Process Safety and Environmental Protection 119 (2018) 115–130

Contents lists available at ScienceDirect

Process Safety and Environmental Protection

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

Pharma Industry 4.0: Literature review and research opportunities in

sustainable pharmaceutical supply chains
Baoyang Ding
School of Business, Management and Economics, University of Sussex, Brighton, UK

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

Article history: The exploitation of the emerging technologies of Pharma Industry 4.0 facilitates sustainable value cre-
Received 18 December 2017 ation, leads to more agile, smart and personalised pharma industry, and thereby, in the long-run, enables
Received in revised form 11 June 2018 pharma companies to obtain competitive advantages. A more sustainable pharmaceutical supply chain
Accepted 22 June 2018
(PSC) should be implemented to match future operations and management of the pharmaceutical prod-
Available online 10 July 2018
ucts across the entire life cycle. The main purpose of this study is to identify the potential sustainability
barriers of PSC and to investigate how Industry 4.0 can be applied in the sustainable PSC paradigms.
Keywords:
This paper systematically reviews 33 relevant articles concerning sustainable PSC and Industry 4.0, taken
Pharmaceutical
Sustainability from peer-reviewed academic journals over a decade (2008–2018). Based on content analysis, we find
Supply chain that the major challenges that inhibit inclusion of sustainability in the PSCs are: high costs and time
Industry 4.0 consumption, little expertise and training, enforcement of regulations, the paucity of business incen-
Sustainable operations tives, ineffective collaborations and coordination across the PSC, lack of objective benchmarks, and poor
end-customer awareness. The technologies and innovations based on Industry 4.0 can solve these bar-
riers with regards to four aspects: enhancing the flexibility of the PSC for patient-centric drug supplies;
improving the effectiveness of coordination and communication across different entities within the PSC;
mitigating waste and pollution at different stages; and enabling a more autonomous decision-making
process for supply chain managers. Our analysis reveals that future research interest should focus on:
cross-linking coordination and cooperation, eco-friendly end-of-life products disposal, proactive prod-
uct recall management, new benchmarks and measurement of sustainable performance, new regulation
system design, and effects of incentives for sustainable activities.
© 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

1. Introduction ent and efficient actions for information exchange, both vertically
inside the company and horizontally across the holistic value chain
Since the concept of ‘Industry 4.0 was established in Germany (Barreto et al., 2017; Hofmann and Rüsch, 2017; Li, 2017; Wagner
in 2011, the USA, Japan and China successively implemented their et al., 2017; Zhong et al., 2017). These technologies assist companies
own plans for industry revolution (Prause, 2015; Li, 2017; Wagner to achieve more robust, closer and flexible linkages in manufactur-
et al., 2017; Zhong et al., 2017). Industry 4.0 comprises four core ing, and thus fulfill the optimisation of value chains, cost reduction
elements, including Internet of Things (IoT), Internet of Services and energy saving (Branke et al., 2016; Hofmann and Rüsch, 2017;
(IoS), Cyber-physical Systems (CPS), and Smart Factory (Hermann Zhong et al., 2017).
et al., 2016). The IoT is regarded as a “network of physical objects”, In current years, the techniques of Industry 4.0 have been
in which the Radio-frequency identification (RFID), Wireless sen- employed in the pharmaceutical industry (see Lee et al., 2015;
sor networks (WSN), and middleware and Cloud computing are Stegemann, 2016; Herwig, 2017; Yu and Kopcha, 2017), and has
the most essential techniques employed (Trappey et al., 2017; Ben- been strictly regulated by several stakeholders to ensure safety and
Daya et al., 2017). Based on the technologies of IoT and a close loop to protect the wellbeing of whole society (Xie and Breen, 2012;
of sensors, actuators and other devices, the CPS integrates physical Brown and Vondráček, 2013). Over many years, the majority of
and cyber networks, and thus provides more intelligent, transpar- pharmaceutical industries are still under batch-based mass pro-
duction processes rather than continuous production (Lee et al.,
2015; Stegemann, 2016). Lack of robust on-line quality control and
E-mail address: [email protected]
flexible production are the bottleneck of reliable drug supplies, and

https://doi.org/10.1016/j.psep.2018.06.031
0957-5820/© 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
116 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

sometimes shortages occur even when encountering emergency Table 1

Keyword search strings.
situations (Lee et al., 2015). It is worthy to note that improving
access to medicines is a core responsibility for pharmaceutical com- Details
panies, given that medicines are special commodities – as access to Primary Pharmaceutical supply chain
and affordability of these commodities directly influence the lives Keywords string Pharmaceutical reverse logistics/reverse supply
of patients (Schneider et al., 2010; Nematollahi et al., 2017). With chain
the exception of availability issues, when compared with the more Pharmaceutical manufacturing
Pharmaceutical procurement
flexible and efficient continuous production that requires lower
Pharmaceutical logistics
raw material consumption, as well as decreased hazardous sol- Secondary Keyword Industry 4.0
vent, traditional batch productions impose more serious impacts on string Sustainable/sustainability
the ecosystem in terms of air emissions, chemical pollution, waste Social/social responsibility
Environment/environmental
water and residual waste (Stegemann, 2016; Klatte et al., 2017). As
responsibility/green/ecology/ecological
“the second largest source of GHG emissions” (Bengtsson-Palme
et al., 2018: pp. 138), the increasing energy price, the potential
impacts on climate change, and the strict regulations have resulted
The paper is organised as follows: The review methodology and
in the pharmaceutical industry, focusing more on energy usage
sample selection are described in Section 2. Then Section 3 out-
and emission reduction throughout the entire life-cycle of pharma
lines the major challenges within different stakeholders of PSC
products (Schneider et al., 2010; Low et al., 2016).
and implications of Industry 4.0 for them. Subsequently, Section
Benefiting from the Process Analytical Technology (PAT), real-
4 discusses the main enablers, inhibitors and research gaps in the
time data processing, 3D printing, robots, and other techniques
sustainable PSC. Finally, Section 5 presents the conclusions and
emerging from Industry 4.0, the key point “close-loop” and “on-
limitations of this literature review.
line” quality monitoring of continuous process can be realised,
thereby resulting in the industry reducing its carbon footprint,
improving its energy efficiency, solvent utilisation, as well as mit- 2. Review methodology
igating other potential environmental impacts while enhancing
the quality and control of the entire system (Gernaey et al., 2012; The main purpose of literature review is to consolidate the past
Stegemann, 2016; Aquino et al., 2018). Moreover, with the devel- and current findings of a specific domain through comprehensive
opment of genomic information, along with an increasing number and novel interpretations, and identify research gaps and trends
of old people with chronic diseases, the demand for future patient- for the future research (Jaberidoost et al., 2013; Campos et al.,
centered medicines is increasing (Stegemann, 2016). Furthermore, 2017; Govindan and Soleimani, 2017). In this study, the content-
the value chain creation and higher data density reducing pro- analysis based literature review was carried out using the steps
ductivity also motivate the pharma industry to manufacture more below. Bibliographic databases including ScienceDirect, EBSCO,
tailored and personalised pharmaceutical products, suitable for Scopus, Emerald and Taylor & Francis were chosen for our search.
individualised drug therapy instead of the current “one-size-fits- The keywords were categorised into primary keyword strings and
all” approach (Gernaey et al., 2012; Branke et al., 2016; Stegemann, secondary keywords strings based on the articles which concep-
2016). tualised the frameworks of Industry 4.0; sustainable supply chain;
Apart from pharma manufacturers, the other participants supply chain 4.0 and pharmaceutical supply chain management
within the pharmaceutical supply chain, including distributors, (Seuring and Müller, 2008; Narayana et al., 2014a; Brandenburg
healthcare providers, pharmacies, etc., should also upgrade their and Rebs, 2015; Hofmann and Rüsch, 2017; Witkowski, 2017). The
services and technologies to cater to the demands of the future primary keyword strings used for the initial search correspond to
Pharma 4.0, including technologies from smarter logistics to different stages of the pharmaceutical supply chain; while the sec-
specifically personalised medication therapies. The relevant tech- ondary keyword strings reflect the dimensions of sustainability and
niques, i.e. auto-ID tags, smart vehicles, patient-centric information Industry 4.0. The keyword strings selected for the search are shown
exchanges, cloud computing, big data analytics, etc. thus provide in Table 1. The initial search was carried out using primary search
a feasible solution (Campbell, 2017; Herwig, 2017; Hofmann and strings AND secondary keyword strings; which match the key-
Rüsch, 2017; Yu and Kopcha, 2017; Zhao et al., 2017). However, word strings available in title OR abstract OR keywords of previous
extending the concept of Pharma Industry 4.0 from solely being studies. The articles are defined all in English; published by schol-
manufacturers to the entire pharmaceutical supply chain includes ars/academics; and from peer-reviewed journals available in online
several other challenges such as additional human involvement, databases. Since sustainability aspects and Industry 4.0 in the PSC
end-to-end collaboration, sustainable issues, safety, and disastrous are emerging topics and are evolving as nascent research topics; the
consequences if there are any mistakes, etc. The conventional search of previous published articles is restricted between January
research focus of the PSC on solely economic aspects, such as 2008 and January 2018.
profitability, cost, lead time, etc. (see Narayana et al., 2014a), is All retrieved papers were screened through four steps (shown
incomplete; it is imperative to understand how to establish a smart as Fig. 1). First, the titles and abstracts of articles collected through
and sustainable PSC across the holistic life-cycle of pharmaceutical the primary screening were reviewed. The selection criteria for
products that is suitable for future pharma industry developments. the secondary screening consisted of the four following steps:
As mentioned above, the exploitation of new technologies of i) Articles that included any one of the keywords, such as sus-
Industry 4.0 will facilitate sustainable value creation that will lead tainability or environmental or social responsibilities and/or plus
to more sustainable PSC designs and management, which, in turn, economic factors, were considered, while purely economic papers
will assist pharma companies to obtain competitive advantages in were excluded; ii) Articles that include the new concepts and tech-
the long run (Stock and Seliger, 2016; de Man and Strandhagen, nologies of Industry 4.0 were selected; iii) Articles that focused on
2017; Ansari and Kant, 2017). Therefore, this study will investigate medical devices or healthcare services were eliminated, because
the key challenges that inhibit the implementation of sustainable these are not explicitly related to the pharmaceutical supply chain
practices within the PSC, and, by merging the findings from current in which drugs or vaccines are perishable products; iv) articles that
literature, explore how the PSC can benefit from the new technolo- only depicted pharmaceutical synthesis or other scientific issues
gies of Industry 4.0. were excluded, given that they are less relevant for a managerial
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 117

Fig. 1. The systematic literature review processes.

literature review; and v) the same publications found in different manufacturers. Apart from the traditional criteria such as cost,
database and/or different groups of keyword strings and the articles quality, service, risk management, etc., they all choose regula-
to which we do not have access were excluded. After that, a brief tory compliance (social responsibility) and environmental impact
content analysis was used to review all pre-selected papers one (GHG emissions). In terms of environmental performance, suppli-
more time to closely look at the three dimensional perspectives ers accredited with the ISO14000 will reduce the environmental
of sustainability and how Industry 4.0 is applied in pharma sup- risks involved in raw material procurement (Xie and Breen, 2012;
ply chain management. Lastly, four extra articles were added from Low et al., 2016). Besides, Roschangar et al. (2017) suggest a sim-
the bibliographies of all pre-reviewed articles. In total, after care- ple “Green Scorecard” that consolidated Green Aspiration Level
ful review, our sample consisted of 33 articles for further content (GAL) to quantify supplier’s contributions on “green”. However, the
analysis. ISO14001 is not the sole criterion to judge whether a company is
environmentally friendly or not. Given that the ISO14000 certifi-
3. Implementation of a sustainable PSC to embrace Pharma cate is a voluntary standard, only a few pharmaceutical companies
4.0 in developing countries choose to obtain the ISO14000 certificate
(Li and Hamblin, 2016).
The pharmaceutical supply chain comprises of primary Except for the “green” aspect, through increasing the investment
manufacturers, secondary manufacturers, logistics service on suppliers’ development (either direct or indirect) and managing
providers/wholesalers, healthcare providers and retail outlets suppliers to comply with sustainable business practices (Rossetti
(Savage et al., 2006; Zahiri et al., 2017). In this section, the current et al., 2011; Mahapatra et al., 2012), pharma company can thus
implementation of sustainable PSC and how the techniques of improve supply chain social responsibility performance. Firstly,
Industry 4.0 employed is depicted into four stages, which are man- focal company (the manufacturer) needs to provide standard oper-
ufacturing, logistics, procurement and consumption in healthcare ating procedures (SOPs) as the guideline and requirements for
sectors, and household waste disposal. suppliers, which will guarantee suppliers’ activities to keep con-
sistence with ethical and sustainable standards. Then audits will
be conducted under planned and unannounced basis in order to
3.1. Pharmaceutical manufacturing
proactively investigate potential risks and hence find appropriate
corrective actions. Moreover, strategic collaboration facilitates sup-
3.1.1. The sustainable issues in manufacturing process
pliers to improve their operation and management to fulfil focal
As sourcing pharmaceutical productions and related services
company’s CSR requirement. However, this kind of collaboration is
from emerging countries are more and more common in pharma-
still not very efficient, given the dominant position of focal company
ceutical industry (Schneider et al., 2010; Zhang et al., 2017). Prior to
in pharma industry. Furthermore, training, as a knowledge transfer
the manufacturing process, pharmaceutical manufacturers should
process, is also essential for improve supplier’s CSR performance,
select the most suitable raw material and pharmaceutical excipient
which can be conducted combined with rewards or incentives
suppliers and production bases that highly comply with environ-
(i.e. excellent performance award) to motivate them (Zhang et al.,
mental and social responsibility (Xie and Breen, 2012; Low et al.,
2017).
2016).
After selecting suppliers and manufacturing plants, it is essential
To measure the environmental and social impacts incurred
to evaluate the burdens within manufacturing processes. Gener-
by either suppliers or manufacturing sites, Enyinda et al. (2010)
ally, there are three main stages in pharmaceutical manufacturing:
and Low et al. (2016) both suggest the analytic hierarchy process
active pharmaceutical ingredients (API) preparation, primary prod-
(AHP) technique to select high-priority suppliers and outsourced
118 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

