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NOVEL ANALYTICAL TECHNOLOGIES FOR CHARACTERIZATION AND QC OF NEXT-GENERATION VACCINES
- 1. Novel analytical technologies for characterization and QC of next- generation vaccines September 16, 2022 Fredrik Sundberg Global Director Cytiva Cytiva © 2022 – All Rights Reserved
- 2. Cytiva Outline • Understanding global bioprocessing trends and regulatory update • Introducing novel approaches for improving vaccine characterization • Case-study: Implementation of biosensors to accelerate purification and quality control of viral vectors (AdV, AAV) Cytiva © 2022 – All Rights Reserved
- 3. Cytiva Modern technology has accelerated vaccine development 3 Dec 31 Jan 3 Jan 9 Jan 30 Feb 6 Feb 25 China: Reports dozens of cases of pneumonia with unknown cause China: Researcher identifies a new virus WHO announces discovery of a novel coronavirus (2019-nCoV) 2019-nCoV genome sequenced FDA authorizes diagnostic test First drugs enter clinical trials 2019-nCoV 1981 1982 1983 1984 1987 1996 New York: Reports mysterious illness Term AIDS is coined HIV identified as cause of AIDS First diagnostic test approved First drug approved (AZT) Protease inhibitors are introduced HIV Modern drug discovery platforms and sequencing techniques have helped us better identify and understand emerging pathogens, and bring new therapies to the clinic faster. https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview/ending-epidemic-timeline https://www.who.int/news-room/detail/27-04-2020-who-timeline---covid-19 Cytiva © 2022 – All Rights Reserved
- 4. Cytiva Accelerate time-to-market by bridging the gap between R&D and QC labs Trends and applications: • Developability and manufacturability • Impurities (aggregation, HCP, etc.) • Comparability and stability • Release testing (ID, potency, etc.) • Higher throughput and automation • System and method validation Information-rich analytics take center stage! 4 Analytical tools and market trends Cytiva © 2022 – All Rights Reserved Cell line development Upstream development process Downstream development process Clinical manufacturing Manufacturing Analytical development and quality control
- 5. Cytiva We need a predictable, repeatable, and cost-effective process 5 Cytiva © 2022 – All Rights Reserved QC-friendly potency and HCP assays are the weakest analytical links in the total control strategy
- 6. Cytiva SPR is a key technology for vaccine R&D and manufacturing Broad range of applications: • Study structure, function, and mechanism of action • Virus quantification • Antibody identification and characterization • Immune response 6 Cytiva © 2022 – All Rights Reserved
- 7. Cytiva • mRNA-based vaccines • DNA-based vaccines • Vector-based vaccines • VLP • Recombinant vaccines • Peptide-based vaccines • Adjuvants 7 Some vaccines developed using SPR technology Cytiva © 2022 – All Rights Reserved
- 8. Cytiva Assay setup • Biacore™ X100 system • Histidine (His)-tagged 2019-nCoV S or His-tagged SARS-CoV RBD-SD1 was captured onto Sensor Chip NTA Summary • Cryo-EM structures of ACE2 bind to 2019-nCoV S ectodomain with a binding mode that is similar to SARS-CoV S. • Biacore assay revealed that compared to SARS-CoV, ACE2 has 10- to 20-fold higher affinity to 2019-nCoV S. • This could potentially explain why 2019-nCoV can spread so easily between people. 8 SPR provides information about function and mechanism of action From Wrapp et al., "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation" Science. 13 Mar 2020: Vol. 367, Issue 6483, pp. 1260-1263 DOI: 10.1126/science.abb2507 ACE2 Sensor chip NTA 2019-nCoV Cytiva © 2022 – All Rights Reserved
- 9. Cytiva Common challenges during vaccine development and production • Sampling Scientists perform hundreds of tests per run, both in development and production. • Time to results Tests can take a few minutes, hours, or days – and in vivo testing is particularly lengthy. • Assay performance The accuracy of tests can vary. 9 Cytiva © 2022 – All Rights Reserved
