Se ha denunciado esta presentación.
Utilizamos tu perfil de LinkedIn y tus datos de actividad para personalizar los anuncios y mostrarte publicidad más relevante. Puedes cambiar tus preferencias de publicidad en cualquier momento.
Implementation of Single-Use
Fermentation Technology
Andrew Lowell
KBI Biopharma, Inc.
Boulder, Colorado
Confidential
2
• KBI Biopharma, Inc. Overview
• Drivers and Strategy for Single-Use Fermentation Implementation
• Coupling...
Confidential
3
Durham, NC (2004)
Mammalian
• Clinical & Commercial (pre-PAI)
cGMP Manufacturing
• Analytical, Formulation,...
Confidential
4
SelexisKBI
Selexis, Geneva, Switzerland
(2017- an affiliate of KBI)
Best in class cell line development &
c...
Confidential
5
• Process & Analytical Development for First in Human
and Clinical Programs
• Late stage commercialization:...
Confidential
6
Microbial Process Development: Built for Speed with Proven Scalability
250mL Scale
• Ambr250®
• Screening
•...
Confidential
7
• Early-phase programs with relatively small pre-clinical and clinical material needs
• Quicker process des...
Confidential
8
• 30-liter pilot system
located in
fermentation
development
laboratory (non-GMP)
• 300-liter SUF is a GMP
s...
Confidential
9
Development of fermentation process into our single-use fermentation platform begins as
early as cell line ...
Confidential
10
• High microbial growth demands exist in aggressive microbial
fermentations
• High oxygen mass transfer ra...
Confidential
11
• Batch phase is
platformed to
support optimal
growth matching
culture demand
• Late growth phase
limits O...
Confidential
12
• Feed rate in growth phase
is optimized to maximize
culture growth while
limiting OUR
• Fermentation proc...
Confidential
13
• Aeration and cooling performance of 300L
single-use system typically superior to 30L pilot
system
• Comp...
Confidential
14
Performance across Single-Use Fermentation Systems at KBI
0
10
20
30
40
50
60
70
80
90
00:00 04:48 09:36 1...
Confidential
15
• Five Single-Use Fermentation Programs through USPD lab to date
400+ x 250mL SUF Fermentations
21 x 30L S...
Confidential
16
• Single-Use fermentation systems have allowed greater throughput and efficiency in
laboratory leading to ...
Confidential
17
Robert Todd – VP, Process Development Aaron Pilling - Director, USPD
Erik Nordwald - Scientist, USPD Emil ...
Próxima SlideShare
Cargando en…5
×

Implementation of End-to-End Disposable Single Use Systems for Rapid Fermentation Process Design to GMP Manufacturing | KBI Biopharma

Authored and Presented by: Andrew Lowell, Erik Nordwald PhD., Thatsinee Johnson, Robert Todd PhD., Aaron Pilling PhD.

  • Inicia sesión para ver los comentarios

  • Sé el primero en recomendar esto

Implementation of End-to-End Disposable Single Use Systems for Rapid Fermentation Process Design to GMP Manufacturing | KBI Biopharma

