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Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 15 which critical quality attributes (CQAs) can affect that, and MAM enables better understanding of the product and these effects," said Josephs. Thermo Fisher Scientific, whose products were used in some of the original development work for MAM, has developed a portfolio of analyti- cal products and software specifically designed to work with MAM, as have other vendors such as Sciex. "MAM allows the direct assessment of biotherapeutic attributes to improve product un- derstanding," said Sean McCarthy, global techni- cal market manager for biologics at Sciex, during a webcast presented by BioPharm International in May, 2018 (3). "It aligns well with the International Council for Harmonization's (ICH's) guidelines for product and process understanding, quality by design (QbD), and product lifecycle management, and can be applied across a range of biopharma- ceutical developmental stages," he said. Streamlining impurity testing Conventionally, a large number of tests are used to detect impurities that are introduced by deami- dation, isomerization, oxidation, and glycosyl- ation during biopharmaceutical manufacturing (2). MAM combines peptide mapping with mass spectrometric analysis, allowing developers to use a unified method to monitor a wide range of impu- rities, the absence of which is critical to the qual- ity of complex biopharmaceutical products such as monoclonal antibodies. The approach was pioneered by scientists at Amgen, led by Richard Rogers. They had ap- proached Thermo Fisher Scientific with the goal of developing hardware and software that would utilize peptide mapping and offer an alternative to the daunting number of traditional character- ization and release assays required, explained Jo- sephs (2). Their work resulted in the publication of a seminal paper in 2015 (4), which was updated at the end of 2017 (5). In 2016, Rogers, now with Just Biotherapeutics, established the MAM Consor- tium, a group of biopharmaceutical manufactur- ers, vendors, and researchers, to help standardize approaches to MAM and drive increased accep- tance of the approach throughout the industry. As Josephs said, efforts are continuing on all fronts, and a number of papers are being published to advance the method. Interest in the consortium is also growing, and currently, active participants include the National Institute of Science and Technology (NIST) and FDA; biopharmaceuti- cal manufacturers—not only Amgen but Biogen, Genenetech, Just, MedImmune, Merck, Pfizer, and Regeneron—as well as mass spectroscopy equip- ment vendors Agilent, Fujifilm, Genedata, Protein Metrics, Sciex, Thermo Scientific, and Waters. In 2017, a standard monoclonal antibody devel- oped by NIST and Medimmune, was provided to consortium members as a reference sample that would allow biopharmaceutical manufacturers to run tests using MAM to share best practices, see how their approaches may differ, and help standard- ize methods. Studies using this material are pro- gressing as more papers are published, Josephs said. References 1. A. Shanley, PharmTech, 42(7) pp 42-45 (2018). 2. BioPharm International Webcast, "Multi Attribute Methods: Advancing Biopharmaceutical Discovery, Development, and Manufacturing," October 3, 2018. 3. BioPharm International Webcast, "Multi Attribute Methods for Biotherapeutics Using LC-MS," May 17, 2018. 4. R. Rogers et al., MAbs 7(5), pp 881-890 (2015). 5. R. Rogers et al., AAPS Journal 20(1) (2017). PT