Biomanufacturing Sciences Concentration in CBE

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Biomanufacturing Sciences Concentration in CBE

• H. Henry Lamb
• Professor
• Chemical and Biomolecular Engineering

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What is biopharmaceutical (biologics)
manufacturing?

• Production of therapeutic proteins (enzymes,
  monoclonal antibodies, clotting factors, growth
  hormones, etc.) typically via large-scale
  mammalian cell culture.
• Relies on recombinant expression systems (e.g.,
  transfected CHO cells) cultured under strict
  aseptic conditions.
• Advanced engineering systems required in
  comparison to traditional small-molecule API
  synthesis.

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Genentech Biologics Timeline
www.genentech.com
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John Machulski - Lonza Biologics
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What is BTEC?

• Unique 85,000 ft2 academic facility
• cGMP-like pilot plant
• State-of-the-art process analytics, automation,
  control
• Full-time professional operations staff
• Test-bed for advanced biomanufacturing technology

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BTEC Pilot-Scale Manufacturing Suite
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Unit Operations in GFP Production Using E. Coli
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GFP Production Using Recombinant E. Coli
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BTEC 300L Production Fermentor

• Sartorius BBI D300
• Microbial Operations
• fully automated
• SIP/CIP capable
• DCU-3 control system
• MFCS/Win SCADA
• CFR 21 Part 11 compliant

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Bioreactor PID Screen Shot
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Disk-Stack Centrifuge

• Alfa-Laval LAPX404
• Disk-Stack Centrifuge
• 120-150 lph (E. Coli)
• CIP capable
• ABB 800xA DCS
• Industrial PC HMI
• Centrate turbidity sensor

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Homogenizer

• Niro Soave NS3006H
• VHP Homogenizer
• 50-120 lph (single stage)
• product heat exchanger
• CIP capable
• AB CompactLogix PLC
• AB PV Plus HMI

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LS Chromatography

• ÄKTAprocess (GEHC)
• Gradient LC skid
• 6-mm PP (4-180 lph)
• 3-wavelength UV detector
• Unicorn software
• industrial PC interface

• BPG 300/500
• Glass LC column
• 300/500 mm (D/H)
• axial compression packing
• 17.9 l max. resin volume

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What do bioprocess engineers do?

• Scale-up and optimize manufacturing processes,
  reducing the cost of biologics and vaccines to
  patients.
• Automate and control biologics manufacturing
  processes, ensuring the safety and efficacy of
  the drug product.
• Design facilities and equipment for biologics
  manufacturing, complying with current good
  manufacturing practice (cGMP) standards.

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Penicillin Production Process
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Recent Biomanufacturing Trends

• Large-Scale Cell Culture Manufacturing
• Driven by high dosage requirements for MAb
  products
• 15,000-20,000 L fed-batch bioreactors typical
• Higher MAb Titers from Cell Culture
• 100-fold increase for CHO in last 15 years
• Titers gt1 g/L typical and 10 g/L reported
• Shifts production bottleneck downstream
  (recovery/purification)
• Requires smaller bioreactor capacity
• Serum-Free and Animal Protein-Free Media
• Single-Use (Disposable) Bioreactor Technology
• Process Analytical Technology (PAT) and Quality
  by Design (QbD)

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Bioprocess Engineering Positions

• Manufacturing Sciences
• Process Development
• Scale-up and Optimization
• Automation and Control
• Corporate/Project Engineering

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Biomanufacturing Sciences Concentration

• Learning Objectives (in addition to CBE core)
• Overview of biomanufacturing and established
  biotechnology platforms.
• Design, scale-up and control of bioreactors for
  microbial and cell culture operations with
  hands-on training at the bench and intermediate
  scales.
• Downstream processing for recovery and
  purification of active biomolecules with hands-on
  training at the bench and intermediate scales.
• Large-scale cGMP manufacturing campaign
  experience including batch records, SOPs,
  trouble-shooting, and regulatory compliance.

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GFP Biomanufacturing Using Recombinant E. Coli
Material and Energy Balances Design and Analysis
of Bioreactors Fluid Dynamics, Heat and Mass
Transfer Unit Operations Theory and
Practice Bioseparations Bioprocess Modeling and
Optimization Statistics/Design of
Experiments Process Control/Automation
Fermentation
Recovery
Purification
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GFP Biomanufacturing Using Recombinant E. Coli
Material and Energy Balances Design and Analysis
of Bioreactors Fluid Dynamics, Heat and Mass
Transfer Unit Operations Theory and
Practice Bioseparations Bioprocess Modeling and
Optimization Statistics/Design of
Experiments Process Control/Automation
Fermentation
Recovery
Purification
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GFP Biomanufacturing Using Recombinant E. Coli
Material and Energy Balances Design and Analysis
of Bioreactors Fluid Dynamics, Heat and Mass
Transfer Unit Operations Theory and
Practice Bioseparations Bioprocess Modeling and
Optimization Statistics/Design of
Experiments Process Control/Automation
Fermentation
Recovery
Purification
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Textbooks in Bioprocess Engineering
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Biotechnology in NC

• 3, 400 72,962 ? 1 Opportunity
• Amino Acid, Biofuel, BioPharma, Dairy, DNA,
  Enzyme, Food Products Vaccines
• UNC System, Private Colleges, Community Colleges
  and Technical Schools
• Fastest growing and most profitable ()
• NC Biotechnology Center, RTP BTEC

Source NC Biotechnology Center
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Contact Information

• Prof. Henry Lamb (lamb_at_ncsu.edu)
• Biomanufacturing Training and Education Center
  (BTEC) web site (http//www.engr.ncsu.edu/btec/)