  1. 1. Implementation of Single-Use Fermentation Technology Andrew Lowell KBI Biopharma, Inc. Boulder, Colorado
  2. 2. Confidential 2 • KBI Biopharma, Inc. Overview • Drivers and Strategy for Single-Use Fermentation Implementation • Coupling Process Design to Boundaries of at-scale Single-Use Fermentors • Challenges and Success of Single-Use Fermentation (SUF) Systems at KBI Implementation of Single-Use Fermentation Technology: Agenda Coupled Process Design to the SUF equipment is enabling 6-7 g/L and 200 OD600nm in soluble processes
  3. 3. Confidential 3 Durham, NC (2004) Mammalian • Clinical & Commercial (pre-PAI) cGMP Manufacturing • Analytical, Formulation, Stability & QC • Mass Spec Core Facility • Cell Based Assays Boulder, CO (2014) Microbial • Strain Development • Process & Analytical Development • Clinical & Commercial (Approved) cGMP Manufacturing • QC, Analytical, Formulation, Stability • Particle Characterization Core RTP, NC (2013) Venture Center, NC (2018) Mammalian • Cell Line Development • Process & Analytical Development • Process Characterization • Small scale Process Validation The Woodlands, TX (2017) Cell Therapy • Process and Analytical Development • cGMP Manufacturing & Testing • Cell Based Assays San Diego, CA (2017) Alliance Protein Labs • Analytical Technologies • Leading AUC expertise KBI Sites KBI’s North America Locations March 2018 Louisville, CO (2018) Elion Labs • Analytical Technologies • Leading Biophysical Chara
  4. 4. Confidential 4 SelexisKBI Selexis, Geneva, Switzerland (2017- an affiliate of KBI) Best in class cell line development & candidate selection technologies KBI Leuven, BE (2018) Analytical, Formulation and QC services for GMP & non-GMP product testing European Offerings
  5. 5. Confidential 5 • Process & Analytical Development for First in Human and Clinical Programs • Late stage commercialization: Process Characterization, Process Validation • Technology Transfer, NPI, Materials Management • Two Manufacturing Streams: 1500L and 100L SS, 300L Single-Use production fermentors • QA/QC (EM, RM, IPC, Release, Stability) • Validation (AM, IOQ, PV) • Operations (MFG, Document Management, Training) • MS&T (Process Engineering, Tech Ops, Modeling) • Engineering, Calibration, Maintenance, Facilities Microbial Development & Manufacturing Capabilities – Colorado, USA
  6. 6. Confidential 6 Microbial Process Development: Built for Speed with Proven Scalability 250mL Scale • Ambr250® • Screening • Optimization • DOE/PC/SSMQ 10L Scale • Sartorius/Biolaffite • Harvest development • Scale-up confirmation 30L Scale – Single Use • Thermo Fisher SUF • Harvest development • Scale-up confirmation 100L SS GMP (Custom) 1500L SS GMP (Custom) 300L GMP Scale – Single Use (Thermo Fisher SUF)
  7. 7. Confidential 7 • Early-phase programs with relatively small pre-clinical and clinical material needs • Quicker process design to GMP production – platformed and equipment-based • Higher throughput through GMP and pilot suite resulting in more flexibility in schedule • Validation requirements much less with single-use technology at GMP scale • Decreased cross-contamination risk between products • Ease of operational requirements equate to time and cost savings • Greater flexibility for KBI as a CMO organization for rapid execution of projects Drivers for Implementing Single-Use Fermentation Systems at KBI
  8. 8. Confidential 8 • 30-liter pilot system located in fermentation development laboratory (non-GMP) • 300-liter SUF is a GMP system in KBI’s small- scale manufacturing suite Thermo Fisher Single-Use Fermentation Systems at KBI Boulder
  9. 9. Confidential 9 Development of fermentation process into our single-use fermentation platform begins as early as cell line development • Understanding boundaries of at-scale 300L SUF performance • Cell line screening and initial evaluation in 250mL SUFs. Platforming and optimization of fermentation with equipment-based process design follows. • 30L SUF process demonstration and confirmation of design Single-Use Fermentation Implementation Strategy
  10. 10. Confidential 10 • High microbial growth demands exist in aggressive microbial fermentations • High oxygen mass transfer rates are necessary • Lack of pressurized system limits OUR potential • Process Development approaches generally aligned to scalability in stainless systems Single-Use Fermentation Limitations Dictate Design Approach Oxygen Demand Biomass OUR At-scale SUF defines boundaries of platform PD approach Parallelized development designed within at-scale constraints
  11. 11. Confidential 11 • Batch phase is platformed to support optimal growth matching culture demand • Late growth phase limits OUR capacity through tightly controlled feed rates and decreased temperature Platform for Single-Use Fermentations
  12. 12. Confidential 12 • Feed rate in growth phase is optimized to maximize culture growth while limiting OUR • Fermentation process optimization is focused on production phase Platform for Single-Use Fermentations: Full Fermentation
  13. 13. Confidential 13 • Aeration and cooling performance of 300L single-use system typically superior to 30L pilot system • Comparable biomass and product titers at both scales (comparable to S-S outputs) Scaling Single-Use Fermentation 30L (PD) 300L (GMP) Parameter 30L 300L Aeration (% max O2 pull) 85% < 60% Cooldown time (h) 1-2 < 0.5-2 Titers (g/L) 3-6 ≈ 3-6 Cell density (OD600nm) 130 - 200 ≈ 130 – 200 Cell density (WCW) 22-29% ≈ 22-29%
  14. 14. Confidential 14 Performance across Single-Use Fermentation Systems at KBI 0 10 20 30 40 50 60 70 80 90 00:00 04:48 09:36 14:24 19:12 24:00 28:48 OpticalDensity(AU/cm) EFT (hh:mm) 250mL SUF 30L SUF 300L SUF Run ID Final WCW (%) Final OD600 (AU/cm) Final Titer SDS- PAGE (g/L) 250mL SUF 14.4 80 3.1 30L SUF 15.6 85 3.1 300L SUF 12.3 75 2.7 Present SUF Max Output* 29 200 6 *30L Thermo Fisher SUF Comparable performance across single-use systems in same fermentation process
  15. 15. Confidential 15 • Five Single-Use Fermentation Programs through USPD lab to date 400+ x 250mL SUF Fermentations 21 x 30L SUF Fermentations 6 x 300L GMP Fermentations • Three new programs planned in next 2 months • High throughput and success resulting from platforming our single-use fermentation process design Single-Use Fermentation Programs at KBI Boulder
  16. 16. Confidential 16 • Single-Use fermentation systems have allowed greater throughput and efficiency in laboratory leading to accelerated project timelines to GMP production • Coupling process design to the SUF equipment capabilities has enabled processes capable of high cell densities and high titers. Platforming single-use fermentation allows rapid scaling among single-use systems • Improved flexibility of KBI as a CMO organization to address multiple and diverse programs through our single-use systems Success of Single-Use Fermentation Implementation at KBI Boulder
  17. 17. Confidential 17 Robert Todd – VP, Process Development Aaron Pilling - Director, USPD Erik Nordwald - Scientist, USPD Emil Raubach – Scientist, USPD Vanna Yu – PD Assoc, USPD Molly Kruse – PD Assoc, USPD Thatsinee Johnson – PD Assoc, USPD Aliyah Dennert – Sr. PD Assoc, USPD Michelle Yang – Sr. PD Assoc, USPD Cassie Riehl – PD Assoc, USPD Michelle Giuntini – PD Assoc, USPD Aaron Kuhl – Engineer, MS&T Craig Mays – Engineer, MS&T Acknowledgements

×