Computers & Industrial Engineering 79 (2015) 130–147

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Computers & Industrial Engineering

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

Hybrid genetic optimization for solving the batch-scheduling problem

in a pharmaceutical industry q
A. Costa ⇑

University of Catania, DII, Viale Andrea Doria 6, 95125 Catania, Italy

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

Article history: In today’s manufacturing outlook, production planning and scheduling may represent a leading leverage
Received 20 March 2014 to enhance the competitiveness of firms which aim to address the new challenge coming from emerging
Received in revised form 14 September markets and globalization. In this paper a real-world parallel machines scheduling problem from the
2014
pharmaceutical environment has been tackled. Though in the last decades literature extensively
Accepted 1 November 2014
Available online 8 November 2014
approached such an issue, a set of constraints and compulsory dispositions strongly increase the
complexity of the level of the problem in hand; thus, in order to fulfill the firm’s objectives in terms of
production rate increase and rapidity of solution, a dedicated hybrid genetic algorithm equipped with
Keywords:
Case study
a two-stage encoding and a proper local search has been developed. A twofold validation procedure
Encoding has been adopted for the proposed optimization technique. First, it was compared with a set of meta-heu-
Decoding ristic algorithms on the basis of a real-world data set. Once the outperformance of the proposed genetic
Production planning optimization was demonstrated, a further comparison with a set of empirical schedules, manually per-
Parallel machines formed by the production supervisor, had been carried out.
Multi-processor  2014 Elsevier Ltd. All rights reserved.

1. Introduction highlighting their vulnerability against most real-world problems.

Nowadays firms have to tackle an ever increasing global compe-
tition as well as an ever changing market demand fluctuation. Such
a stressing condition pushes firms to continuously improve the
performance of their production processes as to deliver the fin-
ished products as early as possible and at the lowest production
cost. Scheduling optimization methods play a key role in manufac-
turing performance improvement and cost reduction and, as a con-
sequence, they may represent a leading leverage in increasing
firms’ competitiveness.
Since most industrial scheduling problems are highly combina-
torial and involve complex decision-making issues, they rarely can
be optimally solved in a reasonable amount of time. Further, the
computational effort to find a good solution is strongly dependent
on the problem size itself. Although mathematical formulations are
able to describe a large number of scheduling problems, in practice,
they can only solve problems of modest size in a reasonable
computational time (Kopanos, Mendez, & Puigjaner, 2010), thus
q to face a real-world scheduling problem related to the packing
This manuscript was processed by Area Editor T.C. Edwin Cheng.
⇑ Tel.: +39 095 7382457; fax: +39 095 337994.
E-mail address: antonio.costa@dii.unict.it
URL: http://www.dii.unict.it/users/costa
According to Hermann (2006), algorithms that can find optimal
solutions to these hard problems in a reasonable amount of time
are unlikely to exist.
However, in the last decades, two different research streams
concerning the optimization of real-life scheduling problems have
captured the attention of both practitioners and scholars. The for-
mer consists of the integration between heuristics and mathemat-
ical programming models, as demonstrated by the following
literary contributions.
Kopanos et al. (2010) proposed a mixed integer programming-
based decomposition strategy to cope with a scheduling problem
of a multi-stage pharmaceutical process. Their solution strategy
approach entails a MIP-based core and consists of two major pro-
cedures: the constructive step and the improvement step. The
objective of the former step is the generation of a feasible schedule
in a short amount of time. Afterwards, the obtained schedule is
gradually improved by implementing some elaborate rescheduling
techniques by the latter step. Similarly, Stefansson, Sigmarsdottir,
Jensson, and Shah (2011) used the decomposition-based approach
stage of a pharmaceutical company. After a thorough analysis of
the process flow, they observed that there was a very critical
bottleneck in the overall production process at the last stage, i.e.

