Characterization of Residual Impurities in Gene Therapy Drug Products

Characterization of residual impurities for gene therapy drug products is particularly challenging due to the complex nature of the final products as well as the complicated processes required to manufacture them. As these products advance through clinical development, the identification, characterization, and control of the process- and product-related impurities are important to define early on, and require careful assessment of impurity clearance and risk related to each impurity. This talk will focus on risk assessment and characterization of product-related impurities in lentiviral vector-based gene therapy products.

Predicting Viral Clearance Through the Use of Non-Infectious MVM and RVLP Surrogates

Key Learning Objectives • Learn how viral clearance prediction is possible using non-infectious mock virus particles that mimic the physiochemical properties of live mammalian viruses • Understand how this approach can be applied to downstream efforts such as design of experiments and high throughput screening, and can help facilitate process development/optimization • Review several case studies utilizing MockV MVM and RVLP particles in a BSL-1 lab setting.

Best Practices in HCP Assay Development and Integration of Advanced Orthogonal Methods

Best practices in HCP immunoassay development, common mistakes and misconceptions that can misguide assay developers, and advanced orthogonal methods of immunoaffinity chromatography and mass spectrometry to fully qualify HCP ELISA and characterize individual HCPs in in-process and drug substance samples

Best Practices in Host Cell Protein Assay Qualification and Bridging to a New Assay

A case study using a specific HCP immunoassay and advanced orthogonal Antibody Affinity Extraction (AAE™) and Mass Spectrometry (MS) methods for assay qualification is presented. Data showing HCP identification by MS in product harvest, in–process samples and final drug substance is reviewed. We also discuss integration of MS proteomics methods with ELISA and AAE for a comprehensive characterization of HCP impurities, and how these data-driven approach aids in objective determination whether a process–specific assay is necessary and superior to a well–developed generic or platform method.

A Quality by Design Approach to Viral Clearance_Predicting LRV through the Use of a Non-Infectious MVM Surrogate

To determine viral clearance efficacy of biomanufacturing steps, viruses are “spiked” into in-process solutions, processed and analyzed for reduction. Due to the infectivity of these viruses, studies are conducted in BSL-2 facilities. Costs and logistics limit analysis during process development. Discussed here are results from several studies that utilized a non-infectious Mock Virus Particle (MVP) as an MVM surrogate. The results demonstrated the value to be gained from such a QbD approach during process optimization.