uct formulation, and secondary pack processing. As mentioned, not only to control the pollution and consumptions in the manu-
the emerging technologies based on Industry 4.0 facilitate pharma facturing process, but also to mitigate the negative impact on the
manufacturers to upgrade from batch-based mass production to entire eco-system (Li and Hamblin, 2016). The eco-friendly prac-
agile, smart, sustainable and patient-centred continuous produc- tices depicted in reviewed articles include using bio-fuel; applying
tion, with close-loop and on-line quality management, in which biocatalysis instead of metal catalysts; developing more efficient
“materials are continuously charged into the system while the heating processes; selecting non-coal fired boilers; sewer water
product is continuously discharged” (Lee et al., 2015: pp. 192). and reusing water treatments; and implementing odour reduction
In this sense, personalised manufacturing can be realised via pro- (Gernaey et al., 2012; De Soete et al., 2014; Li and Hamblin, 2016).
ducing combined medication regimes for specific populations, or After the API manufacturing, companies should focus on product
even “zero-lag” real-time production for individual demand, once packaging that is recyclable, lightweight, and consists of renew-
receiving the digital prescription from the hospital or pharmacy able content packaging, making pharmaceuticals more eco-friendly
(Stegemann, 2016). Nevertheless, there is significant difference (Raju et al., 2016). Previous studies report seven main factors that
between batch-based and continuous production, given that batch need to be included in designing sustainable packaging (Kumar
variability existed in various batches (Kadlec et al., 2009). There- et al., 2008). The environmental impact and the energy use of dif-
fore, the design of the entire manufacturing process should be ferent packaging materials can be evaluated through the life cycle
converted to accommodate future trends. assessment (LCA) method and CML 2001, among which CML 2001
Due to strict regulations and the extremely complex applica- is the most widely applicable impact assessment method classify-
tion of new drugs that are launched in the market, the whole ing lifecycle inventory results into midpoint categories (De Soete
manufacturing processes (i.e. production techniques, solvent, APIs, et al., 2014; Raju et al., 2016). In addition, the appropriate packag-
excipients, packaging materials, quality assurance, etc.) must be ing design of medicine influences the logistic efficiency, given poor
confirmed before being approved by regulatory bodies (Kadlec packaging quality may damage the product when in transportation,
et al., 2009). Considering this, the ICH Q8 (R2) guideline, together storage or on the retail shelf. Besides, packaging also has an influ-
with the other document from FDA, emphasise that pharma man- ence on reverse logistics, where package-related wastage needs to
ufacturers should reserve “design space” where changes (e.g. be processed taking into consideration package sizes, shapes and
pollution prevention) responding to disturbances appearing in pro- materials (Xie and Breen, 2014). The waste can be attributed to the
duction can be manipulated to guarantee the quality, without oversized or inappropriate packaging that can hardly be emptied
expensive and time-consuming post-approval regulatory revalida- and recycled (Xie and Breen, 2014). For instance, De Soete et al.
tion (US Food and Drug Administration (FDA), 2004; ICH, 2009). (2014) illustrate that different packaging of same bioequivalent
The call for greener drug production processes was raised from products may affect the drug adherence of patients, thereby reduc-
western countries, where the traditional pharma industry was ing waste. Generally, most medicine package units have 28, 30 or
regarded as a “high polluting” industry (Gernaey et al., 2012). The 31-day dosages, which will induce leftovers because in most cases
design of pharmaceutical formulations focus more on safety and the NHS prescription is for 28-day dosages (Xie and Breen, 2014).
quality, thus potential environmental substitutes cannot be used Therefore, the size of pharmaceutical packaging should encourage
for the main pharmaceutical active ingredients (APIs) unless they customers to use the product completely and thus minimise waste
are formulated with less chemicals and toxic substances. However, generation in households.
medicines still can be designed to be more eco-friendly, e.g. higher
efficacy under lower doses, containing less detrimental excretions, 3.1.2. Implications of Industry 4.0 in manufacturing process
longer shelf life (Kreisberg, 2007; Xie and Breen, 2012). In addi- In the manufacturing process, embracing new technologies
tion to APIs, albeit with substantial volume of solvents utilized based on Industry 4.0 will help pharmaceutical companies to estab-
in manufacturing process, solvent recovery and recycling are still lish more robust and agile manufacturing processes that have fewer
scant since cross-contamination and the high level of purity will interruptions, less defects, and higher levels of quality manage-
significantly increase the fixed cost (Gernaey et al., 2012). The ment (Herwig, 2017; Tjahjono et al., 2017; Yu and Kopcha, 2017).
computer-aided solvent selection tools enable managers to identify The vertical integration of Industry 4.0 will upgrade the pharma
alternative solvents with less lab experiments, thereby employ- production plant to become a “reconfigurable factory”, in which
ing most suitable and eco-friendly solvent for different processes the highly flexible, agile and smart production line can support
(Gerneay et al., 2012). Simply producing greener medicines without mass customisation of personalised drugs for different demands
integrating innovative processes will not lead the manufacturers (Qin et al., 2016; Tjahjono et al., 2017). The horizontal integra-
to effectively implement green production. Therefore, the con- tion significantly improves the responsiveness of the entire supply
tinuous production process is capable of improving the process chain actors to personalised patients demand (Tjahjono et al.,
efficiency, reducing carbon footprint, optimizing energy and water 2017). The more efficient communication across company walls
consumption, minimizing raw material and solvent waste, thereby and big data analytics improve process monitoring performances,
mitigating potential impact on eco-system (Schaber et al., 2011; and thus identify and reduce material waste, overproduction and
Gernaey et al., 2012; Stegemann, 2016). The process mass intensity energy consumption (Branke et al., 2016; Wang et al., 2016;
(PMI) can be utilized to quantitatively evaluate how environmen- Waibel et al., 2017). For instance, the Cyber-physical system can
tal sustainability practice implemented in the design of continuous guarantee the Just-in-Time delivery as an essential part of lean
process (Gernaey et al., 2012). The key components of continu- production, thereby reducing waste caused by high level of safety
ous production are on-line quality control system and close-loop stocks, and facilitating the production of personalised products on
feedbacks, which are based on the PAT concepts and digital data small batches by upstream suppliers (Hofmann and Rüsch, 2017;
processing (Gernaey et al., 2012; Stegemann, 2016). Wagner et al., 2017). In addition, the new energy management
Moreover, both pharmaceutical products and manufacturing techniques supported by Industry 4.0 can realise the monitoring
utilities, for example heating and cleaning media, and electrome- and optimisation of energy consumption (water, electricity, gas,
chanical power are carbon intensive with a huge consumption etc.) through a series of automotive sensors. In developing coun-
of fossil fuels (De Soete et al., 2014; Zahiri et al., 2017). Li and tries, most pharma companies have started to implement some
Hamblin (2016) describe six critical control points that are essen- primary energy management actions that focus more on individ-
tial for a cleaner pharmaceutical production process to manage ual production machine. The new techniques will help pharma
the wastage and pollution. The meaning of cleaner production is companies to upgrade their management system suitable for multi-
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 119

production lines or even multi-sites based on big data from energy tion processes without being constrained by pharma intermediate
and cost, thereby automatically achieving load forecasting and reg- manufacturers (Lee et al., 2015). Moreover, given its flexibility, it
ulation. will foster pharma products in line with the regulation differences
As mentioned earlier, the pharma industry is still based on in different countries, where the dose, specification, packaging unit
the batch manufacturing process that cannot be effectively con- or quality test requirements may vary (Branke et al., 2016).
trolled. Industry 4.0 provides a feasible solution, integrating the 3D printing is an essential supplement of continuous produc-
Process Analytical Technologies (PAT). Considering there are still tion, given that it also realises rapid production for personalised
some manual procedures within traditional pharmaceutical pro- demand (Goole and Amighi, 2016). Just as we use traditional print-
duction processes, the automation based on Industry 4.0 will ers at home, a 3D printer is capable of producing high quality
increase the efficiency and quality of drug manufacturing, which individualised drugs instantly on a small scale. In addition, a 3D
can mitigate human instability errors and control environmental printer does not require high standard intermediates, and enables
factors (i.e. sterility, particles, etc.) more effectively. This includes pharma companies to make “low-stability” drugs for urgent use.
various sensors that collect on-line quality test data without inter- Hence this on-demand production can be operated in resource-
rupting manufacturing, allowing real-time data to be calculated, constrained situations in order to improve the accessibility of drugs,
analysed and shared throughout every members of the PSC in such as in emergency rooms, ambulances, etc. (Norman et al., 2017).
order to find the control point. The quality control and quality Moreover, on account of its special production mechanism, 3D
assurance equipped with the PAT can fulfil the real-time release printing can break the boundaries of dose and shape, and can intro-
demand, thereby preventing the potential bottleneck caused by duce more complex drug release profiles to reduce side-effects and
the increasing number of customers. With regard to traditional improve drug adherence (Aquino et al., 2018; Norman et al., 2017).
batch production, if the APIs or other materials are not satisfied Another significant issue is that the lack of accurate supply
with the quality standards, they can be discarded before moving chain information causes decision makers to feel uncertainty (Low
to downstream working stations (Lee et al., 2015). However, if et al., 2016). For example, the evaluation of potential environmen-
the same situation occurs in the continuous production process, tal impacts should consider previous performances from various
it will cause disruption for downstream steps (Lee et al., 2015). sources, i.e. environmental incidence databases, regulatory com-
Therefore, the design of the entire production process must guar- pliance history, unfavourable media coverage, word of mouth
antee effective process control and reliable quality of material flow. reputation, etc. With the help of more transparent data provided
In this manner, the quality-by-design (QbD) paradigm that arises by Pharma Industry 4.0, managers can use big data analytics to
from the FDA assists the pharma industry to adopt the require- assist them to evaluate the potential suppliers based on their his-
ment of continuous manufacturing from the top-level design and torical performance, which, in turn, enables managers to make
understand the medicines and processes comprehensively − since final decisions in more autonomic ways. Furthermore, based on
the higher quality of medicines leads to less safety problems for the big data analytics, pharma companies can set best practices and
patients and a lower recall/return rate due to substandard drugs performance indicators of individual suppliers with a customised
that directly influence the quantity of pharmaceutical wastage approach, and can manage suppliers more effectively (Wang et al.,
(Lee et al., 2015; Branke et al., 2016; Yu and Kopcha, 2017). To 2016).
some extent, the design space from QbD broke the role of tra-
ditional supervision, which encourages pharma company to fulfil 3.2. Pharmaceutical logistics
continuous improvement on quality management. Comparing with
conventional quality control strategy based on automated process 3.2.1. The sustainable issues in pharma logistics
control (APC), the application of Pharma 4.0 is far beyond sim- The pharmaceutical manufacturers directly control the out-
ply process control. The higher level of control and management bound transport to distributors and wholesalers. Thus the transit of
across the entire life cycle will enable predictive analysis and proac- medicines is conducted by distributors, generally 3PLs and whole-
tive actions in according to the big data gathering from various salers. The demand for preventing drug shortages at any time
sources. For example, after being well trained by big data, machine and increasing the accessibility of medications can be regarded
learning algorithms are able to reflect potential machine failures as one of the main social responsibilities in the pharmaceutical
and hence conduct proactive maintenance (de Sousa Jabbour et al., supply chain (Nematollahi et al., 2017). In other words, socially
2018; Tiwari et al., 2018). concerned members should ensure the service fill-rate to prevent
Traditional manual data record will be gradually replaced by potential stock-outs rather than solely considering economic fac-
automation system in which the standard and quality of data collec- tors (Nematollahi et al., 2018; Borumand and Beheshtinia, 2018).
tion will also be improved. The embedded sensors not only collect The wholesaler and distributors have to be kept high inventory
relevant data with regard to production processes, but also record levels and thereby hindering the JIT or lean logistics. Enhancing
the environmental data, which thus realise the monitoring and resilience of supply chain to overcome the disruptions or disasters
traceability of real-time environment within production line. The and providing a minimum service level for patients to guaran-
sensors then upload all data to the cloud computer, thereby the data tee target fill rates will result in a negative impact on revenue of
can be collected, stored, traced and analysed. In this sense, the com- different entities in the PSC (Zahiri et al., 2017). In this manner,
pliance of GxP will be guaranteed, given that the electronic records SC managers, governments or NGOs are responsible for providing
avoid potential risks that irresponsible companies may tamper data certain compensation that can at least maintain the profit of the
to satisfy quality inspection under paper-based records (Gaertner, PSC participants when they involve in social collaboration activi-
2015). ties. The cross-boundary collaborative decision-making enhances
Besides, the small-scale continuous productions, to some extent, the accessibility to medicines rather than just gaining more profits
also mitigate the time-consuming gap between scale-up and com- (Nematollahi et al., 2017).
mercial production, and thus expedite the breakthrough drugs’ Apart from the accessibility of drugs, the quality of drugs in dis-
launch in the market, especially in emergency situations (Lee et al., tribution process is also important (Enyinda and Tolliver, 2009).
2015). In addition, since the intermediates that are indispensable Maintaining the constant transit temperature, especially for some
elements of batch-based production are unnecessary, the continu- temperature sensitive vaccines in cold chain, is a big challenge for
ous process can shorten pharma supply chains and even promote distributors who transport or store pharmaceutical products. In
the centralised manufacturing into regional decentralised produc- order to guarantee the quality of drugs, distributors develop several
120 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

