Systematic Evaluation of Single-Use Systems Using

Process Simulation Tools – A Case Study Involving MAb

Production
Victor Papavasileiou is a senior applications engineer with Intelligen Europe, Leiden, Netherlands
(vpapavasileiou@intelligen.com), Charles Siletti, Ph.D. is the director of scheduling and planning
applications (casiletti@intelligen.com) and Demetri Petrides, Ph.D. is the president of Intelligen, Inc.,
Scotch Plains, NJ, USA, +1 908 654-0088 (dpetrides@intelligen.com).

Abstract
Single-use systems are an option that has gained popularity in the biopharmaceutical
industry in the last few years. The choice of single-use vs. stainless steel depends on a
variety of process and other parameters, such as bioreactor scale, product titer, product
changeover frequency, etc. Computer-aided process design and simulation tools facilitate
analysis and evaluation of process alternatives and assist scientists and engineers in their
decision making process.

This article describes the steps required to build a comprehensive model in a batch process
simulator that accounts for the consumption of single-use systems for buffer preparation and
storage. The process is subsequently compared to a more traditional one employing
stainless steel tanks for preparation and storage of buffers. The impact of single-use systems
on production cost, demand for cleaning materials, demand for consumables, and the cycle
time of the process is thoroughly evaluated. The analysis is done for a typical cell culture
facility producing therapeutic monoclonal antibodies.

Keywords
Single-Use Systems, Disposables, Manufacturing of Biopharmaceuticals, Bioprocess
Economics, Bioprocess Simulation.

1
Introduction
As the number of biopharmaceutical molecules that are entering clinical trials is rising, there
is increased demand for technologies that can expedite the commercialization process.
Disposables or single-use systems constitute such an enabling technology. They are
commonly used for inoculum expansion using wave rocking bioreactors that are available for
working volumes of up to 500 L.1 More recently, stir tank disposable bioreactors have
become available with working volumes of 1,000 L and even 2,000 L aimed at replacing
small to medium scale stainless steel bioreactors.2 Preparation and storage of cell culture
media and product purification buffers in disposable bags is another common application.3
Their use greatly reduces the need for piping, CIP & SIP infrastructure, and the consumption
of cleaning materials.1 This in turn reduces the requirements for up-front capital investment
and speeds up the commercialization process. The above attributes of single-use systems
make them particularly attractive to start-up companies that are short in capital and are under
pressure to meet development milestones.

Single-use systems, however, are not a panacea. They result in increased cost of
consumables and their application ceases to be advantageous beyond a certain scale of
production. Detecting the turning-point scale is a challenging task that depends on process
and other parameters. Process simulation and other modeling tools can play an important
role in this task by facilitating the analysis and evaluation of alternatives at various scales.
The focus of this article is on the role of such tools in the evaluation of process alternatives
and in particular the evaluation and comparison of single-use systems versus the traditional
stainless steel approach.

The evaluation is done for a typical monoclonal antibody (MAb) facility at the clinical
manufacturing scale. Two process alternatives are evaluated in detail. In the first option
production buffers and media are prepared and stored in traditional stainless steel tanks; in
the second option, buffers and media are prepared and stored in single-use bags.

Process simulation tools can assist in the evaluation of process alternatives in all the stages
of process development and product commercialization by facilitating the following and other
related tasks:4,5,6,7

• Documentation and process understanding

• Calculation of material and energy balances
• Sizing of equipment and utilities
• Cost-of-goods analysis
• Process scheduling
• Cycle time analysis and debottlenecking
• Resource tracking as a function of time
• Environmental impact assessment
The cost analysis and resource tracking capabilities of such tools are the features
predominantly employed in this case study. Capital and operating costs are used to compare
the two alternatives at various production scales. The impact of single-use systems on the
demand for cleaning materials, cleaning-in-place (CIP) skids, labor, utilities are also
considered.

2
Commercially Available Simulation Tools
Computer-aided process design and simulation tools have been in use in the chemical and
petrochemical industries since the early 1960s. Established simulators for those industries
include: Aspen Plus and HYSYS from Aspen Technology, Inc. (Cambridge, MA), ChemCAD
from Chemstations, Inc. (Houston, TX), and PRO/II from SimSci-Esscor, Inc. (Lake Forest,
CA).

