Computers & Industrial Engineering 129 (2019) 354–367

Contents lists available at ScienceDirect

Computers & Industrial Engineering

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

A model-based decision support framework for the optimisation of T

production planning in the biopharmaceutical industry
Miguel Vieira, Tânia Pinto-Varela , Ana P. Barbosa-Póvoa
⁎

CEG–IST, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal

ARTICLE INFO ABSTRACT

Keywords: The enterprise management of current industrial processes has becoming increasingly complex, imposing novel
Decision support challenges to the implementation of efficient decision support tools. Manual-based planning/scheduling systems
Optimisation model have been replaced by integrated computational tools for core business processes, often in real-time, to enable a
Production and maintenance planning collaborative platform for the control and analysis of information. Despite the advances in process modelling, the
Biopharmaceutical industry
implementation of optimisation support has been fairly discussed on how to improve industrial competitiveness
and responsiveness to market variability while addressing different profitability criteria. In this work, we discuss
a proof-of-concept implementation prototype of a model-based decision support tool for the production and
maintenance planning optimisation in a biopharmaceutical industrial case – ICOMPASS, defining its application
framework for a successful deployment in a real production environment.

1. Introduction
The dynamic structure of most production systems requires the as-
sessment of different business factors for the majority of strategic and
operational decisions (Varma, Reklaitis, Blau, & Pekny, 2007). In par-
ticular, production planning activities have been striving for the im-
provement of operational efficiency to deal with the multiple process
constraints and market competition. With the digital transformation of
current facilities, companies have adopted the use of process automa-
tion technologies that enable an enhanced control of tasks parameters
and access to on-line operational data. These capabilities unveiled an
opportunity to potentiate its use to support decision-making, providing
the replacement of inefficient manual spreadsheets with advanced
analytical tools. As reviewed by Harjunkoski et al. (2014), model-based
methodologies have been successfully applied to industrial problems to
address the optimisation of multiple operational criteria. But despite
the major research advances in modelling approaches towards the in-
dustrial complexity, the ability to implement optimisation methodolo-
gies in decision-making faces significant challenges with insufficient
discussion among research works. An effective decision support tool
needs to consider, for example, the process network interconnectivity,
the operational uncertainty and the computational performance, al-
lowing the decision-maker to evaluate the quality of solutions ac-
cording to strategic options. However, as noted by Figueira et al.
(2015), most industrial systems still tend to focus on simplistic models
and heuristics, often leading to sub-optimal solutions with time-con-
suming procedures and subject to the decision maker expertise.
With the systematisation of industrial optimisation problems, sev-
eral research contributions have targeted industrial problems related to
supply-chain networks, energy demand, process design regulations,
social impact or environmental load, by exploring different approaches
to explore the solutions’ space rapidly, reduce uncertainty and make
better, faster and safer decisions (Barbosa-Póvoa, 2012; Castro,
Grossmann, Veldhuizen, & Esplin, 2014; Grossmann, 2012; Maravelias,
2012; Méndez, Cerdá, Grossmann, Harjunkoski, & Fahl, 2006). One of
the main research fields relies in industrial planning and scheduling
optimisation, where major achievements include exact (LP, MILP and
MINLP), non-exact (meta/heuristics, evolutionary algorithms and arti-
ficial intelligence methods) and simulation-optimisation approaches.
Some methodologies tackle the uncertainty associated with operational
parameters by introducing stochastic optimisation, allowing decisions
to occur at points in time driven from previous outcomes. However,
most of these cases tend to focus on the modelling point of view and
disregards the implementation challenges as a decision support appli-
cation. For example, several issues arise on how to structure the in-
dustrial planning and scheduling decisions into a functional operational
system. The reference to protocols as ISA-95 has provided as interna-
tional standard for the interactions of the different information layers in

⁎
Corresponding author at: CEG–IST, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal.
E-mail addresses: migueljvieira@tecnico.ulisboa.pt (M. Vieira), tania.pinto.varela@tecnico.ulisboa.pt (T. Pinto-Varela),
apovoa@tecnico.ulisboa.pt (A.P. Barbosa-Póvoa).

https://doi.org/10.1016/j.cie.2019.01.045
Received 15 September 2017; Received in revised form 11 May 2018; Accepted 22 January 2019
Available online 25 January 2019
0360-8352/ © 2019 Elsevier Ltd. All rights reserved.
M. Vieira et al. Computers & Industrial Engineering 129 (2019) 354–367

4 - Establishing the basic plant schedule – production,

material use,delivery and shipping. Determining inventory
levels
Time Frame: Months, weeks, days

3 -Workflow/ recipe control to produce the desired end-

products. Maintaining record and optimising the
production process
Time Frame: Days, shifts, hours, minutes, seconds

2 - Monitoring, supervision control and automated control

of production process
Time Frame: Hours, minutes, seconds, subseconds
1 - Sensing the production process,manipulating the
production process
0 - The actual production process

Fig. 1. Hierarchical automation pyramid (ANSI/ISA-95).

automated interfaces between enterprise and control systems (ANSI/
ISA-95.00.01-2000, 2000). As shown in Fig. 1, the referential hier-
archical automation pyramid considers the bottom levels composed by
the monitoring control systems/sensors, followed by the manufacturing
execution system (MES) which deals with more advanced production
controls and models, while the top the pyramid drives the long-term
strategic and tactical business decisions of the supply chain manage-
ment based on enterprise resource planning (ERP). And, although the
integration proposed by the standardised automation pyramid may not
work on in all environments, it can provide a general structure for
successful implementations.
Some successful implementations in process industries can provide
relevant inputs for the development of a framework solution approach:
the studies by Janak, Floudas, Kallrath, and Vormbrock (2006) and
Shaik, Floudas, Kallrath, and Pitz (2009) discussed a model approach to
the scheduling problems involving recipes for hundreds of products and
pieces of equipment in a large-scale chemical process, either involving
batch and continuous processes, to be used in a daily basis for an effi-
cient medium-term utilisation of the main equipment units; Wassick
(2009) and Wassick and Ferrio (2011) presented an integrated chemical
case analysing different optimisation problems related to production
planning, energy scheduling, plant design and waste treatment sche-
duling, proposing a solution tool that resulted in a significant reduction
on scheduling related shutdowns, reduction of third party drumming
providers and improved customer level; Choy, Leung, Chow, Poon, and
Kwok (2011) proposed a simulation-optimisation support on make-to-
order scheduling problems in the mould industry, improving opera-
tional functions by reducing the time in performing tasks and number of
late projects; Pehrsson, Ng, and Stockton (2013) developed a decision
support methodology combining production engineering data, financial
data and optimisation technology applied to an automotive production
system with improved investment solutions; Vieira, Pinto-Varela and
Barbosa-Póvoa (2015) presented an model-based optimisation case in
the paint industry for the production scheduling improvement, pro-
viding the decision maker with the workload capacity for a given de-
mand plan, which proved relevant to study the requirements of tem-
porary workforce according to the production demand variability
throughout the year; Figueira et al. (2015) developed a model-based
decision support system for the planning and scheduling activities of a
pulp and paper mill company to generate plans with different levels of
customization; Eberle et al. (2016) suggested a model solution for the
optimisation scheduling of a liquid-drug pharmaceutical process by
established planning horizons for real commercial productions with a
potential reduction of makespan when compared to standard expert
schedules; and Dehghanimohammadabadi, Keyser, and Cheraghi
(2017) developed an effective optimisation based simulation frame-
work for manufacturing processes allowing to reduce the problem
complexity resulting in better performance measures of scheduling
strategies. Some of these support tools presented practical interfaces
using the capabilities of common spreadsheet/database software (e.g.
MS Excel) and optimisation solvers with new integration approaches of
ERP systems. For example, to extract production orders and launch the
optimisation model on a remote server, and then allowing the scheduler
to make final adjustments in the solution. Other tools can be found in
commercial software like ABB CPM P&P Suite for a pulp and paper
plant, that offers a collaborative solution able to manage most planning
tasks (order planning, trimming, quality, delivery planning, asset
management, etc.) for the improvement of the overall efficiency of the
plant.
In this work, we assess the implementation of a proof-of-concept
model-based decision support systems in the operational management
of biopharmaceutical industrial processes, to our knowledge, not yet
addressed in literature. Following a systematic approach towards the
optimisation of industrial planning problems, the discussion is focused
on the core decision-making characteristics of industrial processes,
considering the guidelines for an analytical model approach to the
planning problem optimisation, and addresses the application chal-
lenges of real production environments with a prototype interface of a
decision support tool ICOMPASS. The structure of this paper starts with
the discussion of the applicability of planning/scheduling decision
support solutions and its industrial deployment challenges in Section 2.
Based on that, in Section 3 we discuss the decision support framework
applied to the biopharmaceutical planning problem, exploring the in-
dustrial requirements by extending a model of the literature and de-
fining the decision-making process. This solution approach is illustrated
with the development of an application tool applied to an industrial

