Perspective

Received: 8 September 2014

Revised: 21 October 2014

Accepted article published: 3 November 2014

Published online in Wiley Online Library:

(wileyonlinelibrary.com) DOI 10.1002/jctb.4584

A systems engineering perspective on process

integration in industrial biotechnology
Anton A. Kiss,a,b* Johan Grievinkc and Marco Rito-Palomaresd
Abstract
Biotechnology has many applications in health care, agriculture, industry and the environment. By using renewable raw
materials, biotechnology contributes to lowering greenhouse gas emissions and moving away from a petro-based towards a
circular sustainable economy. However, major developments are still needed to make industrial biotechnology an economic
alternative to conventional processes for fuels, specialty and/or bulk chemicals production.
Process integration is a holistic approach to process design, which emphasizes the unity of the process and considers the
interactions between dierent unit operations from the outset, rather than optimizing them separately. Furthermore, it also
involves the substitution of two or more unit operations by one single novel unit capable of achieving the same process goal.
Conversely, process systems engineering (PSE) deals with the analysis, design, optimization, operation and control of complex
process systems, as well as the development of model-based methods and tools that allow the systematic development of
processes and products across a wide range of systems involving physical and chemical change. Mature tools and applications
are available for chemical technology and steps have been taken to apply PSE principles also to bioprocess technology.
This perspective paper argues that an interdisciplinary approach is needed towards integrated bio-processing in order to
link basic developments in biosciences with possible industrial applications. PSE can foster the application of existing and
the development of new methods and tools for bioprocess integration that could promote the sustainable production of
bio-/chemical products. The inclusion of PSE principles and methods in biochemical engineering curricula and research is
essential to achieve such goals.
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Keywords: PSE; process integration; design; optimization; bioprocess; separation

INTRODUCTION
Bio-based economy refers to all economic activity derived from
biotechnology, which applies scientic and engineering principles
to the processing of (bio-)materials by biological agents. Biotechnology focuses on understanding the mechanisms and processes
at the genetic and molecular levels and its application to industrial
process. The dening technologies include, but are not limited
to: genetic engineering, metabolic engineering, culture of recombinant micro-organisms, cells of animals and plants, hybridoma
technology, nano-biotechnology, bioelectronics, protein engineering, tissue and organ engineering, transgenic animals/plants,
genomics and proteomics, immunological assays, bio-separations
and bioreactor technologies. Biotechnology can oer signicant
environmental and economic benets in manufacturing, waste
management and monitoring, such as: improved economics of
production, reduced pollution of industrial processes and products, decreased dependence on non-renewable resources, and
sustainable production of existing and novel products.1,2 However, the upcoming problems of society turning to a bio-based
economy cannot be solved without major developments in
biotechnology. This involves the development of improved and
highly ecient microbial production systems, the establishment
of generic approaches to feedstock processing and bio-products
production, as well as novel and easy to implement bioseparation
technologies to process complex fermentation broth and waste
materials.
J Chem Technol Biotechnol (2014)

Sustainable process integration and PSE, complemented by process intensication, are core drivers for economical and sustainable biochemical production. The biochemical process industry
dedicates much attention to the ecient use of resources, minimization of energy use, and reduction of the detrimental impact
on the environment. A key aim is to shift these eorts from a
unit-based approach to a systems-level paradigm, and develop
holistic process design tools and methodologies that target sustainability (balancing the social, economic and environmental
spheres, as shown in Fig. 1), energy conservation and waste reduction from a systems perspective.3 Therefore, an approach based on
process integration, process intensication and process systems

Correspondence to: A.A. Kiss, AkzoNobel Research, Development & Innovation, Process Technology SRG, Zutphenseweg 10, 7418 AJ Deventer,
The Netherlands. E-mail: Tony.Kiss@akzonobel.com

a AkzoNobel Research, Development & Innovation, Process Technology SRG,

Zutphenseweg 10, 7418 AJ Deventer, The Netherlands
b Sustainable Process Technology Group, Faculty of Science and Technology,
University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands
c Delft University of Technology, Chem E, Julianalaan 136, 2628 BL Delft,
The Netherlands
d Centro de Biotecnologa-FEMSA, Tecnolgico de Monterrey, Campus Monterrey, Ave Eugenio Garza Sada 2501 Sur, Monterrey, NL 64849, Mxico

