PRODUCTION OF HIGHLY PURIFIED BOVINE TRANSFERRIN Group 5B Arjun Goel, Connie Marcelli, Lianne Kark, Sara Dang, Vivien Tai Faculty Advisor Prof C.A. Mims

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Timetable Progress

Isolation of Transferrin OBJECTIVE To isolate transferrin from bovine blood PROCESS Part A: Partial purification Paste  Intermediate Product Part B: Chromatography and Lyophilization Intermediate Product  98% Pure transferrin

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Technical Design - Scope of Design -  Process Flow Diagram  Plant Layout  Choice of Technology  Process Component Specifications  Key Unit Design

Operational Considerations - Scope of Design -  Hazard prevention  Pollution control  Socio-economic impact

Cost Analysis - Scope of Design -  Construction costs  Operating costs  No transport or storage  NPV and IRR

Feasibility Evaluation - Scope of Design - Considerations:  Technical  Environmental  Economic  Social

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Part A - The Process -  Operates once a week  Run 1 shift + setup / cleanup  g Feed  g Product + Waste  1 batch A = 2 batches feed B

Part B - The Process -  Operates twice a week  Run 2 shifts + setup/cleanup  g Feed  350 g Transferrin + Waste

Scaling - The Process - 1 batch A = 2 batches B  Part A = extraction, iron saturation, or ultrafiltration Mostly labour intense  Part B = separation by ion chromatography Better quality Less waste Smaller equipment I (E.g. DEAE column, lyophilizer) Lower cost

Economics - The Process -  Part A: 44 quality batches/year  Part B: 88 quality batches/year  Feed 18 kg/week = $ Reagents  Product 700 g/week = $42 000

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Separation - Choice of Technology - FILTRATION  Simpler design  Less operating time CENTRIFUGATION  Higher costs  Complex design

Prefiltration - Choice of Technology - DEPTH CARTRIDGE FILTERS  Cheaper than membrane filters  High flow rates  Fibers released into the filtrate HYDROPHILIC MEMBRANE CARTRIDGE FILTERS  Particles are retained on surface  Plugs more quickly than depth filters

Ultrafiltration - Choice of Technology - TURBULENCE PROMOTED:  Dissolved solids  Minimize pumping requirements  Eddy stresses and cavitation OPEN CHANNEL:  High concentration of solids  High degree of recirculation  High shear rates

Ultrafiltration Configurations - Choice of Technology - HOLLOW FIBER:  Operate at low pressure  High shear rate FLAT SHEET:  High shear rate  Lower boundary-layer resistance SPIRAL-WOUND:  Higher pressure drop  Greater resistance to flux  Difficult to sterilize

Ultrafilter Membranes - Choice of Technology - CELLULOSIC MEMBRANES  Bind the least amount of protein POLYSULFONE  Less susceptible to damage by extremes of Temperatures and pH CERAMIC  More expensive

TFF Used for Diafiltration Feed Tank Buffer Tank Retentate Feed TANGENTIAL FLOW FILTRATION

Agenda Timetable Scope of Design Process Choice of Technology Current Challenges

Current Challenges - Choice of Technology -  Economics  Flux rate  Ease of maintenance

Current Challenges - Process Flow Diagram -  Layout design  Composition of streams for batch process  Composition of intermediate streams  Representation of lyophilization units  Delivery of solid reagents

Next Steps  Selection of Key Unit  Frozen PFD  Equipment Selection  Plant Tour on October 11, 2001