chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384

Contents lists available at ScienceDirect

Chemical Engineering Research and Design

journal homepage: www.elsevier.com/locate/cherd

Review

A review of integrated supply chain network design

models: Key issues for vaccine supply chains

Stef Lemmens a,∗ , Catherine Decouttere a , Nico Vandaele a , Mauro Bernuzzi b

a KU Leuven, Research Center for Operations Management and Department of Decision Sciences and Information
Management, Naamsestraat 69, 3000 Leuven, Belgium
b GlaxoSmithKline Vaccines, Avenue Fleming 20, 1300 Waver, Belgium

a r t i c l e i n f o a b s t r a c t

Article history: In general, vaccines are recognized as an important means to protect populations against
Received 9 January 2015 infectious diseases. We show that vaccines do not behave like commodity goods and elab-
Received in revised form 15 October orate on the key issues for vaccine supply chain design. This paper reviews the literature
2015 on model-based supply chain network design in order to identify the applicability of these
Accepted 10 February 2016 models to the key issues of the design of a vaccine supply chain. We study whether the deci-
Available online 21 February 2016 sions at strategic, tactical and operational levels of the reviewed literature are able to address
vaccine supply chain key issues as limited shelf life, cold chain distribution and accessing
Keywords: remote areas. Furthermore, we provide an overview of how uncertainty is incorporated in
Vaccine supply chain the reviewed literature and is able to incorporate disease epidemics, tender procurement,
Rotavirus lead time variability and demand variability. Our future vaccine supply chain network needs
Supply chain network design to be sustainable, hereby taking the preferences of different stakeholders into account for
Literature review obtaining a set of economical, technological and value key performance indicators that need
Uncertainty to be satisfied by the design. Finally, we discuss the real-life applicability of the research
Multi-criteria decision making up to now and discuss similarities and dissimilarities of vaccine supply chains with other
pharmaceutical supply chains.
© 2016 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
2. Previous literature reviews on SCND modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
3. Vaccine supply chain key issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
3.1. Network characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
3.2. Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
3.3. Performance measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
3.3.1. Economical criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
3.3.2. Technological criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
3.3.3. Value criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

∗
Corresponding author. Tel.: +32 16379065.
E-mail addresses: stef.lemmens@kuleuven.be (S. Lemmens), catherine.decouttere@kuleuven.be (C. Decouttere),
nico.vandaele@kuleuven.be (N. Vandaele), mauro.bernuzzi@gsk.com (M. Bernuzzi).
http://dx.doi.org/10.1016/j.cherd.2016.02.015
0263-8762/© 2016 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384 367

3.4. Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

3.5. Applicability of research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
4. Methodology of content analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
4.1. Content analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .372
4.1.1. Material collection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .372
4.1.2. Descriptive analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
4.1.3. Category selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
4.1.4. Material evaluation and methodological rigor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
5. Classification results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
5.1. Network characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
5.1.1. Strategic decisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
5.1.2. Tactical decisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
5.1.3. Operational decisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
5.2. Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
5.2.1. Strategic uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
5.2.2. Operational variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
5.3. Performance measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
5.3.1. Economical criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
5.3.2. Technological criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
5.3.3. Value criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
5.4. Research methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
5.4.1. Multiple criteria mathematical programming methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
5.4.2. Multiple criteria analytical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
5.5. Applicability of research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
6. Conclusions and implications for further research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380

1. Introduction In this work we use the rotavirus vaccine as an illustra-

tive case as sufficient literature is available and our other
Companies all over the world are confronted with designing research elaborates on the design of a rotavirus vaccine sup-
and redesigning their supply chain. A typical supply chain ply chain (Decouttere et al., 2015). However, the requirements
consists of the following stages: suppliers, plants, distribution addressed are generally applicable for vaccine supply chains.
centers and customer markets. The location of Distribution Rotaviruses are double-stranded RNA viruses that replicate
Centers (DC’s) is, for example, an expensive and an almost in the intestine and represent the worldwide major cause
irreversible long-term, strategic decision that can be tackled of severe diarrhea for children younger than 5 years (Smith
with supply chain network design (SCND). However, tactical et al., 1980). Tate et al. (2012) estimated that this virus caused
and operational decisions are often taken into account when the deaths of 453 000 children worldwide in 2008. Since 2006,
addressing SCND issues: the material flow and the order quan- two effective rotavirus vaccines have been licensed and are
tities between consecutive supply chain stages depend on recommended for use in all countries by the World Health
the network design. The complexity of supply chain design Organization (WHO), particularly in those countries with a
increases with the number of stages, products and integrated high diarrhea mortality rate for children younger than 5 years.
decision levels. The importance of integrating these decision The production and distribution of such a vaccine needs to
levels can hardly be overestimated. Production capacities and undergo a long way before it can be finally administered to
inventory decisions regarding the determination of the size patients. The virus needs to be cultured and this is a time-
and location of the different stock levels can be, for example, consuming process that can take up to 100 days. In contrast
taken into consideration when addressing strategic network to conventional medicines, such a vaccine contains an inac-
design issues. tivated virus manufactured with a biological process (bulk)
This paper reviews the existing literature on SCND mod- which is inherently more variable than a chemical one (IFPMA,
els and discusses whether this literature could be used for the 2014). Moreover further processing such as purification, qual-
design of a vaccine supply chain. The design of such a sup- ity control and assurance needs to be performed before packs
ply chain is challenging and will be illustrated with evidence of vaccines can be released and are ready to be shipped. In
from literature. We develop a framework to identify whether total, the manufacturing lead time can vary between 9 and
the existing SCND models address the specific requirements 22 months and the quality control and quality assurance pro-
of vaccine supply chains. This framework summarizes rele- cesses can take up to 70% of this time (Vaccines Europe, 2014;
vant classifications from previous literature reviews on SCND IFPMA, 2014). This makes it challenging to design a respon-
models and matches the vaccine supply chain’s key issues. sive, cost-effective and humanitarian global vaccine supply
The contribution of this paper is twofold: (1) we conduct an chain.
updated literature review of SCND models and (2) we discuss Fig. 1 introduces the framework that will be used to
whether this literature is able to address the key issues for the evaluate whether the model-based SCND literature is able
design of a vaccine supply chain. to address the key issues for the design of a vaccine
368 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384

Network Performance Applicability of

Uncertainty Methodology
characteristics measures research

Existing literature
- Schmidt & Wilhelm (2000) - Meixell & Gargeya (2005) - Meixell & Gargeya (2005)
reviews on SCND - Klibi et al. (2010) - Melo et al. (2009)
- Farahani et al. (2014) - Farahani et al. (2014) - Melo et al. (2009)
(Section 2)

- Strategic level - Low-impact events - Data for validation

General issues in - Economical considerations - Single criterion
- Tactical level - High-impact-low-likelihoo d - Instance size
SCND - Alternative considerations - Multi criteria
- Operational level disruptions - Industrial sector

Results (Section 5.1)

Results (Section 5.2)
Results (Section 5.3)
Results (Section 5.4) Results (Section 5.5)

- ”Process equals product”

- Regulatory requirements
- Disease and
for facility location
epidemiological epidemics - Responsiveness
Key issues for - Regulatory requirements - Global supply chain
- Tender procurement - Vaccine availability - Multiple stakeholders’
vaccine supply for production capacity - Biopharmaceutical
- Lead time variability - DALY preferences
chains (Section 3) planning industry
- Facility disruptions - Equity
- Access remote areas
- Transportation disruptions
- Limited shelf life
- Cold chain distribution

Fig. 1 – A framework for the review of the SCND literature and the vaccine supply chains’ key issues.