techniques such as refrigerated carriers, insulated packaging, ther- reducing potential leftovers caused by high inventories, while at
mal blankets, and dry ice to maintain consistent temperatures, and the same time guaranteeing the acceptable service level (Hofmann
equip sensors to record the temperature during the entire deliv- and Rüsch, 2017; Tiwari et al., 2018).
ery process (Kabir, 2013). Another issue in pharma logistics is to Autonomous and smart vehicles can aid distributors to save
minimizing carbon footprint in transportation process. Borumand more operation costs in the delivery and sorting processes, and
and Beheshtinia (2018) utilize genetic algorithm model to solve the optimise lead times and ecological impacts (Alicke et al., 2017).
scheduling problem in which the emission by vehicles was consid- The flexible and innovative delivery processes (i.e. drone delivery)
ered as an essential factor, thereby vehicle routing optimization is will solve the “last mile delivery” and accomplish the emergency
integrated into decision-making. demand from specific patients (Alicke et al., 2017). Of note is
Except for the forward flow, there are two main reverse flows that although the automations can be used in operational level
in distribution process: returned and recalled drugs. The total cost practices, big data analysis, based on the transparent data from
of returned drugs is accounted for 3–6% of pharmaceutical sales the end-to-end “supply chain cloud”, can only assist strategic
per year (Hunter et al., 2005). The main issues in this process level decision-making (i.e. the storage location, routes of haz-
include handling return requests, selecting the right routing to ardous, analyse storage conditions with flammable materials, etc.)
control cost, anti-counterfeits, crediting consumers and suppliers, rather than replace human workforce (Hofmann and Rüsch, 2017;
and evaluating the returns and performance (Kumar et al., 2009). Witkowski, 2017).
Compared with pharmaceutical returns, recalls have several dif- In addition, the EU stipulates that, after 2018, prescription drugs
ferences. First, product recalls have a greater sense of urgency, should have a unique serial number (Branke et al., 2016). Likewise,
considering this is a regulatory compliance issue. Second, unlike China also has its own “Drug Electronic Supervision Code” for every
some returned drugs, which need to be redistributed, recalled drug (CFDA, 2012). In this way, every patient could easily check the
medicines all need to be destroyed. Thus, some limitations, such distributing data stored in cloud computing systems that record
as the consistent temperature required during outbound transit, every step of the products along the pharma supply chain, just
are not necessary. In addition, given defects may only exist in one through scanning the bar code, QR code or specific identification
or more specific batches, more efficient methods to identify tar- numbers on the packaging (Branke et al., 2016; Hofmann and Rüsch,
get batch are required for recalled drugs than for returned drugs 2017). As a widely used and mature technique in pharma logistics,
(Kabir, 2013). The reverse supply chain has relatively asymmet- radio frequency identification (RFID) has relatively minimal error
rical information, compared with the forward supply chain. The rates and higher cost-effectiveness (Trappey et al., 2017). However,
different flow of materials and the uncertainty of the information the investment on IT systems that utilise the RFID technologies
concerning demand lead to the difficulty in forecasting the reverse throughout the entire PSC, from manufacturers to retailers, is still
logistics activities. Only through declaration to regulatory author- more expensive than traditional printed labels. Thus, small or
ities and proper documentation can recalled pharmaceuticals be medium companies feel reluctant to equip the RFID readership,
taken back, which is both cumbersome and time-consuming (Kabir, sensors and the IT database (Kongar et al., 2015; Hofmann and
2013). Therefore, companies should collaborate more comprehen- Rüsch, 2017). The real-time data gathered by the RFID tracking can
sively to operate a more efficient reverse supply chain. To some help the manufacturer, partnered with the downstream distribu-
extent, the impact of returns is overlooked in most manufacturing tors, to ensure a true demand of the exact quantity, lead time and
firms, given that the core business of manufacturers is producing locations of products, so that the better communication improves
and selling drugs to end-customers. In fact, companies benefit from the use of warehouse space, and decreases the potential errors in
the effective handling of returned drugs, which not only increases transaction and time for forecasting the demand. Moreover, the
the overall reverse logistics efficiency, but also contributes to their RFID can provide expiration date information that is regarded as
public image and thus builds customer loyalty (Cheah et al., 2007). the main cause for returned drugs, and thus forecast the return of
expired or near to expire drugs. Therefore, all members of the PSC
3.2.2. The implications of Industry 4.0 in logistics should work collaboratively to eliminate miscommunication and
The distribution process can benefit from “smart logis- perception errors, and utilise the common information database
tics”, thereby becoming more transparent, traceable and well- and processes for handling the RFID. Although RFID tags for seri-
coordinated. The CPS, IoT, and cloud computing provide a high alisation enables traceability, it is noteworthy that the prolonged
level of connection and traceability for both information flow and exposure to the RF signals may affect the quality of some biophar-
physical flow (Trappey et al., 2017). maceuticals (Kabir, 2013). Another indispensable issue is these new
All of the PSC logistic managers are capable of sharing infor- techniques (i.e. RFID, cloud computing) must be in line with well-
mation, managing their performance and implementing actions in accepted international standards to avoid data variation (Hofmann
real time, instead of the traditional retrospective-based manage- and Rüsch, 2017).
ment through cloud computer or distributed ledger that establishes
a virtual ERP system (Alicke et al., 2017; Hofmann and Rüsch, 3.3. Pharmaceutical procurement and consumption in healthcare
2017). Consumption data can be collected by real-time data sharing sectors
beyond companies, which enhance the flexibility and capacity to
respond to the emerging demand of medicines, thereby enhancing 3.3.1. The sustainable issues in healthcare sectors
the availability and accessibility of drugs to customers (Hofmann Generally, the main participants in this process are hospitals,
and Rüsch, 2017). Moreover, through more accurate real-time data especially public sector hospitals. The core missions in procure-
supported by the CPS, distributors can adapt to a more flexible and ment process are “expression of needs, the procurement stage itself
autonomous replenishment and inventory management, where and the monitoring of markets throughout the duration of the rela-
there is less human interaction in the decision-making, and the sen- tionship” (Oruezabala and Rico, 2012: pp. 574).
sitive indicators – such as temperature, humidity, cleanliness, air Unlike purchasers in other industries, hospitals that are worked
pressure, etc. – are able to be measured, and the abnormal value as dependent entities have to interact with their suppliers (dis-
would be reported automatically (Branke et al., 2016; Hofmann tributors) frequently or even on a daily basis, since the demand
and Rüsch, 2017). Meanwhile, the higher level of collaborations can hardly be anticipated accurately and the supply of pharma
realised by smart logistics enable lower buffer levels, based on products always need to be adjusted to meet short-term patient
sharing of more reliable planning and forecasting data, thereby demand (Oruezabala and Rico, 2012: pp. 574). Therefore, new rela-
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 121