http://dx.doi.org/10.1016/j.cie.2014.11.001
0360-8352/ 2014 Elsevier Ltd. All rights reserved.
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147
packing. Thus, because of the limited capacity at that stage, the
problem was decomposed into two main components, one of
which involving the single packing stage. The aim of their study
was to compare the discrete and continuous representations for
solving the individual parts of the decomposed problem. The opti-
mality of the linear programming approach for small-size prob-
lems was exploited by Lin and Liao (2012), who studied the
batch-scheduling problem for an assembly shop in a machinery
factory. As concerns both medium- and large-size problems they
compared three distinct heuristics, and confirmed the effectiveness
of a properly developed batch family sorting heuristic also by
means of a real-life implementation. Missbaurer, Hauber, and
Stadler (2009) implemented an integrated approach involving lin-
ear programming along with heuristics for a scheduling system
from the steel-making industry. In this research an LP model has
been embedded within a properly developed heuristic procedure
with the aim of iteratively improving each obtained schedule.
Extensive numerical tests with real-life data demonstrated the
effectiveness of the proposed scheduling tool. Another significance
example of integration between mixed integer programming and
evolutionary algorithms was provided by Sand et al. (2008) who
made full use of a stage decomposition-based hybrid algorithm
to deal with a realistic batch scheduling problem with uncertain
data.
The second research stream gathers tailor-made heuristics and
metaheuristics algorithms able to find near-optimal solutions
through a quick and at the same time smart exploration of the
solution space. Since real-life scheduling problems are usually
characterized by several constraints emphasizing their complexity
with respect to the theoretical models usually approached by liter-
ature, metaheuristic techniques may represent a valid and versatile
alternative to quickly solve such combinatorial issues. In fact,
metaheuristic algorithms do not require any mathematical pro-
gramming modeling, but their efficacy and efficiency strongly
depend on the problem encoding as well as on the way a given
problem code is decoded to generate a feasible solution of the
problem itself. Several excellent contributions mentioning the
application of meta-heuristic optimization algorithms to real-life
industrial scheduling issues are reported in the following
paragraphs.
Pearn, Chung, Chen, and Yang (2004) investigated a case study
on the multistage integrated-circuit final testing scheduling prob-
lem, wherein jobs are clustered by their product types, and they
must be processed on group of parallel machines. The job process-
ing time depends on the product type and the machine setup time
is sequentially dependent on the orders of processed jobs. They
presented three fast network algorithms to efficiently solve the
scheduling problem and provided a performance comparison
among the proposed techniques on eight test problems.
A simulated annealing algorithm was implemented by Loukil,
Teghem, and Fortemps (2007) for addressing a real-case produc-
tion scheduling problem in a flexible job shop with particular con-
straints. Indeed, the authors arranged a multi-objective SA in order
to yield efficient schedules in terms of: makespan, mean comple-
tion time, maximum tardiness and mean tardiness.
A job shop case study from the apparel industry was
approached by Guo, Wong, Leung, Fan, and Chan (2006) through
a genetic optimization technique. In order to properly tackle the
mixed- and multi-product assembly environment under investiga-
tion, authors adopted a new chromosome representation and
equipped the genetic engine with a heuristic initialization process
and with modified crossover and mutation operators as well.
Another demonstration about the leading role of expert systems
in real-world manufacturing arises from the study of Soyuer,
Kocamaz, and Kazancoglu (2007), wherein a scheduling tool based
on a unique constructive algorithm has been developed to manage
131
the short-term production planning of a firm producing copper
wires. The hierarchical procedure provided the by authors revealed
its applicability and optimality in solution.
Soman, Van Donk, and Gaalman (2007) presented a combined
production planning and scheduling framework for a food process-
ing company. Since the short-term batch-scheduling problem
plays a key role in the proposed conceptual framework, a proper
heuristic algorithm to solve that problem has been developed.
The wirebonding scheduling issue, which basically consists of
an equal parallel machine scheduling problem, has been
approached by an evolutionary simulation-optimization technique
(Yang, 2009). The effectiveness of the proposed optimization strat-
egy was confirmed by comparing the empirical results with a set of
lower bound solutions.