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M. Vieira et al.
case in Section 4; finally, in Section 5 is summarized the advantages of
the decision support system and the directions for further improve-
ments.
2. Decision-support implementation
The development of highly automated operational control has en-
abled the digital transformation of industrial processes with the in-
tegration of advanced decision support systems (Biel & Glock, 2016;
Kallestrup, Lynge, Akkerman, & Oddsdottir, 2014; Ngai, Peng,
Alexander, & Moon, 2014). In concept, these systems involve a human-
computer interaction with the knowledge/experience held by the pro-
cess stakeholders, structured in a way that a model-based methodology
provides the information to managers decide the best solution for a
complex problem. Shim et al. (2002), Power and Sharda (2007) and
Stephanopoulos and Reklaitis (2011) have reviewed the evolution of
functionalities and applications for decision support systems using
flexible infrastructures for the data acquisition/processing, decision
analysis, mathematical optimisation and simulation technologies,
identifying behavioural/technical issues with impact in its performance
and adoption. But, as also noted as Harjunkoski et al. (2014), one of
main challenges for its application in industrial optimisation relies on
the deployability issues. These authors discussed the importance, in one
hand, of the role of the production scheduler towards the conflicting
organisation goals and the reliability of information available, and on
the other hand, the planning impact induced by day-to-day disruptions
from the supply-chain, manufacturing and logistics functions (e.g. rush
orders, late deliveries, equipment breakdown, economics variability,
etc.), demanding an ongoing monitor, negotiations and adjustments of
the schedule. With this wide variability in process metrics, it is re-
cognised that if the information flow could be computerized, then each
decision could rely less on the scheduler’s expertise. But acknowledging
that a fully automated decision process is unreasonable for the majority
of industrial problems, an accurate evaluation of the impact of the
improved planning/scheduling results is crucial to establish the align-
ment and commitment of all stakeholders. Therefore, with a proof-of-
concept study it is be possible to approach each industrial problem
specifications and, based in the previous reviewed examples, follow
some key guidelines for a successful industrial application development
and implementation:
• The modelling approach should be flexible to accommodate dif-
ferent decisional problems and generic enough to integrate several
information sources to improve data quality and control, exploiting
particular problem specifications for computational efficiency;
• The scheduler requirements should be the main focus of the solution
provided, allowing an effective user interface control of inputs
modifications, data processing, schedule manipulations, and gra-
phical visualisation (e.g. Gantt chart) with KPI trends analysis or
reporting, which could be easily recognisable as an enhancement to
their current job;
• Amid the scheduler assumption of the constraints contingencies of
the problem, the solution must be robust, scalable, and stable (with
at least a coherent feasible solution reported), allowing the possi-
bility to efficiently generate new adjusted solutions reactive to
process disturbances;
• The solution should be easily integrated and maintainable with in-
dustrial software platforms (e.g. ERP-software and plant control
systems), representing a good return-on-investment on the hard-
ware/software structure deployment costs and license fees.
Concerning the IT infrastructure requirements and the commercial
considerations for a decision support tool, the architecture for an
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Computers & Industrial Engineering 129 (2019) 354–367
Fig. 2. IT application architecture.
application concept should include (Fig. 2): (i) an interface environ-
ment for the problem formulation/representation and analysis of so-
lution results, (ii) a database spreadsheet for the input parameters
processing and platform for generated data, and (iii) a processing
modelling system for the optimisation model and solver. The mathe-
matical models are commonly expressed in an equation form (typically
MILP models, or MINLP when considering explicit nonlinearities)
which allows to be easily implemented in commercial modelling sys-
tems like AMPL, GAMS or ILOG, that runs optimisation proprietary
solvers such as CPLEX, XPRESS or BARON. Furthermore, these model-
ling systems offer the interface with spreadsheets, database or graphics
packages in common MS Office environments, facilitating the deploy-
ment of a user interface to be managed by non-specialists. Finally, the
selected applications must have a compatible application programming
interface (API) with the protocols for the developed software integra-
tion and connectivity of components. As well, recognising the techno-
logical advances in computer network security, cloud-based server
systems can reduce the implementation investment. For example,
considering an in-house database platform that communicates with the
modelling environment (via an API) to define/validate the optimisation
problem, then submitting the data commands/conditions to centralized
hosted servers which generates the solution with the solver (con-
sidering a predefined solution termination/convergence criteria), and
connects the output results in the form of raw data to the database for
further analysis and graphical display (subject to pre- and pos-proces-
sing data architecture).
With a reasonable number of commercial software for industrial
planning/scheduling support suited for the process industry (e.g.
aspenONE PM&E, SuperPro Designer, BioSolve Process, etc.), some
decision support tools can also be found as extension packages in
common business planning software, such as SAP or Oracle systems.
However, certain issues can be identified upon the quality and accuracy
of the solution provided, since most systems rely on heuristic ap-
proaches which often lead to sub-optimality, as well as to the suitability
extent of its functionalities to the problem case. The system integration
with the technology of the process enhances the flow of information
across the hierarchical functions, but the analysis, control, revision and
translation of that data for an effective decision support requires par-
ticular attention performed by a decision manager. With regard to the
complexity of the industrial problem, its on-site implementation could
require a timeline of several months, concerning the requirements
analysis of process specifications, the system design/development with
M. Vieira et al.
validation/testing, and its installation with the necessary training and
operation.
2.1. Bio/pharmaceutical planning optimisation challenges
The pharmaceutical industry has been the scope for several en-
terprise optimisation studies due to the strong competition among
manufacturers and its process network complexity (Shah, 2004). The
research field on applied optimisation methodologies spreads from the
management of drug development portfolio pipelines (e.g. SimBio-
pharma prototype decision support tool proposed by Farid, Washbrook,
and Titchener-Hooker (2007)) to the cost-effective design of specific
steps of the manufacturing process (e.g. processing optimisation of
bioreactor and chromatography sizing strategies by Liu, Farid, and
Papageorgiou (2016)). In particular, the collaboration between aca-
demia and industry has promoted the development of multiple mod-
elling approaches for the optimisation of planning/scheduling solutions
in real pharmaceutical plants (Kopanos, Méndez, & Puigjaner, 2010;
Stefansson, Sigmarsdottir, Jensson, & Shah, 2011). As examples, Moniz,
Barbosa-Povoa, and de Sousa (2014) proposed a unified scheduling
methodology based in a discrete-time optimisation model for an in-
tegrated decision support solution in a chemical-based pharmaceutical
industry, while Costa (2015) presented a metaheuristic optimisation
engine embedded in a production scheduler for medium-term forecast
analysis applied to lyophilised drug manufacturing processes.
Despite the dominance of chemical-pharmaceutical cases, the pro-
duction of highly effective bio-based drugs (e.g. cell or gene therapies,
therapeutic proteins hormones, monoclonal antibodies, cytokines and
tissue growth factors) have defined new modelling challenges, either to
address the strict process regulatory policies on products storage shelf-
life and biological variability, or with the operational equipment
compliance to product quality. In fact, each production step requires a
legal validation by the regulatory authority, subject to the control and
supervision of government agencies such as EMA (European Medicines
Agency) and FDA (US Food and Drug Administration). These autho-
rities establish documented evidence to assure a consistent production
according to the pre-determined specifications and quality attributes,
imposing a set of regulations to comply with Good Manufacturing
Practices (GMP). Regarding planning/scheduling optimisation appli-
cations, it is acknowledged that only a short number of literature re-
search is dedicated to modelling formulations to address biopharma-
ceutical production constraints, from the optimal capacity planning to
campaign-lots scheduling with maintenance integration (Eberle et al.,
2016; Kabra, Shaik, & Rathore, 2013; Lakhdar, Zhou, Savery, Titchener-
Hooker, & Papageorgiou, 2005; Liu, Yahia, & Papageorgiou, 2014;
Shaik, Dhakre, Rathore, & Patil, 2014; Siganporia, Ghosh, Daszkowski,
Papageorgiou, & Farid, 2014; Vieira, Pinto-Varela, Moniz, Barbosa-
Póvoa, & Papageorgiou, 2016; Vieira, Pinto-Varela, & Barbosa-Póvoa,
2017b). However, the work by Leachman, Johnston, Li, and Shen
(2014) is one of the few that developed a database and optimisation
application engine for the supply chain planning of a real biopharma-
ceutical company, generating the batch processing schedule for each
production facility and finished (single) product availability, according