tionship management rather than operational level is essential the consumption process. Due to the inherent complexity of ther-
for purchasers. Actors in sustainable procurement process should apeutic regimens, physicians prefer to focus more on drug–drug
collaborate to concentrate on reducing distribution waste, shar- interactions and pharmacokinetics. Thus environmental impacts
ing sustainable data, and managing other social issues (Gualandris are not considered to be a priority concern. Traditional dis-
and Kalchschmidt, 2014). Controlling the amount of smaller size pensing practices, with regard to environmental issues, involve
distribution supplier and concentrating on managing key leading promoting patient adherence to reduce accumulated medication,
suppliers with knowledge and experience on sustainable develop- supplementary dispensing (lower quantity or shorter duration pre-
ment can enhance the efficiency of logistics and provide innovative scriptions), and alternative therapies instead of medications (Xie
services in compliance with sustainable requirement (Oruezabala and Breen, 2012; Daughton, 2014). In future, doctors can also
and Rico, 2012; Ahsan and Rahman, 2017). reduce the dose for certain APIs through the “off-label” lower-
Except for the supplier factor, the professional practitioners dose dispensing and focus on prescribing medicines whose APIs
in hospitals are doctors, pharmacists or other healthcare officials have more favourable excretions, e.g. a lower half-life period in
without adequate supply chain management, environmental pro- the environment (Daughton and Ruhoy, 2013; Daughton, 2014).
tection expertise. To understand relevant policies and operation The prescription, referred as co-directed sustainable prescribing
processes of sustainable procurement, key personnel should be (EDSP), combines these two methods and takes into considera-
educated and trained (Oruezabala and Rico, 2012). Senior man- tion the integration of environmental, economic and social issues.
agers who understand environmental and social impact incurred First, by reducing the dose of medicines, a sustainable prescription
by products and have preference to implement sustainable pro- approach reduces healthcare expenditures both for government
curement policies can make decision for tender evaluation after and patients, and decreases the cost for handling pharmaceuti-
integrating adverse environmental, social impacts and potential cal leftovers. Second, this approach improves therapeutic efficacy
expenditure of the entire life-cycle rather than just reducing cost via minimising off-target side-effects related to dosage, and thus
on procurement (Ahsan and Rahman, 2017). Hence senior man- enhances pharmaceutical compliance. Moreover, the morbidity
agers set strategic goal to lead and assist mid-level managers to and mortality of young child and elders due to unexpected toxicoses
allocate more resources on conducting sustainable procurement resulted from inappropriate storage or disposal can be decreased
policy (Ahsan and Rahman, 2017). Despite that sustainable crite- by non-redundant prescriptions (Daughton, 2014).
ria are accounted for approximately 5% to 20% of decision-making,
in fact, senior managers can hardly acquire adequate information 3.3.2. The implications of Industry 4.0 in healthcare sectors
and measure the performance concerning how suppliers behave in Personalised medication treatment and supply is one of the most
compliance with sustainable requirement throughout entire life- significant issues in healthcare sectors. For example, through super-
cycle of product in an objective and direct way (Oruezabala and computers that can analyse and mine cloud database of patients,
Rico, 2012). In this manner, emerging technologies of Industry 4.0 IBM enables doctors to use accurate historical information for
remarkably enhance the transparency of information of suppliers customised therapy (Zhong et al., 2016). Individual monitoring
and their pharma products, which will assist the purchasing prac- devices (i.e. smart wristband sensors, smart watches), along with
titioners to make decision. data sharing systems, can aid hospitals and even manufacturers
It is noteworthy that hospitals are always belonged to public to manage information flow focusing on patient-centred biomet-
sectors governed, that means government plays a vital role on ric and medication data, by which real-time alerts of side-effects
promoting sustainable procurement process. The legislation and will be reported immediately in order to avoid detrimental impacts
regulations enacted by government that explicitly explain how to (Stegemann, 2016). The habit of drug usage, biometric data, as well
implement sustainable procurement practice is the key driver to as medication adherence of every individual, can be analysed, and
encourage or even force them to purchase sustainable product and thus doctors are able to implement individualised medication reg-
select suppliers who prefer to conduct sustainable practice (Ahsan imens and interventions in order to improve the efficiency and
and Rahman, 2017). For example, France implements the Sustain- efficacy of medicines (Branke et al., 2016). Moreover, the increas-
able Public Procurement (SPP) based on the entire legal system ingly open and detailed digital information from specific websites
from guidelines to laws, which not only stipulate purchasers to and some healthcare Apps provide more access for patients to learn
obey sustainable rules, but stimulate them to improve themselves the latest professional knowledge, and hence they can make con-
in order to fulfil the new criteria (Veal and Mouzas, 2011; Rahman sent to decisions on their own (Stegemann, 2016). In this sense,
and Subramanian, 2012). Likewise, the main government agency Pharma 4.0 improves the ability of self-tracking and monitoring of
called Health Services Purchasing and Logistics (HSPL) in Queens- drug efficacy, and the rapid detection of adverse drug reactions,
land State of Australia has a Carbon Management Unit in which thereby decreasing the waste of drugs. Meanwhile, the additional
an eco-economic program was implemented to guide how health- services (i.e. E-health management) provided by pharma compa-
care agents to manage the energy and water efficiency issues (HSPL, nies beyond the product itself will also increase both customer
2011; Ahsan and Rahman, 2017). Besides, governmental incentives loyalty and brand image.
like tax benefit or price subsidy will motivate purchase more sus- For healthcare professionals, the technologies of Industry 4.0
tainable products without considering too much about the cost will assist their decision-making. For instance, all hospitals have
issues (Ahsan and Rahman, 2017). to prepare high levels of safety stocks to guarantee the minimum
Within the healthcare providers, the dose of drugs prescribed by level of service to every patient. Through the real-time data shar-
physicians and pharmacists plays a paramount role on the quan- ing of consumption information in different departments of the
tities of APIs released in the environment (through sewers as well hospital, and big data analytics for planning and forecasting, pur-
as disposal of unwanted leftovers) (Daughton and Ruhoy, 2013; chasing managers are able to manage every single product more
Deblonde and Hartemann, 2013). Given that pharmaceutical left- flexibly and effectively (Alicke et al., 2017). Purchasing managers
overs only account for a minor proportion of APIs released in the also need to manage their suppliers, which are always big distrib-
environment, current approaches that merely control or prevent utors or 3PLs rather than manufacturers. As mentioned above, the
pollution, especially those simply focus on the “take-back pro- evaluation of supplier performance and supplier selections has an
gram” of household unused/unwanted drugs, cannot meet the high inevitable problem: the lack of expertise due to their healthcare
requirement. Therefore, it is essential to control excess medica- background. With the help of the more autonomous information
tion prescription and thus avoid wastage and contamination in system and transparent data, managers can make decisions in a
122 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

Fig. 2. Research Framework of sustainable PSC.

more convenient and objective way, hence mitigating the influence

of human intervention (Tiwari et al., 2018).

3.4. Household pharmaceutical waste disposal

3.4.1. The sustainable issues in household waste disposal

Drugs stored in households can cause unintended poisoning,
particularly in children and elders, which may lead to drug abuse,
misuse, and other risks due to self-medication (Xie and Breen, 2012;
Xie and Breen, 2014). Most of waste medicines are not disposed Fig. 3. Longitudinal distribution of review articles considered in the study.
of properly. According to Kongar et al. (2015), the proportion of
households in the US that dispose of unused/unwanted drugs in the
garbage and water streams almost accounts for 90%. Given that the 3.4.2. The implication of Industry 4.0 in household waste disposal
sewage plants are not equipped with special filters for these sub- As mentioned, the technologies provide real-time, end-to-end
stances, they can easily reach the consumption water, producing transparency throughout the entire PSC. As end-users, patients and
effects that are not visible immediately but have a major nega- other customers can benefit from the techniques as well. With
tive impact on the health of the population (Bungau et al., 2015). regard to the numerical identification code of every single unit of
Even though these leftovers are picked up through the drug take- pharmaceutical products, patients are able to check all the logistics,
back program and properly incinerated under the strict purview of from manufacturers to pharmacies, through their smart phones.
concerned authorities, the toxic incinerated ash that goes to land- Once a pharma company announces a drug recall due to quality
fills and water streams will ultimately lead to a negative impact problems or other safety issues, this more effective communication
on humans, aquatic life and the entire eco-system. Moreover, the can assist pharma manufacturers to identify involved customers
unused painkillers, antibiotics and other drugs may lead to abuse and implement proactive actions to prevent greater detrimental
and overdose, especially in youth, which has a negative impact on impacts on customers. On the other hand, through scan the code,
the safety aspects (Daughton, 2014). the smart pharma Apps or smart pill boxes can remind customers of
Unlike other products, expired or waste drugs have almost the expiry dates, thereby reducing leftovers. Moreover, these new
zero-salvage value, hence they need to be inspected and sorted technologies foster closer and more effective interactions between
before being destroyed or properly disposed (Xie and Breen, 2012; doctors and patients, and thus improve the effectiveness of educa-
Kwateng et al., 2014). Generally, the common applied disposal tion by healthcare professionals.
approaches include incineration, deep burial, landfill, sewer, etc.
(Kwateng et al., 2014; Sreekanth et al., 2014). Only small quantity 4. Discussion
of unused medicines collected by take-back programs are intact,
with good efficacy and within a useful date-use (Department of The findings will be discussed based on the following approach.
Health (DoH), 2011). The most feasible fraction can be recycled and First we will review the descriptive analytics of our samples. Next
reused are their packages and containers (Weraikat et al., 2016b). we will subsume our findings from the PSC stages under a research
Therefore, the lack of commercial value in waste medicines has framework following the work of Fawcett et al. (2008), and adapt
a negative impact on active engagements in the recycling process. it as per our research aim (Fig. 2). This framework covers the PSC
For example, the UK community pharmacies only get incentives for sustainability implementation, antecedents like enablers and chal-
accepting returns, but not for the in-depth analysis of why the drugs lenges for the implementation, as well as performance implications
are returned or how to address the issue of reducing wastage. Thus of Industry 4.0. Finally, the future research opportunities will be
they are reluctant to encourage and educate more customers to discussed.
participate in take-back programs (Xie and Breen, 2012). Likewise,
in Ghana, end-use patients will not obtain refund or compensation 4.1. Descriptive analysis
for returned medicines, thereby refusing to participate in this activ-
ity (Kwateng et al., 2014). GPs and pharmacists should be more cost The sampling process yielded 33 articles for review. The distri-
sensitive in prescribing and dispensing excess medicines to avoid bution of studies based on the year of publication is shown in Fig. 3.
fines and to preserve the community’s future wellbeing (Xie and Higher numbers of articles were published over the last five years,
Breen, 2012). Therefore, manufacturers can share financial incen- which means the interest in researching the sustainability aspects
tives, such as tax exemption or capital motivations to encourage all of the PSC is increasing in popularity.
members to participate in the recycling process (See i.e. Weraikat In terms of publication outlets, 14 out of the 33 articles con-
et al., 2016a,b) In addition to business incentives, limited economic sidered for the study were published in operations management
revenue can be recaptured from resale and donations to the subsidy journals or other business journals. Interestingly we didn’t find
market. These drugs are required to be packaged intact and within substantial studies (4 articles) in pharmacy related journals (see
their shelf life, and must be inspected by government-authorised Table 2). So far, it can be concluded that the topic is still a niche
drug stores or pharmacies. Then they can be made available to cus- topic for pharmaceutical scholars since major supply chains and
tomers who have limited insurance coverage (Kongar et al., 2015). pharmaceutical outlets have not yet picked up on the topic despite
This will be a win–win situation. its practical relevance.
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 123

Table 2
Journal distribution.

Journal title Numbers of

papers

Journal of Cleaner Production 4

Supply Chain Management: An International Journal 3
Science of the Total Environment 2
Computers and Chemical Engineering 2
Computers and Industrial Engineering 1
EcoHealth 1
Global Journal of Business Research 1
Green Chemistry 1
Independent Journal of Management & Production 1
Industrial Marketing Management 1
Information Technology Management 1 Fig. 5. Sustainable dimensions addressed in the review articles.
International Journal of Business, Marketing, and Decision Sciences 1
International Journal of Logistics Management 1
International Journal of Production Economics 1 topics focused on quality management in manufacturing process
International Journal of Productivity and Performance Management 1
(Herwig, 2017), reverse logistics (Kumar et al., 2009), and com-
International Journal of Physical Distribution & Logistics Management 1
International Journal of Supply Chain Management 1 munity drug supply chain (Xie and Breen, 2012). The final six
Journal of Environmental Protection and Ecology 1 articles completed the literature review. However, only one of them
Journal of Pharmaceutical Innovation 1 (Campos et al., 2017) conducted a systematic literature review
Kybernetes 1
on reverse logistics, and the others analysed various sources of
Pharmaceutical Engineering 1
Perspective in Science 1
literatures, reports and other secondary data without screening
Production Planning & Control 1 processes.
Regulatory Toxicology and Pharmacology 1 As for the dimensions of sustainability, Fig. 5 shows that over
Resources, Conservation and Recycling 1 half of the articles involved the social responsibilities. As a special
Transportation Research Part E Journal 1
product, four main specific areas mentioned in these articles are to
improve the quality, affordability, accessibility, and safety of drugs
in PSCs. As a traceable technology, the RFID was widely used in the
PSC in order to prevent counterfeit drugs and thus control the qual-
ity of products, especially when manufacturers and distributors
govern their recall and return medicines (i.e. Kongar et al., 2015).
The affordability of drugs is fulfilled in two aspects. First, through
subsidy market and donation some unused drugs within their shelf
life can be redistributed and then reused by people who are unable
to afford new drugs at a high price (Kongar et al., 2015). Second, the
sustainable prescription by tuning the dose properly could greatly
assist to reduce the cost to patients (i.e. Daughton and Ruhoy, 2013).
In terms of accessibility, the cooperation and emerging techniques
across the supply chain can ensure the minimum required service
of drugs without stock-out (i.e. Zahiri et al., 2017). Lastly, in terms
Fig. 4. Research methodologies considered in the review articles. of the safety of drugs, the rational selection of a drug dose and
the personal monitoring devices could minimise the multiple and
interconnected adverse effects. At the same time, the appropriate
As a still under-explored, emerging research field, 18% of articles disposal of waste medicines can prevent unintended exposure of
selected in this study focus on the case-study method that depicts bystanders. Except for these four areas, establishment of new facil-
rich insights into complex phenomena and is helpful in develop- ities including manufacturing plants or distributor centres provide
ing further theories (Fig. 4). Cross sectional data collected by either more working opportunities and increase regional development
questionnaires or interviews constitutes 18% of the study. In terms rate (Zahiri et al., 2017). On the other hand, smart factory equipped
of the conceptual framework, the three articles focus on: holistic with robots may occupy positions of human, which is an inevitable
quality control within the manufacturing process (Herwig, 2017); problem incurred by Industry 4.0 (Waibel et al., 2017). However,
reverse logistics (Kumar et al., 2009; Kongar et al., 2015); and green some traditional social issues mentioned in other industries, such
community PSC (Xie and Breen, 2012). As for the modelling method, as decent work and employment, human rights, gender equality,
eleven articles establish either qualitative or quantitative models education, organisation-individual relationships, work conditions,
in sustainable PSCs. Specifically, two researches selected the AHP societal commitment, housing, safety, mental and physical health,
method for supplier selection and evaluation (see Enyinda et al., etc. (Mani et al., 2014; Luthra et al., 2017; Zhang et al., 2017), are
2010; Ahsan and Rahman, 2017); one study (Narayana et al., 2014b) not discussed in any of the articles.
used the casual loop model to explain the relationship between In the light of environmental issues, 27 out of the 32 arti-
price, quality, cost, and reverse logistics; two researches (Weraikat cles considered for the review focused on environmental issues.
et al., 2016a,b) established coordination models to enhance the The high waste to product ratios in pharma industry attracts sub-
effectiveness in reverse logistics; three articles (Nematollahi et al., stantial research interests on environmental protection, pollution
2017; Borumand and Beheshtinia, 2018; Nematollahi et al., 2018) minimization and waste management. There is a stronger need
focused on replenishment, vehicle route, and visiting intervals in to consider pollution from the manufacturing process to reduce
forward distribution processes; and the remaining three articles waste disposal and improve their environment management sys-
(Susarla and Karimi, 2012; Low et al., 2016; Zahiri et al., 2017) tem (Luthra et al., 2017). Pharmaceutical manufacturers equipped
provided the models for entire supply chain network design. The with new technologies and switched into continuous production
articles that established the conceptual framework for related processes can significantly reduce GHG emissions, energy use,
124 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

Table 3
Research Themes in Selected Articles.