supply chain. Previous literature reviews on model-based and asset. Another conclusion is the need for more diverse
SCND, which were used to obtain our paper sample, are dis- industrial settings to be investigated in the context of global
cussed in Section 2. From these literature reviews we derive supply chain design. The authors state that a number of indus-
general issues according to five structural dimensions rele- tries in the model-based SCND have been explored (apparel,
vant for vaccine supply chains. These issues are shown by automotive, electronics, fiber and textile), but other industries
the solid arrows. Section 3 introduces the key issues for have not been investigated (such as aircraft, heavy machinery
vaccine supply chains and the related research questions and services). Other review papers on integrated supply chain
to be evaluated with our literature sample on model-based design models with an emphasis on globalization are con-
SCND. Section 4 describes the applied methodology of con- ducted by Vidal and Goetschalckx (1997) and by Goetschalckx
tent analysis for composing our paper sample. The results et al. (2002).
of the paper coding and the solutions for our research ques- Shen (2007) offers a review of integrated supply chain
tions are discussed in Section 5. The dashed two-sided arrows design models. He mainly targets three types of integrated
in Fig. 1 refer to the evaluation of key issues for vaccine decision making models: (1) location-routing models, (2)
supply chains using the reviewed SCND literature. Finally, Sec- inventory-routing models and (3) location-inventory models.
tion 6 concludes and identifies the implications for further The routing decision refers to the integration of the vehicle
research. routing problem and is out of the main scope of our research.
Melo et al. (2009) classify the existing literature on facility
2. Previous literature reviews on SCND location in the context of supply chain management accord-
modeling ing to (1) the supply chain structure (2) the decision variables
in SCND, (3) performance measures, (4) solution approaches
This section summarizes former literature reviews on SCND. and (5) applications. The performance measures are classified
Our framework shows the impact of these reviews on the into three analytic categories: (a) cost minimization, (b) profit
choice of the relevant issues of our five structural dimensions. maximization and (c) multiple objectives. The latter one is the
Schmidt and Wilhelm (2000) provide an extensive definition smallest group and represents a variety of measures such as
of the operational, tactical and strategic decision levels. They responsiveness, resource utilization, product lateness mini-
classify the reviewed literature according to these decision mization and environmental measures. These environmental
levels and discuss modeling issues in the remainder of their measures are not defined. One conclusion of the literature
work. The authors agree that these three decision levels inter- review of Melo et al. (2009) is that the literature integrating
act and that a unified approach is necessary for the design of uncertainty in supply chain management with location deci-
a competitive global supply chain. sions is scarce.
Meixell and Gargeya (2005) review decision support mod- Klibi et al. (2010) focuses on the integration of uncertainty
els for the design of global supply chains. They include the in model-based SCND. The authors distinguish planning to
following four review dimensions: (1) decisions addressed in protect against recurrent low-impact events and high-impact-
the model, (2) performance metrics, (3) the degree to which the low-likelihood disruptions. They discuss different disruptions
model supports integrated decision processes and (4) global- that can threaten a supply chain network and relevant
ization considerations. One conclusion of Meixell and Gargeya evaluation criteria. One challenge for future research is
(2005) is that the performance measures used in global supply the development of appropriate methodologies to integrate
chain models need to be broadened in definition to address robustness, responsiveness and resilience in stochastic supply
alternative objectives. The authors refer to the identification chain design models. Though these concepts are overlapping
of five important performance metrics identified by the Sup- and intuitive, the authors provide the following definitions:
ply Chain Council: reliability, responsiveness, flexibility, cost, robustness is the quality of a supply chain to remain effective
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
for all plausible futures, responsiveness is the capability of a
supply chain to respond positively to variations in business
conditions and resilience is the capability of a supply chain to
avoid disruptions or quickly recover from failures.
The most recently published literature review on SCND,
is the work of Farahani et al. (2014) which focuses on
competitive SCND. The competition models are out of the
main scope of our research. The authors classify the litera-
ture according to the (1) network characteristics and SCND
decisions, (2) performance measures, (3) uncertainty con-
siderations and (4) solution approach. They distinguish the
different performance measures into economical consider-
ations, environmental considerations, social considerations,
agility considerations and uncertainty considerations and
relate the recently new emerged paradigms in the field of
Supply Chain Management (SCM) to these different consid-
erations (lean SCM, sustainable SCM, green SCM, responsive
SCM and risk management in SCM).
3. Vaccine supply chain key issues
The bottom layer of our framework shows the key issues
for vaccine supply chains and how they are related to our
five structural dimensions. This section further elaborates on
these issues.
Moalla et al. (2007) explain how vaccines differ from other
products in the chemical and pharmaceutical industry. The
active ingredient of a vaccine is an antigen which is typically a
large complex molecule that is difficult to characterize in vitro
(poorly characterized proteins) because the manufacturing of
vaccines involves biological processes (bulk) which are inher-
ently variable. A conventional medicinal product contains a
small, chemical synthesized molecule with well-defined char-
acteristics or well characterized proteins (IFPMA, 2014). To
ensure control of the vaccine product, the process needs to be
strictly controlled in terms of equipment and process parame-
ters. Ekambaram and Shamir (2014), Rader (2008) and Ball et al.
(2009) mention that this view is often expressed as “process
equals product”. It therefore follows that the manufacturing
facilities need to ensure that the vaccine is produced in a
consistent manner and is free of contamination. Numerous
samples are taken in every step of the production process and
are transferred to both internal and external laboratories to
make sure that the produced vaccine is of appropriate qual-
ity (Smith et al., 2011). Remark that regulatory requirements
may vary greatly from country to country and lead to multiple
manufacturing and testing processes to be executed (IFPMA,
2014).
Linhares et al. (2008) mention that the rotavirus vaccine is a
live, attenuated vaccine. This means that the vaccine contains
an innocuous duplicate of the actual rotavirus. Hence, when
such a vaccine is administered, the immune system develops
the antibodies to respond to an infection. Growing the atten-
uated virus is the most critical step in the production process
of the rotavirus vaccine supply chain.
The remainder of this section consists of five subsections,
whereby each of the next five subsections corresponds to a
structural dimension for the content analysis and lists the
deductively obtained analytic categories. We add findings
from different research fields to support the relevance of our
structural dimensions. An appropriate research question cor-
responds to each structural dimension.
369
3.1. Network characteristics
Allocation. In developing countries, the population density
can differ drastically across different regions. In some regions,
the density is very high, while in other regions people are hard
to reach. Global vaccine manufacturers continuously strive
for increasing the accessibility of their products, especially
in developing countries. Establishing local DC’s is a decision
which is complementary with allocating people to these DC’s.
Such location-allocation models have been used extensively
within quantitative analysis in health services like immuniza-
tion for increasing demand coverage based on travel distances.
We refer the reader to Ayer et al. (2014) which elaborate on
five dimensions of access to health care services and to Verter
and Lapierre (2002), Gu et al. (2010) and Shariff et al. (2012)
for detailed examples of mathematical programming formula-
tions. When striving for the eradication of a particular disease
through vaccination, John and Samuel (2000) explain that
the herd immunity phenomenon is triggered when a certain
coverage level has been achieved: the vast majority of the
population being vaccinated prevents the virus from circu-
lating and subsequently protects the remaining people. For
the rotavirus vaccine, such herd immunity phenomenon is
studied by Pollard et al. (2015).
Location. Locating a new vaccine manufacturing facility
is a capital intensive strategic cost decision. However, other
metrics besides costs are relevant for establishing a new
facility. Griffith (2006) emphasizes the importance of human
capital in supply chains of global firms. Indeed, a new produc-
tion facility requires appropriate human capital and training
these people can take years. MacCarthy and Atthirawong
(2003) investigate and identify factors affecting international
location decisions. Ekambaram and Shamir (2014) emphasize
that regulatory authorities assess the reliability of a new vac-
cine production facility. Such assessment is also subjected
to the “process equals product” view. Therefore, reducing
the lead time for the design, construction, qualification and
approval is still a challenge for facility designers.
Limited shelf life and cold chain distribution. van Hoek
et al. (2012) mention that the shelf life of rotavirus vaccines
is relatively short (up to 24 months) and that the customer
requests a fixed remaining shelf life after delivery. Rotavirus
vaccines are temperature sensitive products and are required
to be kept at refrigerator temperature (between 2 ◦ C and 8 ◦ C
as in van Hoek et al., 2012). Vaccines exposed to temperatures
outside the recommended ranges can have reduced potency
and protection. Maintaining the cold chain from production
until the final administration is an expensive and difficult task,
especially in hot, large, developing countries. Assi et al. (2011,
2012, 2013) report transport capacity utilization and storage
capacity utilization as supply chain performance measures
for a custom designed discrete event simulation model which
simulates all processes, storage locations, administering loca-
tions, and storage equipment in the vaccine supply chain.
Kaufmann et al. (2011) explain that the required transporta-
tion and storage capacity is heavily impacted by the product
density which may vary significantly with respect to the vac-
cine delivery format. Chen et al. (2014) present a planning
model for the vaccine distribution in developing countries.
The effective refrigerator, freezer and transportation capac-
ities between locations are parameters for generating the
constraints of the proposed model.
Production capacity planning. Generally, Smith et al. (2011)
emphasize that the vaccine production capacity is sized and
370 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
built on routine demand. Installing more production capacity
for events (e.g. pandemics) that might only occur a very few
times per century is seen as unaffordable as highly trained
capital needs to be permanently available to manage this
capacity. However, the availability of ready to use surge capac-
ity is a laudable goal.
Shah (2004) discusses capacity planning as one of the key
issues for the optimization of pharmaceutical supply chains.
The long lead times make it very difficult to take capac-
ity decisions in advance. Gatica et al. (2003) and Levis and
Papageorgiou (2004) research how pharmaceutical industries
deal with the use of limited resources to obtain the highest
possible profit from a potential product portfolio. The authors
study the problem of capacity planning under the uncertainty
of the outcomes of clinical trials. Levis and Papageorgiou (2004)
and Papageorgiou et al. (2001) include the time for scale-up
and qualification runs of new products. This reflects the time
needed to learn how to manufacture the product in a repeat-
able fashion and for the qualification of the first batches by
the relevant regulatory authorities.
Batch sizing. In the early stages of the manufacturing pro-
cess, the manufacturing batch size is not only determined by
the capacitated volume of a bioreactor, but also by the “pro-
cess equals product” view: every change in the manufacturing
process needs to be validated to ensure reproducibility and
approved by regulatory authorities before being implemented
(Gupta et al., 2015).
We formulate the related research question to be answered
in Section 5.1 accordingly:
1. Which of these network characteristics are integrated in
the existing literature on model-based SCND and can be
related to the vaccine SCND problem?
3.2. Uncertainty
Disease and epidemiological dynamics. The demand of vac-
cines depends on how the corresponding disease propagates.
A number of manuscripts model the dynamics of the rotavirus
disease. Atchison et al. (2010) and Atkins et al. (2012) model the
impact of a mass vaccination program on rotavirus disease
transmission in England and Wales. In such models, the birth
rate, the duration of vaccine immunity and vaccine efficacy
are sources of uncertainty.
Tender procurement. Smith et al. (2011) explain tenders
as one of the three types of vaccine procurement (tenders,
repeated orders and random demand). Vaccine manufacturing
companies compete for winning a tender based on price, vol-
ume and reliability of supply in a tender-dominated market.
The candidate suppliers learn two months before the delivery
date whether the tender is won or lost. The long manufactur-
ing lead time of vaccines implies that vaccine manufacturers
are forced to begin production before knowing the outcome of
the tender. If the tender is lost, then the demand forecast drops
to zero. de Treville et al. (2014) explore the marginal value of
time for a vaccine supply chain and incorporate the tender
loss uncertainty.
Manufacturing lead time. We mentioned earlier that the
manufacturing lead time of a batch of vaccines can vary
between 9 and 22 months (VaccinesEurope, 2014). This implies
that a vaccine supply chain is often considered as slow (Shah,
2004, 2005; de Treville et al., 2014). One source of uncertainty of
the manufacturing lead time is the quality control and assur-
ance which cannot be neglected in the design of the rotavirus
vaccine supply chain. The importance of reducing lead times
and its practical relevance is elaborated thoroughly by Suri
(1998). Moreover, the manufacturing lead time cannot only be
measured and managed in an existing supply chain, but may
also be highly determined by the design of a new supply chain.
Lieckens and Vandaele (2007) incorporate the manufacturing
lead time in a reverse logistics network design by modeling
the reprocessing steps as a queueing system. This queue-
ing approach is motivated by the high degree of uncertainty
caused by the lack of control over the quantity, quality and
timing of returned products in the reverse logistics network.