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SOCIAL
Responsible in the
local and global
communities

ECONOMIC
Growth and
financial health of
the company

Socioefficiency

Sustainability
vision
Eco-social
Ecobalance
efficiency

ENVIRONMENTAL
Performance excellence
of process and products

Figure 1. Sustainability pillars: social, economic and environmental.

Time
scale

small

Chemical scale

intermediate

large

month
Enterprise

week
day
h
min
s

e
oc
Pr

ss

si
en
nt

fic

n
tio

Plants
Plants
Process units
Single & multiphase systems

Particles,
thin films
Molecular
clusters

ms
ns

e
oc
Pr

ss

s
Sy

s
m
te

ee
in
ng

g
rin

Molecules

ps

pm

nm

mm

km

Length scale

Figure 2. Scale of study in process intensication and process systems

engineering.

engineering (PSE) must be used to tackle the challenges faced by

industry.3 PSE focuses on decision making for the development,
design and operation of supply chains, including the design, operation, control, and optimization of chemical, physical, and bioprocesses with the aid of systematic model-based methods. An even
wider denition of PSE has been used by Stephanopoulos and
Reklaitis.4 PSE covers a large range of scales, varying from molecular to enterprise wide as shown in Fig. 2.5,6
Process integration is an objective for process design, but the
same name is used for process design skill area within the wider
envelope of PSE. Process integration is a holistic approach to
process design, which emphasizes the unity of the process, using
tools developed to achieve productivity enhancement, process
improvements, conservation of mass and energy resources, and
reduced investment and operating costs of chemical processes.7,8
The major applications of process integration tools focus on
resources conservation, energy management and pollution
prevention, but the recent decades have also witnessed the development and application of process integration tools for networks
related to: heat and mass exchange, heat-/energy-induced separation, waste minimization, as well as water conservation and
minimized usage.9 The principles of process integration and
in a wider circle process systems engineering have resulted in

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mature methods and tools for chemical process technology.10

The potential and ambitions of PSE are to move on to bio- and
nano-technology.4 While the formal decision making framework
of PSE is wide and rich to support such an expansion, the deeper
challenge is in understanding and mastering new problems in bioprocess technology and its domain knowledge. The rst inroads
are being made in the synthesis and design of bioreneries11,12
and biofuel supply chain optimization.13 In a wider setting,
an interdisciplinary approach is needed towards integrated
bio-processing14 that includes protein, genetic, metabolic and
process engineering in order to link the basic developments in
biosciences with possible industrial applications.15 PSE can play
an important role in the development of new concepts, methods
and tools required for the sustainable production of bio-/chemical
products.16 Also, there is a strong need to develop the people,
work processes, working cultures and environments in order to
make a signicant impact at industrial scale.

PROBLEM STATEMENT
Bioprocessing systems are complicated for a number of reasons.
Figure 3 shows the range of feeds and products for a bioprocessing
system with common processing routes. Human food, animal
feeds and pharmaceuticals are not shown as products. There is a
potentially wide range of combinations for feeds, products and
processing routes. The processing routes are enabled by biological
agents, water and other solvents, power. Process and supply chain
designs are strongly coupled for economic and ecological reasons.
Last but not least, the values of the various stakeholders in the
process often have opposing eects on the process design and
operation. Process design and integration must nd harmonizing
and sustainable solutions to such opposing eects of values. In
order to embark on any holistic changes that deal with the core
processing units, it is unavoidable to completely understand and
appreciate the integrated nature of the bioprocess. Modications
in a unit or a stream often propagate throughout the process
and can have crucial implications for the process operability and
protability. Hence, several process objectives (e.g. economic,
technical, social, safety and environmental) must be integrated
and then reconciled. These grand challenges can be addressed via
a unique framework of integrated process synthesis and design
methodologies a set which can be collectively referred to as
sustainable process integration.
Within the bioprocess systems box quite a variety of processing routes exist. In contrast to chemical processes, bioprocesses
take place under milder conditions and exhibit high selectivity
towards a specic product, although a key drawback is that the
downstream separation and recovery of the products from the
diluted aqueous streams (less than 20%wt product) account for
6080% of the total production cost. In addition, downstream
processing technologies face new challenges derived from the
biochemical engineering developments. These challenges involve
the treatment of complex feedstock, as well as the purication of
new products.
The focus of this perspectives paper will be mainly on the white
bioprocess technology for the production of biofuels and platform
chemicals for bulk and ne chemicals.