The above simulators have been designed to model primarily continuous processes and their
transient behavior for process control purposes. Most biopharmaceutical products, however,
are manufactured in batch and semi-continuous mode. Such processes are best modeled
with batch process simulators that account for time-dependency and sequencing of events.
In the mid 1990s, Aspen Technology introduced Batch Plus, a recipe-driven simulator that
targeted batch pharmaceutical processes. At around the same time, Intelligen, Inc. (Scotch
Plains, NJ) introduced SuperPro Designer. The initial focus of SuperPro Designer was on
bioprocessing. Over the years its scope has been extended to include modeling of small
molecule API and secondary pharmaceutical manufacturing processes.

Discrete-event simulators have also found applications in the pharmaceutical industries,

especially in modeling of secondary pharmaceutical manufacturing processes. Established
tools of this type include ProModel from ProModel Corporation (Orem, UT), Arena and
Witness from Rockwell Automation, Inc. (Milwaukee, WI), and Extend from Imagine That,
Inc. (San Jose, CA). The focus of models developed with such tools is usually on the minute-
by-minute time-dependency of events and on animation of the process. Material balances,
equipment sizing, and cost analysis tasks are usually out of the scope of such models. Some
of these tools are quite customizable and third party companies occasionally use them as
platforms to create industry-specific modules. For instance, BioPharm Services, Ltd. (Bucks,
UK) have created an Extend-based module with emphasis on biopharmaceutical processes.

MS Excel from Microsoft is another common platform for creating models for pharmaceutical
processes that focus on material balances, equipment sizing, and cost analysis. Some
companies have even developed Excel applications that capture the time-dependency of
batch processes. This is typically done by writing extensive code (in the form of macros and
subroutines) in VBA (Visual Basic for Applications) that comes with Excel. The K-TOPS tool
from Biokinetics, Inc. (Philadelphia, PA) belongs to this category.

Building a Model in a Batch Process Simulator

SuperPro Designer (Intelligen, Scotch Plains, NJ) will be used to illustrate the modeling and
evaluation of the MAb manufacturing process alternatives. The first step is to create a flow
diagram of the overall process (Figure 4). The various equipment-shaped icons, called Unit
Procedures, represent the processing steps required for making a batch of a certain product.
The lines that connect the unit procedures represent material transfers. Batch process
simulators usually come with a library of unit procedures. A unit procedure represents the set
of activities or operations that are carried out in a piece of equipment during a processing
step. The Bioreaction procedure (P-11) of Figure 4 includes the following operations: SIP-1,
SET UP, TRANSFER-IN-1, TRANSFER-IN-2, FERMENT-1, TRANSFER-OUT-1 and CIP-1
(Figure 1). The dialog in Figure 1 is used for adding operations to a unit procedure. On the
left-hand side of the dialog, the program displays the operations that are available for the unit
procedure (in this case a Bioreaction procedure); on the right-hand side, it displays the user-
selected operations. The combination of unit procedures and operations enables the user to
represent and model the various activities of batch processing steps in detail.

3
Figure 1. Operations associated with the production bioreaction unit procedure.
For every operation of a unit procedure, the simulator includes a mathematical model that
performs material and energy balance calculations and equipment-sizing calculations. If
multiple operations within a unit procedure dictate different sizes for the equipment, the
program reconciles the different demands and selects an equipment size that is appropriate
for all operations. If the equipment size is specified by the user, the simulator checks to make
sure that the vessel is not overfilled. In addition, the tool checks to ensure that the vessel
contents will not fall below a user-specified minimum volume (e.g., a minimum stir volume)
for applicable operations.

In terms of cost analysis, simulation tools facilitate estimation of capital as well as operating
cost. Some tools are equipped with built-in functions and databases for estimating equipment
cost as a function of size, material of construction, operating pressure, and other
parameters.8,9 They may also include databases for materials (pure components as well as
mixtures), utilities, consumables, and other resources. The size and unit cost of single-use
systems is stored in the consumables database. The user associates consumables with a
processing step and the tool calculates the number of units and the cost (Figure 2).

4
 2.Specify properties

3.Assign to equipment

1.Create new consumable

in database

Figure 2. Specifying single-use systems.

Since biopharmaceutical processes operate in batch mode, the simulator must also facilitate
process scheduling and cycle time analysis. The results of process scheduling are typically
visualized with Gantt charts that display equipment occupancy as a function of time (Figure
3).