This work is extended by the authors Lieckens and Vandaele
(2012) and takes stochastic transportation lead times of one
transportation mode, quality dependent routings and multiple
levels into account.
Facility disruptions. The recovery from a major plant fail-
ure is more difficult for the vaccine industry compared to
most other industries. The manufacturing process needs to
be validated again after the failure is fixed. This is also in
line with the “process equals product” view: variations due
to process changes need to be submitted to external author-
ities (Ekambaram and Shamir, 2014). In such case, the total
recovery time can take several years.
Transportation disruptions. We mentioned earlier that the
cold chain requirements are a challenge for of the last mile
logistics, especially in developing countries. Two other factors
aggravate the last mile distribution. First, some parts of the
infrastructure can be perceived as unreliable due to potential
aftershock earthquakes, after-disaster weather conditions or
wars. This can result in the decrease of the accessibility of
particular regions for a significant amount of time and can
cause the resurgence of nearly eradicated viruses. Second,
vehicles can be ransacked when traveling. Such after-disaster
conditions and ransacking probabilities are discussed in the
humanitarian logistics research field by Vitoriano et al. (2009,
2011) and Ortuño et al. (2011). As a consequence, (unsafe) vac-
cines might be sold on the black market. Also, Chen et al.
(2014) highlight that a small fraction of vaccines is lost during
transportation (and storage) due to breakage and pilferage.
We formulate the related research question to be answered
in Section 5.2 accordingly:
2. Which uncertainties are integrated in the existing liter-
ature on model-based SCND and can be related to the
uncertainties for the vaccine SCND problem?
3.3. Performance measures
A supply chain design can be assessed against multiple perfor-
mance measures. We insist to evaluate a vaccine supply chain
design not only based on cost or profit. Responsiveness and the
number of life-years saved of a population are just two exam-
ples of highly relevant KPI’s for assessing the vaccine supply
chain design’s performance. We adopt the classification into
economical, technological and value performance measures
used by Vandaele and Decouttere (2013) and Decouttere and
Vandaele (2013) for sustainable Research and Development
(R&D) portfolio assessment and Nuclear Magnetic Resonance
service system design respectively.
Brewer and Speh (2000) show how to present the perfor-
mance of a supply chain according to multiple dimensions
by the use of the balanced scorecard. The authors formulate
supply chain goals and measures for the four perspectives of
Kaplan and Norton (1992): (1) the customer, (2) the internal
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
business, (3) the financial and the (4) learning and innovation
perspective. Such a scorecard is interesting as it is particularly
developed to reconcile our general definition of value criteria
and the economical and technological criteria. In Decouttere
et al. (2015) we further elaborate on how these three types of
criteria are derived from the stakeholders’ preferences for the
rotavirus vaccine supply chain.
3.3.1. Economical criteria
The economical dimension of the vaccine supply chain
includes both profits and costs. Hence, the global pricing of a
vaccine is complex and its profitability is not only determined
by internal factors such as high costs of production and R&D
(Light et al. (2009) estimate the R&D costs of rotavirus vac-
cines), but also external factors such as competition, donor’s
policies and governmental policies.
3.3.2. Technological criteria
The technological dimension represents the performance
of the supply chain’s load in terms of resource utilization,
(excess) capacity, lead time, throughput and vulnerability to
the different uncertainties described above. Its meticulous
quality requirements, cold chain conditions and complex mar-
ket structure are a few examples of important factors that
influence the performance of such technological criteria.
Responsiveness. Quick response enables supply chains to
meet the customer demands with short lead times. Shah
(2004, 2005) states that a future research challenge is the devel-
opment of rapid responsive vaccines supply chains and other
treatments that arise from emergencies (e.g. bioterrorism or
fast developing epidemics). The author emphasizes that par-
ticularly the vaccine supply chain is slow and unresponsive.
3.3.3. Value criteria
The value dimension refers to the related ethical, societal and
individual values of the vaccine supply chain. For the rotavirus
vaccine supply chain Decouttere et al. (2015) specify the value
criteria for different stakeholders by the use of publicly avail-
able information on the manufacturer’s and stakeholders’
mission statement, values, objectives and strategies.
Vaccine availability. Assi et al. (2011, 2012, 2013) and Haidari
et al. (2013) mention the importance of vaccine transportation
and storage in supply chain management. They define vac-
cine availability as an important supply chain performance
measure. The vaccine availability at a health center is com-
puted as the number of patients receiving a vaccine divided by
the number of people arriving for a vaccine. A similar perfor-
mance criterion is maximized by the work of Chen et al. (2014).
The objective of the proposed model maximizes the number of
fully immunized children (children that received the multiple
doses for complete immunization) across all vaccination loca-
tions. The authors assume that vaccine manufacturers can
supply enough vaccines to satisfy the demand.
Equity. In general, humanitarian logistics provide assis-
tance in the form of food, water, medicine, shelter, and
supplies to areas affected by large-scale emergencies. In some
of these emergencies, vaccines need to be distributed. We
are interested in which humanitarian performance measures
are taken into account for modeling a humanitarian relief
chain. Vitoriano et al. (2009, 2011) and Ortuño et al. (2011)
consider equity as one of the six criteria for the distribu-
tion of humanitarian relief. Equity is a fairness criterion that
tries to satisfy the same proportion of each demand node by
371
preventing humanitarian aid to be delivered only to the more
accessible areas and hard-to-reach areas to be neglected.
Disability-Adjusted Life Years (DALY). The DALY is
introduced by the WHO and is a generally accepted measure
to quantify the burden of disease on a population. The WHO
(2014) defines DALYs for a disease or health condition as the
sum of the years of life lost due to premature mortality in the
population and the years lost due to disability occurring for
people living with the health condition or its consequences.
We refer the reader to Murray (1994), Murray and Acharya
(1997) and Devleesschauwer et al. (2014) for a detailed anal-
ysis of the computation of the DALY performance measure.
The DALY has been used in numerous studies on the cost-
effectiveness analysis for introducing the rotavirus vaccine in
a national immunization program. Comparing the vaccination
cost per DALY (cost-effectiveness) with the Gross Domestic
Product per capita of the population is one way to deter-
mine whether to introduce the rotavirus vaccine. The applied
approach for this study varies between different countries and
is therefore reviewed by Aballéa et al. (2013) and De la Hoz-
Restrepo et al. (2013) for rotavirus vaccination.
Conflicts between these three types of performance indica-
tors are outspoken and require to strive for the best balanced
performance. We formulate the related research question to
be answered in Section 5.3 accordingly:
3. Which performance measures are integrated in the existing
literature on model-based SCND and can be related to the
performance measures for the vaccine SCND problem?
3.4. Methodology
We already emphasized that researchers should not evaluate
a new vaccine supply chain design based on one (econom-
ical) performance measure. We are interested in evaluating
a new supply chain design based on at least one KPI of
each category (economical, technological and value indicator).
These criteria are derived from the stakeholders’ preferen-
ces and might be conflicting. Decouttere et al. (2015) draw a
stakeholder map and their interactions for the rotavirus vac-
cine. The involvement of more stakeholders in the design
of a vaccine supply chain is challenging, but might be very
rewarding. De Oliveira et al. (2008) describe the success of
rotavirus vaccine introduction in the Americas with the help
of the improved coordination between stakeholders, including
ministries of health, vaccine manufacturers and interna-
tional immunization partners. Dealing with multiple KPI’s
and multiple stakeholders in a supply chain design prob-
lem requires an appropriate multi-criteria decision making
(MCDM) methodology. For this structural dimension, we use
a framework based on Sasikumar and Kannan (2009) and
Brandenburg et al. (2014) and provide a clear distinction
between single criterion and multi-criteria methodologies.
We formulate the related research question to be answered
in Section 5.4 as follows:
4. Which MCDM methods are applied in the existing literature
on model-based SCND and can be related to the vaccine
SCND problem?
3.5. Applicability of research
As our research is stimulated by a real-life application, we
are interested in whether the paper sample encompasses
372 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
real-life data and real-life sized instances. We also report in
what industries current research on model-based SCND is
applied. We formulate the related research question to be
answered in Section 5.5 accordingly:
5. Which kind of data and industrial sectors are present in
the existing literature on model-based SCND? And is this
literature able to handle real-life sized instances?
4. Methodology of content analysis
4.1. Content analysis
This paper conducts a literature review on SCND model-
ing papers by means of content analysis. Krippendorff (2012)
defines content analysis as a research technique for making
replicable and valid interferences from texts (or other mean-
ingful matter) to the context of their use. Replicable means
that different researchers should draw the same conclusions
when applying the same technique to the same paper sam-
ple. Replicability is needed to ensure reliable research. Validity
refers to whether a study is able to scientifically answer the
research questions it is intended to answer and confirms the
results for independently available evidence. Similar to the lit-
erature reviews of Brandenburg et al. (2014) and Seuring and
Gold (2012) in the field of supply chain management, we distin-
guish four steps for employing content analysis in a rigorous
way:
1. Material collection: the material to be analyzed is delimited
and the unit of analysis is defined.
2. Descriptive analysis: formal characteristics of the material
are assessed.
3. Category selection: structural dimensions and related ana-
lytic categories are selected, which will be applied to the
collected material (material classification).
4. Material evaluation: the material is analyzed according to
the structural dimensions and analytic categories.
4.1.1. Material collection
The paper sample of our literature review is bounded to
include only English-speaking SCND modeling papers. We use
peer-reviewed journal articles as the unit of analysis because
these articles represent an important mode of communica-
tion among researchers. Each reviewed paper had to match
the following criteria:
1. The English-speaking manuscript must be published in a
peer-reviewed journal between 1997 and 2015.
2. The content of the manuscript focuses on quantitative
SCND modeling.
3. Papers focusing on reverse logistics network design, closed-
loop SCND and open-loop SCND were excluded from the
analysis as the vast amount of this literature focuses on
the design of a supply chain with activities dedicated to the
collection and recovery of products. Such activities are not
included in the primary scope of our future vaccine supply
chain design research.
We emphasize that it is not mandatory that the content is
related to vaccines or the vaccine supply chain. However, in a
first step, we started our search process based on the keywords
“vaccine” and “supply chain network design”. These keywords
were entered in the Limo search engine (www.limo.libis.be)
accessing the Primo Central database and we broadened our
search by extensively searching the Elsevier, Emerald, Google
Scholar, Scopus, Springer and Wiley databases. The resulting
papers did not match the criteria described above.
In a second step, we broadened our search space by enter-
ing combinations of (1) “vaccine” and (2) “supply chain”,
“supply chain management”, “distribution”, “production”.
This resulted in a set of papers related to the vaccine sup-
ply chain, but the focus on quantitative SCND modeling was
clearly absent when reading the manuscripts. However, the
manuscript of Chen et al. (2014) is worthwhile mentioning
here. To the best of their knowledge, the authors state that
they provide the first mathematical programming model for
vaccine distribution planning in developing countries.
As a third step, we searched for previous literature reviews
on SCND. We started by checking the complete reference list
in the literature reviews of Vidal and Goetschalckx (1997),
Schmidt and Wilhelm (2000), Goetschalckx et al. (2002), Meixell
and Gargeya (2005), Shen (2007), Melo et al. (2009), Klibi et al.
(2010) and Farahani et al. (2014), mentioned in Section 2 and
adding them to the sample. A citation analysis shows that
about 1314 publications refer to at least one of these review
papers.
In the fourth step, the paper sample was completed by
typing keywords based on “supply chain network design”
and terms that we often observed to supply chain design
modeling manuscripts in the third step: “inventory-location”,
“location-inventory”, “facility location”, “location-allocation”
and “production-distribution”. Also the reference lists in these
sets of papers were checked. Remark that we studied the lit-
erature for a time range of more than 20 years. By reading the
papers we observed that more recent literature is particularly
interesting and set the cut-off year to 1997 as (1) the quantita-
tive models are generally more advanced (e.g. the integration
of allocation, location, inventory, production and/or distribu-
tion decisions) and (2) the emergence of SCND papers which
addresses alternative performance criteria (e.g. Daskin et al.,
1997; Badri, 1999).
Altogether, we identified 86 manuscripts, distributed over
33 journals. These manuscripts will be classified in the next
sections.
4.1.2. Descriptive analysis
Table 1 shows the journals of our paper sample that
contributed the most to the research area of SCND. The
manuscripts from the International Journal of Production
Economics, Transportation Research Part E: Logistics and
Transportation Review and the European Journal of Operations
Research represent 1/3 of our paper sample. Fig. 2 gives infor-
mation on the distribution of the paper sample over time. One
peak is clearly visible in the diagram, i.e. in the year 2013.
4.1.3. Category selection
The five research questions in Section 3 correspond to
the derivation of five corresponding structural dimensions:
network characteristics, uncertainty, performance measures,
research methodology, applicability of research. The analytic
categories are derived both deductively and inductively. The
analytic categories may be supplemented with “Various” and
“Not Applicable (N.A.)” categories to facilitate an exhaustive
classification of each paper.
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384 373