Author Region Major Themes

1 Enyinda et al. USA Supplier selection

2 Zhang et al. UK Supplier development
3 Gernaey et al. Denmark Continuous production
4 Herwig et al. Swiss Holistic approach to production control
5 Joakim Larsson and Fick Sweden Environmental issue disclosure
6 Li and Hamblin UK Cleaner Production
7 Raju et al. India Environmental Packaging
8 Roschangar et al. USA Process greenness evaluation
9 Stegemann Austria advanced manufacturing
10 Soete et al. Belgium Resource consumption and efficiency
11 Borumand and Beheshtinia Iran Forward logistics
12 Bravo and Carvalho Portugal Reverse logistics and QbD
13 Campos et al. Brazil Reverse logistics
14 Kabir Bangladesh Reverse logistics
15 Kongar et al. USA Reverse logistics, take back program and RFID
16 Kumar et al. USA Reverse logistics and communication
17 Narayana et al. India Reverse logistics and different stakeholders
18 Nematollahi et al. Iran Forward distribution and cooperation
19 Nematollahi et al. Iran Replenishment management
20 Weraikat et al. (a) Canada Reverse logistics coordination
21 Weraikat et al. (b) Canada Green reverse logistics coordination
22 Ahsan and Rahman Australia Green procurement
23 Kumar et al. India Hospital purchasing
24 Kwateng et al. Ghana Returned products and waste disposal
25 Oruezabala and Rico France Sustainable procurement
26 Daughton USA Sustainable prescription
27 Daughton and Ruhoy USA Lower dose prescription
28 Vatovec et al. USA Pharmaceutical handling and disposal
29 Xie and Breen UK Waste management
30 Low et al. Singapore Early stage network design
31 Susarla and Karimi Singapore Integrated planning
32 Xie and Breen UK Green community supply chain
33 Zahiri and Zhuang USA Integrated sustainable-resilient supply chain

water wastage, and improve the raw material and by-products 4.2.1. Enablers
management (see i.e. Li and Hamblin, 2016). At the same time, The organizational awareness of sustainable development is the
through selecting and evaluating suppliers who comply with the key internal enabler. Li and Hambin (2016) note that companies
environmental practice, manufacturers can track the whole prod- with a better eco-friendly organisational culture contribute to the
uct life-cycle from root source. In addition, it is noteworthy that the environment and society and are proactive in considering sustain-
packaging of drugs should also be designed to enhance the aware- ability, even if they have not been certificated with the ISO14000.
ness of costumers to minimise medication waste rather than just The high awareness of sustainability means the management team
focus on recycled, light-weight and renewable material (Xie and and employees tend to participate in these activities. If support and
Breen, 2012). In the distribution process, the inappropriate man- encouragement by senior managers influence the mid-level man-
agement of returned or recalled drugs results in environmental agers to participate in sustainable practice, the organization will
impact, while at the same time the emissions caused by vehicles reallocate more resources towards conducting sustainable activ-
should be concentrated as well. Lastly, in customer end consump- ities and apply new Industry 4.0 techniques (Blome et al., 2014;
tion, the release of APIs in the environment is a major problem, Ahsan and Rahman, 2017). In addition, the high demand of cost sav-
including API excretions from urine or sweat, release to sewers, and ing is another essential internal enabler. The close-loop monitoring
the disposal of leftovers in landfills. In this manner, pharmaceuti- of the continuous production and entire life-cycle management,
cal take-back programs and sustainable prescriptions are aimed at supported by PAT, CPS, IoT and other technologies, allow pharma
solving these environmental problems. companies to reduce the cost on pollution disposal and waste
Table 3 reveals that pharmaceutical reverse logistics (includ- resource, as well as save expenditures on fines due to incompli-
ing recalled and returned products) is the most common theme ance with environmental regulations (Bravo and de Carvalho, 2013;
addressed in these articles. In considering the regions, it is obvious Weraikat et al., 2016b).
that developed countries emphasise sustainability aspects in the In terms of the external enablers, the pressure from external
PSC much more compared with emerging economies. Only 9 of the stakeholders, strict regulation, and innovation of Industry 4.0 can
33 articles considered for the review were from developing coun- be regarded as the top three motivators. In recent years, the exter-
tries (India, Brazil, Bangladesh, Ghana and Iran). Considering that nal stakeholders (i.e. customers, investors, shareholders, NGOs,
implementation of PSC practice need extremely expensive invest- etc.) not only require robust quality of pharma products but also
ment and long-term payback period, developing countries still have the implementation of sustainable practices and CSR performance,
a long way to go in the future. which is the intangible value that represent company image and
reputation (Zhang et al., 2017). Second, as one of the most strictly
regulated industries (Li and Hamblin, 2016), pharmaceutical com-
panies are under extreme pressure from regulatory authorities and
4.2. Sustainable PSC 4.0 enablers and inhibitors other third-party supervisory organisations. The rules and regula-
tions explicitly stipulate how to punish the improper behaviours
According to the articles reviewed, the enablers and inhibitors of pharmaceutical organisations in the PSC, from clean produc-
are categorised into internal and external (shown as Table 4).
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 125

Table 4
The Enablers and Inhibitors coding from reviewed articles.

Enablers Internal Organisational/institutional awareness (Oruezabala and Rico, 2012; Li and Hamblin, 2016; Ahsan and
Rahman, 2017; Zhang et al., 2017)
Cost saving (Bravo and de Carvalho, 2013; Weraikat et al., 2016b)
External Customer awareness and satisfaction (Larsson and Fick, 2009; Kwateng et al., 2014; Ahsan and
Rahman, 2017; Roschangar et al., 2017)
Investors/shareholders recognition and pressure (Bravo and de Carvalho, 2013; Roschangar et al.,
2017)
NGOs monitoring (Ahsan and Rahman, 2017)
Pressure from regulatory agents (Oruezabala and Rico, 2012)
Competitive advantages (Oruezabala and Rico, 2012; Narayana et al., 2014b
New and more strict regulations (Oruezabala and Rico, 2012; Xie and Breen, 2012; Xie and Breen,
2014)
New techniques (Larsson and Fick, 2009; Gernaey et al., 2012; Stegemann, 2016; Aquino et al., 2018)
Inhibitors Internal High Cost (Gernaey et al., 2012; Oruezabala and Rico, 2012; Kwateng et al., 2014; Ahsan and Rahman,
2017; Zhang et al., 2017)
Time consuming (Gernaey et al., 2012; Kwateng et al., 2014; Zhang et al., 2017)
Senior manager support (Ahsan and Rahman, 2017)
Little expertise (Oruezabala and Rico, 2012; Vatovec et al., 2013; Ahsan and Rahman, 2017; Zhang
et al., 2017)
Insufficient training (Vatovec et al., 2013; Daughton, 2014; Ahsan and Rahman, 2017)
Knowledge management (Gernaey et al., 2012)
External Lack of simple and fair benchmarking/countermeasures (Oruezabala and Rico, 2012; Roschangar et al.,
2017)
Lack of legitimacy (Oruezabala and Rico, 2012; Ahsan and Rahman, 2017; Campos et al., 2017; Zhang
et al., 2017)
Legal complexity (Kabir, 2013)
Poor regulatory agent support (Gernaey et al., 2012; Larsson and Fick, 2009)
Inadequate financial support/incentives (Narayana et al., 2014b; Xie and Breen, 2014)
Poor supplier commitment/support (Oruezabala and Rico, 2012; Xie and Breen, 2012; Ahsan and
Rahman, 2017)
Lack of trust between entities (Weraikat et al., 2016b)
Inefficient communication between entities (Xie and Breen, 2014; Ahsan and Rahman, 2017)
Falsified information and lack of information quality (Stegemann, 2016)
Poor openness, accessibility and availability (Kumar et al., 2008; Larsson and Fick, 2009; Narayana
et al., 2014b)
Lack of standardisation of information (Kumar et al., 2008)
Lack of public/end-user awareness (Larsson and Fick, 2009; Xie and Breen, 2012; Daughton, 2014; Xie
and Breen, 2014; Campos et al., 2017)

tion to pharmaceutical wastage disposal. Despite the paucity of systems are almost unaffordable (Zhang et al., 2017). However,
social responsibility criteria and low-carbon concepts in current improvement of these systems, and their successful application, is
regulations, developing countries in particular, they still deeply a long-term systematic process. Therefore, not all senior managers
encourage pharmaceutical companies to participate in sustain- consider the long-term benefits and, as such, prevent the com-
able activities. In addition, based on the innovation guided by the pany from embracing sustainable practices (Ahsan and Rahman,
new concepts and technologies of Industry 4.0, pharma compa- 2017). Another issue is lack of expertise within companies (see i.e.
nies are more likely to achieve these missions. For example, the Oruezabala and Rico, 2012; Zhang et al., 2017). It means that even if
breakthrough of gene-tech provides in-depth explanations of the those at top levels tend to conduct more sustainable practices and
mechanism how drugs work in every individual and realize the apply new technologies in their businesses, they can rarely find
personalized medication design (Branke et al., 2016; Stegemann, adequate and eligible staff to implement these practices.
2016). Within production process, the PAT techniques allow on- With regard to the external inhibitors, the successfulness of sus-
line quality monitoring without disturbing production procedure tainable PSC highly depends on the sharing of real-time data across
(Gernaey et al., 2012). The 3D printing offer another solution of different sectors; effective communication and cooperation among
small scale customized manufacturing (Aquino et al., 2018). In the PSC; the fair and objective evaluation systems to benchmark the
the light of real-time information systems, the RFID tags, Auto- performance and forecast the sustainability challenges of partici-
ID labels, sensors provide a reliable solution for the long-standing pants; and the monetary incentive to enhance the operation of the
problem that cross-boundary cooperation is highly needed in every entire sustainable PSC. Furthermore, relevant laws and regulations
step of the PSC, especially for reverse logistics (Kumar et al., 2008; stipulated by regulatory authorities encourage more companies
Branke et al., 2016). Through the RFID-enabled information system, and society in general to participate in sustainable development.
the database that shares real-time information with multiple par- Since the manufacturing information is sensitive, companies
ticipants involved in the PSC facilitates the information exchange would not tend to share private information with distributors.
and communication among different members and enhances the Every company that is involved in the PSC is not able to integrate
traceability of pharmaceutical products (Kongar et al., 2015). all of the information obtained from the different sectors of the PSC
(Kumar et al., 2009; Kongar et al., 2015). As aforementioned, when
4.2.2. Inhibitors pharmaceutical producers do not treat pharmaceutical reverse
As a new trend, the implementations of sustainable PSC still logistics as core business, 3PLs and other distributors are discon-
need to overcome certain barriers. In terms of the inhibitors within nected from manufacturers, and thus they cannot quickly respond
organisations, the most inevitable issues of high expenditure exist to customer demands (Kwateng et al., 2014). In addition, manu-
within every part of the supply chain, from equipment upgrade to facturers’ paucity of information about the amount of medication
human training. For small companies and companies in develop- waste, the willingness of end-customers to participate in the take-
ing countries, the substantial costs in improving their supporting back programs, and the cost of the disposal and recycling of
126 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