CIP Skids
Reuse of Buffer Prep. tanks

Buffer
Prep Tanks

Buffer
Reuse of Buffer Hold tanks Hold Tanks

Bioreactors

Multiple (x4) Production Bioreactors DSP

Figure 3. The equipment occupancy chart for the stainless steel process.

5
Sensitivity and parametric analysis are other common benefits from the use of such tools.
Input parameters can be varied manually or automatically and their impact can be evaluated
in a matter of minutes. If statistical data are available for certain input parameters, their
impact on output (decision) variables can be evaluated using Monte Carlo simulation.10

It should be noted, however, that the GIGO (garbage-in, garbage-out) principle applies to all
computer models. If critical assumptions and input data are incorrect, so will be the outcome
of the simulation. Consequently, a certain level of model validation is necessary. In its
simplest form, a review of the results by an experienced engineer can play the role of
validation.

Process Description
Figure 4 displays the flow diagram of the overall process (the way it is represented in
SuperPro Designer). Please note that, for simplicity, the buffer preparation and holding
activities are omitted from Figure 4. Those activities, however, were taken into account in the
detailed models that were built for the evaluation of the alternatives. The complete flow
diagrams (in PDF format) as well as the detailed SuperPro models can be downloaded from
the internet by pointing your browser to www.intelligen.com/literature. The computer models
can be opened and studied in detail using the free evaluation version of SuperPro Designer
which can be downloaded from the internet (www.intelligen.com).

Upstream Processing
The inoculum is initially prepared in 225 mL T-flasks. The material is first moved to roller
bottles (2.2 L), then to 20 L and subsequently to 100 L disposable bag (wave rocking)
bioreactors. The broth is then moved to a stirred-tank seed bioreactor. The media solution for
the seed bioreactor (165 L per batch) is prepared in a tank (MP-101) and then sterilized/fed
to the reactor through a 0.2 μm dead-end filter (DE-101).

Serum-free, low-protein media powder is dissolved in WFI in a stainless steel tank (MP-103).
1,628 L of diluted medium (3%) is prepared per batch. The solution is sterilized using a 0.2
μm dead-end polishing filter (DE-103). A stirred-tank bioreactor (PBR1) is used to grow the
cells, which produce the therapeutic monoclonal antibody (Mab). The production bioreactor
operates under a fed batch mode. High media concentrations are inhibitory to the cells so
half of the media is added at the start of the process and the rest is fed at a constant rate
during fermentation. The concentration of media powder in the initial feed solution is 17 g/L
whereas the concentration of the medium added during the fed batch phase is 156 g/L. The
fermentation time is 12 days. The volume of broth generated per bioreactor batch is
approximately 2,000 L, containing roughly 4 kg of product. The product titer is approximately
2 g/L.

6
 Monoclonal Antibody Production ProtA-Equiil.

ProtA-Wash

S-001
S-003 S-107 ProtA-Elut.
Inoculum Prep S-108
Primary Recovery Protein-A
ProtA-Reg.

0.47 L/batch 1.97 L/batch

S-034
S-031 S-037 500.70 L/batch
S-002 S-032
P-1 / TFR-101 P-2 / RBR-101
S-004
T-Flask Roller Bottle P-14 / V-101 P-16 / DE-108 S-036
P-15 / DS-101 P-17 / V-103 P-19 / DE-109
Surge Tank P-18 / C-101
Polishing Fitler
Centrifugation Centrifugation Pool Tank Polishing Fitler
PBA Chromatography ProtA-Waste S-038
S-033 6080.37 L/batch
S-035 S-039

S-008 S-009
S-006

S-109 S-043
S-041 Chemical Virus Inactivation

7.70 L/batch 30.72 L/batch S-110

S-045
S-007 S-102
S-05 P-3 / BBS-101 S-103
P-4 / BBS-102 S-101
Bag Bioreactor Bag Bioreactor
S-044
S-046
S-010 P-20 / V-107 P-21 / DF-101 P-22 / V-111
Diafiltration Virus Inactivation P-23 / DE-110
Storage
Polishing FIlter
S-042
100.15 L/batch S-048
100.18 L/batch
S-047
S-011

Vent-3
S-030

IEX-Equil HIC-Equil
Amm. Sulfate
S-015 IEX-Wash HIC-Wash
S-012
S-013 IEX-WFI IEX Chrom HIC-El
HIC Chrom
196.03 L/batch