to demand regulations of the different markets. As noted by the author,
the structure of most biopharmaceutical facilities tends to be small in
comparison to typical chemical-pharmaceutical plants, since many
plants are only dedicated to one product to control cross-contamination
and storage regulations. However, it has been verified a steady growth
in this sector following the clinical success revenues with the devel-
opment of new biologic drugs and biosimilars (Otto, Santagostino, &
Schrader, 2014). Significant investments are also required in manu-
facturing technologies (batch or continuous operation) to enhance the
process control of each stage and comply to rigorous quality testing,
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Computers & Industrial Engineering 129 (2019) 354–367
which commonly dominates the processing cycle time (e.g. a purifica-
tion stage, following the active biological ingredient fermentation
harvest, can take 2–3 days while quality control 3–4 weeks). With such
multiple constraints arising from the complexity of biopharmaceutical
manufacturing, the optimisation approach to these problems should
assess the overall structure of a novel decision support tool to provide
valuable, flexible and efficient solutions for an industrial production
scale.
3. Solution framework
Considering the application case to the biopharmaceutical industry,
the development framework for a decision support system is now dis-
cussed for the planning optimisation of the production process. Based in
the methodology proposed by Moniz, Barbosa-Povoa, de Sousa, and
Duarte (2014), this framework can be designed under three compo-
nents, depicted in Fig. 3: the first is related to the definition of the
problem structure, providing the components of the decision-making
and the processing of the operational data for the optimisation model;
secondly, the optimisation component defines the modelling approach
to generate the solutions set for the given problem; and finally, the
analysis of solutions via an user-interface provides the interactive
procedure to support the decision taken. This framework structure
discusses a generic approach to industrial planning/scheduling pro-
blems in order to allow a flexible adaptation to different problem cases.
For the defined scope, the detail of the different components will allow
the definition of an integrated electronic decision support tools suitable
for the problem specificities of biopharmaceutical production, named as
ICOMPASS.
3.1. Problem structure
The problem structure addresses not only the definition of the in-
dustrial process network but foremost the definition of the essential
objectives to the decision-making. In particular, it should be able to
integrate the different types of knowledge and evolve according to the
decision process complexity. Understandably, the increasing problem
complexity leads to the discussion on how to solve large scale industrial
cases, to which the computational restrictions for the mathematical
optimisation are a known topic (Méndez et al., 2006). In order to ad-
dress the flexibility and scalability of problem representations, several
advantages were identified with the development of model re-
presentation based in general networks. As reviewed by Harjunkoski
et al. (2014), numerous examples of State-Task Network (STN) (Kondili,
Pantelides, & Sargent, 1993) and Resource-Task Network (RTN)
(Pantelides, 1994) representations applied to planning/scheduling
problems can be found in literature, exploring different modelling scale
configurations with integrated operational decisions (e.g. plant/process
design). The general network structure of a production process enables
the required trade-off between the required detail of the optimal solu-
tions and the computational intractability of the problem. And the in-
dustrial collaboration becomes essential to improve the development of
such optimisation approaches, supporting the structure of how the data
is generated and related decisions are made at the production en-
vironment.
For our approach, the problem consists in determine the optimal
production planning of an arbitrary process network of a biopharma-
ceutical process, addressing the campaign plan of batch and/or con-
tinuous process steps, multiple intermediate deliveries, sequence de-
pendent changeovers operations, product storage restricted to shelf-life
limitations, the track-control of the campaign lots due to regulatory
policies, and the maintenance requirements of equipment subject to
performance decay. The manufacturing process is commonly refereed
M. Vieira et al.
Fig. 3. Structure of the planning framework methodology based in Moniz et al. (2014b).
as two-stages: biological raw-materials undergo upstream cell-fermen-
tation to produce the intermediate active biological ingredient, fol-
lowed by downstream purification and stabilisation processing to ob-
tain the final product. The final product is later labelled/packaged and
shipped to retail distributors/consumers. Since each bioprocess stage
involves multiple sequential steps with long processing times, the main
optimisation decisions are usually focused on the campaign size, allo-
cation and sequencing for each aggregated upstream/downstream
suite, as proposed by Lakhdar et al. (2005). This aggregated approach
considers problems with 1–2 years horizons, which are typically de-
fined as medium-term planning. However, the problem formulation
should enable the possibility to consider any problem configuration, for
example, the short-term scheduling of a more task detailed sequence to
match the planning supplies. The definition of a standard representa-
tion is of key importance for this problem adaptability, as the RTN that
addresses all process representations in terms of tasks and resources:
each task is defined to consume and/or produce resources, either ma-
terials, utilities or equipment, constrained through a given set of pro-
cess parameters. And, while considering a given demand plan and all
the process data, the set of equipment resources available is allocated to
perform the corresponding process tasks, subject to an objective func-
tion. The decision-maker should then be able to draw different sce-
narios and analyse key performance indicators (KPI) of the problem
solution, as well as to provide the ability to generate new solutions
when process data or demand is revised. Thus, for each problem case,
the goal is to determine the optimal solution for the task-unit assign-
ment and sequencing, sequence dependent changeover/set-up, the
temporary storage allocation, produced campaign lots, sales/late de-
liveries and maintenance tasks schedule of process units, given:
(i) the product recipes in terms of their respective RTN framework;
(ii) the time horizon, product demands and due dates;
(iii) the characteristics of the processing/storage units allocated and
sequence-dependent changeover/setup times;
(iv) processing times and the task-unit suitability;
(v) the shelf-life storage of intermediaries/products;
(vi) the manufacturing, changeover and storage costs for all materials,
the value of the products, and late delivery penalties;
(vii) the duration and cost of maintenance operation, with information
of the decaying yield with the number of batches produced of the
corresponding process unit.
Finally, the objective function can be defined according to the
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Computers & Industrial Engineering 129 (2019) 354–367
decision targets, with some objective functions modelled to allow dif-
ferent solution analysis, being the most common the production profit
maximisation of the process operation.
3.2. Optimisation methodology
The development of a mathematical optimisation approach implies
the identification of the characteristics of the industrial problem in
order to formulate the constraints of the process. However, the com-
binatorial nature of these planning/scheduling problems quickly esca-
lades with the binary decisions of task-lot-unit assignment and se-
quencing, storage or sequence-dependent changeovers tasks. For
problems considering a significant number of processing units for long
time horizons tend to be difficult to solve by exact methods, being
necessary to resort to decomposition techniques or heuristic approaches
to obtain a satisfactory solution in a reasonable time. This enables the
wide research on multiple models and solutions required to fit the re-
quirements of the decision-making process and its suitability to the
scope of the industrial problems (Grossmann, 2005).
With the definition of the problem structure, the model develop-
ment could test different mathematical approaches, constraints or ob-
jective functions to ensure solutions feasibility. As noted by Moniz,
Barbosa-Povoa, de Sousa, and Duarte (2014), in the periodic planning
of real manufacturing environments, the optimisation system is highly
relevant for rescheduling purposes, since, at every time point, is ex-
pected that some processing units are under operation with allocated
production orders. So, the disturbance of new orders arrival could
justify the revision of current plans or evaluate operational alternatives.
The model responsiveness should provide the decision-maker a com-
parison and analysis of solutions, as well as relevant KPI computed at
the post-processing phase. Moreover, multi-objective approach method
(e.g. augmented ε-constraint method by Mavrotas, 2009) can also be
implemented to analyse Pareto sets according to strategic process in-
dicators, providing a useful insight on how the production reacts to
changes in each criterion (Korošec, Bole, & Papa, 2013; Vieira, Pinto-
Varela, & Barbosa-Póvoa, 2017a).
With a preliminary study of a model approaches suitable to the
industrial problem, we have researched in the literature a MILP for-
mulation to address the main bioprocess constrains. Noteworthy, the
lead work by Lakhdar et al. (2005) firstly proposed a discrete- time
MILP model for the optimal production and cost effective sequence of
manufacturing tasks for a medium term horizon, underlining the ad-
vantages of planning optimisation for industrial practices. More
M. Vieira et al. Computers & Industrial Engineering 129 (2019) 354–367