ROLE OF PROCESS SYSTEMS ENGINEERING

PSE aims to address a large range of important questions related
to process integration in biotechnology, as for instance: When

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Competing interests of many stakeholders

social / economic / environmental

Bio-processing system & routes

Aquatic feed stocks
(micro-algae
biomass, sea weeds)

Algae harvesting and conversion

Bio oils
Sugars

Thermochemical
(pyrolysis, gasification, combustion)
Terrestrial crops
(Corn, Sugar cane,
Soy bean, oil seeds)

Lipids, oil

Biofuels

(alcohols & diesel)

Biochemical

Terrestrial crops
(Cellulosic biomass,
from agriculture,
forestry, energy crops)

Platform chemicals

Pre-treatment
(HMF, levulinic acid)
Hydrolysis
Biological processing (e.g. fermentation) Syngas and hydrogen
Chemical processing (catalytic)
Product upgrading & recovery
Power & heat

Solar power/ Water

wind energy

Solvents

Figure 3. Inputoutput diagram of a bioprocessing system.

should a bioprocess be implemented, instead of a chemical process?

Can the existing infrastructure be used for a new bioprocess? How
can a plant be adapted for various biomass feedstock from dierent
regions? What is the optimal conguration of a biorenery? Which
is the most economically feasible process alternative? What options
exist in practice for sustainable process integration?3
Next to qualitative reasoning, quantitative tools are required to
solve such problems and PSE has many of these tools ready to be
applied to the complete set of bioprocesses, including ne chemicals, pharma, bulk chemicals and biofuels. It will be argued that
PSE can and will play a crucial role in the design, development
and improvement of industrial bioprocesses as formal decision
making with computing assisted tools are in place. The caveat is
that proper domain knowledge (species characterization, thermodynamics, biocatalytic kinetics, uid ow and rheology) with the
associated models is decient for bioprocess technology.
Transition to bio-based chemicals and fuels
Besides the production of biofuels, the production of specialty
chemicals from biomass is of equal importance. In the present
world aiming to reduce the use of fossil fuels due to climate
changes, the origin of the chemicals of the future remains
unclear. The existing infrastructure is based on the use of several established platforms: methane, ethane, ethylene, propylene,
1,3-butadiene, aromatics (BTX). An important direction is to use
the existing infrastructure and just create the chemicals from
alternative, renewable sources. However, the long-term direction
is to develop novel processes established on a dierent set of platform chemicals, as for example around glucose. In a biorenery it
will be required to develop a structure that can cope with a large
range of feedstocks, a variety of technologies and products. This
presents a signicant challenge for process integration, design
and optimization. In addition, experimental validation, design of
experiments (DoE) and high-throughput experimentation (HTE)
will be required for an optimal integrated design.
Process synthesis and conceptual design
Biotechnology industry is growing at high rate demanding the
development of novel and ecient bioprocesses. In this context, considerable cost reduction can be achieved only by considering innovative methodologies in the early stage of process
J Chem Technol Biotechnol (2014)

