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Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) represent a promising frontier in therapeutic antibody development, offering unique capabilities not achievable with traditional monoclonal antibodies. Despite their potential, significant challenges remain due to their increased molecular complexity. One prominent challenge is the correct assembly of light and heavy chains, as improper pairing leads to mispaired or incompletely assembled species that lack therapeutic efficacy and possess undesired properties, impairing the developability, manufacturability, and safety. There is a critical need for rapid, sensitive analytical tools to monitor and control these undesired species and ensure the quality assessment of bsAbs and msAbs. To address this need, we present a novel high-throughput, format-agnostic intact mass workflow that significantly enhances the efficiency of detecting and quantifying biotherapeutic products and related impurities. This workflow integrates automated sample preparation, novel high-resolution rapid mass detection powered by SampleStream-MS, and an advanced data analysis pipeline. It offers increased throughput and data quality while substantially reducing analysis turnover time and labor. This was demonstrated in a pilot program where ∼800 multispecific antibodies were processed in 10 working days. The article details the evaluation and validation of our method, demonstrating its repeatability and intermediate precision in terms of measurement accuracy and relative quantification of various product-related species. We underscore the transformative potential of this end-to-end high-throughput workflow in expediting bispecific and multispecific antibody discovery, optimizing production processes, and ensuring high-quality development and manufacturing for therapeutic antibodies.

Background: Latin American and Caribbean populations include three main ethnic groups: indigenous people, people of African descent, and people of European descent. We investigated ethnic inequalities among these groups in population coverage with reproductive, maternal, newborn, and child health interventions., Methods: We analysed 16 standardised, nationally representative surveys carried out from 2004 to 2015 in Latin America and the Caribbean that provided information on ethnicity or a proxy indicator (household language or skin colour) and on coverage of reproductive, maternal, newborn, and child health interventions. We selected four outcomes: coverage with modern contraception, antenatal care coverage (defined as four or more antenatal visits), and skilled attendants at birth for women aged 15-49 years; and coverage with three doses of diphtheria-pertussis-tetanus (DPT3) vaccine among children aged 12-23 months. We classified women and children as indigenous, of African descent, or other ancestry (reference group) on the basis of their self-reported ethnicity or language. Mediating variables included wealth quintiles (based on household asset indices), woman's education, and urban-rural residence. We calculated crude and adjusted coverage ratios using Poisson regression., Findings: Ethnic gaps in coverage varied substantially from country to country. In most countries, coverage with modern contraception (median coverage ratio 0·82, IQR 0·66-0·92), antenatal care (0·86, 0·75-0·94), and skilled birth attendants (0·75, 0·68-0·92) was lower among indigenous women than in the reference group. Only three countries (Nicaragua, Panama, and Paraguay) showed significant gaps in DPT3 coverage between the indigenous and the reference groups. The differences were attenuated but persisted after adjustment for wealth, education, and residence. Women and children of African descent showed similar coverage to the reference group in most countries., Interpretation: The lower coverage levels for indigenous women are pervasive, and cannot be explained solely by differences in wealth, education, or residence. Interventions delivered at community level-such as vaccines-show less inequality than those requiring access to services, such as birth attendance. Regular monitoring of ethnic inequalities is essential to evaluate existing initiatives aimed at the inclusion of minorities and to plan effective multisectoral policies and programmes., Funding: The Bill & Melinda Gates Foundation (through the Countdown to 2030 initiative) and the Wellcome Trust., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)