results of our classification at one national workshop 1 and

Table 1 – Journal perspective of paper sample.
Journal
International Journal of Production Economics
Transportation Research Part E: Logistics and
Transportation Review
European Journal of Operational Research
Naval Research Logistics
IIE Transactions
Transportation Science
Computers & Industrial Engineering
American Institute of Chemical Engineers Journal
Expert Systems with Applications
International Journal of Industrial Engineering
Computations
Computers & Chemical Engineering
Computers & Operations Research
Industrial & Engineering Chemistry Research
International Journal of Production Research
Journal of Intelligent Manufacturing
Management Science Letters
Network and Spatial Economics
Omega
Others journalsa
Total
a
Other journals with one paper each: Annals of Operations
Research, Applied Mathematical Modeling, Arabian Journal for
Science and Engineering, Chemical Engineering Science, Decision
Support Systems, Industrial & Chemistry Research, International
Journal of Operations & Production Management, International
Journal of Sustainable Engineering, Journal of Applied Mathe-
matics, Location Science, Manufacturing & Service Operations
Management, Papers in Regional Science, The International
Journal of Advanced Manufacturing Technology, Transportation
Research Part C: Emerging Technologies, Transportation Research
Part D: Transport and Environment.
4.1.4. Material evaluation and methodological rigor
To guarantee the required internal validity of the material
evaluation, each paper is coded by three researchers. This also
ensures the inter-coder reliability. Differences in paper coding
were resolved by reaching a discursive alignment of inter-
pretations. The external validity of our material evaluation is
strengthened by presenting and discussing our intermediate
18
16
14
Number of publications
two international conferences 2 . We evaluate the material in
Frequency
the next sections.
10
10
5. Classification results
9
5 5.1. Network characteristics
4
4 This section classifies the reviewed literature according to the
4 SCND decisions and reflects on the corresponding key issues
3 in Fig. 1. We follow the distinction between strategic, tacti-
3
cal and operational decisions. Table 2 shows the results of the
3
decision variables in the reviewed SCND models and empha-
2 sizes the strategic focus of SCND. One paper can be classified
2 into multiple categories. The remainder of this section clar-
2 ifies the analytic categories shown in Table 2 and discusses
2 their relevance for our future research.
2
2
2
5.1.1. Strategic decisions
2 Allocation. The reviewed literature often determines the
15 transportation cost based on the distance between the local
DC’s and the customers. Achieving the coverage level to trigger
86
the herd immunity phenomenon implies that travel distances
between individuals and health care centers cannot only be
taken into account to determine the accessibility of a health
care system: the time and the difficulty to reach customers
are important factors which are not necessarily proportional
to the travel distance, especially in a vaccine supply chain
context.
Location. The reader can easily derive from Table 2 that
almost all of the reviewed manuscripts include a location deci-
sion. Such a location decision refers to locating production
facilities, DC’s and/or suppliers in the supply chain network.
Badri (1999) includes qualitative criteria to evaluate a can-
didate set of location alternatives. Hammami et al. (2009)
propose a mathematical formulation for a supply chain design
problem in a delocalization context. The authors emphasize
that facility location and technology selection decisions are
intertwined: on the one hand, manufacturers would like to
profit from the low labor costs in developing countries, but
on the other hand they want to use the same manufactur-
ing technologies as in the original plant to maintain a high
labor productivity level and high standards of quality. For the
design of a vaccine supply chain, the integration of the facil-
17 ity location and technology selection is highly recommended.
However, this approach lacks the lead time consequences of
locating a vaccine manufacturing facility: the adoption of an
old or a new production technology at a facility has a large
impact on the time for regulatory approval (Ekambaram and