leftovers result in a lack of coordination among manufacturers, the entire life cycle of medicines will prove more effective. In future,
3PLs, retailers and customers. Except for the reverse flow, the insuf- if persuasive information obtained from various sensors can help
ficient information sharing also incurs the high inventory level in regulatory agents build to a comprehensive understanding of every
wholesalers, distributors and hospitals, which lead to more wastage process and key control points of sustainable PSC, they will make
in storage (Nematollahi et al., 2018). The feedback information col- more effective regulations on the holistic view.
lected from end-retailers, including pharmacies, GPs, clinics and Although companies have taken sustainability into account, the
other drug retailers, assists doctors to dispense medicines more lack of incentives in the form of tax abatement or tax reimburse-
prudently, which in turn help regulatory authorities and other ment that is advocated by government inhibits pharmaceutical
stakeholders (manufacturers, 3PLs, and waste disposal companies, companies from proactively participating in sustainability pro-
etc.) to analyse the reasons for returned medications and thus grams. Through implementing sustainable activities, companies
mitigate pharmaceutical wastage. All of these issues result in an and other actors involved in the PSC avoid potential fines from
inefficient pharmaceutical supply chain. Therefore, more atten- regulatory bodies due to pollution, pharmaceutical quality prob-
tion should be paid to the frequent coordination and negotiations, lems, counterfeits, improper disposal of waste medicines, and so
and especially to pharmaceutical reverse logistics (Xie and Breen, forth (see i.e. Kumar et al., 2008; Weraikat et al., 2016a; Ahsan
2012; Campos et al., 2017). In this way, the real-time data shar- and Rahman, 2017). Manufacturers also achieve profit from the
ing accompany with track-to-trace capability based on the CPS sales of unused drugs in subsidy markets. However, those are far
network of Industry 4.0 can provide an effective solution for the less than enough. Sustainable initiatives are usually long term,
cross-boundary cooperation (Barreto et al., 2017; Hofmann and as seen in green manufacturing processes, such as low-carbon
Rüsch, 2017; Tjahjono et al., 2017). emission equipment, waste water treatment, or process innova-
Second, compared with the mature evaluation methods used tion. In particular with regard to pharmaceutical reverse logistics,
to estimate economic firm performance, finding appropriate mea- given there is no residual value, the lack of monetary incentives
surements or indicators for sustainable performance for the PSC reduces investment in infrastructure construction, such as incin-
is quite complex. Although there are some assessment systems eration plants, medication waste classification centres, collection
being utilised in pharma industry, such as GRI, CML 2001 impact points, and information system, and even restricts the range of
assessment, ISO14000, and EPA performance track, most measure- cooperation among different participants (Xie and Breen, 2014).
ments are used in the manufacturing process. Although potential Economic incentives within companies and organisations are also
supplier selection criteria can be used for estimating manufac- emphasised as barriers to end users and GPs, pharmacists, and
turers (i.e. Mani et al., 2014; Luthra et al., 2017; Kolotzek et al., physicians, since none of the aforementioned are obligated or moti-
2018), within the distribution and consumption processes, there vated to fully engage in sustainable PSC activities (Xie and Breen,
are still not any appropriate indicators concerning how to evalu- 2012).
ate sustainable operations in 3PLs, wholesalers, retailers, hospitals, Lastly, public awareness of the importance of sustainability
pharmacies. Information, such as detailed sustainable indicators needs to be raised, especially among professionals such as general
that are in accordance with the specificity of the pharmaceuti- practitioners, purchase agency officers, GPs and pharmacists who
cal industry, is needed, where the strict regulation, high quality directly participate in downstream supply chains. For example,
requirement, filling rate for patients, safety of drugs, and other pharmacies and customers should focus more on pollution preven-
relevant issues should be combined into the new measurement sys- tion rather than pollution mitigation, which means actions should
tem. Pharma companies should break the boundary and collaborate be taken to prevent the occurrence of leftovers rather than just con-
with each other to establish the sustainable PSC benchmark (Zhang centrating on processing pharmaceutical waste (Daughton, 2014).
et al., 2017). Once the benchmark is established, the computer- In addition to the role of prescriptions, GPs, doctors or pharmacists
based big data analytics will assist decision-making process in a should undertake the responsibility to educate patients about how
more autonomous way. to properly dispose pharmaceutical leftovers and encourage them
In addition, despite several laws and regulations have been to return the unused drugs, as these professionals are the first point
enacted by the US and EU to control pollutions and emissions in of the PSC and the first direct point of contact with the patients. It
the pharmaceutical manufacturing process and to punish improper is worthy to mention that greater personal or direct contact made
disposal of medication waste, there are still lack of regulations with patients results in an increased effectiveness (Xie and Breen,
that focus on a low-carbon concept and CSR, especially in devel- 2014). In this manner, the backward information from end-users
oping countries. However, in certain circumstances, regulations will enhance this kind of relationship between retailers and cus-
that have been stipulated by different authorities may have differ- tomers. Moreover, the environmental concerns can be consolidated
ent standards and requirements, which result in potential conflicts into clinical training practice, in order to enhance the awareness of
that may occur when handling these issues. For instance, Vatovec green purchasing strategies. In the light of end-customers, there
et al. (2013) state that the disposal of narcotics in hospitals, as is no control over returned drugs unless the customer is willing
stipulated in the Environmental Protection Agency (EPA), is con- to engage in this process (Xie and Breen, 2012; Kwateng et al.,
tradictory to the requirements set in the Drug Enforcement Agency 2014). Thus it is crucial for healthcare providers or the government
(DEA). Given that the DEA is more powerful than the EPA, hospital to enhance public recognition and end-customers education with
staffs have to comply with the DEA and thus flush unused narcotics regard to the importance of reducing pharmaceutical waste and the
down the drain, even they know that this causes negative envi- proper methods of disposal.
ronmental impacts. Moreover, traditional regulations promulgated
by pharmaceutical regulatory authorities, such as Good Manufac- 4.3. Implications for theory and practice
turing Practice (GMP), Good Supply Practice (GSP), do not take
sustainable development into consideration, e.g. the mandatory 4.3.1. The implications for theory
implemented Chinese GMP only requires good product quality and As discussed above, the majority of research concentrates on
hence it cannot reflect whether pharmaceutical companies pursue the economic and environmental aspects of sustainable PSCs, while
environmental or social responsibilities (Li and Hamblin, 2016). In the social impacts are still inadequate. The reviewed articles apply
addition, the regulation of end-of-life medications is not the main resource-based theory and institutional theory (i.e. Zhang et al.,
responsibility of pharmaceutical supervisory authorities, and cross- 2017) to explain how pharma companies can reallocate their
boundary regulatory affairs (e.g. FDA, EPA and DoH) that supervise resources and manage different stakeholders to accomplish the
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 127

sustainable goals. In addition, life cycle assessment is also widely labour-intensive workforce, which may incur social issues in local
used in several reviewed articles (see De Soete et al., 2014; Li communities (Waibel et al., 2017).
and Hamblin, 2016; Raju et al., 2016; Roschangar et al., 2017),
which ensure the “cradle to grave” management of pharma prod- 4.4. Future research opportunities in the sustainable PSC
ucts – from raw materials to waste disposal – and mitigates the
impact on the eco-system. For the sake of exploring human and Future research interest in the sustainable PSC would focus on
societal issues more comprehensively, future studies can select following topics. Firstly, in terms of the manufacturers, all selected
organisational behaviour theories to investigate how individuals articles focused on environmental issues during production and
representing various organisations with different levels of demand packaging process. Under current circumstance, the cross-linking
can affect the implementation of sustainable practices in the PSCs coordination and cooperation among PSC is still insufficient, which
(Touboulic and Walker, 2015). Moreover, another tool, namely the means once the drugs leave factory, manufacturers can hardly track
“social life cycle assessment” (see i.e. Dreyer et al., 2006), that the details of distribution. Therefore, how to improve the supply
integrates various social matrices, including human health, human chain collaboration that can assist manufacturers effectively con-
dignity, well-being, etc., may be considered by future researchers. trol and manage the entire life cycle (both forward and reverse flow)
of pharma products throughout PSC is still unexploited, which is
also one of the most essential problems under the Industry 4.0 con-
text (Stock and Seliger, 2016; de Man and Strandhagen, 2017). In
4.3.2. The implications for Industry 4.0 in sustainable PSC addition, more eco-friendly disposal methods of medication waste
The emerging of Industry 4.0 technologies in the pharma indus- (including recalled products), rather than the traditional incinera-
try has led to significant evolution across the holistic PSCs. The PAT tion or landfill method should be considered (Kwateng et al., 2014).
techniques support the close-loop and on-line quality monitoring Secondly, as for distributors, most researches concentrated
that will ensure the robust quality of pharma products (Gernaey on information systems of reverse logistics or product recall.
et al., 2012; Branke et al., 2016). The more flexible and efficient Given the serious impact incurred by problematic drugs, how to
continuous production process and 3D printing improve the pro- increase the response speed of drug recall supply chain through
ductivity and flexibility of the manufacturing processes, allow mass cross-company symbiosis to control and mitigate dissemination of
customisations that cater for the demand of personalised medica- defected products to the public are crucial problem (de Man and
tion, and reduce the waste of materials across the whole product Strandhagen, 2017). Besides, environmental issues for this stage
life cycle, thereby allowing for more environmentally sustainable are still underdeveloped. Despite with slight pollution compared
and energy efficient manufacturing (Lee et al., 2015; Aquino et al., with manufacturing process, the potential pollutions caused by
2018). Additionally, the CPS system increases the transparency and transportation vehicles, recalled and returned products disposal,
traceability of the distribution process, and both the lead time or operation of warehouse still need to be reduced through appropri-
delivery responsiveness, and the capability of detecting counter- ate method. In this area, how smart logistics based on Industry 4.0
feit products, will thus be improved. The transparent and real-time can provide sustainable and agile delivery service can be investi-
information systems motivate more effective collaboration and gated in the future.
communication among suppliers, manufacturers, distributors, hos- In procurement and consumption process, since hospitals are
pitals and end-users. The big data analytics and the CPS mitigate always public-sector organizations and sometimes even non-
human intervention in decision-making, identify potential risks to profit organizations, the buyer-supplier relationship is different
avoid disruption, implement appropriate strategies, and thus lead compared with the purchasers in other industries. The local gov-
to more flexible and sustainable supply chains (Wang et al., 2016; ernmental policies, private partnership and localized suppliers
Ben-Daya et al., 2017; Tiwari et al., 2018). Moreover, the real-time have direct influence on hospitals sustainable decision-making
feedback collected from end-use patients can assist physicians to (Oruezabala and Rico, 2012). Therefore, future research should col-
adjust the therapy in time and obtain potential adverse drug reac- lect data from boarder regions and quantitatively investigate the
tions. special relationship in hospital procurement. In addition, as men-
Despite with substantial number of benefits, there are still sev- tioned in Chapter 3, purchasing managers in hospitals can hardly
eral challenges and barriers that need to be solved. First, since the estimate the long-term profit of sustainable procurement, hence
IoT improves the cross-organisational or even cross-national com- how to measure the benefit of sustainable requirement is high in
munication, how to implement the widely acceptable standards demand. If the result is persuasive, purchasers even for those who
of data (i.e. the ID-labels of product) and data sharing protocols do not fully understand supply chain management will aware the
are the prior issues in PSC, considering the differences among lan- importance of sustainable procurement practice. The transparency
guages (Branke et al., 2016; Wagner et al., 2017; Tiwari et al., and seamless data generated from Pharma Industry 4.0 offer an
2018). Meanwhile, given the high complexity within pharmaceuti- opportunity to achieve smart decision-making in this process.
cal manufacturing processes, the massive volume and unstructured Moreover, future researches can design appropriate indicators
dynamic data need effective data cleansing methods (Song et al., and assessment systems integrated extant sustainable indicators
2017). In addition, data safety and security are also essential for (i.e. GRI) to evaluate the holistic sustainable PSC performance,
pharma companies (Tiwari et al., 2018). Considering the right of especially for downstream entities such as distributors, hospi-
intellectual property, company data, including process data, for- tals, pharmacies. As mentioned above, future researchers may pay
mulation data, R&D data, etc., should be protected. Also, customer more attention to social sustainability areas, especially consider-
health data, which reflects the individual privacy of customers, is ing the social indicators for evaluating organisation performance
also very sensitive (Branke et al., 2016). Additionally, given that are always indirect (Yawar and Seuring, 2017). The instant transfer
machine-to-machine (M2M) communication rather than human- of sourcing, production, distribution and consumption data on real-
to-machine (H2M) interaction is more likely occur in Industry time basis will help decision-makers to complete the assessment
4.0, intelligent, self-organised decision-making processes should be system.
responsible for every correct decision. However, due to the inherent Lastly, considering the strict regulation of pharma industry,
complexity in the pharma industry, the reliability of such decisions main regulatory authorities (i.e. FDA in the US, MHRA in the UK,
may be questioned (Branke et al., 2016). Moreover, this kind of CFDA in China) should systematically review their legal framework
smart factory would, to some extent, hinder the opportunity of a and amended the laws and regulations to integrate environmen-
128 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

