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Here are all the modifications we intend to make to the existing BTEC department building at NC State University to make it suitable for the production of the estimated scale of Rituximab Biosimilar that is proposed in our project.

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Select a level to get started on the virtual facility tour- Shivani Sutrave Catherine MathesHaroon DarArshad Ahmed

Interactive poster

Rituximab Biosimilar Production Facility

Click here to view the facility's first floor.

Click here to visit the facility's floor 2.

This is the first floor of BTEC. As we enter through the doors we step into the Lobby which we have not touched, The drug substance moves from the Production suite into the Harvest, Protein A, Viral inactivation, CEX, AEX , viral filtration and bulk fill suites. All this movement is sequential and follows all the cGMP flows and regulations by the FDA.

Floor 1

200 L Reactors ( x 6 )

200 L Reactors ( x 4 )

Buffer and media prep room

autoclave/ equipment sterlization room

harvest

Protein A chromatography

Viral Inactivation

cation exchange chromatography

Lobby

waste management

bulk fill room

viral filtration

anion exchange chromatography

Autoclave/Equipment Sterilization room Sterilization Room features AMSCO® Evolution™ Floor Loader Steam Sterilizer, processing 25 trays/cycle, double door for pass-through, ensuring efficient, safe floor-loading of high-capacity carts. It will have the following equipment:

  1. Steris GMP Autoclave
  2. Steris Decon Autoclave
  3. Branson Sonicator
  4. Lancer parts & glass washer

Waste Management All waste is processed here. Provides temporary storage of infectious waste or combustible material.

200 L Reactors ( x 6 )

200 L Reactors ( x 4 )

Buffer and media prep room

autoclave/ equipment sterlization room

harvest

Protein A chromatography

Viral Inactivation

cation exchange chromatography

Lobby

bulk fill room

viral filtration

anion exchange chromatography

waste management

Floor 1

Floor 1 - Personnel Flow

200 L Reactors ( x 6 )

200 L Reactors ( x 4 )

Buffer and media prep room

autoclave/ equipment sterlization room

harvest

CEX

waste management

viral filtration

AEX

Protein A chromatography

Lobby

Viral Inactivation

bulk fill room

Floor 1 - Personnel Flow

200 L Reactors ( x 6 )

200 L Reactors ( x 4 )

Buffer and media prep room

autoclave/ equipment sterlization room

harvest

CEX

waste management

viral filtration

AEX

Protein A chromatography

Lobby

Viral Inactivation

bulk fill room

Floor 1 - MATERIAl Flow

200 L Reactors ( x 6 )

200 L Reactors ( x 4 )

Buffer and media prep room

autoclave/ equipment sterlization room

harvest

CEX

waste management

viral filtration

AEX

Protein A chromatography

Lobby

Viral Inactivation

bulk fill room

This is the second floor of the BTEC facility. Here we have the seed train expansion suites right across the stairs, buffer prep areas, training classrooms for our personnel, PAT section and offices for our employees.

Floor 2

250 ml shake flasks/ vial thaw

conference

2 l shake flasks

5 l bioreactors

20 L bioreactors

buffer formulation /prep

cold storage room

custodial

qc teaching lab

bioreactor instructional lab

storage

autoclave

training room

instructional lab

equipment sterlization

offices

pat

Spectroscopy

microscopy suite

servers

Imaging Suite

Analytical Chromatography

Floor 2

250 ml shake flasks/ vial thaw

conference

2 l shake flasks

5 l bioreactors

20 L bioreactors

buffer formulation /prep

cold storage room

custodial

qc teaching lab

bioreactor instructional lab

storage

autoclave

training room

instructional lab

equipment sterlization

offices

Spectroscopy

microscopy suite

servers

Imaging Suite

Analytical Chromatography

250 ml shake flasks/ vial thaw

conference

2 l shake flasks

5 l bioreactors

20 L bioreactors

buffer formulation /prep

cold storage room

custodial

qc teaching lab

bioreactor instructional lab

storage

autoclave

training room

instructional lab

equipment sterlization

offices

Spectroscopy

microscopy suite

servers

Imaging Suite

Analytical Chromatography

Floor 2 - Personnel Flow

This is the second floor of the BTEC facility. Here we have the seed train expansion suites right across the stairs, buffer prep areas, training classrooms for our personnel, PAT section and offices for our employees.

250 ml shake flasks/ vial thaw

conference

2 l shake flasks

5 l bioreactors

20 L bioreactors

buffer formulation /prep

cold storage room

custodial

qc teaching lab

bioreactor instructional lab

storage

autoclave

training room

instructional lab

equipment sterlization

offices

Spectroscopy

microscopy suite

servers

Imaging Suite

Analytical Chromatography

Floor 2 - material Flow

250 ml shake flasks/ vial thaw

conference

2 l shake flasks

5 l bioreactors

20 L bioreactors

buffer formulation /prep

cold storage room

custodial

qc teaching lab

bioreactor instructional lab

storage

autoclave

training room

instructional lab

equipment sterlization

offices

Spectroscopy

microscopy suite

servers

Imaging Suite

Analytical Chromatography

Floor 2 - material Flow

Basement - Personnel Flow

Basement - Personnel Flow

Basement - Material Flow

Basement - Material Flow

This room will have an ISO 5 classified section as depicted. The eluate from the polishing chromatography steps is brought in here in bags, and processed in the ISO 5 sterile area and sent out to FujiFilm Diosynth for the final fill process. This room will have:

Bulk Fill Room

  • Allegro Connect Bulk Fill System (1)
  • ASI Aseptic Single-Use Filling System Model 4MP6000
  • Watson Marlow 620 Di/R Pump
  • Millipore M Air T air testing system (2)
  • Climet CI-150t particle counter (2)
  • Heraguard ECO Clean bench (2)

We will have the following main equipment here:

  • Millipore ETU TFF skid (2)
  • Millistak+ Pod Filter Holder (2)
  • Millistak+ HC Pro Pods
  • Parvovirus retentive filter
We will employ citric acid and Tris buffers and all the common utilities. Viral filtration, UF/DF will have classification of ISO 7. The AEX eluate is brought in here in carboys and we will utilize a parvovirus-retentive filter, which retains smaller viruses as well as larger viruses (20 nm+) while allowing mAbs to pass downstream.

Viral Filtration

We will prepare all buffer/ media required throughout the processes in our facility in this room. This room will have the following main equipment:

Buffer Formulation/Prep

  • Feldmeier Media Prep tank V-4150 400 L
  • Feldmeier Buffer prep tank V-4100 600 L
  • Hyclone Mobius Mixer MX-1530 200 L
  • Fisher refrigerator RF-1530
  • Puffer Hubbard Freezer (3)
  • Chemical fume hood
  • Steril Gard II biosafety cabinet
  • Watson Marlow 520s/R2 pump
  • Sartocheck 4 integrity tester
  • Ohaus scale (4)
  • Fisher heat/stir plate (4)
  • Hyclone stir plate

This is our (n-1) production suite. We have the following equipment in here:

20 L Bioreactor Suite

  • Sartorius BIOSTAT Cplus 20L Bioreactor (10)
  • Spare tubing + connectors
  • Fisherbrand™ accumet™ Basic AB330 Conductivity/TDS/Salinity Benchtop Laboratory Meter
  • Mettler Toledo FiveEasy Conductivity meter F30-Std-Kit
  • BioPAT Trace Glucose/Lactate Measurement
  • Computer with BioPAT MFCS SCADA software
  • 50mL conical sampling tubes
  • Biohazard waste bag and bin
  • 4 degree C fridge

This is where the WCB will be thawed. We will have the following equipment in here:

250 mL Shake Flasks/Vial Thaw

  • 250 ML ERLENMEYER CELL SHAKER FLASK ( x 30)
  • Infors HT Mulitron Shaking Incubators (x 3)
  • Pipette set
  • Biohazard waste bag and bin
  • Biological Safety Cabinets (2)

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The CCF from the Production step is transfered to this room in carboys. Here our desired secreted protein is removed from the cells and cell debris using a disc stack centrifuge, followed by depth and membrane filtration steps. This will have the following:

Harvest

https://www.biopharminternational.com/view/harvest-and-recovery-monoclonal-antibodies-large-scale-mammalian-cell-culture

  • Membrane filtration system
  • Alfa Laval Disc stack centrifuge (1)
  • Millistak+ HC Pro Pod Depth Filter C0SP
  • MCE Membrane Filter, 0.22 um
  • Carboys

Centrifugation separates solids based on density. Post-centrifugation, cell culture fluid undergoes depth filtration, removing larger contaminants before microfiltration, preventing quick clogging, termed prefiltration.

After depth filtration, the refined Cell Culture Fluid (CCF), with reduced particulates, undergoes Tangential Flow Filtration. This technique yields a particle-free harvest stream, minimizing the need for additional filtration.

This is the new floor plan for the 2nd floor in this facility, navigate through different flows for 2nd floor with the icons below

Welcome to our rituximab biosimilar Facility

Basement Material Flow

Basement Personnel Flow

Material Flow

Personnel Flow

The CEX pool is brought in carboys to this room & processed through AEX column. The AEX will operate in the flow through mode and it will be the second step in our polishing chromatography processes. This room will have:

Anion Exchange Chromatography Suite

  • TOYOPEARL NH2-750F resin
  • BPG Glass 300/500 column and skid (11)
  • Sterile disposable bags
  • Sterile tubing and gaskets

This room will have the following equipment:

Spectroscopy

  • DXR3 Flex Raman Spectrometer
  • Orbitrap Exploris™ 120 Mass Spectrometer
  • Fisherbrand™ accumet™ Basic AB330 Conductivity/TDS/Salinity Benchtop Laboratory Meter
  • Biohazard waste bag and bin

The filtered VI pool is processed through an CEX column. The CEX operates in bind and elute mode, and we have 10 BPG Glass columns in this room processing in multiple cycles. This room contains the following equipment:

Cation Exchange Chromatography

  • TOYOPEARL Sulfate-650F resin
  • BPG Glass 300/500 column and skid (11)
  • Sterile disposable bags
  • Sterile tubing and gaskets

This room will have the following equipment:

Analytical Chromatography

  • Sartorius PATfix
  • GE AKTA AVANT 150 CHROMATOGRAPHY SYSTEM
  • GE AKTA AVANT 25 CHROMATOGRAPHY SYSTEM
  • Sterile disposable bags
  • Sterile tubing and gaskets
  • Biohazard waste bag and bin

This is the new floor plan for our facility.