development.17 In process development, considerable attention

must be given to the use of downstream processing methodologies (e.g. aqueous two-phase partition and expanded bed
adsorption21 ) that address the bottleneck of bioprocesses as
bioseparation contributes to 6080% of the total annual costs. The
establishment of strategies that allow the integration of several
unit operations for recovery and purication of bioproducts in one
single stage must be favored. In the typical situation, there are several competing routes to the same product, and biotechnology is
just one of the possible options for the production of chemicals or
fuels. The economic drivers for implementation heavily depend on
the feedstock costs and availability, existing infrastructure, and the
eciency of the available biocatalysts and bioprocesses.3 Clearly,
the biotechnology alternative will be a true option only if the bioprocess represents a unique route with superior advantages and
benets. This leads to a set of alternative routes and technologies
from a given feedstock to a given product.18 PSE has a particular
role to enable such evaluations on a qualitative and quantitative
basis, while bringing the advantages of rapid computational methods to enable rapid evaluation of alternatives. A parallel set of evaluations is required regarding the need to retrot existing plants or
build new plants. The objective functions to be optimized will need
to be based not exclusively on economics but also on sustainability
metrics (socio-eco-eciency) and integrated with safety and life
cycle analysis, in order to include the complete evaluation of feedstocks, products and processes.8
Optimal design of bioreneries
One type of biorenery is based on oil-derivative-compatible
material from biomass, while the other is based on ligno-cellulose
biomass utilization to produce a variety of sugars for subsequent fermentation or biocatalysis. A crucial research direction is
to ensure that all the fractions of a particular biomass are fully
exploited, and also that the development of downstream products is explored.19 Novel eco-ecient processes can be developed for the cost-eective synthesis of biofuels (e.g. biodiesel and
bio-alcohols20 ), that consider also the production of high value
natural colorants, enzymes and in general protein-based products.
The focus should be on the concept of the production of next generation biofuels and additional bioproducts for alternative industries (e.g. food and pharmaceutical). Such an approach will require
the development of novel processes, since the raw materials are

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bio-based and the petro-chemistry platforms become outdated.
For example, the glycerol byproduct from biodiesel production
can be used as a platform chemical, to produce 1,3-propanediol
or other derivates.3 An additional example is the production of
intracellular products (e.g. colorants and enzymes) obtained from
the further processing of used biomass.14,17 Evaluating the integration of product and feed streams in this way, along with the use
of products as fuels or platform chemicals is a key research direction where PSE plays a very important role. The increasing range
of opportunities and technologies, as a result of fermentationor enzyme-based catalysis, will lead to complex integration problems, which will certainly require novel or properly adapted PSE
methodologies and tools.
Pre-treatment of biomass
Pre-treatment can contribute to 2040% of the overall production
costs and so has a signicant impact on the valorization of the
biomass.16 When (moist) biomass is collected at distributed harvesting locations, the local ecient removal of redundant materials (e.g. sand, water) prior to centralized processing is a bonus. The
classical thermo-chemical pre-treatment techniques tend to break
down the diversity of molecular structures in the biomass to standard chemical building blocks (C1 ). The challenge here is to recover
as much suitable molecular structures in the biomass feed as possible for making products. The selection of suitable (ionic) solvents
to open up feed structures can play an important role. Also here,
PSE can oer methods and tools to search for synthesis routes from
identied suitable chemical structures present in the biomass feed
to the product molecules.18
Design and development of biocatalysts and bioreactors
Several types of bioprocess can be identied depending on the
type of the biocatalyst:3
fermentation processes that are carried out in stirred tank
or bubble columns, with low yield on substrate, and catalyst
potentially recyclable via a continuous process;
microbial catalysis carried out in stirred tank or bubble
columns, having medium yield on substrate, and catalyst
recyclable via ltration;
enzymatic catalysis, with high yield on substrate, and recyclable
catalyst via immobilization, carried out in stirred tank or membrane reactors, but also in uidized or packed bed when the
enzyme is immobilized.3
An important research direction is the modication of biocatalysts. New modied enzymes may have tolerance to reactor conditions (e.g. T or pH), as well as improved activity and selectivity
on a given reactant or substrate. The individual enzymes can be
over-expressed in case of cellular catalysts hence increasing the
reaction rate of a given cell, while the control scheme can be xed
in order to improve the yields and rates, via metabolic engineering.
Enzymes can be cloned into single host in order to make a new
pathway via a combination of de-novo pathway and genetic engineering. PSE and biological engineers need to agree upon what is
actually required in a given case and therefore set suitable targets.
The implementation may come via process enhancements and/or
via catalyst improvements. It is anticipated that the majority of new
processes will be based upon the use of recombinant enzymes
as highly ecient catalysts. These new improved biocatalysts will
result in more ecient and cost- eective processes. An important