12
Shamir (2014)).
10
10
8 8 5.1.2. Tactical decisions
8
7 Distribution capacity. The distribution capacity, as shown
6
6 in Table 2, refers to the available storage space of installed
5
4 DC’s. Tancrez et al. (2012) present a SCND model which takes
4
3 3 3 vehicle shipment sizes into account. The authors emphasize
2 2 2 2 that previous SCND manuscripts never considered capacitated
2
1 1 1 1
0
1
16th Workshop on Logistics and Supply Chain Management
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015

(June 2014, Louvain-la-Neuve, Belgium).

Year 2
International Conference on Operations Research (September
2014, Aachen, Germany), INFORMS Annual Meeting (November
Fig. 2 – Temporal distribution of paper sample. 2014, San Francisco, US).
374 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
Table 2 – Classification according to network decisions.
Strategic decisions Tactical decisions
Allocation 57 Distribution capacity
Location 82 Inventory level
Production capacity planning
transportation. As the cold chain conditions bound the trans-
portation capacity and is often seen as a bottleneck of the
distribution part of the vaccine supply chain (Assi et al., 2011,
2012, 2013), researchers should take this capacity into account
in future work.
Inventory level. Nozick and Turnquist (1998) and Shen
et al. (2003) show different approaches to integrate the inven-
tory cost impact into facility location problems. However, the
perishability of vaccines is one important factor that limits
stock building. Firoozi et al. (2013) emphasize that the life-
time of products is not considered in network design models.
These authors integrate products with a fixed lifetime or pre-
determined expiry date in their SCND model. A constraint
takes the delivery lead time from the supplier to the DC and
the lifetime of the product into account for determining the
economic order quantity at a DC. The authors also show the
trade-off between enhancing storage conditions and inven-
tory costs. Researchers should further elaborate on taking the
shelf life as requested by the customers into account.
Production capacity planning. Table 2 shows that less than
1/5 of the paper sample models the available production
capacity or the production level as a decision variable. Sabri
and Beamon (2000) measure the capacity slack in their work.
We did not observe a further elaboration on the availability of
capacity in case of high-impact disruptions. Furthermore, we
did not find any SCND model that includes a similar problem
of capacity planning under the uncertainty of the outcomes
of clinical trials or the inclusion of the time for scale-up and
qualification runs of new products.
5.1.3. Operational decisions
Batch sizing. As shown in Table 2, about 1/10 of the reviewed
manuscripts integrates a batch sizing decision into the pro-
posed model. The determination of the batch size is mainly
driven by economical criteria. However, for vaccines, the bio-
chemical and regulatory consequences of changing batch
sizes may not be overlooked.
From this section, we observe that it might be hard to model
all the relevant decisions and their impacts in one mathe-
matical programming model. For some decisions, qualitative
factors and stakeholders come into play and their require-
ments are of great importance for the rotavirus vaccine supply
chain design, e.g. the requirement of appropriate human cap-
ital and regulatory assessment for the functioning of a new
Table 3 – Classification according to uncertainty incorporation.
Strategic uncertainty
Supply:
Unreliable facilities 12
Unreliable transportation 5 Processing time
Demand:
Demand scenarios 11
Operational decisions
15 Batch sizing 8
20
14
production facility. Decouttere et al. (2015) discuss how to
construct scenarios that take design requirements of relevant
stakeholders into account for the vaccine supply chain. These
scenarios check the feasibility of the model-based decisions
and are validated by stakeholders. Such an approach might be
beneficial for the real-life applicability of the SCND model.
5.2. Uncertainty
This section emphasizes the importance of incorporating
demand and supply uncertainty in a SCND for the vaccine
industry and reviews how previously published manuscripts
take these uncertainties into account. In this paper, we clas-
sify the existing literate according to the first dimension of
supply chain risk management of Tang (2006). This dimen-
sion addresses the risk level of the events and distinguishes
disruption risks and operational risks. We will use the terms
disruption risks and strategic uncertainty and the terms oper-
ational risks and operational variability interchangeably. In
line with Tang (2006), strategic uncertainties are events that
have a major impact on the supply chain such as plant failures,
earthquakes or epidemic outbreaks. Operational variability
influences operational factors that are inherently uncertain.
The impact of disruptions on a supply chain network is con-
siderably larger than the impact of operational variability.
Table 3 shows to which extent uncertainty is incorporated in
the current literature. Remark that one paper can be classi-
fied into multiple categories. The analytic categories for the
uncertainty and variability at both the supply and demand
side are derived inductively and will be further clarified in the
remainder of this section.
5.2.1. Strategic uncertainty
5.2.1.1. Supply. Table 3 shows that less than a quarter of the
reviewed manuscripts integrate supply disruptions. Most of
the disruptions in this subset of manuscripts are attributed to
facility disruptions.
Unreliable facilities. Snyder and Daskin (2005) incorpo-
rate reliability in the classical p-median problem and the
uncapacitated facility location problem. The authors assume
that facilities fail with a predefined probability and that cus-
tomers are subsequently served by the nearest non-disrupted
facility. Lim et al. (2010) consider the presence of random
facility disruptions in reliable SCND. Two types of DC’s are
Operational variability
Supply:
Delivery lead time 5
1
Transportation time 1
Demand:
Fuzzy 3
Normal distribution 25
Poisson 7
Triangular 1
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
distinguished in their model: unreliable and reliable DC’s.
When a random disruption occurs in an unreliable DC, it
totally fails and the customers assigned to it are reassigned
to a reliable DC. The authors also consider the option of facil-
ity hardening, an investment for hedging against the risk of
disruption. Qi and Shen (2007) incorporate supply reliability
by modeling the product flow from a facility to a retailer using
the product of the order quantity from the retailer and a ran-
dom variable associated with the facility, which is called the
reliability coefficient.
Madadi et al. (2014) confirm that some (health care) sup-
ply chain disruptions may be catastrophic in spite of their
low probability of occurrence. They explicitly mention the
disruption of flu vaccine manufacturing which resulted in
disastrous consequences. The government stopped the vac-
cine production when regulators inspected a manufacturing
plant and found evidence of bacterial contamination problems
which subsequently heavily reduced the supply of vaccines
during the flu season. The authors implement a scenario-
based approach: the fraction of tainted products before and
after inspection are scenario dependent parameters. Although
various ways are observed to model unreliable facilities, the
catastrophic impact of a plant failure such that the recovered
production process needs to be validated again by regulatory
authorities seems hard to model with the existing model-
based SCND literature.
Unreliable transportation. Azad et al. (2014) present a SCND
model which includes disruptions at the locations of DC’s and
at the transportation modes between DC’s and customers.
There exists a number of unsafe transportation modes and a
single safe transportation mode between a DC and its assigned
customers. The unsafe transportation modes can be disrupted
with a given probability and safe links are more expensive and
outsourced.
5.2.1.2. Demand: demand scenarios. Strategic demand uncer-
tainties are modeled as demand scenarios in the existing
model-based SCND literature (e.g. Daskin et al., 1997). Win-
ning or losing a tender has a large impact on the vaccine
demand and can be interpreted as two distinct scenarios.
However, in the reviewed literature such a scenario has a spec-
ified probability of occurrence. Specifying such a probability of
occurrence for winning or losing a tender is very hard. To the
best of our knowledge, we did not observe any manuscript that
deals explicitly with tenders although this way of procurement
occurs in several industries. Another conclusion is that none
of the reviewed manuscripts integrates dynamic disease mod-
eling into model-based SCND. Integrating such disease models
might be useful to get more insights about the timing, the level
and the location of the final vaccine demand.
5.2.2. Operational variability
5.2.2.1. Supply: delivery lead time, processing time and
transportation time. We previously mentioned the long man-
ufacturing lead times and corresponding variability due
to permanent quality control and quality assurance. We
are interested whether the published model-based SCND
literature deals with supply variability in terms of lead
time such as machine processing times, machine setup
times, transportation times between successive supply
chain stages, replenishment time and waiting times for
processing/shipment.
Table 3 shows that less than 10% of the reviewed papers
include non-deterministic lead times. The manuscripts of
375
Nozick and Turnquist (1998, 2001a,b) and Shen et al. (2003)
focus on integrating inventory management into facility loca-
tion modeling and consider the replenishment time between
successive supply chain stages as non-deterministic. Sabri
and Beamon (2000) show an approach to simultaneously inte-
grate the strategic and operational planning in SCND. The
operational submodel computes the variance of the total pro-
duction lead time, which is the sum of setup time, waiting time
at the workstations, processing time and material delay times.
However, the setup times and processing times are considered
to be deterministic.
None of the reviewed papers integrates an elaborated
approach into SCND to determine the manufacturing lead
time under these operational variabilities in the supply chain.
Such an approach can be beneficial for determining the
responsiveness of a supply chain in a more accurate way. A
number of the quality control tests are processed in parallel
with the actual manufacturing process to increase the vaccine
supply chain’s responsiveness. Such parallel processes can be
part of the critical path in the supply chain and should there-
fore not be overlooked. This is not only relevant for the vaccine
supply chain. However, none of the reviewed manuscripts
explicitly emphasizes the integration of such parallel quality
processes in a SCND model formulation.
5.2.2.2. Demand: demand variability. Table 3 shows that the
normal distribution is the most frequently used distribution
for modeling the demand variability. The mean and vari-
ance parameter drawn from a normal distribution can be
customer-, product-, time- or even scenario dependent. Some
manuscripts emphasize that it is difficult to assign a prob-
ability distribution to the demand in a real environment.
Therefore, Zhou and Liu (2007), Mousavi and Niaki (2013) and
Yazdian and Shahanaghi (2011) consider the demand as fuzzy.
Fitting an appropriate distribution or using a fuzzy approach
is relevant for modeling the private vaccine demand which is
not characterized by tenders.
We will build scenarios for different uncertainties. Such
scenarios may differ according to the realized uncertainties:
e.g. the achievement or the loss of a tender, different variability
levels for manufacturing lead times, a disastrous production
failure at a manufacturing plant or after-disaster conditions
that make last-mile transportation extremely difficult. The
impact of these scenarios will be measured against multiple
KPI’s. In contrast to the existing literature, we will avoid the
assignment of probabilities of occurrence to such scenarios.
How to generate, validate and compare relevant scenarios for
the vaccine supply chain is further elaborated in Decouttere
et al. (2015). We also refer the interested reader into an elabo-
rated scenario-based risk modeling approach in supply chain
design to Klibi and Martel (2012, 2013).
5.3. Performance measures
We already mentioned the importance of imposing multi-
ple performance criteria on the vaccine supply chain. This
section identifies the performance measures encountered
during our review of the model-based SCND manuscripts. We
are interested whether the alternative considerations in our
framework represent the key issues for the design of a vac-
cine supply chain. As mentioned before, these performance
criteria will be classified into three types as distinguished by
Vandaele and Decouttere (2013) and Decouttere and Vandaele
(2013): economical, technological and value criteria. The main
376 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384

