Interview Xiong
development for characterization and quantitation of antibody drug conjugates (ADCs), and well as host cell protein (HCP) quantitation. These topics were widely discussed this year and were focal points for many major conferences such as the Workshop on Recent Issues in Bioanalysis (WRIB), Clinical and Pharmaceutical Solutions through Analaysis (CPSA), as well as the American Society of Mass Spectrome- try (ASMS). For example, as the technology around ADCs has progressed it has pushed bioanalytical sci- entists to further explore novel ways in which to char- acterize and quantify these molecules. For example, the inherent heterogeneous nature of ADCs makes developing a comprehensive pharmacokinetic (PK) profile extremely challenging. However, utilizing data- independent acquisition technology (SWATH®
acqui-
sition) on a high-resolution accurate mass MS, such as a TripleTOF®
system, scientists can quantify total anti-
body, conjugated antibody, and the free drug (with or without linker) by acquiring a single data file. Imple- mentation of this type of novel workflow is a powerful tool in ADC bioanalysis as it provides a fast and com- prehensive PK profile, providing a more complete view of the biotherapeutic.
Q What do you think is the greatest technological obstacle faced by bioanalysts
today? It remains true that a critical technical challenge is around understanding potential quantitation discrep- ancies between LBA and LC-MS/MS assays for bio- therapeutics. These variable quantitation differences have triggered industry-wide discussions for several years. Quantitative discrepancies can arise from speci- ficity differences between sample preparation methods used in each analysis, or it can be due to differential affinities of LBAs to molecules such as ADCs that may have heterogeneous drug loads, among other things. Having a greater level of understanding around the exact form of the therapeutic target being detected in each assay can help to explain and resolve these dis- crepancies. There is also an opportunity here to utilize a combination of techniques from LBA, to MS, and hybrid LBA–LC-MS as complementary tools to more
thoroughly characterize and quantify these increas- ingly complex biomolecules.
Looking to the future
Q What are you excited about working on in 2016? I am excited to continue working on high-impact solu- tions for our bioanalysis customers. I think we’ll see further incorporation of lower flow micro-liquid chro- matography to drive down lower limits of quantitation, as well as SWATH®
-based acquisition, and further
advancements in selectivity using differential mobility separations. We’re going to continue exploring hybrid LBA–LC-MS/MS methodologies and ways to incor- porate higher multiplexing capabilities to push our routine sample to answer speeds. We are dedicated to tackling the toughest problems in the field and focus- ing our effort on further simplifying complex bioanal- ysis quantitation by creating user friendly solutions from sample prep to analysis and reporting.
Q What do you think will be the top research topics in the next few years?
This next year I see monoclonal antibody, biosimilar, and ADC quantitation continuing to be hot areas, with discussion expanding into streamlining assay validation, regulatory processes and data management. Moreover, the growth of novel therapeutic configura- tions such as bispecific antibodies, nanobodies, bispe- cific T-cell engagers, as well as oligonucleotides, will bring in higher requirement on assay sensitivity and selectivity, driving further technological advancements and innovation in LC-MS/MS.
Financial & competing interests disclosure The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or fi- nancial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony,
grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this
manuscript.
Bioanalysis (2016)
future science group
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