Jia and Mason (2009) compared a set of polynomial – time heu-
ristics approaches for investigating the identical parallel machine
scheduling problem related to a semiconductor manufacturing
process. Although a mixed integer programming model was gener-
ated for the problem in hand, a heuristic based approach was
required to solve the problem in a satisfactory amount of time.
An experimental analysis made the authors able to identify the
most promising heuristic procedure to cope with this practically
motivated scheduling problem.
Another application of metaheuristics techniques is ascribable
to Venditti, Pacciarelli, and Meloni (2010), who studied a packag-
ing department of a pharmaceutical industrial plant. They modeled
the problem as a multi-purpose machine scheduling problem with
setup and removal times, release and due dates and additional con-
straints related to the scarce availability of tools and operators. In
particular, they developed a proper tabu-search algorithm, whose
objective was minimizing both makespan and maximum tardiness
in lexicographic order.
He and Hui (2010) tackled the scheduling problem related to a
typical multi-purpose batch plant with a network structure. Since
mathematical programming is not able to solve large-sized issues,
the authors proposed a genetic algorithm (GA) equipped with a
binary encoding. Due to the logical heuristics utilized to decode a
chromosome into a schedule, only feasible solution space is
searched. Comparative studies performed by authors show as their
technique takes much shorter search time for the proposed algo-
rithm to obtain the optimal solutions for both small and medium
instances with respect to the MILP model. On the other hand, the
same algorithm solved the large-sized instances obtaining good
quality solutions within a very short time.
Huang, Cai, and Zhang (2010) addressed a real-world schedul-
ing problem on parallel dedicated machines in which setup times
are sequence dependent and setup operations are performed by a
single server. A hybrid genetic algorithm was developed and tested
on the basis of a comprehensive data set from a printing industry.
More recently, Meeran and Morshed (2012) coped with a job
shop scheduling problem related to a real machining department.
In order to efficiently solve the problem under investigation, the
authors implemented a novel hybrid genetic tabu search, namely
an integrated technique that combines the diversified global
search and intensified local search capabilities of GA and TS,
respectively. Again in the field of the parallel machine scheduling
problem, Chen, Cheng, Wang, and Chen (2013) studied a solar cell
industry which is similar to the traditional hybrid flow shop (HFS)
scheduling problem. Since the challenge in solar cell manufactur-
ing is allocating sublots to parallel machines of each stage such
that the makespan time is minimized, a hybrid approach based
on the Variable Neighborhood Search and particle swarm (VNPSO)
was implemented to obtain the near-optimal solution. Preliminary
computational studies demonstrated that the metaheuristics algo-
rithm proposed by the authors provides good quality solutions in
an acceptable amount of time and also outperformed the classic
132 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147
branch and bound method and the heuristic currently practiced by
the case company.
This paper deals with a real-life case study from the pharma-
ceutical industry, which may be formally configured as a flow shop
with multiple processors (FSMP) wherein several constraints
involving products, material resources and workforce have to be
taken into account. In reality, since a specific bottleneck stage
characterizes the whole process, and due to the specific kind of
tasks connected to such a critical stage, the multi-stage problem
was relaxed to a single-stage scheduling problem with identical
parallel machines.
The objective is the minimization of the total completion time,
i.e. the makespan, for a provided mix of jobs. Notably, since each
machine may process an indivisible set of product units of the
same type, a job can be configured as a batch and an optimal sche-
dule would consist of a sequence of batches.
According to these last considerations, the present problem
could be also assimilated to a parallel-batch scheduling problem
wherein a machine can process several parts simultaneously in a
batch. In the last decades parallel-batch scheduling has been
widely researched. As far as the unbounded problem is concerned,
Liu, Ng, and Cheng (2009) developed a polynomial-time approxi-
mation scheme for the problem of scheduling jobs with release
dates on parallel unbounded batch processing machines to mini-
mize the maximum delivery completion. Fu, Cheng, Ng, and Yuan
(2013) provided an optimal algorithm for the online scheduling
of incompatible job families on an unbounded parallel-batch
machine to minimize the makespan, where jobs arrive over time
and the number of job families is known in advance. The makespan