Table 4 – Classification according to performance measures.

Economical criteria Technological criteria Value criteria

Costs 73 Demand satisfaction 9 Environmental 7

Economic value added 1 Flexibility 1
Financial risk 4 Quality of supplier’s products 2
Net present value 3 Reliability 5
Profit 8 Resource utilization 2
Variance of total supply chain costs 4 Responsiveness 5

driver for our classification of the performance metrics focuses
on the goal of imposing the KPI’s and not the way that they
are actually measured. Table 4 shows the results of the cod-
ing of the performance measures dimension and reveals that
the presence of technological dimension is subordinate to the
economical dimension and that the value dimension is scarce.
Fig. 3 shows the presence of these three categories of perfor-
mance measures in time. If a manuscript has more than one
performance criterion of the same analytical category, then
the paper only contributes once for the determination of the
number of publications. Fig. 3 clearly shows the increasing
attention toward value KPI’s in recent years. The analytic cat-
egories of the performance measures dimension are derived
inductively and discussed in the remainder of this section.
5.3.1. Economical criteria
At least one economical objective is present in almost every
reviewed manuscript. Minimizing costs, maximizing profit,
maximizing economic value added and maximizing net
present value are well-known concepts. The financial risk
associated with the supply chain is defined, by Franca et al.
(2010), as the probability of a certain objective of cost or profit
not meeting a target level. Guillén et al. (2005), Azaron et al.
(2008) and Hamedani et al. (2013b) adopt the same defini-
tion of financial risk. These papers minimize the financial
risk criterion, which is the weighted sum of the probability
of occurrence of each scenario times the achievement of the
target level corresponding to that scenario. Hamedani et al.
(2013b) integrate financial risk and the variance of the total
costs in a multi-objective SCND model considering inven-
tory decisions. The latter criterion is defined as variance of
the purchase, transportation, inventory holding, shortage and
25
20
Number of publications
ordering costs and similar definitions are used by Hamedani
et al. (2013a), Azaron et al. (2008) and Teimuory et al. (2013).
5.3.2. Technological criteria
Demand satisfaction. Badri (1999) and Sabri and Beamon
(2000) minimize the deviation to the targeted demand and the
deviation to the targeted fulfilled orders respectively. Nozick
and Turnquist (2001a) and Shen and Daskin (2005) minimize
the uncovered demand based on the customer zones that are
too far away from the newly located facilities. Guillén et al.
(2005), Shankar et al. (2013a,b) and Hiremath et al. (2013) max-
imize the demand satisfaction which is defined as the division
of the total sales by the total demand. Altiparmak et al. (2006)
maintains the same definition and adds that the demand has
to be fulfilled within a stipulated access time.
Flexibility. The already mentioned work of Sabri and
Beamon (2000) suggests flexibility, besides a cost and demand
satisfaction criterion, as a third performance measure. The
authors define two types of flexibility: volume and delivery
flexibility. Volume flexibility is defined as capacity slack. For
a plant, this slack is measured as the difference between the
plant capacity and its utilization and for a DC this slack is
calculated as the difference between the available through-
put and the demand requirements. The delivery flexibility
is measured as the lead time slack which is the length of
time between the time when an order for an item is placed
and when it is actually available for satisfying the customer’s
demand.
Quality of supplier’s products. Naimi Sadigh et al. (2013)
maximize a quality metric by multiplying the quality of each
part of each supplier by the quantity ordered of the considered
part. Franca et al. (2010) increase the quality level by minimiz-
ing the number of raw material defects. A quality level and
a weight estimating the impact of the material defect on the
manufacturing process is assigned to each material from each
supplier.
Reliability. Daskin et al. (1997) propose the ˛-reliable p-
median minimax regret model for locating facilities. This
model identifies the reliability set, a set of locations, that mini-

mizes the maximum regret with respect to an endogenously

15
determined subset of scenarios. The total probability associ-
ated with the reliability set is at least the reliability level, ˛.
10
Chen et al. (2006) build further on this work and present the
˛-reliable mean-excess regret model.
Resource utilization. The manuscript of Altiparmak et al.
5 (2006) proposes a third criterion, besides a cost and demand
satisfaction criterion: equity of the capacity utilization of
plants and DC’s. This equity criterion ensures that the demand
0
volumes are fairly distributed among the installed DC’s and
plants and is measured by the mean square error of the capac-
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015

