating labs) using pre-digested samples of the NISTmAb RM 8671 and pre-defined experimental protocol has been conducted to test the robustness of MAM methods ( Mouchahoir et al, 2021 ) ( Supplementary Table S7 ). A version of the methods suitable for process development has been successfully implemented in three Sanofi sites with automatization of sample preparation as well as data interpretation ( Song et al, 2021 ).…”

Interlaboratory Studies Using the NISTmAb to Advance Biopharmaceutical Structural Analytics

“…This series of reports provided a useful baseline to identify measurements for which method advancement and regulatory assimilation would benefit from additional technology development and interlaboratory studies. Highly focused interlaboratory studies have since been reported by NIST and independent communities to harmonize best practices, deepen community consensus on method performance, and document a baseline performance upon which future method evolution may be based ( DeLeoz et al, 2017 ; Hudgens et al, 2019a ; Brinson et al, 2019 ; Coffman et al, 2020 ; Srzentić et al, 2020 ; Mouchahoir et al, 2021 ). A number of those interlaboratory studies are reviewed here, with the intention to spur future partnerships to target additional assays and/or method evolution through well-planned interlaboratory studies.…”

“…(B) Corresponding dates and key milestones for each NISTmAb interlaboratory study (MAM, glycosylation, NMR HOS, and HDX-MS). a MAM New Peak Detection Publication ( Mouchahoir et al, 2021 ). b MAM Attribute Analytics Publication (In progress).…”

Enhancing the multi-attribute method through an automated and high-throughput sample preparation

“…Importantly, specific setting for new peak detection were used to look for species ≥ 0.1% of the TIC signal and that had a 5× fold change, in line with parameters previously. 18 No new peaks were observed between the six manual preparations prepared by two analysts and the three automated preparations performed on the Hamilton 1 system. These data demonstrate the ability of the automation to reliably reproduce the manual sample preparation.…”