tal and social aspects. Meanwhile, they should consider how to making, and the potential risks due to the reduction of low-skilled
upgrade the current scrutiny system of product quality and com- labour being replaced by machines, are all areas which need greater
pliance of GxP, to match those new requirements of Industry 4.0 attention.
(Gaertner, 2015). The applications of PAT techniques reform the The research limitations lie in the selection of review articles.
current off-line quality control system, by which all quality index Our search criteria on Industry 4.0 and sustainability are a niche
of drugs will be tested on-line within entire continuous produc- field in pharmaceutical supply chain management, and hence we
tion processes without any disruption. The important procedure only yielded only 33 articles and only about one third of them
under batch-based production − the final quality inspection of from top journals. In future, researchers can compare other rel-
drugs before being released to the market is no longer useful − evant industries, such as the chemical industry, medical device
means the GMP must be upgraded. In addition, despite there are industry, cosmetics industry, etc., to learn from their sustainable
several incentives implemented by government, future researches journeys. Moreover, this study mainly focuses on the downstream
need investigate the relationship between business incentives and PSC; thus, the upstream supply chain (i.e. sustainable clinical trial
engagement in sustainable activities and thus find most effective supply chain) can be investigated in the future. Furthermore, to
approach to motivate the involvement of pharma companies. deal with data issues, future research can rely on empirical data
from real world to explore how to apply the new paradigm in
pharmaceutical industry.
5. Conclusion

As a heavily contaminating, high waste and energy-intensive Acknowledgement

consumption industry, emerging technologies of Industry 4.0 will
allow pharma supply chain managers to upgrade their entire oper- The author would like to thank the Chinese Scholarship Council
ation systems to become smarter, more flexible and sustainable in (CSC) that funded this research (No. 201609370039).
achieving better company reputations, brand images, and compet-
itive advantages in the long-term.
To implement the sustainable PSC practice, there are several References
main obstacles that need to be overcome: i) the high investment Ahsan, K., Rahman, S., 2017. Green public procurement implementation challenges
and time consuming on infrastructures and supporting system con- in Australian public healthcare sector. J. Clean. Prod. 152, 181–197.
struction; ii) poor support by some senior managers; iii) lack of well Alicke, K., Rexhausen, D., Seyfert, A., 2017. Supply chain 4.0 in consumer goods,
available at: https://www.mckinsey.com/industries/consumer-packaged-
training expertise to conduct the sustainable practice; iv) the lack of
goods/ourinsights/supply-chain-4-0-in-consumer-goods.
laws or regulations stimulating members in the PSC to participate Ansari, Z.N., Kant, R., 2017. A state-of-art literature review reflecting 15 years of
in sustainable development; v) the insufficient collaboration and focus on sustainable supply chain management. J. Clean. Prod. 142, 2524–2543.
communication beyond the boundaries of the PSC; vi) the paucity Aquino, R.P., Barile, S., Grasso, A., Saviano, M., 2018. Envisioning smart and sustain-
able healthcare: 3D printing technologies for personalized medication. Futures,
of assessment systems to measure the entire process of the PSC; vii) in press https://doi.org/10.1016/j.futures.2018.03.002.
the ineffective business incentives and funds to guarantee engage- Barreto, L., Amaral, A., Pereira, T., 2017. Industry 4.0 implications in logistics: an
ment in the sustainable PSC and; viii) the inadequate education overview. Procedia Manuf. 13, 1245–1252.
Ben-Daya, M., Hassini, E., Bahroun, Z., 2017. Internet of things and supply chain
about the awareness of the sustainable PSC within the general pub- management: a literature review.International. J. Prod. Res., 1–24.
lic. Bengtsson-Palme, J., Gunnarsson, L., Larsson, D.J., 2018. Can branding and price of
Generally, the new technologies and concepts of Industry 4.0 pharmaceuticals guide informed choices towards improved pollution control
during manufacturing? J. Clean. Prod. 171, 137–146.
enable the PSC managers to solve these problems with regards to Blome, C., Hollos, D., Paulraj, A., 2014. Green procurement and green supplier devel-
four main areas. First, these innovations based on Industry 4.0 sig- opment: antecedents and effects on supplier performance. Int. J. Prod. Res. 52
nificantly improve the coordination and communication efficiency (1), 32–49.
Borumand, A., Beheshtinia, M.A., 2018. A developed genetic algorithm for solving
of the entire PSC, through which the information flow incorpo-
the multi-objective supply chain scheduling problem. Kybernetes, http://dx.doi.
rated manufacturing, logistics, sales and consumption processes org/10.1108/K-07-2017-0275.
can be shared and achieved in real-time. Managers are capable Brandenburg, M., Rebs, T., 2015. Sustainable supply chain management: a modeling
perspective. Ann. Oper. Res. 229 (1), 213–252.
of monitoring the whole process, from raw materials to end-of-
Branke, J., Farid, S.S., Shah, N., 2016. Industry 4.0: a vision for personalized medicine
life products, more effectively. Second, these new technologies will supply chains? Cell Gene Ther. Insights 2 (2), 263–270.
allow more agile PSC to catch up with the trend of “patient-centric” Bravo, A.M.S., de Carvalho, J.C., 2013. Understanding pharmaceutical sustainable
personalised drug supplies. From the flexible small scale continu- supply chains—a case study application. Independ. J. Manage. Prod. 4 (1),
228–247.
ous production to 3D printing, and from smart vehicles to personal Brown, S., Vondráček, P., 2013. Implementing time-based manufacturing practices
biometrics monitoring devices, every component will enhance the in pharmaceutical preparation manufacturers. Prod. Plan. Control 24 (1), 28–46.
responsiveness of mass customisation suitable for every single Bungau, S., Bungau, C., Tit, D.M., 2015. Studies about last stage of product lifecycle
management for a pharmaceutical product. J. Environ. Prot. Ecol. 16 (1), 56–62.
patient, thereby mitigating the safety hazards caused by the side- Campbell, R., 2017. Pharma to table: 3-D printing and the regulatory future of home
effects due to individual differences, ultimately reducing potential remedies. Conn. L. Rev. CONNtemplations 49, 1–12.
waste and leftovers owing to non-adherence. Additionally, the evo- Campos, E.A.R.D., Paula, I.C.D., Pagani, R.N., Guarnieri, P., 2017. Reverse logistics
for the end-of-life and end-of-use products in the pharmaceutical industry: a
lution of Industry 4.0 improves the productivity of the pharma systematic literature review. Supply Chain Manage.: Int. J. 22 (4), 375–392.
industry. The continuous production can reduce the material util- Cheah, E.T., Chan, W.L., Chieng, C.L.L., 2007. The corporate social responsibility of
isation, energy consumption and GHG emission, which thus leads pharmaceutical product recalls: an empirical examination of US and UK markets.
J. Bus. Ethics 76 (4), 427–449.
to greater contributions to environmental protection. Finally, the
CFDA, 2012. The notice about pharmaceutical electronic supervision in 2012, avail-
IoT, CPS and big data analytics enable supply chain managers to able at: http://samr.cfda.gov.cn/WS01/CL0844/73098.html. (Assessed 28th June
make decisions in more autonomous ways, especially for those staff 2012).
Daughton, C.G., Ruhoy, I.S., 2013. Lower-dose prescribing: minimizing side effects
who are working in healthcare sectors without adequate exper-
of pharmaceuticals on society and the environment. Sci. Total Environ. 443,
tise on supply chain management and sustainable practices. In this 324–337.
sense, they can make decisions more objectively and faster, with- Daughton, C.G., 2014. Eco-directed sustainable prescribing: feasibility for reducing
out the interventions of external factors. However, information water contamination by drugs. Sci. Total Environ. 493, 392–404.
De Soete, W., Boone, L., Willemse, F., De Meyer, E., Heirman, B., Van Langenhove, H.,
safety caused by the sharing of big data, the obstacle of big data Dewulf, J., 2014. Environmental resource footprinting of drug manufacturing:
cleansing, the reliability of autonomous computer-aided decision- effects of scale-up and tablet dosage. Resour. Conserv. Recycl. 91, 82–88.
 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130 129