P-6 / MP-101 P-7 / DE-101 P-5 / SBR1

Media Prep Sterile Filtration Seed Bioreactor
S-016
S-014 149.14 L/batch
IEX-El S-049
HIC-Reg S-051
IEX-Strip
S-1 IEX-Rinse
S-050 P-27 / DE-106
P-25 / V-109 Dead-End Filtration
175.55 L/batch
IEX Pool Tank P-26 / C-103
P-24 / C-102
HIC Chromatography S-052
IEX Chromatography HIC-Waste
S-025 IEX-Waste S-172
1271.56 L/batch
1643.48 L/batch

Bioreaction

Vent-5 Viral Exclusion

S-024 Final Filtration
S-026
S-028
S-025b
P-12 / MP-103 P-13 / DE-103 S-106
S-058
Sterile Filtration S-057
Media Prep
S-054
S-056 99.43 L/batch
S-027
S-053 S-062
P-28 / V-108 Final Product
1983.06 L/batch P-30 / V-110 S-105 P-33 / DCS-101
S-028b P-29 / DE-105 S-104 P-32 / DE-107
HIC Pool Tank
Storage Freeze in 50L Plastic Bags
Viral Exclusion Filtration Final Polishing Filtration
P-11 / PBR1
S-024b
Production Bioreactor S-059
S-026b P-31 / DF-102
P-34 / MP-104 P-35 / DE-104 99.43 L/batch
Diafiltration S-061
Media Prep S-055 S-060
Sterile Filtration
S-029

S-027b

Figure 4. The flowsheet of the main MAb process.

7
Downstream Processing
The generated biomass and other suspended compounds are removed using a disc-stack
centrifuge (DS-101). During this step, roughly 2% of the product is lost in the solids waste
stream. The bulk of the contaminant proteins are removed using a 62 L protein-A affinity
chromatography column (C-101) which operates in 4 cycles. The product yield for this step is
90%. The protein solution is then concentrated 5x and diafiltered 2x (in P-21 / DF-101). The
total membrane filtration area for the diafilter is 2.6 m2.The yield on product is 97%. The
concentrated protein solution is then chemically treated for 1.5 h with Polysorbate 80 to
inactivate viruses (in P-22 / V-111). An ion exchange (IEX) chromatography step follows (P-
24 \ C-102) with a product yield of 90%. The IEX column has a volume of 28 L and the batch
is processed in 3 cycles. Ammonium sulfate is then added to the IEX eluate (in P-25 \ V-109)
to increase the ionic strength for the hydrophobic interaction chromatography (HIC) step (P-
26 \ C-103) that follows. The recovery yield of the HIC step is 90%. The HIC column has a
volume of 25 L and it processes a batch in 3 cycles. A viral exclusion step (DE-105) follows.
This is a dead-end type of filter with a pore size of 0.02 μm. Finally, the HIC elution buffer is
exchanged for the product bulk storage buffer (PBS) and concentrated 1.5-fold in DF-102.
The approximately 100 L of final protein solution is stored in a 200 L disposable storage bag
(DCS-101). 2.5 kg of purified product are produced per batch. The overall yield of the
downstream operations is approximately 63%.

Buffer and Media Preparation

Several buffers and media are required at different quantities. These have to be prepared
and transferred to the use points in time for processing. Two alternatives for the buffer and
media preparation activities are investigated.

The first option employs single-use preparation and storage systems. Media are prepared in
200 L single-use bags and transported to the use point. The various buffers are prepared in
500 L and 1,000 L bags (utilizing a skid) and then transferred through sterile filters into 200 L
storage bags. The 200 L bags are subsequently moved to the point of use. Specifying single-
use bags in SuperPro Designer is a simple process (Figure 2). The first step involves
specification of the type of bag, capacity, purchase and disposal costs and other properties in
the consumables database. The bag can then be allocated to a unit procedure that
represents buffer preparation or storage. The tool calculates the number of required bags per
batch and campaign during simulation. Other consumables, such as chromatography resins
and membrane cartridges are specified and calculated in a similar manner. In this case
study, the three types of bags used have working volumes of 200 L, 500 L and 1,000 L and
their assumed purchase costs are $300, $400 and $570 per item, respectively.