recently, Kabra et al. (2013) developed a multiple-grid continuous-time 3.2.1. Resources balance constraints
model for multi-product campaign scheduling of biopharmaceutical Regarding the resources constraints given by Eqs. (1)–(7), the
processes based on State Task Network (STN) framework and Liu et al. availability in each time event t considers the amount available in the
(2014) later proposed the simultaneous production and maintenance previous event adjusted by the amounts discretely or continuously
planning under a performance decay by extending Lakhdar et al. (2005) consumed/produced by all tasks starting or ending on that event. By
discrete time model. Both these models were compared in the recent considering that in each step could exist equipment technology options
work by Vieira et al. (2017b), which have discussed the advantages of a with either batch and continuous operation modes, it is necessary to
continuous-time single-grid formulation in an integrated production assure the correct task sequencing of the corresponding batch and
and maintenance planning of processes under performance decay, with continuous tasks in consecutive time intervals given by the optimisation
improved planning solutions applied to industrial-based examples. The solution. Following the same reasoning discussed by Vieira et al.
proposed model now extends the formulation by Vieira et al. (2017b) to (2016), along with the set of continuous tasks which consumes an in-
address process steps with either batch and continuous operation mode, termediate material r produced by both operation modes, IrBCc
, it is now
in order to generalise the multiple technological process equipment necessary to define a subset of continuous tasks that produced the same
possibilities. Therefore, additional terms are introduced in the con- intermediate r in the previous process step, IrHyb
c
, to assure that both
straints to consider either batch Ib and continuous Ic tasks, since the continuous tasks (production/consumption) can occur at the same time
model proposed by Vieira et al. (2017b) assumed that all equipment/ interval [t , t + 1].

