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Pharmaceutical Technology LABORATORY BEST PRACTICES 2018 43 Gorm Yoder, scientific director of analytical small molecule at Janssen, identifies analytical innovations for both small and large molecules. Large-molecule drug development focus is on monoclonal antibodies (mAbs), ADCs, peptides, and oligonucleotides. Chris Roberts has multiple roles as a professor in chemical and biological engineering at the Univer- sity of Delaware, associate Institute Director at the National Institute for Innovation in Manufacturing of Biopharmaceuticals, and director of the Biomo- lecular Interaction Technologies Center. Research goals are to develop better mechanistic understand- ing and predictive models for protein stability, physical interactions of proteins with their environ- ments, critical drug formulation properties such as viscosity, visual appearance, and particle formation, "essentially anything in the space of physical char- acterization and physical behavior of the protein in solution and sometimes in solid state," he says. Information is used to build better predictive ap- proaches, some are qualitative, and some are more quantitative, which are used in computer modeling. Characterization is paramount Protein characterization is a crucial part of the overall quality control strategy for biopharmaceutical drugs including an understanding of the product attributes. "When proteins are produced by a biological system, they create a lot of impurities and product-related sub- stances that need a number of tools to characterize the primary structure, the higher-order structures, and the biological activity," says Kendrick. Types of analysis depend on the product and can include vari- ous glycoforms; protein aggregates; covalent changes like oxidation, deamidation, and misincorporation; and product-related impurities that need character- izing and understanding to form a control strategy to control the purity and content of a drug to ensure safety and efficacy, he explains. KBI Biopharma works on a variety of biologics including antibodies, cytokines, proteins, pegylated peptides, cell-based therapies, and viruses. In addition to manufacturing and process development, the com- pany characterizes product structures, purity, stability and degradation profiles, develops and runs analyti- cal methods for quality control, performs formula- tion development, and consults on regulatory filings from pre-investigational new drug application (IND) to commercial manufacturing. Immunogen is developing ADCs for the treatment of various types of cancer. The conjugation process can be dependent on the type of linker you are using and the type of drug, but, the process of doing the conjugation itself can disrupt the structure of the pro- tein and alter its physical and biophysical properties and its stability, says Fleming. "We are heavily reli- ant on protein characterization to look at issues that come from the nature of the ADC, how hydrophobic they become once you do the conjugation, how that impacts the stability, whether the HOS is modified in some way that affects the stability, and whether it affects the solubility during the conjugation process." Immunogen scientists use analytical techniques to look at stability and to help develop the formulation of the ADC. "Eventually, we take that forward into developing the drug product processes where we—in a lot of cases—use a lyophilization procedure to help stabilize the drug product," Fleming says. "We use protein characterization and analytics to advance programs through different phases in clini- cal development and eventually commercial develop-