1/19/2011

CBB 30903
Bioprocess Plant & Equipment
Design

Madam Rozyanti Mohamad

Bioengineering Section

Universiti Kuala Lumpur, Malaysian Institute of Chemical Engineering Technology (UniKL MICET)

Lecture : All (Tue : 2p.m – 4p.m)

Practical : 6BCB A (Fri : 8.30a.m – 11a.m)
6BCB B (Tue : 8.30a.m – 11a.m)

Assessments:
Written Tests

Test 1 (Week 7) 10%

Test 2 (Week 13) 10%
Mini Projects

Assignment 1 10%

Assignment 2 10%
Lab Reports

Total five experiments 20%

Final Exam 40%

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Syllabus
Chapter 1 Introduction
1.1 Overview of reactor types
1.2 Scale-up
1.3 Scale-down
1.4 Dimensional analysis

Chapter 2 Vessel for Bioprocess

2.1 Components of vessels
2.2 Selection of materials
2.3 Guidelines for fabrication
2.4 Welding and surface treatment

Syllabus
Chapter 3 Fundamentals of bioreactor design
3.1 Introduction
3.2 Stoichiometry
3.3 Kinetics of cell population growth, product
formation, and substrate utilization

Experiment 1
Simulations of growth kinetics using programming
simulations

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Syllabus
Chapter 4 Downstream Processing Equipment
4.1 Conventional filters
4.2 Membrane filters
4.3 Centrifuges
4.4 Chromatographic columns
4.5 Cell disruption systems

Experiment 2
Exposure to TFF membrane filters, centrifuge

Syllabus
Chapter 5 Scale-up
5.1 Introduction
5.2 Scale up procedure at unavailability of model
materials system
5.3 Scale up under condition of partial similarities
5.4 Similarity theory
5.5 Scale-up methods used in various bioprocess
equipments
5.6 Application and case studies
5.7 Consequences of changing the scale of operations

Experiment 3
Scale up considerations using from 2L to 10L stirred
type bioreactors

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Syllabus
Chapter 6 Utility Requirements, Equipment Operation
and Auxiliary Systems
6.1 Steam
6.2 Water
6.3 Air
6.4 Electrical
6.5 Specialty gas
6.6 Cleaning and maintenance practices
6.7 Sterilization procedures
6.8 Piping
6.9 Valves
6.10 Pumps
6.11 Materials
6.12 Maintenance

Experiment 4
Sterilization process and techniques

Syllabus
Chapter 7 Instrumentation and Control of Bioprocess
7.1 Fundamentals of Process
7.2 Control
7.3 Measurement Elements
7.4 Instrumentation for indicating, controlling and
recording
7.5 Signal Transmission
7.6 Maintenance and Calibration

Experiment 5
Engineering aspect of bioreactor

Chapter 8 Bioprocess Plant

8.1 Case study
8.2 Various operations and equipment used
8.3 Sterility requirements in bioprocess

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Student Learning Time (hours)

Face to face (F2F):
 Lecture 24
 Practical 18
 Others (Test & Exam)
5

Non F2F 73

TOTAL SLT 120

References
1. Lydersen, B.K., Elia, N.A.D. & Nelson,K.L. (1994).Bioprocess
Engineering: System,Equipment and Facilities, John Wiley &
Sons, Inc.
2. Doran, P.M. (1995). Bioprocess Engineering Principles, Academic
Press, Harcourt Brace & Company
3. Kargi, F. (1991). Bioprocess Engineering: Basic Concepts,
Prentice Hall.
4. Asenjo,Juan A. (1995). Bioreactor System Design, Marcel Dekker
Inc.
5. Marko Zlokarnik. (2002). Scale-Up in Chemical Engineering,
Wiley-VCH Verlag GmbH.
6. Harrison, R. G., Todd, P., Rudge, S. R., Petrides, D. P. (2003).
Bioseparations Science and Engineering, Oxford University
Press.

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Course Learning Outcomes

Upon completion of this subjects, students should be able
to:
 Discuss various components & materials of vessel in bioprocess
industry
 Compare types & design criteria of bioprocess equipments
 Explain scaling up process of bioprocess plant
 Discuss the utility requirements, equipment operation and
auxiliary systems for bioprocess industry
 Describe instrumentation & control of bioprocess
 Demonstrate ability to work in team either as a leader or
ordinary member

Chapter 1

Introduction

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Learning Outcomes
1. Identify various types of reactor.

2. Explain basic concept of scale-up / scale-down.

3. Apply dimensionless analysis in solving simple

problems.

BIOREACTOR
 Definition:
a system in which conditions are
closely controlled to permit or induce
certain behavior in living cells or tissues

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TYPES OF REACTORS

Batch

TYPES

Fed batch Continuous

BATCH REACTORS

No flow of material in or out of reactor

Changes with time

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FED BATCH REACTOR

Either inflow or outflow of material but not both

Changes with time

CONTINUOUS REACTORS

Flow in and out of reactor e.g. CSTR, PFR

Steady State Operation

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EXAMPLE OF REACTORS

EXAMPLE OF REACTORS

Trickle bed,
immobilized enzyme

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SCALE UP & DOWN

WHAT IS SCALE UP?