Rr , l, t = Rr0, l t =1 + Rr , l, t 1t>1 + Rrp, l, t + Rrc, l, t Wr , l, t + r , l, t r M, l Lr , t T (1)

Rrp, l, t = vp
i Ib i, r i, l, t 1
+ c
i Ic (Ima IrHyb ) i, r i, l, t 1 + i Ima i, r FPi, l, t + c
i IrHyb i, r i, l, t

r M, l Lr , t T (2)

tasks in each process step had a continuous operation mode. This im-
Rrc, l, t = vc + +
plies that the formulation now considers the diverse balance and se- i Ib i, r i, l, t c
i Ic IrBC i , r i, l , t 1 c
i IrBC i, r i, l, t

quencing of these tasks, since batch tasks interact with resources dis- r M B, l Lr , t T (3)
cretely at its start and finish, while continuous tasks flow continuously
at a rate that remains constant throughout its duration. By process
definition, in a batch operation mode the materials are entirely con-
l LBr
Rrc, l, t = l LBr ( vc
i Ib i, r i, l, t
+ c
i Ic IrBC i, r i , l , t 1 + c
i IrBC i , r i, l , t )
r B, t T
sumed at the start of the respective production task, and the amount
(4)

Rr , t = Rr0 + Rr , t 1 + (µi,pr Ni, l, t 1 + µic, r Ni, l, t ) r E, t T

(t = 1) t>1 i Ib Ic l Lr (5)

produced is made available only at its finish. However, in a continuous

0 Rr , l, t Rrmax r M, t H
operation, a production flow rate is verified along the duration of the
l Lr (6)
task, which allows that sequential continuous tasks can occur simulta-
neously. A resume of the mathematical formulation is here presented,
the detailed explanations can be found in the seminal paper. Con- Rr , l, t = 0 t= T
sidering the indices, sets, parameters and variables notation detailed in r M RM l Lr (7)
Appendix A, it should be noted that the main decision variables respects

Tt + 1 Tt i Ib Ic
µirp ( l Li
( i Ni, l, t + i i, l, t |i Ib + i, l, t i
max
|i Ic ) + i Ib Ic i, i )
Ci, i , t + 1 + r MAr , t

r E Est , t T, t |T | (8)

Tt + 1 Tt H 1 ( i Izw Imr l Li )
µi,pr Ni, l, t + i Izw Imr
µi,pr ( l Li
( i Ni, l, t + i i, l, t |i Izw + i, l , t i
min
|i Imr ) + i Izw Imr i, i )
Ci, i , t + 1 + r MAr , t

r E Est , t T, t |T | (9)

the RTN representation given by Ni, l, t (binary) and i, l, t (continuous/ 3.2.2. Timing constraints
integer), respectively related to the occurrence of task i (batch or con- The timing constraints given by Eqs. (8)–(15) considers the duration
tinuous) of lot l in the slot [t , t + 1] of a common time-grid to the of the interval composed by a single processing task (batch or con-
equipment resources. tinuous) per unit plus, the corresponding sequence-dependent change-
over/setup time (feasible connections given by duration parameter i, i )

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or maintenance operations required, and can be bounded when tasks l Lr

( r , l, t ) t T
d Dr
(Yt , d Qr , d ) t T
l Lr
( r , l, t )
are subject to zero-wait policies. The duration of each processing task is t t t <t

related to parameters i, i , for batch tasks, and the processing rates r P, t T, t > 1 (19)
min
, imax for continuous tasks. And considering a set of time events t to (20)
i r , l , t =0 r M P , l Lr , t T
be arbitrary placed in a given horizon H, [T 0, T H ], the allocation of each
multiple due date d is optimised with variable Yt , d .
3.2.5. Operational constraints
Yt , d = 1 d D
The boundaries of each task extent are limited by Eqs. (21) and (22),
t T
t 1 (10) by the capacity of the equipment Vimax
,l in the case of batch tasks, or to a
maximum campaign length Campimax ,l in the case of continuous tasks.
Tt hd Yt , d t T, t 1 Lower bounds can be useful to impose a minimum batch/campaign size
d D (11)
Vimin
, l Ni, l, t i, l, t Vimax
, l Ni, l, t i Ib, l Li , t T, t T (21)
Tt hd Yt , d + H 1 Yt , d t T, t 1 max
Campimin Ni, l, t Campimax max
Ni, l, t i Ic , l Li , t T, t T
d D d D (12) ,l i i , l, t ,l i

(22)
Tt + 1 Tt 1 t T, t T (13)

T1 = T 0 (14) 3.2.6. Sequence-dependent changeover/setup constraints

Eqs. (23)–(26) constraint the sequence of tasks for changeover
TT TH (15)
procedures, considering also the allocation to each task the required
setup time for every new production. The model ability to allocate this
3.2.3. Lot constraints changeover time to the boundary intervals of a time event needs to
Regarding the lots of material resources that are able to be blended/ avoid the overlap of sequential continuous tasks, therefore, this feature
splitted, Eqs. (16) and (17) controls the lot assignment constraints, is only applied to batch process steps and to the first step of a con-
where for a given set of lots, the sequential allocation of lot number tinuous process sequence.

l Li
µi,pr Ni, l, t 1 + l Li
µi p, r Ni , l, t i Ib Ic l Li
t T µi p, r Ni , l, t 1 + µi,pr µip, r Ci, i , t |i Ib Ic
first + µi,pr µip, r Ci, i , t + 1
t t <t t >t
r EEst , i Ib Ic , i Ib Ic , i i, t T , t > 1, t T, t t, t |T| (23)

index l is able to provide the tracking control of each productions

throughout the planning horizon for regulatory protocols.

vi,pr Ni, l, t vi,pr Ni, l 1, t

vip, r Ni , l 1, t
+ i, r Ni, l, t i, r Ni, l 1, t i , r Ni , l 1, t 0
t T i Ib t T t T i Ic t T
t t 1 i i t t t t 1 i i t t
i Ib i Ic

r M RM , i Ib Ic , l Lr , l > 1, t T, t T (16)

p
t T vi, r Ni, l, t + t T i, r Ni, l, t 1
i Ib
t |T|
i Ic
t |T| l Li
µi,pr Ni, l, t i Ib Ic l Li
t T µi p, r Ni , l, t µi,pr Ci, i, t + 1 + µi,pr Ci, i, t |t > 1
t <t
(17)
t>1
r M RM , l Lr
r Esu, i Ib Ic , t T, t |T| (24)

3.2.4. Multiple deliveries constraints i Ib Ic µi,pr µ i p, r Ci, i , t 1

i Ib Ic
Eqs. (18)–(20) considers the total demand profile with corre- i i

sponding due dates per each final product Qr , d , while the amount of r E Est , t T , t > 1, t |T| (25)
production lots delivered r , l, t is balanced with the unmet demand ur , l, t
in each time event t .
µi,pr C 1 r Esu
u u i, i, t
(Yt , d Qr , d) ( r , l, t ) i Ib Ic t T
d Dr l Lr r , l, t l Lr l Lr r , l, t 1
t >1 (26)
r P, t T, t > 1 (18)