Table 1. Media and buffer prep and holding tanks for the stainless steel option

Tank Name Size (L) Tank Name Size (L)

MP-101 200 HV-101 3400
MP-102 1900 HV-102 1400
MP-103 200 HV-103 900
PV-101 3400 HV-104 300
PV-102 1400 HV-105 300
PV-103 900 HV-106 400
PV-104 300 HV-107 30
PV-105 30 HV-108 1100

The second option employs traditional stainless steel tanks for buffer and media preparation
and holding. Media are prepared and fed using a single tank (dedicated) per bioreactor. The
buffer preparation area includes a number of preparation tanks connected to a group of
holding tanks using a set of transfer panels. The holding tanks are in turn connected with the

8
main process using buffer delivery lines. The amount and number of buffers that need to be
prepared determines the size and the number of the tanks. Table 1 displays the required
tanks and their sizes. Three tanks are required for media preparation (MP-101, 102, and
103); five tanks are required for buffer preparation (PV-101, 102, 103, 104, and 105) and
eight tanks are required for buffer holding (HV-101 to HV-108). Since, the stainless steel
tanks are reused, cleaning in place (CIP) is essential after every buffer preparation batch.

Results and Discussion

The main process parameters are summarized in Table 2. The fermentation time is 12 days;
the facility is equipped with 4 production bioreactor resulting in a cycle time of 3.5 days. 80
batches can be executed per year (20 per bioreactor). The product titer in the production
bioreactors is 2 g/L. With a broth volume of approximately 2,000 L and a downstream yield of
62.5%, the amount of purified MAb produced per batch is 2.5 kg.

Table 2. Summary of the main process parameters

Fermentation Time 12 days

Production Bioreactors 4
Purification Trains 1
Process Cycle Time 3.5 days
Batches Per year 20/bioreactor
Product Titer 2 g/L
Bioreactor Broth Volume 2,000 L
Recovery Yield 64,40%
Batch Throughput 2.5 kg
Annual Throughput 202.5 kg

Figure 3 displays the equipment occupancy chart (also known as Gantt chart) for thirteen
consecutive batches of the 2,000 L stainless steel process option. The activities (unit
procedures) of each batch are displayed with a unique color. The various equipment groups
are displayed on the chart. The occupancy of CIP skids is represented by the top six lines.
The next two equipment groups correspond to the occupancy of the buffer preparation and
holding tanks, respectively. Most of these tanks are reused within a batch. Reuse of a tank
(e.g., HV-101) within a batch is represented by multiple rectangles of the same color (one
rectangle for each unit procedure utilizing that equipment). Reuse of tanks (for preparing and
holding different buffers within a batch) reduces the number of vessels and consequently the
capital investment for a new facility. However, it also increases their occupancy and cycle
times making them likely scheduling bottlenecks.

The next equipment group corresponds to the three seed (SBR1a, b, and c) and the four
production bioreactors (PBR1a, b, c, and d). Both the seed and the production bioreactors
operate in staggered mode (out of phase) in order to reduce the cycle time of the overall
process to 3.5 days. A single downstream line (DSP group) handles all purification batches.

The equipment occupancy chart enables users to visualize the utilization of equipment and
readily identify equipment scheduling bottlenecks that determine the cycle time of the overall
process. The production bioreactors (PBR1a, b, c, and d) have the longest cycle time and
constitute the scheduling (or cycle time) bottlenecks for the base case. However, if the
number of production bioreactors is increased, then, the bottleneck will shift to the buffer
preparation and holding tanks that have the next highest utilization. Scheduling bottlenecks
linked to buffer preparation equipment is not a consideration for the disposables option
unless the buffer preparation bag skids are reused.

9
In general, media and buffer preparation cycle times for the disposables option are shorter
than the stainless steel case because disposable bags do not require SIP or CIP steps. The
reduced need for cleaning also has a positive impact on the required number of CIP skids
and the volume of cleaning materials. Figure 5 displays the required number of CIP skids (as
a function of time) for the stainless steel and the disposables options, respectively. Six CIP
skids are required in the first case while this number is halved for the single-use option,
which in turn reduces the capital cost of the single-use option. Table 3 provides information
on the demand for cleaning materials for the two cases. The use of disposables reduces the
volume of cleaning materials by more than 50%.

Figure 5. CIP skid requirements (peaks) for the stainless steel (a) and single-use (b) options.

The two options were also compared from an economic perspective Table 4 and Figure 6
display the breakdown of operating costs for both options and their respective unit production
costs. The unit production cost for the disposables option is 24% lower than that of the
stainless steel option ($317/g versus $415/g). The facility dependent cost, which mainly
accounts for the depreciation and maintenance of the facility, is $27 million per year for the
single-use option versus $38 million per year for the stainless steel option. The cost of raw
materials, which includes the cost of cleaning materials, is also considerably higher for the
stainless steel case. On the other hand, the consumables cost is higher in the case of
disposables ($8 million per year versus $5 million per year).