Welcome to our rituximab biosimilar Facility

Floor 2 Layout

Material Flow

Personnel Flow

This room will have the following equipment:

  • Steris GMP Autoclave
  • Steris Decon Autoclave
  • Branson Sonicator
  • Lancer parts & glass washer

Equipment Sterilization room

Using ten Biostat D-DCU 200L twin Bioreactors with CIP and SIP, our production process in the 2 production suites culminates in Cell Culture Fluid transfer to the Harvest room.

200 L Bioreactor Suite

  • Biostat D-DCU 200L Bioreactors
  • Hartel CIP Skid
  • Denver Instruments pH/conductivity meter
  • Thermo Scientific UV Spectrophotometer
  • Nuaire biological safety cabinet
  • New Brunswick Scientific incubator shaker
  • YSI Biochemistry analyzer
  • Scientific instruments vortex
  • Biohazard waste bag and bin

The HCCF is transferred here. ProA uses reversible and specific binding between immobilized protein A ligand and antibodies, it retains antibodies on the column, allowing elution in a purified and concentrated form. This room has the following equipment:

Protein A chromatography

  • TOYOPEARL AF-rProtein A HC-650 Resin
  • Cytiva BPG Glass 300/500 Column and skid (11)
  • Sterile disposable bags
  • Sterile tubing and gaskets

The proA eluate is subjected to viral inactivation which inactivates potential adventitious enveloped viruses by low pH treatment, incubation and the pH is readjusted and filtered. This room has the following equipment:

Low pH Viral Inactivation

  • Millipore ETU TFF skid
  • Millistak+ Pod Filter holder
  • Millistak+ HC Pro Pods

This is the new floor plan for our facility.

Welcome to our rituximab biosimilar Facility

Floor 2 Layout

Material Flow

Back to Floor 1

This is the new floor plan for the 2nd floor in this facility, navigate through different flows for the 2nd floor with the icons below

Welcome to our rituximab biosimilar Facility

Floor 1 Layout

Material Flow

Personnel Flow

This room will have the following:

  • Cytation 5 system
  • Thermo Scientific™ NanoDrop Lite Plus Spectrophotometer (2)
  • Biohazard waste bag and bin

Imaging Suite

This room will have:

Microscopy suite

  • Cytation 5 system
  • Viranova Bioanalytics mini-TEM
  • Micropipette set
  • Biohazard waste bag and bin

The server room will encompass:DELL PowerEdge R7525 Rack Server (x15) 25U Server rack Uninterrupted Power Supply

Servers Room

This room employs the following equipment:

5 L Bioreactors

  • Sartorius BIOSTAT Cplus 5L Benchtop Reactors (15)
  • Biological safety cabinet
  • Micropipette set
  • 2mL sampling syringes
  • 4-degree C fridge
  • Biohazard waste bag and bin

We will transfer the cells to this room for scale-up. These are the main equipment in this room:

2 L Shake Flasks

  • 2L Erlenmeyer Flask w/ Vent Cap, Polycarbonate, Sterile (x 24)
  • Infors HT Mulitron Shaking Incubators (x 3)
  • Pipette set
  • Biohazard waste bag and bin
  • Biological Safety Cabinets (2)

This is the new floor plan for the Basement in this facility, navigate through different flows for the basement with the icons below

Welcome to our rituximab biosimilar Facility

Basement Personnel Flow

Floor 1 Layout

Floor 2 Layout

Basement Material Flow

Any extra cold storage requirements will be met here. This room will have the following equipment:

Cold Storage room

  • Fisher refrigerator RF-1530
  • Puffer Hubbard Freezer (x 2)
  • Steril Gard II biosafety cabinet

Our buffer room formulates diverse buffers crucial for upstream processes, regulating pH, optimizing cell growth, and preserving protein functionality during primary recovery in preparation for purification. It will have the following equipment:

  • Feldmeier Media Prep tank V-4150 400 L
  • Feldmeier Buffer prep tank V-4100 600 L
  • Hyclone Mobius Mixer MX-1530 200 L
  • Fisher refrigerator RF-1530
  • Puffer Hubbard Freezer (3)
  • Chemical fume hood
  • Steril Gard II biosafety cabinet
  • Watson Marlow 520s/R2 pump
  • Sartocheck 4 integrity tester
  • Ohaus scale (4)
  • Fisher heat/stir plate (4)
  • Hyclone stir plate

Buffer / Media Prep room

This is the new floor plan for the Basement in this facility, navigate through different flows for the basement with the icons below

Welcome to our rituximab biosimilar Facility

Basement Personnel Flow

Floor 1 Layout

Floor 2 Layout

Basement Material Flow