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3.2.7. Storage and Shelf-life constraints NMr , t 1 (j 1) + NMrmax ·(1 + MAr , t 1 ABr , j, t ) r Ema, j, t > 1
Eqs. (27)–(35) accounts for the storage and shelf-life constraints, (40)
assessing the general case of a storage task activation in the interval
[t , t + 1] when an excess material of an intermediary/product is verified NMr , t j NMrmax ·(1 ABr , j, t ) r Ema, j, t > 1 (41)
at event t . The amount of material wasted Wr , l, t is determined when
shelf-life is exceeded Si, l, t , t and the corresponding storage tasks are QMr , j, t 2 r Ema, t > 1
j (42)
verified in the interval [t , t ], t > t . The variable x r , l, t is also modelled to
account of a storage time cost penalty in the objective function (Section QMr , j, t ABr , j, t ABr , j 1, t r Ema, j > 1, t > 1 (43)
4.2.9).
QMr , j, t ABr , j 1, t ABr , j, t r Ema, j > 1, t > 1 (44)
Vimin
, l Ni, l, t Rr , l, t Vimax
, l Ni, l, t i IstB IstC , l Li , t T, t T
r Irst
ABr , j, t + 1 = µi,pr i, l, t 1 r Ema, t > 1
(27) j i Ir l Lr (45)
(Tt Tt ) HSi, l, t , t i Ist , l Li , t T, t T , t > t, t T FPrtot
,t = ydr , j · ABr , j, t r Ema, t > 1
i, l

(28) j (46)
(Tt Tt ) H (Si, l, t, t 1) I Ist , l Li , t T, t T , t > t, t T FPrtot µi,pr FPi, l, t
,t = r Ema, t > 1
i, l

(29) i Ir l Lr (47)

Wr , l, t Rr , l, t 1 Vstmax 1 + (t t) Si, l, t , t + Ni, l, t r M RM , l Lr , t T , t < |T|, t > t

i Irst t t <t (30)

Wr , l, t Rr , l, t 1 r M RM , l Lr , t T, t > 1 (31) FPi, l, t i, l , t 1 i Ima , t > 1 (48)

Wr , l, t =0 r M RM , l Lr
t T (32) NMr , t = NMr0 r Ema, t = 1 (49)

x r , l, t (Tt + 1 Tt ) (
H 1 i Irst
Ni, l, t )
r M RM , l Lr , t T , t < |T| (33) 3.2.9. Objective functions
In compliance with the decision-maker needs, the solution objective
xr , l, t (Tt + 1 Tt ) evaluates the profit maximisation of final products sales rs by pena-
r M RM , l Lr , t T , t < |T| (34) lising the costs of manufacturing cimf , storage allocations crst , inter-
mediate changeovers/setup cich
, i , extended shelf-life wasted amounts cr ,
d

x r , l, t H Ni, l, t r M RM , l Lr , t T , t < |T| late backlogs c r and cost of maintenance operations cr , given by
u ma

i Irst (35) equation (50).

max profit = r( r,l,t ) c mf

i i,l,t c str r R r,l,t + x r,l,t 60 Nii,l,t c ch
i,i Ci,i ,t
r P l Lr t T i I l Li t T r Mst l L r t T i I i I i I t T
t >1 t |T| t |T| i i t> 1

c dr Wr,l,t c ru u
r,l,t cma
r MA r,t
r M RM l L r t T r P l Lr t T r Ema t T
t> 1 t> 1 t >1 (50)

3.2.8. Maintenance constraints 3.3. Decision-making approach

The maintenance operations are constraint by Eqs. (36)–(49), where
the binary variable MAr , t indicates whether the maintenance is per- The complexity of the overall decision process in an industrial plant
formed in equipment resource subject to maintenance r Ema at time can be perceived with the enterprise functions network of the Purdue
event t , accounting the number of productions with NMr , t and con- reference model from ISA-95 (Fig. 4). Whereas planning and scheduling
sidering that each plan starts with a defined maintenance condition. decisions can be a function of the planning department, they generally
involve the collaboration and analysis of other areas such as sales,
NMMr , t NMrmax ·MAr , t 1 r Ema, t > 1 (36) procurement or R&D. The challenge for a decision support system relies
in the definition of the core decision processes able to be optimised,
NMMr , t NMr , t 1 r Ema, t > 1 (37) which can vary according to the company’s strategies and the scheduler
expertise.
NMMr , t NMr , t 1 NMrmax ·(1 MAr , t 1) r Ema, t > 1 (38) The assessment of the solutions provided should not disregard that
some simplifications are required for the formulation of the problem.
NMr , t = NMr , t 1 NMMr , t + ABr , j, t r Ema, t > 1 For example, in some cases a linear approximation/aggregation of
j (39) constraints is needed to keep the problem computationally tractable,

