Materials related to Chp11

Bioprocess/Bioseparation
Design Consideration
Given a product and a desired annual production rate (PROCESS
THROUGHPUT), bioprocess design endeavors to answer the
following and other related questions:

 What are the required amounts of raw materials and utilities

needed for a single batch?
 What is the total amount of resources consumed per year?
 What is the required size of process equipment and supporting
utilities?
 Can the product be produced in an existing facility or is a new
plant required? What is the total capital investment? What is the
manufacturing cost?
 What is the optimum batch size? How long does a single batch
take?
 How much product can be generated per year?
 Which process steps or resources constitute scheduling and
throughput bottlenecks?
 What changes can increase throughput?
 What is the environmental impact of the process (i.e. amount
and type of waste materials)?
Which design is “best” among several plausible alternatives?
Recall-1: Overview of Bioseparations
 Recall-2: The Challenge
of D.S.P. of Bioproducts

to efficiently & economically recover a high purity

biochemical product from a complex mixture of related &
functional molecules, impurities & contaminants which have
similar physical and chemical properties

Recall-3: The Goals of

D.S.P. of Bioproducts

maximize purity of bioproduct

&
minimizing processing time, yield losses & costs
 process design should be
efficient & economical

Two main activities in

BIOPROCESS DESIGN

PROCESS SYNTHESIS: PROCESS ANALYSIS:

selection & arrangement of a set evaluation and comparison of
of unit operations (process steps) different process synthesis
capable of producing the desired solutions
product at an acceptable cost &
quality
In general, a synthesis step is usually followed by an analysis step, and the
results of analysis determine the subsequent synthesis step.
 SYNTHESIS OF
BIOSEPARATION PROCESSES

Figure 12.2 provides a generalized structure for

creating an initial block diagram
representation of a product recovery process.
When Selecting
Unit Operations,
there are
Choices &
Decisions Must be
Made
 “Rules of Thumb” consideration when
designing a flowsheet for DSP of
bioproduct:
a.k.a. heuristics

 Remove the most plentiful impurities first

 Remove the easiest-to-remove impurities first
 Make the most difficult & expensive separations last
 Select processes that make use of the greatest
differences in the properties of product & its impurities
 Select the sequence processes that exploit different
separation driving force
 Sample of a Flowsheet
(Fermentation Process Development)

A sample flowsheet (this one from MIT open-courseware website) illustrating the recovery
of the enzyme alkaline phosphatase which is recovered downstream in the retentate.
 In addition to “Rules of Thumb” for
synthesizing bioseparation processes,

“Pairing of Unit Operations” in process synthesis

should also be considered to improve process
efficiency

Examples:
 Extraction and Precipitation
 Precipitation and HIC
 Filtration and Extraction
 PROCESS ANALYSIS

To decide which ideas to consider further,

the flowsheets created during process synthesis must
be analyzed and compared, among others, on the
basis of:

 capital investment
 manufacturing cost
 environmental impact
 other criteria
 Main criteria used for developing and
evaluating a bioseparation process:

 Product purity: maximize purity of bioproduct, including

removal of virus & pyrogens
 Cost of production as related to yield: minimizing
processing time, yield losses & costs
 Scalability: the process must go beyond the lab & pilot
scale, all the way to commercial-production scale
 Reproducibility & ease of implementation: cGMP & fulfills
other requirements
 Robustness with respect to process stream variables
PROCESS SIMULATORS:
software applications that enable user to readily
represent & analyze integrated processes

Example:
SUPERPRO DESIGNER –
a flowsheet-driven simulator which handles
 material & energy balances
 equipment sizing & costing
 economic evaluation
 environmental impact assessment
 process scheduling
 debottlenecking of batch & continuous processes.
A flowsheet on the main window of SuperPro Designer
Window for adding operations to a unit procedure using
SuperPro Designer
Dialog window of the elution operation
Benefits from the use of
process simulators depend on
 type of product
 stage of development
 and size of investment

Examples:
For commodity biological
products, such as biofuels,
minimization of capital &
operating costs are the
primary benefits.
For high-value
biopharmaceuticals,
systematic process
development that shortens
the time to commercialization
is the primary motivation.
Figure 12.3
A pictorial representation of the benefits from the use of process
simulator tool at various stages of the commercialization process
 PROCESS ECONOMICS

Involves:
 estimation of capital investment
 estimation of operating costs, and
 analysis of profitability

For biopharmaceuticals, the average cost of new

drug development also should be included
 Capital Cost Estimation

Direct Start-up &

Working Capital
Fixed Capital Validation
cash that must be available for Start-up and
For preliminary design investments in on-going validation costs can
purposes, various items expenses and consumable also represent a
of DFC are estimated materials. significant capital
based on the total investment for a
equipment purchase may include raw materials for biopharmaceutical
cost (PC) using several 1 to 2 months, labor for 2 to 3 plant. A value of 20 to
multipliers months, utilities for a month, 30% of DFC is quite
waste treatment/disposal common
for a month, and other
miscellaneous expenses.

usually 10 to 20% of DFC

 Operating Cost Estimation

Operating Cost & Ranges

*
e.g. ongoing R&D

* the depreciation of the fixed capital investment, maintenance costs for equipment,
insurance, local (property) taxes, and possibly other overhead-type expenses
 Profitability Analysis

• Gross profit = Annual revenue – annual operating cost

• Net profit = gross profit – (income tax + depreciation)
• All variables are average over the lifetime of project.