ity utilization ratios of the plants and DC’s. A smaller value

Economic Technologic Value of this mean square error means a smaller deviation of the
capacity utilization ratios of the plants and DC’s from the equal
Fig. 3 – Trends in performance measures. capacity utilization ratio levels.
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
Responsiveness. We already mentioned that the literature
emphasizes the development of more rapid response vaccine
supply chains. The SCND model formulation of Cardona-
Valdés et al. (2011) captures an objective that minimizes the
maximum lead time from the plants to the customers through
the DC’s. Naimi Sadigh et al. (2013) minimizes the maximum
time from suppliers to customers. The responsiveness objec-
tive of Rajabalipour Cheshmehgaz et al. (2013) minimizes the
maximum order response time from DC’s to customers and
from suppliers to customers by direct shipment.
You and Grossmann (2008a) minimize the maximum
expected lead time of the supply chain network. The expected
lead time is defined as the delivery lead time plus the pro-
duction lead time multiplied by the stock-out probability. The
delivery lead time and the production lead time are in turn
equal to the summation of all the deterministic production
and transportation delays incurred in the corresponding path.
Another quantitative characterization for responsiveness for
the design of process supply chains is proposed by the authors
You and Grossmann (2011). The authors propose the mini-
mization of the maximum guaranteed service time of the last
echelon as a measure for supply chain responsiveness. The
guaranteed service time is the time quoted for a node by which
it will satisfy the demand of its downstream node (for detailed
information about the guaranteed service approach, see also
Graves and Willems, 2000, 2003). This approach emphasizes
that, for a multi-echelon inventory system, the lead time of a
node in the supply chain network depends on the upstream’s
node inventory level.
5.3.3. Value criteria
Environment. During the last decade, a large amount of
literature emerged on the concept of green supply chain man-
agement. Manufacturing processes are often viewed as the
culprit of the degradation of the environment. In the sup-
ply chain design phase, environmental investment decisions
can be undertaken to build a sustainable supply chain. We
briefly mention how the environmental criteria are modeled
in the existing model-based SCND literature. A single objec-
tive green SCND model is shown by Elhedhli and Merrick
(2012). The minimizing objective function contains a pollu-
tion cost to the environment. Wang et al. (2011) propose a
multi-objective SCND optimization model that captures the
trade-off between the total cost and the environmental influ-
ence. The total cost objective function contains an investment
cost on environmental protection equipment. The environ-
mental objective function minimizes the total CO2 emission
in the supply chain. Guillén-Gosálbez and Grossmann (2009),
Duque et al. (2010) and Pinto-Varela et al. (2011) measure
environmental performance through an elaborated imple-
mentation of the Eco-indicator 99 which incorporates recent
advances made in life cycle assessment. The computation of
this Eco-indicator 99 is complex, but surprisingly interesting.
It introduces a weighted damage function approach that rep-
resents the relation between the impact and the damage to
(1) human health, (2) availability of natural resources and (3)
quality of the ecosystem. Damages to human health (e.g. car-
cinogenic, respiratory effects) due to emissions are translated
into DALYs.
We will take at least one economical criterion into
account (Decouttere et al., 2015). Literature and practical
evidence show that supply chain responsiveness is partic-
ularly interesting for vaccine supply chains. We reviewed
different model-based approaches for modeling supply chain
377
responsiveness and will take one of these approaches into
consideration for our future work and further elaborate on the
integration of the long lead times and their variability. How-
ever, reliability, flexibility and resource utilization are related
concepts which are not irrelevant for the design of the vaccine
supply chain. The impact of catastrophic events can be miti-
gated upfront by making the right design choices. Such design
choices are related to investments in appropriate buffers:
adding capacity slack is one way to lower the resource utiliza-
tion and to improve the reliability and flexibility of the supply
chain network.
We did not observe a value criterion that may be suitable
for the design of a vaccine supply chain. Instead, we find value
indicators which focus on ecological performance. Guillén-
Gosálbez and Grossmann (2009) emphasize that defining a
suitable environmental performance measure for the supply
chain operation is not an easy task. They also mention that
there is no agreement so far about the index that should
support objective environmental assessments, and it is very
likely that such an agreement will never be reached. We pre-
sume strongly that this statement also holds for the definition
of our humanitarian criterion for our vaccine supply chain
design problem. The determination of relevant (value) KPI’s
for the vaccine supply chain is discussed in Decouttere et al.
(2015).
5.4. Research methodology
This section studies the modeling techniques and solution
methods that are able to deal with multiple KPI’s. The ana-
lytic categories of the methodology dimension are based
on the framework used by Sasikumar and Kannan (2009)
and Brandenburg et al. (2014), but we further elaborate on
the difference between single criterion and multiple criteria
model-based SCND manuscripts. For every model type (math-
ematical programming, heuristics, analytical models), Fig. 4
shows the distinction between these categories and illustrates
that some methods are specifically attributed to single crite-
rion or multiple criteria problems while other methods can
be adapted to both cases. Table 5 shows the analytic cate-
gories and the results of the paper coding. From these results,
it is noticeable that the Lagrangian relaxation decomposi-
tion is the most frequently used single criterion heuristic
method. Such method is not applied to SCND problems with
multiple KPI’s. Furthermore, we conclude that multi-objective
programming and the epsilon constraint method are the most
frequently used multiple criteria mathematical programming
method and multiple criteria heuristic method respectively.
The multiple criteria cases are clarified in the remainder of
this section.
5.4.1. Multiple criteria mathematical programming
methods
Goal programming. Goal programming is a branch of
multi-criteria decision analysis to model multiple, usually
conflicting performance measures. Each of these performance
metrics has a goal or target value to be achieved and unwanted
deviations are subsequently minimized in an achievement
function. This methodology is used by the manuscripts of
Badri (1999) and Azaron et al. (2008).
Multi-objective programming. Table 5 shows that multi-
objective programming is the most frequently used multiple
criteria mathematical programming method and models each
performance criterion as an objective function. The reviewed
378 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384

Modeling approaches in SCND research

Model type

Mathematical Heuristic Analytical

programming method method method
Model technique

Single Multiple Single Multiple Multiple

criterion criteria criterion criteria criteria

Weighted
GP MOP
method
Solution method

(M)IP (MI)NLP FP and PP LR SA TS GA PSO ECM AHP

AHP: Analytic hierarchy process, ECM: Epsilon constraint method, FP and PP: Fuzzy and possibilistic program-
ming, GA: Genetic algorithm, GP: Goal programming, LR: Lagrangian relaxation, (M)IP: (Mixed) integer program-
ming, (MI)NLP: (Mixed integer) nonlinear programming, MOP: Multi-objective programming, PSO: Particle swarm
optimization, SA: Simulated annealing, TS: Tabu search

Fig. 4 – Analytic categories of the structural dimension “Methodology” (based on Sasikumar and Kannan, 2009;
Brandenburg et al., 2014).

multi-objective programs handle two or three objective func-
tions.
Nonlinear terms may arise in the objective functions or
constraints. We briefly mention the cause of these nonlinear
terms, supported by the reviewed literature: Altiparmak et al.
(2006) impose an objective function regarding equity of the
capacity utilization ratio; Guillén-Gosálbez and Grossmann
(2009) integrate life cycle assessment into their model; the
relationship between production and physical properties
or blending ratios is captured in the work of You and
Grossmann (2008a); the integration of the guaranteed service
approach was investigated by the authors You and Grossmann
(2011); Shankar et al. (2013b) integrate an elaborated eco-
nomic order quantity inventory system; Hamedani et al.
(2013b) impose an objective function regarding the prob-
ability of not meeting a predetermined budget level and
another objective function regarding the variance of the total
costs.
The use of fuzzy set theory and possibility theory can
also be included in multi-objective optimization. We define
fuzzy programming as mathematical programming with fuzzy
parameters and/or fuzzy relations and possibilistic program-
ming as fuzzy programming when fuzzy sets of uncertain
(fuzzy) parameters are regarded as possibility distributions.

Table 5 – Classification according to research methodology.

Mathematical Heuristic Analytical
programming method method method

Single criterion: 59 43
FP and PP 3 GA 6
(M)IP 31 LR 30
(MI)NLP 25 PSO 1
SA 4
TS 2

Multi criteria: 27 21
GP 2 ECM 11 AHP 1
MO FP and PP 1 GA 7
MO (M)IP 7 PSO 3
MO (MI)NLP 11
Weighted (M)IP 5
Weighted (MI)NLP 1