- 10. Cytiva Improving productivity in downstream processing and QC SPR impact in process development and QC Cell culture Cell harvesting Virus clearance Ultrafiltration Intermediate Polishing Sterile filtration QA/QC 10 Process step Mouse IgG ELISA Biacore™ assay Harvest pool 7 h 2 h 30 KD diafiltration 7 h 2 h IEX Chromatography 7 h 2 h TOTAL TIME 21 h 6 h Courtesy of Boehringer-Ingelheim Cytiva © 2022 – All Rights Reserved 20 GxP approved SPR release assays
- 11. Cytiva Higher sensitivity and shorter analysis time than the SRID assay Biacore™ assay SRID Dynamic range Concentration 0.5–10 µg HA/mL 8–30 µg HA/mL Sensitivity LOD 0.5 µg HA/mL 6 µg HA/mL LOQ 1.0 µg HA/mL 13 µg HA/mL Precision Number of samples with CV < 5% 97% 18% Accuracy Range 95%–105% 90%–110% Analysis time for 100 samples Hands-on time 1–2 h 6–8 h Total time 15–16 h 20–22 h 11 Cytiva © 2022 – All Rights Reserved
- 12. Cytiva Need for higher assay precision and high degree of automation Production Purification Measurements performed for AAV • Infectious titer • Virus titer • Host cell impurities • Characterization Labor intensive, low-precision techniques • qPCR • ELISA • Western blot Clarification Concentration and buffer exchange Capture Polishing Concentration and buffer exchange Sterile filtration Cell lysis and DNA fragmentation AAV production Transfection Cell lysis expansion Cytiva © 2022 – All Rights Reserved
- 13. Cytiva Biacore™ SPR assay principle AAV2 Biacore™ SPR assay principle AAV5 Efficient and repeatable quantitation of AAV2 and AAV5 samples Simple and easy to use - from cell culture to final product Improved precision and higher degree of automation compared to ELISA Cytiva © 2022 – All Rights Reserved
- 14. Cytiva Good correlation between Biacore™ assay and ELISA titer assay 14 Analysis of process samples ELISA Biacore™ assay Cytiva © 2022 – All Rights Reserved
- 15. Cytiva Validation of analytical instruments and assays 15 Extended SPR validation support • Training course • Validation guideline Analyst GLP/GMP and system training Instrument qualification Key reagents Assay development Validation Evaluation of specificity and linearity Accuracy (or recovery): 70% – 130% Precision: RSD ≤ 20 % Parameters and acceptance criteria • Re-validation? • Change control? • Data management? • Technology transfer? Cytiva © 2022 – All Rights Reserved
- 16. Cytiva Summary Improved assay performance and productivity Information-rich analytical platform technologies can bridge the gap from R&D to QC and improve bioprocess productivity. Robust Biacore™ SPR AAV titer assays was applied across the bioprocess workflow. Standardizing validation approaches will help support further implementation of novel assay methodologies in regulated applications. 16 Cytiva © 2022 – All Rights Reserved
- 17. Thank you cytiva.com Fredrik Sundberg fredrik.sundberg@cytiva.com 17 Cytiva © 2022 – All Rights Reserved
- 18. cytiva.com Cytiva and the Drop logo are trademarks of Global Life Sciences IP Holdco LLC or an affiliate. ÄKTA, Amersham, Biacore, DIGE, and Superdex are trademarks of Global Life Sciences Solutions USA LLC or an affiliate doing business as Cytiva. Nucala, and Tanzeum are registered trademarks of the GlaxoSmithKline (GSK) group of companies. Zarxio and Binocrit are registered trademarks of Novartis AG. Remsima is a registered trademark of Celltrion Inc. Cyltezo is a trademark of Boehringer Ingelheim International GmbH. © 2018-2022 Cytiva All goods and services are sold subject to the terms and conditions of sale of the supplying company operating within the Cytiva business. A copy of those terms and conditions is available on request. Contact your local Cytiva representative for the most current information. For local office contact information, visit cytiva.com/contact CY26102-05JAN22-PP Cytiva © 2022 – All Rights Reserved