Process of increasing the batch size

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STEPS IN SCALE UP

Using results obtained from

laboratory studies

Designing a prototype & a pilot plant

process

Constructing a pilot plant

Using pilot plant data in designing &

constructing a full scale plant or
modifying an existing plant

WHAT IS PILOT SCALE?

An intermediate scale between R&D &
Laboratory production scale
Studies
Example:
 Manufacturing of drug product by a procedure
fully representative of & simulating that used
Prototype & Pilot for full manufacturing scale
Plant Process  Makes possible the production of enough
product for clinical testing & samples for
marketing
 However, a well-defined process may
Full Scale Plant generate a perfect product in both the lab
and pilot plant scale and then fail quality
assurance test in production**

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PILOT PLANT STUDY

Investigation of product &
Money process on intermediate
scale before large amounts
of money are committed
to full-scale production.

OBJECTIVES

Predict
Insufficient
effects of
lab data
scale up

It is usually not possible to It is not possible to design a

predict the effects of a many- large complex processing plant
fold increase in scale from laboratory data alone

PILOT PLANT STUDY

PURPOSES

Evaluate, Correct & Improve

Sample, evaluation, shelf life, stability

Determine salable by-product , waste

Feasibility

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PILOT PLANT STUDY

1) EVALUATE, CORRECT & IMPROVE
Evaluate lab results & make product & process corrections & improvements

2) SAMPLE EVALUATION, SHELF LIFE & STABILITY

Produce small quantities of product for sensory, chemical, microbiological
evaluations; limited market testing ; furnishing samples to potential
customers; shelf-life & storage stability studies

3) DETERMINE SALABLE BY-PRODUCT OR WASTE

Determine possible salable by-products or waste stream requiring treatment

4) FEASIBILITY
Provide data that can be used in making decision on whether or not to
proceed to a full-scale production process; and in the case of a positive
decision, designing and constructing a full-size plant or modifying an existing
plant

MAJOR FACTORS IN SCALE UP

Expanded
time scale
Monitoring
Chemical
process
hygiene
change

Flexibility Heat
of process transfer
FACTORS

Supporting Temperature
equipment control

Reactor
Operating
mixing &
volume
control

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MAJOR FACTOR IN SCALE UP

1. Expanded time scale
• How long the process will take?
• E.g. charging raw mat, solvent, heating, cooling → different
during lab & pilot scale
• Extended time can cause problem e.g. decomposition of material,
instability of flow & etc.

2. Chemical hygiene
• Handling chemical at large scale > chances for exposure to toxic
substance

3. Heat transfer
• Surface of small to large scale
• Cooling & heating rate

MAJOR FACTOR IN SCALE UP

4. Temperature control
• Water bath vs boil H2O in conical flask using bunsen burner ⇒
which 1 is easiest to control
• Heating using steam?
• Endothermic?

5. Reactor mixing & reaction control

• Sizing & geometry
• Reactant → limiting / excess
• Formation of by-product
• Unexpected retention time
• Mixing duration
• Stirring speed
• Mixing pattern

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MAJOR FACTOR IN SCALE UP

6.Operating volumes
• Small scale ⇒ can be achieved 100%
• Large scale ≈ 80%
• Allowable downtime / rxn life cycle
• Prepare space if any formation of high pressure during rxn
• Avoid build up vol. fr. Unnecessary rxn

7. Supporting equipment
• E.g. Liq-liq, sol-liq, gas-liq separation
• Vol. size, operating condition, flow sizing, etc

8. Flexibility of process parameter

• Allowable range (±)

9. Monitoring process change

• Visual ⇒ color, phase change / separation, fluid properties

DIMENSION VS PHYSICAL QUANTITY

Qualitative
Quantitative
description of a
description of a
physical entity
Dimension physical entity
Physical
Examples Quantity Numerical
Length: Height, depth value x units
Mass: Light, heavy e.g. 20 m, 5 s
Time: Short, long

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DIMENSIONS

Mass
Basic / Length
Primary Time
Temperature
DIMENSION
Velocity
Derived / Energy
Secondary
Volume

DIMENSIONS & UNITS

Based or primary quantities
Base quantity Base dimension SI base unit

Length L m Meter
Mass M kg Kilogram
Time T s Second
Temperature Θ K Kelvin
Amount of N mol Mole
substance
Electric current I A Ampere

Intensity J cd candela

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DIMENSIONS & UNITS

Secondary or derivative quantities
Base quantity Base SI base unit
dimension
Force MLT-2 kg m s-2 (N) Newton
Pressure ML-1T-2 kg m-1 s-2 (Pa) Pascal
Energy ML2T-2 kg m2 s-2 (J) Joule
Power ML2T-3 kg m2 s-3 (W) Watt

DIMENSIONAL CONSTANT
 What is dimensional constant..?
 What happen if secondary quantity has more than
one equation..?
 How to interpret the dimensional analysis…?
Write
Example: down the
dimension..
F=ma & F=m1m2/r2

Which eqn. should leading to F dimension..?

Any idea…? F=Gm1m2/r2

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DIMENSIONAL ANALYSIS
Aim of dimensional analysis..?

 To check whether the physical content under consideration can be

formulated in a dimensionally homogeneous manner or not.

DIMENSIONAL HOMOGENEITY

All equations must

be dimensionally
homogeneous.

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EXAMPLE 1
What determine the period of oscillation of a pendulum?

EXAMPLE 2
What determine the roasting time of meat?

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