Outsourcing Analytical Testing for Biologics – Perspective from a CRO Point of View

Biologics are large molecules with inherently complex structural heterogeneity. Thus, the analytical tests to support CMC (Chemical, Manufacturing and Controls) activities of biologics need to be highly sophisticated to reveal the multifaceted quality attributes. As biopharmaceutical companies are increasingly outsourcing analytical testing to CROs (contract research organizations), the paradigm has shifted for CROs from merely being a pair of extra testing hands to problem-solvers. The new trend is driving CROs to hire top-tier scientists to provide expert solutions for clients with in-depth characterization of the quality attributes. This analysis is performed using cutting edge technologies for structural elucidation, post-translation modification, and degradation pathways, etc. In the meantime, the modalities of biologics are becoming more and more complex, such as antibody drug conjugates, PEGylated proteins, conjugate vaccines, fusion proteins, and gene and cell based therapies. In light of this complexity, biopharmaceutical and biotech companies are demanding innovative and creative solutions from CROs.

The advent of revolutionary technologies offers new instruments to advance analytical science. Many analytical methods are rapidly evolving. For example, high-resolution mass spectrometry enables top-down, or middle-down approaches to characterize structure and modification of the macromolecules, in addition to traditional bottom-up peptide mapping; the workflow for N-linked glycan analysis is integrated with highly active PNGase F and a novel probe for both fluorescence and mass detection, while new endoglycosidase for O-linked glycan is becoming commercially available; capillary electrophoresis is replacing traditional slab gel for SDS-PAGE, IEF and Western blotting. Advances in instrumentation for surface plasmon resonance (SPR) and bio-layer interferometry (BLI) techniques make it feasible for routine testing of receptor binding kinetics. In addition, the Solo VPE technologyenables direct and neat determination of protein concentration without the need for sample dilution and thus received rapid acceptance in the biopharmaceutical industry when it was introduced.

At the center of the field, regulatory agencies have provided specific guidelines for large molecule analytical testing. In the “Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use” document, the US Food and Drug Administration (FDA) requires that “a precise and thorough characterization of antibody structural integrity, specificity, and potency should be conducted and described in the IND.” While the guidance pertained specifically to monoclonal antibody products for human use, it can be applied to all other biologics in general. In July 2017, FDA issued the guidance for “Analytical Procedures and Methods Validation for Drugs and Biologics”, which complements the International Conference on Harmonisation (ICH) guidance Q2(R1), “Validation of Analytical Procedures: Text and Methodology Q2(R1)” for developing and validating analytical methods. The guidance provided general requirements for analytical procedure development and validation using statistical tools, for example, analysis of variance (ANOVA) to assess regression analysis.

In response to the demand from biopharmaceutical and biotech companies, as well as the regulatory agencies, CROs also need to modernize the analytical capabilities to support clients and solve the most challenging problems for large molecules, as well as provide service for release and stability testing. This webinar will provide the audience with a general explanation of how CROs can support biologics testing, ranging from product release and stability to in-depth structural elucidation and degradation pathway studies.

Speaker

Min Zhao, Ph.D., Director, Analytical Services for Biologic Product - CMC Services, Frontage Laboratories, Inc.

Dr. Min Zhao is the Director of Analytical Services for Biologic Product at CMC Services, Frontage Laboratory in Exton, Pennsylvania. With more than 17 years of experience working with a variety of modalities of biologic products, including mAb, ADC, PEGylated proteins and conjugated vaccines, he is proficient in analytical method development and validation to support biologics product development, CMC and regulatory filing. As an industrial expert, he is an expert in analytical methodologies, ranging from chromatography, electrophoresis, mass spectrometry and spectroscopy. In his past experience, he led reference standard qualification, stability, forced degradation, comparability and biosimilarity studies.

Dr. Min Zhao previously held managerial and scientific positions with increasing responsibilities at Adello Biologics, Oncobiologics, Pfizer, Progenics, Johnson and Johnson, etc. He received his Ph.D. in Biological Chemistry from the University of Minnesota at Twin Cities before he became the postdoctoral research associate at Howard Hughes Medical Institute at UCLA.

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