Table 3. Demand for WFI, cleaning materials, and clean steam

Stainles Steel Single-Use Reduction

WFI consumption (L/batch) 46,000 16,000 65.2%
Caustic solution consumption (L/batch) 11,000 3,500 68.2%
Acid solution consumption (L/batch) 14,000 5,000 64.3%
Clean Steam Consumption (kg/batch) 2,600 1,250 51.9%

10
Table 4. Cost-of-goods comparison between the two alternatives

Stainless Steel Single-Use

Cost Item $ % $ %
Raw Materials 5,870,000 7.08 3,532,000 4.95
Labor-Dependent 22,628,000 27.28 21,825,000 30.59
Facility-Dependent 38,093,000 45.93 27,048,000 37.91
Other 11,314,000 13.74 10,912,000 15.38
Consumables 4,946,000 5.96 7,966,000 11.17
TOTAL 82,937,000 100 71,341,000 100
Production Cost ($/g) 415 317

COG's comparison

100%
90%
80%
70% Consumables
60% Other
50% Facility Dependent
40% Labor
30% Raw Material
20%
10%
0%
Stainless Steel Process Single Use Process

Figure 6. Cost-of-goods breakdown for the stainless steel and single-use options.
For the base case comparison it was assumed that both plants manufacture the same
product throughout the year (80 batches per year). If frequent product changeovers are
required, which is common for clinical manufacturing facilities, then the number of batches
per year will go down and the facility dependent cost (per unit of product) will increase. And
since single-use systems facilitate product changeovers (due to reduced validation), the
advantage of single-use systems will be more profound under those conditions.

For the 2,000 L production bioreactor scale, the disposables option is clearly the preferred
alternative. The advantage of the disposables option gradually diminishes as the scale is
increased (Figure 7). For the scale of 8,000 L the options are roughly equivalent from a cost-
of-goods point of view. The analysis reveals that the single-use systems option for buffer
preparation and holding is clearly more economical at smaller scales (under 8,000 L of
production bioreactor scale). The main reason is the significantly lower facility-dependent
and material costs. The facility-dependent cost is lower in the case of disposables due to
reduced requirement for stainless steel vessels, CIP skids, piping infrastructure, and utility
systems. The cost of materials is lower due to reduced demand for cleaning materials.

11
 Production Cost vs Scale

900

800
Base
700 Case
Production Costs ($/g)

600

500 Stainless Steel Process

400 Single Use Process

300

200

100

0
1000 2000 4000 8000
Bioreactor Capacity (L)

Figure 7. Unit production cost of the two options at different scales.

For scales larger than 8,000 L (of production bioreactor working volume), the stainless steel
option starts becoming more attractive. Firstly, the number of buffer bags that need to be
prepared and transported to the point of use becomes impractically high (Figure 8). The
volume of the hold bags is limited to 200 L due to the fact that they have to be manually
transported on a cart to the point of consumption. In addition, multiple buffer preparation
skids are required to avoid bottlenecks associated with preparation of buffers which in turn
affects the capital investment. Labor costs are also considerably increased since more
operators are required for preparing and transporting the bags; labor demand for the
stainless steel case does not change much with scale. It is important to note, however, that
the 8,000 L scale is not a universal turning point for MAb processes. Increased product titers
will most likely result in lower turning points since they are equivalent to higher batch
throughputs.

200L Bags vs Production scale

250
200L Single Use Bags (Items/batch)

230
210
190
170
150
130
110
90
70
50
2000 4000 8000
Bioreactor Capacity (L)

Figure 8. Number of 200 L single-use bags required per batch as a function of production scale.

12
Summary
This article demonstrated how to employ process simulation tools in order to assist in the
evaluation of process alternatives via an illustrative case study. Two options for buffer
preparation and holding activities of a typical MAb process were analyzed from an economic
perspective. The first was employing single-use buffer preparation and storage bags
whereas the second the more traditional stainless steel preparation and holding tanks. The
single use system proved to be more advantageous for smaller scales whereas the stainless
steel option becomes more economical as the production scale increases. The results of the
evaluation are specific to the MAb process analyzed. Additional process options and
alternative technologies can be readily evaluated and compared using such tools.

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