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M. Vieira et al.
Fig. 4. Purdue enterprise-control model with organisational structure of functions (ANSI/ISA-95, 2000).
else it could lead to infeasible solutions. Thus, the quality of the solu-
tions proposed and the computational time required is a critical factor
for the decision-making. Considering the proposed model approach, the
continuous-time formulation requires an iterative search for the
number of time events to find the optimal solution for a given problem
case. To implement an automatic procedure in the decision support
tool, it was defined, based in previous model studies, that the optimal
schedule proposed should be found in a solution pool of up to n + 4
time events, being n the number of due dates, and that each model run
should not exceed 3600 s of computational time. By defining a time
limit for the solutions output for a given problem, it is possible that the
optimality gap could not be closed due to computational limitations,
being the solution quality subject to the decision-maker criteria. Despite
this procedure is find suitable to the proposed problem structure, the
algorithm should evolve according to the diverse requirements by in-
tegrating new types of model constraints, alternative mathematical
approaches or empirical planning rules to convey additional decisional
objectives (e.g. matheuristics and simulation-optimisation approaches).
R1-2An effective decision support system lastly requires an inter-
active flow of information among the different stakeholders of the
process decisions. The development of a suitable software-based tool is
essential to promote an integration with existing plant management and
regulatory systems, allowing the access to the process data and the
analysis of solutions (Saha, Aqlan, Lam, & Boldrin, 2016). The im-
plementation of the software application is typically assigned to IT
consultants, to incorporate all the identified specificities of the decision-
making in a collaborative process. A user–friendly visual interface
should be developed with the relevant planning information displayed
in Gantt charts, and well as advanced options to access solution details
to support the process optimisation analysis. In this work, we propose a
concept of a decision support platform provided as a “Software as a
Service” for the analysis, management and optimisation of an industrial
production planning operation. Following current technology
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Computers & Industrial Engineering 129 (2019) 354–367
approaches, the proposed ICOMPASS tool relies on a centrally hosted
secure system based in cloud servers with API interfaces, attending the
issues related to maintenance and evolution of software, promoting
updated integrations with real-time plant management platforms and
allowing a universal access from web-enabled devices. Acknowledging
that the complexity of the IT programming system represents a field
that far extends the scope of this work, the detailed inferences of the
software architecture for the platform application will be discussed in
future works.
Finally, the successful implementation of the decision support
system will require a progressive adjustment to the production en-
vironment. The assessment of the different stakeholders will benefit
from a preliminary test-case development to show the potentialities of
the optimisation system. This deployment should point the collabora-
tive process and test the robustness of the model performance applied
to different problem scales, adapting the capabilities of the decision
support tool according to the industrial requirements. As follows, we
report the implementation of the ICOMPASS tool applied to a case study
in the biopharmaceutical industry.
4. Case-study application
The architecture of the ICOMPASS prototype tool follows the pre-
viously discussed implementation framework of a computerised system
for the decision support on planning optimisation of a biopharmaceu-
tical production. The structure of the collaborative solution approach is
able to assess the major decisions in a correct way, understanding its
model limitations when the complexity cannot be overcome, and match
the decision maker expectations and needs of its users. The platform
provides easy-to-use visual interfaces and access via mobile devices,
allowing the decision-maker to assess the process data and analyse
different scenarios to take optimal planning decisions. The prototype
was developed in collaboration with the industrial partners, balancing
M. Vieira et al.
Fig. 5. ICOMPASS prototype architecture with the information flows and interaction.
their decision-making protocols, functional requirements and the flow
of communication among different information layers, with the struc-
ture displayed in Fig. 5.
The user interaction with the ICOMPASS tool is sourced at the
Planning department level to set the planning order, edit the database
with the operational parameters (or preferable connection with MES,
ERP and related systems), and analyse the generated optimal planning
solutions through interactive charts and KPI reports. The data is ac-
cessed through web-interfaced menus linked to MS Office tools and the
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Computers & Industrial Engineering 129 (2019) 354–367
solutions are generated from the optimisation algorithm, composed by
Eqs. (1)–(50) and implemented in GAMS modelling software. Using MS
Excel interface capabilities to provide the input/output source data, the
solution is generated using the high performance commercial solver
CPLEX supported by GAMS. A Model manager is advised to control the
performance of generated solutions, assess the reliability of data input/
output processing, and review the mathematical formulation to address
additional production/process constraints to the structure. As follows,
we define a planning problem example to discuss the application of the
M. Vieira et al.
Fig. 6. Plan with optimal solution (464.7 real monetary units).
concept tool to a biopharmaceutical industrial case-study.
4.1. ICOMPASS application example
A case-study was designed from the collected information of in-
dustrial cases (Vieira et al., 2016), considering a biopharmaceutical
company with the following process characteristics:
• The company operates in 24/7 shifts production with a portfolio
composed by four biopharmaceutical products (Bio1-4) and has
available a set of certified equipment (with batch and continuous
operation) which are aggregated in upstream and downstream suites
for planning purposes: the company has recently invested in up-
stream capacity by adding to a batch fermentation reactor, UPX1,
two new continuous perfusion reactors, UPX2 and UPX3, while as
downstream suites there are two continuous chromatography sets,
DWX1 and DWX2;
• The network assessment of the process has characterised all avail-
able production suites in terms of products suitability, operational
limits, process economics and regulatory norms compliance (lots,
storage, changeover, maintenance, etc.), defining the blend of lots
allowed only to Bio1 and Bio2 production for regulatory purposes;
• The processing times of upstream/downstream stages, which re-
presents an aggregated production cycle for an average integer
amount, are assumed constant for each suite specifications and re-
vised accordingly by the scheduler;
• The planning approach considers unlimited storage units, assuming
that the cost of product storage is minor compared to the revenue
loss of unfulfilled deliveries;
• Regarding the downstream units, the yield decay is assumed con-
stant and the planning of maintenance operations is accounted for
the chromatography protein-A resins, while the uncertainty in up-
stream production titres is considered negligible (each new plan is
considered to start with a regenerated resin, MAr , t = 1 t = 1).
Considering the plant production network mapped, the ICOMPASS
platform allows the scheduler to define a planning problem by allo-
cating to the set of equipment suites a given production demand hor-
izon with multiple deliveries, an obtain a solution according to the
selected objective function, in this case, the profit maximisation. The
plan outlined 56 orders of the four products for six delivery dates, ad-
ditional information regarding problem data is available from the au-
thors upon request. The optimal planning solution is generated in a host
server by GAMS/CPLEX (GAMS 24.5.6 WIN VS8 ×86) on an Intel Xeon
X5680 64-bit at 3.33 GHz with 24 GB of RAM and the output results are
stored in the company’s database to generate the Gantt chart solution
for the task-unit assignment and sequencing, sequence dependent
changeover/set-up, the storage allocation, campaign-lots production,
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Computers & Industrial Engineering 129 (2019) 354–367
sales/late deliveries and maintenance tasks schedule.
The ICOMPASS interface provides the interactive visualisation of
the raw planning solution chart with a link to the inventory profile. For
this example, the reported optimal planning solution displayed in Fig. 6
(with the user interface display on the left) was obtained with nine
event points, considering the CPU time limit imposed of 3600 s. The
scheduler can visualise the production plan intervals tracking the size/
length of campaign lots [L#] of the four products (P_Bio# refers to final
product while I_Bio# to the intermediate product in upstream proces-
sing), with thirteen intermediate sequence-dependent changeovers
([CO] mark), eight storage activations ([S] mark) and eight inter-
mediate maintenance operations ([M] mark). In brackets are identified
the amounts processed in each task, being the numbers in downstream
units subject to yield decay. It must be noted that while UPX1 operate in
a batch mode, which implies that the amount of an intermediate pro-
duction is only available at the end of the task, the ones processed in
UPX2 and UPX3 operate in a continuous mode. For example, lot [L2(6)]
of P_Bio2 is scheduled to occur in the [120, 180 days] interval of DWX1,
consuming the lots of intermediary I_Bio2 [L3(4)] (batch) and [L4(2)]
(continuous). Also by definition, only if the amount processed in batch
is not consumed immediately, a storage activation is required, e.g.
I_Bio2[L5].
Further, to allow a reactive approach to production disturbances, an
interface option in ICOMPASS platform allows a rescheduling strategy
of a planning solution already under process. For example, when the
demand of a certain product order is requested to be increased, the
decision-maker can evaluate if the utilisation rate of its production
equipment in the ongoing plan have the capacity to accommodate that
production increase. Since all equipment share the same planning grid,
it is possible to continue the initial plant until a certain time event, from
which the demand profile will be changed. Considering the planning
solution of Fig. 6, the case now considers that on the 250th day of the
ongoing plan the order of Bio3 for the 540th day is requested to be
increased in seven batches. It was approved by the production sche-
duler to follow the initial plan until 300th day event of the ongoing
plan, from which a new planning solution is calculated taking into
account stored materials, downstream yield status and updated order
backlogs, fixing those values for the initial time event. In this solution
the model formulation disregards the setup time of the first replanned
tasks, considering the timing constraints A.1 and A.2 instead of Eqs. (1)
and (2). In Fig. 7 is shown the reported optimal solution displayed in
the platform for the production plan from the 300th day event onwards,
obtained with five time events. Additional KPI reports allows the
scheduler to analyse that the new plan provides a demand satisfaction
of 98.3% (1.05 left), a similar result to the initial plan, 98.6% (0.75
left), but with improved results on sales profit and capacity utilisation,
whereas these minor backlogs can be satisfied before the beginning of
the next production plan.
M. Vieira et al. Computers & Industrial Engineering 129 (2019) 354–367

Fig. 7. Plan with optimal solution for review plan (314.6 real monetary units).