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characteristic needed in the new bioprocesses is the low number of unit operations required to obtain a commercial product.
Process integration approaches that result in product release, contaminant removal and product concentration in one single stage
will be greatly preferred. It is also worth considering the use of
multi-enzymes complexes that will materialize in novel bioprocesses able to produce multi-products (e.g. the production of intracellular enzyme complex and puried protein-based products).21
Integration of separation processes
Bioprocess integration will play a major role in the development
of the required ecient production systems, characterized by the
use of a reduced number of unit operations. With only few minor
exceptions, water is the solvent for all bioprocesses. As a result, the
downstream process is rather dicult, being emphasized by the
need to perform separations at moderate temperatures. Considering the dilute nature of the streams, the majority of the costs are
frequently in the downstream processing. In the case of biofuels,
water removal and reuse via recycle becomes essential to avoid
transporting water and reduce costs bioethanol being a relevant
example. Tools such as pinch technology have a signicant role,
as the issue of water and solvents use in a biorenery is in many
aspects similar to the issue of heat use in a traditional renery.9
Clearly the early removal of water is essential, in order to develop
ecient separation processes. However, the potential application
of novel extraction technologies requires consideration. Bioengineering approaches that result in early capture of the target product and contaminant removal need to be pursued.14 In this context, the use of novel separation technologies such as aqueous
two-phase systems (ATPS) and expanded bed adsorption (EBA) will
facilitate the removal of major contaminant at early stage and provide streams suitable for the purication stages. As a result novel
and compact processes are expected. Although, scientic reports
dealing with the successful implementation of process integration approaches in biotechnology at large scale are not common,
there is a classical paper that demonstrated the in situ isolation
of periplasmic IGF-I from a 10 000 L E. Coli fermentation.22 However, reporting of additional successful cases is warranted. Thus, it
is clear that process integration strategies will need to be directed
to the design of a process stage that combines product release and
purication in a reduced number of unit operations. The new type
of raw material currently considered for bioreneries represents a
great challenge for existing separation strategies.21
Challenges to PSE from characteristic features in bioprocess
technology
(a) Supporting methods, models and tools
In view of the great diversity and variability of biological agents
in processes the development of rst principles models will be
prohibitive, in terms of cost and time. Instead, grey box models can be developed that must be tuned to experimental data
obtained from DoE and HTE. A proper characterization of uncertainties in the model response quantities is essential in view of
the underlying variability. Further development of the existing PSE
tools will be required for property prediction packages and an
ample database for bio-based molecules. More transparent and
robust environmental LCI databases of bio-derived materials, and
better understanding and modeling of socio-economic aspects
and relationships are needed for the sustainability assessment of
bioprocesses.3

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Energy & Mass
Separating
Agents in

(Bio)Reactor
system

Sustainable
Process
Integration

Separation

Environmentally
Acceptable
Gaseous Emissions

Heat &
water
recovery
Raw
materials

In-Plant Unit
Operations

Products and
by-products

Utilities
Environmental
Energy & Mass
Separating
Agents out

Control & safety

Environmentally
Acceptable
Aqueous Emissions

Figure 4. Sustainable process integration (left) and in-plant unit operations (right).

