Next Generation Sequencing for Adventitious Agent Detection in Viral Vaccine Manufacturing
A. S. Khan
US Food and Drug Administration, Silver Spring, MD
Review considerations for using next generation sequencing (NGS) to enhance adventitious virus detection to further assure vaccine safety
Adventitious viruses are a major safety concern in biologics, especially for live viral vaccines, where manufacturing does not generally include rigorous viral clearance steps (inactivation and removal). Detection of known and unknown adventitious viruses is particularly important when new cell substrates are used for development of vaccines or to accelerate production and increase vaccine yield. Next generation sequencing (NGS) is an advanced nucleic acid-based technology with capabilities for broad and rapid virus detection. Recent progress in developing NGS technologies for adventitious virus detection in biologics has focused on method standardization and assay validation . The potential use of NGS as an alternative assay for the currently used in vivo and in vitro assays for adventitious virus detection in vaccines and other biologics is under consideration. The use of NGS can aid in reducing animal use and address limitations of in vitro assays for broadly detecting both known and unknown viruses [2,3]. This presentation will include the current general thinking for using NGS for adventitious virus detection to supplement or replace the currently recommended tests and the regulatory considerations for implementation of NGS in the testing and qualification for various steps of viral vaccine manufacturing.
1. Khan AS, Ng SHS, Vandeputte O, et al. A multicenter study to evaluate the performance of high-throughput sequencing for virus detection. mSphere 2017 2:e0037-17.
2. Victoria JG, Wang C, Jones MS, et al. Viral nucleic acids in live-attenuated vaccines: detection of minority variants and an adventitious virus. J. Virol. 2010 84:6033–40.
3. Ma H, Galvin TA, Glasner DR, et al. Identification of a novel rhabdovirus in Spodoptera frugiperda cell lines. J Virol. 2014 88:6576-85.
Advanced Micro-Modular Manufacturing Systems for the Production of Vaccine Antigens
J. C. Love
Koch Institute at MIT, Cambridge, MA
Discuss a potential new approach to realize vaccine production using new technologies for biomanufacturing
Manufacturing of vaccines and other critical medicines for global health today relies on a consolidated, centralized manufacturing network comprising a small number of global suppliers. This supply network has enabled economies of scale in production to realize low-cost products. Despite this well-established model, annually there are disruptions in supply chains and missed targets for immunization coverage. This talk will consider a new potential alternative that relies on highly integrated and automated manufacturing technologies that could facilitate regional manufacturing networks. End-to-end production systems and next-generation host engineering fit for purpose along with integrated process development concepts suggests new platform-like capabilities for recombinant vaccine and biopharmaceutical production is feasible.
Specifically, this talk will present an example study for a trivalent recombinant subunit vaccine to rotavirus. In this work, molecular design and optimization have facilitated new intensified manufacturing processes that reduce the number of operations and used straight-through purification and continuous production on an automated system. The talk will consider economic models that highlight the key drivers essential to achieving commoditized costs of manufacturing for these types of vaccines. In addition, the talk will consider how simplified logistics and quality assurance may be achieved, and what barriers remain to realize widely distributed manufacturing capacity.
1. Crowell LE, Lu AE, Love KR, et al. On-demand manufacturing of clinical-quality biopharmaceuticals. Nature Biotechnology. 2018;36(10):988-995. doi:10.1038/nbt.4262.
2. Love KR, Dalvie NC, Love JC. The yeast stands alone: the future of protein biologic production. Current Opinion in Biotechnology. 2018;53:50-58. doi:10.1016/j.copbio.2017.12.010.
3. Dalvie NC, Leal J, Whittaker CA, et al. Host-Informed Expression of CRISPR Guide RNA for Genomic Engineering in Komagataella phaffii. ACS Synth Biol. December 2019. doi:10.1021/acssynbio.9b00372.
4. Jiang H, Horwitz AA, Wright C, et al. Challenging the workhorse: Comparative analysis of eukaryotic micro-organisms for expressing monoclonal antibodies. Biotechnology and Bioengineering. 2019;116(6):1449-1462. doi:10.1002/bit.26951.