Deblonde, T., Hartemann, P., 2013. Environmental impact of medical prescriptions: Li, X., Hamblin, D., 2016. Factors impacting on cleaner production: case studies of
assessing the risks and hazards of persistence, bioaccumulation and toxicity of Chinese pharmaceutical manufacturers in Tianjin, China. J. Clean. Prod. 131,
pharmaceuticals. Public Health 127 (4), 312–317. 121–132.
de Man, J.C., Strandhagen, J.O., 2017. An industry 4.0 research agenda for sustainable Li, L., 2017. China’s manufacturing locus in 2025: with a comparison of made-in-
business models. Procedia CIRP 63, 721–726. China 2025 and industry 4.0. Technol. Forecast. Soc. Change, in press https://
de Sousa Jabbour, A.B.L., Jabbour, C.J.C., Foropon, C., Godinho Filho, M., 2018. When doi.org/10.1016/j.techfore.2017.05.028.
titans meet—can industry 4.0 revolutionise the environmentally-sustainable Low, Y.S., Halim, I., Adhitya, A., Chew, W., Sharratt, P., 2016. Systematic framework
manufacturing wave? The role of critical success factors. Technol. Forecast. Soc. for design of environmentally sustainable pharmaceutical supply chain network.
Change 132, 18–25. J. Pharm. Innov. 11 (3), 250–263.
Department of Health (DoH), 2011. Evaluation of the Scale, Causes and Costs of Luthra, S., Govindan, K., Kannan, D., Mangla, S.K., Garg, C.P., 2017. An integrated
Waste Medicines, available at: www.gov.uk/government/publications/making- framework for sustainable supplier selection and evaluation in supply chains. J.
best-use-ofmedicines-report-of-a-department-of-health-roundtableevent- Clean. Prod. 140, 1686–1698.
hosted-by-the-king-s-fund. (Accessed 30 November 2011). Mahapatra, S.K., Das, A., Narasimhan, R., 2012. A contingent theory of supplier man-
Dreyer, L., Hauschild, M., Schierbeck, J., 2006. A framework for social life cycle impact agement initiatives: effects of competitive intensity and product life cycle. J.
assessment (10 pp). Int. J. Life Cycle Assessment 11 (2), 88–97. Oper. Manage. 30 (5), 406–422.
Enyinda, C.I., Tolliver, D., 2009. Taking counterfeits out of the pharmaceutical supply Mani, V., Agrawal, R., Sharma, V., 2014. Supplier selection using social sustainability:
chain in Nigeria: leveraging multilayer mitigation approach. J. Afr. Bus. 10 (2), AHP based approach in India. Int. Strategic Manage. Rev. 2 (2), 98–112.
218–234. Narayana, S.A., Elias, A.K., Pati, R., 2014a. Reverse logistics in the pharmaceuticals
Enyinda, C.I., Dunu, E., Bell-Hanyes, J., 2010. A model for quantifying strategic sup- industry: a systemic analysis. Int. J. Logist. Manage. 25 (2), 379–398.
plier selection: evidence from a generic pharmaceutical firm supply chain. Int. Narayana, S.A., Pati, R.K., Vrat, P., 2014b. Managerial research on the pharmaceutical
J. Bus. Mark. Dec. Sci. 3 (2), 23–44. supply chain-A critical review and some insights for future directions. J. Purchas.
Fawcett, S.E., Magnan, G.M., McCarter, M.W., 2008. Benefits, barriers, and bridges to Supply Manage. 20 (1), 18–40.
effective supply chain management. Supply Chain Manage.: Int. J. 13 (1), 35–48. Nematollahi, M., Hosseini-Motlagh, S.M., Heydari, J., 2017. Economic and social col-
Gaertner, R., 2015. Pharma 4.0: quality management in the digital age, available laborative decision-making on visit interval and service level in a two-echelon
at: https://www.epmmagazine.com/opinion/quality-management/. (Assessed pharmaceutical supply chain. J. Clean. Prod. 142, 3956–3969.
23 October 2015). Nematollahi, M., Hosseini-Motlagh, S.M., Ignatius, J., Goh, M., Nia, M.S., 2018. Coordi-
Gernaey, K.V., Cervera-Padrell, A.E., Woodley, J.M., 2012. A perspective on PSE in nating a socially responsible pharmaceutical supply chain under periodic review
pharmaceutical process development and innovation. Comput. Chem. Eng. 42, replenishment policies. J. Clean. Prod. 172, 2876–2891.
15–29. Norman, J., Madurawe, R.D., Moore, C.M., Khan, M.A., Khairuzzaman, A., 2017. A new
Govindan, K., Soleimani, H., 2017. A review of reverse logistics and closed-loop chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv. Drug
supply chains. J. Clean. Prod. 142, 371–384. Deliv. Rev. 108, 39–50.
Goole, J., Amighi, K., 2016. 3D printing in pharmaceutics: A new tool for designing Oruezabala, G., Rico, J.C., 2012. The impact of sustainable public procurement on
customized drug delivery systems. Int. J. Pharm. 499 (1-2), 376–394. supplier management—the case of French public hospitals. Ind. Market. Manage.
Gualandris, J., Kalchschmidt, M., 2014. Customer pressure and innovativeness: their 41 (4), 573–580.
role in sustainable supply chain management. J. Purchas. Supply Manage. 20 (2), Prause, G., 2015. Sustainable business models and structures for industry 4.0. J. Secur.
92–103. Sustain. Issues 5 (2), 159–169.
HSPL, 2011. Health services purchasing & logistics (HSPL) booklet. Finance, Procure- Qin, J., Liu, Y., Grosvenor, R., 2016. A categorical framework of manufacturing for
ment & Legal Services Division. Queensland Health, 1–23. industry 4.0 and beyond. Procedia Cirp 52, 173–178.
Hermann, M., Pentek, T., Otto, B., 2016. January. Design principles for industrie Rahman, S., Subramanian, N., 2012. Factors for implementing end-of-life computer
4.0 scenarios. In: In System Sciences (HICSS), 2016 49th Hawaii International recycling operations in reverse supply chains. Int. J. Prod. Econ. 140 (1), 239–248.
Conference on, IEEE, pp. 3928–3937. Raju, G., Sarkar, P., Singla, E., Singh, H., Sharma, R.K., 2016. Comparison of environ-
Herwig, C., 2017. A holistic approach to support production control from industry mental sustainability of pharmaceutical packaging. Perspect. Sci. 8, 683–685.
4.0 to pharma 4.0. Pharm. Eng. 37 (3), 44–49. Roschangar, F., Colberg, J., Dunn, P.J., Gallou, F., Hayler, J.D., Koenig, S.G., Kopach, M.E.,
Hofmann, E., Rüsch, M., 2017. Industry 4.0 and the current status as well as future Leahy, D.K., Mergelsberg, I., Tucker, J.L., Sheldon, R.A., 2017. A deeper shade of
prospects on logistics. Comput. Ind. 89, 23–34. green: inspiring sustainable drug manufacturing. Green Chem. 19 (1), 281–285.
Hunter, T.S., Droege, M., Marsh, W.A., Droege, W.L., 2005. Effectively managing phar- Rossetti, C.L., Handfield, R., Dooley, K.J., 2011. Forces, trends, and decisions in phar-
maceutical returns and waste. Drug Top. 149 (2), 36–43. maceutical supply chain management. Int. J. Phys. Distrib. Logist. Manage. 41
ICH, 2009. International conference on harmonisation of technical requirements (6), 601–622.
for registration of pharmaceuticals for human use ICH Harmonised Tripartite Savage, C.J., Roberts, K.J., Wang, X.Z., 2006. A holistic analysis of pharmaceuti-
Guideline, Pharmaceutical Development, available at: https://www.ich.org/ cal manufacturing and distribution: are conventional supply chain techniques
fileadmin/Public Web Site/ICH Products/Guidelines/Quality/Q8 R1/Step4/Q8 appropriate? Pharm. Eng. 26 (4), 1–8.
R2 Guideline.pdf. (Assessed August 2009). Schneider, J.L., Wilson, A., Rosenbeck, J.M., 2010. Pharmaceutical companies and
Jaberidoost, M., Nikfar, S., Abdollahiasl, A., Dinarvand, R., 2013. Pharmaceutical sup- sustainability: an analysis of corporate reporting. Benchmark.: Int. J. 17 (3),
ply chain risks: a systematic review. DARU J. Pharm. Sci. 21 (1), p.1. 421–434.
Kabir, M.I., 2013. Reverse logistics in pharmaceutical industry. Int. J. Supply Chain Schaber, S.D., Gerogiorgis, D.I., Ramachandran, R., Evans, J.M., Barton, P.I., Trout, B.L.,
Manage. 2 (1). 2011. Economic analysis of integrated continuous and batch pharmaceutical
Kadlec, P., Gabrys, B., Strandt, S., 2009. Data-driven soft sensors in the process indus- manufacturing: a case study. Ind. Eng. Chem. Res. 50 (17), 10083–10092.
try. Comput. Chem. Eng. 33 (4), 795–814. Seuring, S., Müller, M., 2008. From a literature review to a conceptual framework for
Klatte, S., Schaefer, H.C., Hempel, M., 2017. Pharmaceuticals in the environment—a sustainable supply chain management. J. Clean. Prod. 16 (15), 1699–1710.
short review on options to minimize the exposure of humans, animals and Song, M., Du, Q., Zhu, Q., 2017. A theoretical method of environmental performance
ecosystems. Sustain. Chem. Pharm. 5, 61–66. evaluation in the context of big data. Prod. Plann. Control 28 (11–12), 976–984.
Kolotzek, C., Helbig, C., Thorenz, A., Reller, A., Tuma, A., 2018. A company-oriented Sreekanth, K., Gupta, N.V., Raghunandan, H.V., Kashyap, U.N., 2014. A review on
model for the assessment of raw material supply risks: environmental impact managing of pharmaceutical waste in industry. Int. J. PharmTech Res. 6 (3),
and social implications. J. Clean. Prod. 176, 566–580. 899–907.
Kongar, E., Haznedaroglu, E., Abdelghany, O., Bahtiyar, M.O., 2015. A novel IT infras- Stegemann, S., 2016. The future of pharmaceutical manufacturing in the context of
tructure for reverse logistics operations of end-of-life pharmaceutical products. the scientific, social: technological and economic evolution. Eur. J. Pharm. Sci.
Inf. Technol. Manage. 16 (1), 51–65. 90, 8–13.
Kreisberg, J., 2007. Green pharmacy: preventing pollution, a cross sector approach. Stock, T., Seliger, G., 2016. Opportunities of sustainable manufacturing in industry
J. Ecolog. Sustain. Med., 25–29. 4.0. Procedia Cirp 40, 536–541.
Kumar, S., DeGroot, R.A., Choe, D., 2008. Rx for smart hospital purchasing decisions: Susarla, N., Karimi, I.A., 2012. Integrated supply chain planning for multinational
the impact of package design within US hospital supply chain. Int. J. Phys. Distrib. pharmaceutical enterprises. Comp. Chem. Eng. 42, 168–177.
Logist. Manage. 38 (8), 601–615. Tiwari, S., Wee, H.M., Daryanto, Y., 2018. Big data analytics in supply chain man-
Kumar, S., Dieveney, E., Dieveney, A., 2009. Reverse logistic process control measures agement between 2010 and 2016: insights to industries. Comput. Ind. Eng. 115,
for the pharmaceutical industry supply chain. Int. J. Prod. Perf. Manage. 58 (2), 319–330.
188–204. Tjahjono, B., Esplugues, C., Ares, E., Pelaez, G., 2017. What does industry 4.0 mean to
Kwateng, K.O., Debrah, B., Parker, D.V., Owusu, R.N., Prempeh, H., 2014. Reverse supply chain? Procedia Manuf. 13, 1175–1182.
logistics practices in pharmaceutical manufacturing industry: experiences from Touboulic, A., Walker, H., 2015. Theories in sustainable supply chain management: a
Ghana. Glob. J. Bus. Res. 8 (5), 17–24. structured literature review. Int. J. Phys. Distrib. Logist. Manage. 45 (1/2), 16–42.
Larsson, D.J., Fick, J., 2009. Transparency throughout the production chain—a way Trappey, A.J., Trappey, C.V., Fan, C.Y., Hsu, A.P., Li, X.K., Lee, I.J., 2017. IoT patent
to reduce pollution from the manufacturing of pharmaceuticals? Regul. Toxicol. roadmap for smart logistic service provision in the context of Industry 4. 0. J.
Pharmacol. 53 (3), 161–163. Chin. Instit. Eng. 40 (7), 593–602.
Lee, S.L., O’Connor, T.F., Yang, X., Cruz, C.N., Chatterjee, S., Madurawe, R.D., Moore, US Food and Drug Administration (FDA), 2004. PAT guideline, available at:
C.M., Lawrence, X.Y., Woodcock, J., 2015. Modernizing pharmaceutical manufac- https://www.fda.gov/downloads/drugs/guidances/ucm070305.pdf. (Assessed
turing: from batch to continuous production. J. Pharm. Innov. 10 (3), 191–199. September 2004).
130 B. Ding / Process Safety and Environmental Protection 119 (2018) 115–130

Vatovec, C., Senier, L., Bell, M., 2013. An ecological perspective on medical care: Xie, Y., Breen, L., 2014. Who cares wins? A comparative analysis of household waste
environmental, occupational, and public health impacts of medical supply and medicines and batteries reverse logistics systems: the case of the NHS (UK).
pharmaceutical chains. EcoHealth 10 (3), 257–267. Supply Chain Manage.: Int. J. 19 (4), 455–474.
Veal, G.J., Mouzas, S., 2011. Changing the rules of the game: business responses to Yawar, S.A., Seuring, S., 2017. Management of social issues in supply chains: a liter-
new regulation. Ind. Market. Manage. 40 (2), 290–300. ature review exploring social issues, actions and performance outcomes. J. Bus.
Wagner, T., Herrmann, C., Thiede, S., 2017. Industry 4.0 impacts on lean production Ethics 141 (3), 621–643.
systems. Procedia CIRP 63, 125–131. Yu, X., Kopcha, M., 2017. The future of pharmaceutical quality and the path to get
Waibel, M.W., Steenkamp, L.P., Moloko, N., Oosthuizen, G.A., 2017. Investigating the there. Int. J. Pharm. 528 (2017), 354–359.
effects of smart production systems on sustainability elements. Procedia Manuf. Zahiri, B., Zhuang, J., Mohammadi, M., 2017. Toward an integrated sustainable-
8, 731–737. resilient supply chain: a pharmaceutical case study. Transp. Res. Part E: Logist.
Wang, G., Gunasekaran, A., Ngai, E.W., Papadopoulos, T., 2016. Big data analytics in Transp. Rev. 103, 109–142.
logistics and supply chain management: certain investigations for research and Zhang, M., Pawar, K.S., Bhardwaj, S., 2017. Improving supply chain social responsi-
applications. Int. J. Prod. Econ. 176, 98–110. bility through supplier development. Prod. Plann. Control, 1–12.
Weraikat, D., Zanjani, M.K., Lehoux, N., 2016a. Two-echelon pharmaceutical reverse Zhao, R., Liu, Y., Zhang, N., Huang, T., 2017. An optimization model for green supply
supply chain coordination with customers incentives. Int. J. Prod. Econ. 176, chain management by using a big data analytic approach. J. Clean. Prod. 142,
41–52. 1085–1097.
Weraikat, D., Zanjani, M.K., Lehoux, N., 2016b. Coordinating a green reverse supply Zhong, R.Y., Newman, S.T., Huang, G.Q., Lan, S., 2016. Big data for supply chain man-
chain in pharmaceutical sector by negotiation. Comput. Ind. Eng. 93, 67–77. agement in the service and manufacturing sectors: challenges, opportunities,
Witkowski, K., 2017. Internet of things, big data, industry 4. 0—innovative solutions and future perspectives. Comput. Ind. Eng. 101, 572–591.
in logistics and supply chains management. Procedia Eng. 182, 763–769. Zhong, R.Y., Xu, X., Klotz, E., Newman, S.T., 2017. Intelligent manufacturing in the
Xie, Y., Breen, L., 2012. Greening community pharmaceutical supply chain in UK: a context of industry 4.0: a review. Engineering 3 (5), 616–630.
cross boundary approach. Supply Chain Manage.: Int. J. 17 (1), 40–53.