(b) Process design and control

In order to cope with uncertainty in the behavior of a process during design, two directions can be used: overdesign the process
equipment, or use smart control to compensate via process inputs
for deviations in the key performance indicators. For many bioprocesses the equipment is standardized, so the remaining option is
the design of smart controls based on a good process performance
monitoring system.
(c) Process operations and supply chain management
If the logistics of the distributed feed supply and products delivery
to customers are tightly coupled to the manufacturing, then
production planning and scheduling become intertwined with
the process operations, while seasonal dynamics also play an
important role. Such (desirable) integration presents a formidable
optimization challenge, as shown by Van Elzakker et al.23 for FMCG.

ROLE OF PROCESS INTEGRATION

AND INTENSIFICATION
Process integration focuses on ecient use of shared physical (heat)
and chemical resources (e.g. solvents) in a process. The mass
integration addresses the generation, separation, and routing of
streams and species throughout the process.3 This is being developed and applied to identify overall insights, synthesize strategies,
and address the root causes of mass processing and environmental
problems at the heart of the bioprocess as illustrated in Fig. 4.8,9
Mass integration is used as a systematic methodology that oers
understanding of the overall ow of mass within the process,
which is used in identifying the performance targets and optimizing the allocation, separation and generation of streams/species.
Energy integration deals with the overall allocation, generation,
and exchange of energy throughout the process. The development of such methodologies for energy integration is strongly
driven by the increasing demand for expensive utilities within the
biochemical process industries. The aim is to identify cost-eective
waste minimization systems, end-of-the-pipe separations, recycle
systems and in-plant separation systems that allow an integrated
solution.3,9
Process intensication aims to develop novel sustainable and
ecient (bio)processes able to reduce the energy requirements
by up to 50% and replace the existing technologies with more
ecient ones: e.g. separations using alternative energy sources,
hybrid operations, PI technologies and integrated equipment conveniently combining multiple functions into a single unit.24 As the
well-known and used concept of unit operations narrows the creativity in search for novel solutions, the aim is to shift the focus from
unit operations to functions.25 A function (or fundamental task)
describes what should happen, and not how it should happen. The
J Chem Technol Biotechnol (2014)

Functions
Functions

Operations
Operations

Processes
Processes

Bio/chemical
reaction
ns Bio/chemical
ns
Bio/chemicalreactions
reactions
Bio/chemicalreactor
reactorr
Affinity
Extraction
s
Combinationsof
of
Affinityseparations
separations
Extractionunit
unit Combinations
unit
Bio-catalytic
activity Fixed/fluidized-bed
unitoperations
operations
Bio-catalyticactivity
Fixed/fluidized-bed
Form
Extruder
change
Formchange
Extruderunit
unit
Phase
Distillation
Bio-processes
Bio-processes
Phasechange
change
Distillationtower
tower
Pressure
change
Flash
vessel
Batch
Batchprocesses
processes
Pressure change
Flash vessel
Temperature
change
Heat
exchanger
Cont.
Cont.processes
processes
e
Temperature change
Heat exchanger
Change
of
pH
Neutralizer
Hybrid
processes
H
Change of pH
Neutralizerr Hybrid processes
Mixing
Mixers
ofmaterial
Mixingof
material
Mixers

Figure 5. Process design strategy shifting from processes and operations

to functions.

functional based design of bio-processes allows the combination

of more functions into one piece of novel equipment hence consisting of fewer steps, and it provides more freedom of equipment
design. Figure 5 shows the shift from process to (unit) operations
to functions.
Such an approach has been successfully developed and applied
to a solution crystallization process.26 As bioprocesses pose new
separation challenges (e.g. diluted aqueous solutions, azeotropes
and non-ideal behavior), hybrid process intensication technologies can pave the way to more eciently integrated bioprocesses.
The main research directions that will have a great technical and
economic impact on all biotechnology based processes include:
Hybrid and reactive separations. This topic includes, but is not
limited to advanced separation technologies,20 such as distillation or extraction processes combined with membrane separations and/or reactive systems. Exploration of using hybrid
processes and technologies will lead to the creation of fundamental knowledge in the synthesis, modeling, design, operation
and control, scale-up and novel industrial applications of such
highly integrated systems. Moreover, this direction also aims for
a better understanding of biochemical interactions in dicult
separations that will facilitate the reliable design of novel bioprocesses.
Processes powered by alternative energy sources. Alternative
energy sources such as light, microwave, plasma, ultrasound, electric elds are novel key methods with potential
for intensication of biosynthesis and separations in terms of
energy and resource eciency.27 This research direction can
develop new methods based on the fundamental mechanism
understanding, advanced modeling, experimentation, and
characterization that will enable targeted supply of alternative
forms of energy in novel reactors and separators to precisely
control the chemical transformations, reaction pathways, and
in situ product recovery (ISPR).