N.A. 10 N.A. 85
Various 12

AHP: analytic hierarchy process, ECM: epsilon constraint method, FP and PP: fuzzy and possibilistic programming, GA: genetic algorithm, GP:
goal programming, LR: lagrangian relaxation, (M)IP: (mixed) integer programming, (MI)NLP: (mixed integer) nonlinear programming, MO FP and
PP: multi-objective fuzzy and possibilistic programming, MO (M)IP: multi-objective (mixed) integer programming, MO (MI)NLP: multi-objective
(mixed integer) nonlinear programming, PSO: particle swarm optimization, SA: simulated annealing, TS: tabu search, weighted (M)IP: weighted
(mixed) integer programming, weighted (MI)NLP: weighted (mixed integer) nonlinear programming.
 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
Table 6 – Classification according to applicability of research.
Data for numerical experiments Size of the instances
Desktop data 68 Large
Real-life data 29 Small
In the work of Yazdian and Shahanaghi (2011), the customer
demand and capacity of each DC are assumed to have some
possibilistic distribution which are expressed by trapezoidal
fuzzy numbers.
Weighted sum method. The weighted sum method con-
verts the multiple criteria problem into a scalar problem by
constructing a weighted sum of all the criteria. Nozick and
Turnquist (2001a) and Shen and Daskin (2005) use the weight-
ing method to evaluate the cost/service trade-off by including
customer demand satisfaction into a cost minimization objec-
tive. Snyder and Daskin (2005) generate a trade-off curve
between the operating cost and expected failure cost by mak-
ing use of this method. Wang et al. (2011) present a SCND
model that captures the trade-off between the total supply
chain cost and the environmental influence using a variant of
the weighting method.
Epsilon constraint method. The epsilon constraint method
is a technique to obtain a set of Pareto-efficient solutions of
a multi-objective program. The main idea of the epsilon con-
straint method is to consider one of the objective functions as
the primary objective and express the other (secondary) objec-
tives as constraints. The allowable levels of the secondary
objectives change iteratively. We refer the interested reader
to the manuscript of Franca et al. (2010) for a detailed step-
wise description of this method applied to multi-objective
SCND.
Genetic algorithms. The computational complexity of the
studied single criterion models motivated researchers to
design efficient iterative algorithms such as tabu search,
simulated annealing and genetic algorithms. In a genetic algo-
rithm, a population of candidate solutions evolves iteratively
toward better solutions. Each candidate solution has a set of
properties which can evolve by different operations. A fitness
function, usually the objective function value, is used to eval-
uate the performance of a candidate solution. As illustrated in
the manuscript of Altiparmak et al. (2006), genetic algorithms
can be used for the generation of Pareto-efficient solutions of
multi-objective problems.
Particle swarm optimization. Particle swarm optimiza-
tion is another evolutionary computation technique besides
genetic algorithms. Shankar et al. (2013b) explain that the
position of each particle represents a solution of the opti-
mization problem and has a memory to keep track of its
own best position acquired so far and the best position any
other particle acquired within the neighborhood. The parti-
cle will then modify its direction toward its own best position
and toward the overall best position. Shankar et al. (2013a,b)
and Hamedani et al. (2013a) develop a multi-objective particle
swarm optimization algorithm to obtain a set of Pareto-
efficient solutions.
379
Industry
33 Automotive 5
53 Chemical 8
Construction 1
Electronics 2
Food &beverages 3
Paper 2
Retail 4
Various 5
N.A. 56
5.4.2. Multiple criteria analytical methods
Analytical hierarchy process. Generally speaking, the analyt-
ical hierarchy process is a technique to structure a decision
problem and represent and quantify its criteria. The method
decomposes the decision problem into a hierarchy of criteria
which can subsequently be analyzed independently. Numeri-
cal weights or priority numbers have to be attributed to each
criterion of the hierarchy. Obtaining and interpreting the crite-
ria weights is generally seen as a disadvantage of this method.
In a final step, numerical priorities are computed for each
of the decision alternatives. A combination of the analytical
hierarchy process and goal programming to solve a facility
location problem in a supply chain network is illustrated by
Badri (1999).
The choice of these multiple criteria methods is rarely
motivated by the presence of multiple stakeholders. The
multi-objective programming methods take two or three
objective criteria into account which might be insufficient for
our future work. Furthermore, the number of efficient solu-
tions obtained by these methods can be enormous and a
method to choose the final solution that satisfies the preferen-
ces of a stakeholder group is often lacking. We also might avoid
weighted methods as the determination of these weights may
be difficult or subjective and have a large impact on the
obtained solution. Because of these reasons we will deviate
from multiple criteria mathematical programming methods
in our future work. A suggestion to deal with multiple criteria
derived from multiple stakeholders is discussed in Decouttere
et al. (2015).
5.5. Applicability of research
Finally, Table 6 classifies the studied literature on the basis
of their applicability context. We are interested whether the
existing literature is able to address the size of a real-life global
supply chain. We report our findings regarding the instance
data, instance sizes and the industrial sector of the paper
sample.
Data for validation. We distinguish the use of real-life data
and desktop data for the validation of the proposed model and
the solution procedure. A number of papers, e.g. Gebennini
et al. (2009), Yao et al. (2010), Berman et al. (2012) and Tancrez
et al. (2012), provide both extensive numerical experiments
and a real-life case study. About 3/10 of the papers validate
their approach with real-life data and about 8/10 with desktop
data.
Instance sizes. To verify whether the existing model-
based SCND literature is able to handle real-life-sized problem
instances, the paper sample is classified according to the size
of the used instances. Various papers (e.g. Shen et al., 2003;
380 chemical engineering research and design 1 0 9 ( 2 0 1 6 ) 366–384
Snyder and Daskin, 2005; Snyder et al., 2007; Ozsen et al., 2008,
2009) of our paper sample use the datasets of Daskin (1995).
The largest dataset of Daskin (1995) contains 150 nodes. We
consider an instance to be large when at least 150 nodes are
present in the supply chain network, small otherwise. Such a
node represents the location or candidate location of a sup-
plier, plant, DC or customer. According to this definition, the
reader can easily derive from Table 6 that about 6/10 of the
reviewed manuscripts are able to handle large instances and
4/10 of the papers solve small instances.
Industrial sector. As we aim to conduct research to be
implemented in the vaccine industry (Decouttere et al., 2015),
we review the industrial sectors of the paper sample. For
about 2/3 of the reviewed papers, the analyzed industry sector
remains unspecified. As mentioned earlier, the biological pro-
cesses (bulk) of the vaccine supply chain are subjected to the
“process equals product” view. Ekambaram and Shamir (2014)
highlight that the formulation, filling and packaging of vac-
cines are less significantly different than those of other classes
of sterile drug products. However, the chemical industry entry
in Table 6 refers to petrochemical, liquid oxygen, polystyrene,
acetic acid supply chains or is not further specified.
6. Conclusions and implications for further
research
The aim of this paper is twofold: we provide a literature review
on model-based SCND and identify whether this literature is
able to address the key issues of a vaccine supply chain. The
literature review on SCND modeling was conducted by means
of content analysis and classified the paper sample according
to five structural dimensions: (1) network characteristics, (2)
uncertainty, (3) performance measures, (4) methodology and
(5) applicability of research. We supported the relevance of
these five structural dimensions and corresponding research
questions by findings from other research fields.
Vaccines differ from conventional medicinal products as
the manufacturing involves biological processes which are
inherently variable. These products contain poorly character-
ized proteins whilst conventional medicinal products contain
well characterized proteins. To ensure the control of the vac-
cine product, the process needs to be controlled. This is also
described as the “process equals product” view. Numerous
samples are taken in the production process to ensure that
vaccines are produced in a consistent manner and meet the
quality requirements.
Our paper reviews the strategic, tactical and operational
decisions integrated in model-based SCND. We concluded that
we need to go beyond the existing SCND literature to model
all typical complexities of a vaccine supply chain: some deci-
sions are highly determined by qualitative factors or require
discussions with the relevant stakeholders.
We studied how strategic uncertainty and operational vari-
ability is incorporated in the SCND literature and motivate
the need for including both in our future work. Plant failures,
contamination problems, epidemiological outbreaks, earth-
quakes, wars, tender markets may all have a serious impact
on the vaccine supply chain. Some of these disruptions have
a very small probability of occurrence but can have disastrous
consequences and should not be overlooked. The literature
sample shows that such disruptions are often taken into
account by the use of a scenario-based approach: a probabil-
ity corresponds to the realization of a particular scenario and
its impact on the supply chain. However, the probabilities of a
plant failure or winning/losing a tender are hard to determine.
The impact of such a plant failure cannot be overestimated:
the adapted production process might need to be validated
again by regulatory authorities and thus require the comple-
tion of clinical trials. Furthermore, the manufacturing lead
times are subject to high variability due to quality control and
quality assurance processes. We show that the incorporation
of variable lead times is often neglected.
We insist to evaluate a new vaccine supply chain design
based on different performance dimensions. Vaccines are
complex, lifesaving products and a large number of stakehol-
ders are involved in the vaccine supply chain. This requires an
appropriate reconciliation of economical, technological and
value KPI’s. Clearly, minimizing the costs of a SCND is the
most frequently occurring (economical) performance mea-
sure. Existing literature mentions the need for rapid response
vaccine supply chains. We reviewed the different model-based
approaches for modeling supply chain responsiveness and
will take one of these approaches into consideration for our
future work. A value criterion may be applied to obtain an
equitable vaccine distribution or to measure the humanitarian
impact of a vaccine supply chain. Such performance meas-
ures are absent in our paper sample. Instead, we observed
an increased integration of life cycle analysis and ecological
performance measures into model-based SCND, especially in
recent years. However, the presence of the value dimension
remains scarce.
Imposing multiple performance criteria requires an appro-
priate multi-criteria decision making method. Our paper
sample reveals multi-objective optimization and the epsilon
constraint method as the most frequently used mathematical
programming and heuristic method respectively to deal with
multiple criteria SCND models. These methods avoid weight-
ing multiple criteria, but lack the practical relevance for the
satisfaction of the preferences of a stakeholder group. As our
future research aims to be applied in real life, we reviewed
the used data and the instance sizes. For a large number
of the reviewed manuscripts, the industrial sector remains
unspecified. Similarities between the vaccine industry and
other industrial sectors are hard to observe and therefore chal-
lenges researchers to study the complexities of the vaccine
supply chain.
Acknowledgment
We gratefully acknowledge financial support from the
GlaxoSmithKline Vaccines Research Chair on Operations Man-
agement. We thank the Editor-in-Chief, Associate Editor and
two anonymous reviewers for their constructive comments
and thoughtful suggestions.
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