5. Conclusions robust user-control planning tools. The ICOMPASS platform represents

In this work, we discussed the importance of decision support
methodologies into industrial production optimisation, surveying in-
dustrial successful applications to structure a framework solution. The
development of a novel solution application for the biopharmaceutical
industry with a model-based decision support tool ICOMPASS, was
validated in an industrial proof-of-concept study for the production and
maintenance planning optimisation of a biopharmaceutical process
under performance decay. The generic approach proposed for the de-
cision support tool is highlighted with the application to a bio-
pharmaceutical production optimisation, matching the decision-maker
requirements with a flexible modular structure that suits these in-
dustrial problems with planning/replanning solutions. And despite the
implementation challenges of these tools in real production environ-
ments, due to inherent complexity of multiple operational criteria,
successful industrial applications proved that the investment on deci-
sion support solutions potentiates several advantages to the decision-
making process.
The deployment of integrated, user-friendly and efficient decision
support platforms still requires an extensive research work, either from
the modelling point of view to tackle different mathematical ap-
proaches (for example, the uncertainties constraints in biopharmaceu-
tical manufacturing), either in the continuous development of more
a prototype concept to explore these operational problems and, in close
collaboration with industrial players, to potentiate the implementation
of planning/scheduling methodologies for the optimisation of industrial
processes. One of the major issues identified relies on how the in-
formation is accessed and translated to the decision-maker in order to
be perceived the competitive advantages with the corresponding op-
erational and economic gains. As future work, ongoing studies with
industrial partners will enable the development of additional features
concerning the interactivity with the user-interface (e.g. software
structure and updates, connection with enterprise systems, input/
output data review, solution sensitivity assessment) and evaluation of
alternative mathematical optimisation methodologies to deal with
larger planning problems with more detailed activities and sub-pro-
cesses variability (e.g. matheuristics and simulation-optimisation ap-
proaches).
Acknowledgments
The authors would like to acknowledge the financial support of
Fundação para a Ciência e Tecnologia under the grant SFRH/BD/
51594/2011 and from FEDER through the POCI program under the
Project POCI-01-0145-FEDER-016418.

Appendix A

• Notation
Indices
d delivery dates
i, i task
l, l lot
r resource (process unit, intermediate or final product)
j number of batches for performance decay tracking
t, t , t event point
Sets
B resources in which lots are allowed to be blended
D delivery dates
Dr delivery dates associated with resource r
E processing equipment
Est subset of equipment related to storage
Ema subset of equipment subject to maintenance
Eutil subset of equipment to verify utilisation rate
Esu subset of equipment subject to initial setup
I process tasks
Ir tasks that require resource r
Ib batch tasks
Ic continuous tasks
Icup continuous tasks (upstream step)

365
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Ist storage tasks

Izw tasks subject to zero-wait policies
Imr tasks that must exceed a certain minimum rate
c
IrBC subset of continuous tasks that consumes the intermediate material r produced by a batch task (or in a hybrid operation step)
c
IrHyb subset of continuous tasks that produces the intermediate material r in a hybrid operation step
IstB , IstC subset of storage tasks related to intermediates and final products produced by batch and continuous tasks
Irst storage tasks associated with material resource r
Ima Processing tasks subject to performance decay in equipment subject maintenance
L lots
Lr lots associated with resource r
Li lots associated with taski
LBr lots of resourcer B that are able to be blended
M material resources
Mst subset of material resources able to be stored
P subset of final products
RM subset of raw material resources
T event points
Parameters
i constant term in the processing time of task i
i proportional term to the extent variable in the processing time of task i
µic, r allocation coefficient for the binary extent of resource r (equipment unit) in task i relative to the start of the task
µi,pr release coefficient for the binary extent of resource r (equipment unit) in task i relative to the end of the task
c
i, r consumption coefficient for the continuous extent of r resource (intermediary or final product) in task i relative to the start of task
p
i, r
production coefficient for the continuous extent of resource r (intermediary or final product) in task i relative to the end of task
r, i, r coefficient for the rate of consumption of resource r (production/consumption of task i)
cimf cost of manufacturing processing task i
cru backlog penalties cost of material resource r
crd waste disposal cost of material resource r
crst storage cost of material resource r
cich sequence dependent task {i, i′} changeover cost
,i
crma maintenance cost at equipment unit r
r sales price of resource r
H time horizon
hd absolute time of demand point d
i, i time relative to sequence changeover/setup {i, i′}
i, l lifetime of the processed products of the task i lot l
Campimin max minimum and maximum campaign length of the processing task i lot l
, l , Campi, l
min
, imax minimum and maximum allowable rate of task i
i
Qr , d demand amount of each resource at delivery date d
Rr0 , Rr0, l resource availability in the beginning of the planning horizon
Rrmax maximum resource availability of resource r
Vimin max
, l , Vi, l
minimum and maximum capacity of resource r (processing units) for task i of lot l
ydr ,j yield of resin for the batch labelled j in unit r
NMrmax maximum number of batches production allowed after maintenance in unit r
Variables
Ci, i , t binary variable that assigns a sequence dependent changeover procedure of tasks i ,i before time event t (i, i corresponds to initial setup)
Ni, l, t binary variable that assigns the task i of lot l to start at event point t
i, l, t total amount of material processed by task i and lot l starting at event point t
Rr , l, t resource availability r of lot l and time point t
Rrc,l, t , Rrp, l, t amount consumed/produced of resource r of lot l and time point t
Si,l, t, t binary variable that accounts when the product lifetime stored through task i lot l was extended within the interval [t, t′]
xr , l, t accounts for the absolute storage time if storage task i lot l is active in the event interval [t, t′]
Wr , l,t waste disposal amount when resource shelf-life is exceeded
Yt ,d binary variable that assigns a specific event point t corresponds to a demand points d
r , l, t amount expedited at a corresponding due date
u
r , l, t unfulfilled demand of product r of lot l
MAr , t binary variable to assigns if unit r is maintained at event t
NMr ,t number of batches of final products produced in unit r since last maintenance by event t
NMMr ,t auxiliary variable ≡ MAr , t × NMr , t
ABr , j, t auxiliary binary variable to assign if the batch labelled j is produced in unit r at even t
QMr , j,t Auxiliary binary variable ≡ |ABr,j,t − ABr,j-1,t|, 0 if two consecutive batches labelled j and j-1 in unit r are produced at event t, otherwise 1
FPi, t amount produced by task i starting at time event t considering yield decay
FPrtot
,t
total amount of final product r starting at time event t

• Auxiliary equations
Tt + 1 Tt i Ib Ic
µirp l Li i Ni, l, t + i i, l, t |i Ib + i, l, t
max + i Ib Ic , i i i, i
Ci, i , t + 1 + r MAr , t
i i Ic

r E\Est , t T, t |T | (A.1)

366
M. Vieira et al.
Tt + 1 Tt H 1 ( i Izw Imr l Li )
µi,pr Ni, l, t + i Izw Imr
µi,pr l Li
r E Est , t T, t |T|
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