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Novel separation methods. The aim here is to identify the challenges in separation and develop new methods that account
for the production of bioproducts from dierent sources. New
separation technologies must be explored and developed
for removing major contaminants and concentrate diluted
aqueous biostreams at an early stage, without utilizing thermal
separation processes (e.g. distillation). Moreover, the recycling
and reuse of wastewater streams and chemicals used in process
stages (for example, extraction) are essential. Novel separation
and recovery methods that do not require the addition of
large amount of other chemicals (to change the pH) should be
investigated for wastewater treatment.

ENGINEERS AND ENGINEERING WORK

PROCESSES
The challenges that biotechnology faces (derived from the need
for ecient, easy to implement low cost bioprocesses) require a
paradigm shift in approaches for production, capture and purication of bioproducts. It is clear that the challenges faces today
are dierent from those of two decades ago. The current bioseparation platforms are unsuitable for the constant increase in cell
concentration in the bioreactor to achieve better yield. The concepts, methods, models and tools for process integration by means
of PSE can only be put to eective use by skilled bioprocess engineers in well-organized work processes. However, the PSE skill
area traditionally belongs to the chemical engineering curriculum
in academia. If biochemical engineering has branched o from
chemical engineering, the emergence of a PSE knowledge gap is
more than likely. However, this gap can be prevented if the academic curricula for biochemical engineering start paying attention
to principles and applications of PSE in bioprocess technology.28
Such teaching will stimulate the application of PSE principles in
academic research as well as challenge the PSE skill area to better
address the specic needs of bioprocess technology.
The second crucial factor is work processes. The authors of this
perspective paper worked with many partners from industry and
academia to build teams and projects, and to eciently develop
work processes and environments for feasible process integration
applications. The key building blocks of this strategy are available
in the paper of Dunn and El-Halwagi.9 Two rules essential to the
use of PSE for bioprocess integration are highlighted here:
Encourage an open and stimulating environment that fosters
creativity and out-of-the-box thinking, where the focus is on
how to do it? instead of it will not work.
Measure, analyze, and use sustainable process integration tools
to synthesize, develop, further improve, provide feedback,
rene and sustain projects and strategies.

CONCLUDING REMARKS
The existing chemical production methods are now complemented by the development of new bioprocesses, in which there
will be a specic role for PSE to bring the benets of rapid simulation, quantitative decision-making tools, process design, and
sustainability principles. The future process models will integrate
sustainability principles into the process design and development,
at various levels: infrastructural level (evaluation of bioreneries
and feedstock integration), process level (assessment of process
integration and alternative technologies), unit and function level

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(new process equipment), and catalyst level (estimation of alternatives for protein and metabolic engineering). PSE is not a single add-on but rather a pervasive technology as shown by the
examples of new contributions at multiple scales ranging from
molecular designs to process unit integration to plant wide control and supply chain operation. Further development of existing
PSE tools will be required, including process modeling and simulation tools that can interface with property prediction packages
and an ample database for bio-based components. For the sustainability assessment of bioprocesses, more transparent and robust
environmental LCI databases of bio-derived materials, and better
understanding and modeling of socio-eco-eciency aspects and
relationships are needed. Along with the improvements in tools
and methods of PSE, an expanding dialogue between chemical
and biochemical engineers, biologists and related areas of expertise, will be required to make sustainable biotechnology at industrial scale a reality.

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