minimization is the target of another research performed by the
same team (Li, Ng, Cheng, & Jinjiang, 2011). They studied the prob-
lem of scheduling n deteriorating jobs with release dates on a sin-
gle batching machine. Both the bounded and unbounded issues
have been investigated. For the unbounded model they obtain an
O(nlog n) dynamic programming algorithm. For the bounded
model they show that the problem is binary NP-hard even if there
are only two distinct release dates. Whether the problem size
should increase, heuristics approaches are a valid alternative to
the exhaustive procedures.
Li, Huang, Tan, and Chen (2013) used several heuristics based
on best fit longest processing time (BFLPT) to minimize makespan
in a scheduling problem involving unrelated parallel batch
processing machines. In their study jobs with non-identical sizes
are scheduled on batch processing machines that can process
several jobs as a batch as long as the machine capacity is not
violated.
Recently, Cheng, Cai, Yang, and Hu (2014) presented a mixed
integer programming model for scheduling incompatible job fam-
ilies on single batching machine with limited capacity. In particu-
lar, they proposed two polynomial time heuristics based on longest
processing time first rule and first fit rule. For the special case
where a larger job also has a longer processing time, the heuristic
for minimizing makespan is optimal.
However, differently from the regular parallel-batch scheduling
problem, the following features characterize the proposed real-
world issue:
- a batch is composed only by identical parts, i.e. product units of
the same type;
- the batch size, i.e. the number of parts included in a batch, is
known in advance and depends on the product type; thus, each
batch processing time is equal to the processing time of the spe-
cific product type it holds;
- regardless of the product type, sequence dependent setup
times and removal times are required for each batch to be
processed;
- a number of fixed time length windows must be planned along
the expected planning time; during such a time interval neither
setups nor removals may occurs;
- several constraints inherent to the interactions among time
windows, setups and removals have to be fulfilled.
In fact, the problem is motivated by the practical implementation
of a decision support system to improve the production scheduling
task at the lyophilization department of a pharmaceutical plant
located in Europe. Up to now, the short-term scheduling task was
handled by means of the production supervisor’s experience. Once
the production supervisor receives the planned production target
in terms of number of batches and type of products to be produced,
he empirically generates an operative schedule by means of a Gantt
chart, as to determine both the expected task completing times and
the related resource requirements. In light of what stated before, due
to an increasing market competitiveness and due to the world wide
enlargement of the market area, the management of the company
decided to optimize the production output by a adopting an engi-
neered scheduling tool aiming to: (i) maximizing the production
rate of the plant, (ii) improving the resource exploitation of the
whole department, (iii) supporting and speeding up the scheduling
and re-scheduling activities pertaining to the production supervisor.
Since the problem under investigation is quite different from
the regular parallel machines scheduling problem usually studied
by literature, a holistic optimization strategy has been developed
as to manage the multitude of constraints affecting the provided
process tasks. The complexity of the problem prevents any devel-
opment of linear programming-based mathematical formulations
and, as a result, a tailor-made optimization method based on a
hybrid genetic algorithm (HGA) has been proposed. The optimiza-
tion framework consists of a genetic algorithm that makes full use
of a proper initialization heuristic procedure aiming to increase the
number of feasible solutions included in the initial population. The
same heuristic procedure, named focused local search, is itera-
tively applied to the most performing individual as to push the
exploitation phase of the optimization algorithm. In addition, both
a specific two-stage chromosome representation and a complex
decoding procedure have been developed in order to minimize
the risk of detecting unfeasible solutions. The effectiveness of the
proposed scheduling tool was tested on the basis of a benchmarked
analysis, which encompasses other performing metaheuristic pro-
cedures. Further, in order to demonstrate both real-world applica-
bility and quality of solutions of the proposed scheduler, a
comparison with a set of schedules manually performed by the
company supervisor has been carried out.
The problem under investigation, also including a detailed
nomenclature is described in Section 2. Section 3 deals with the
structure of the proposed genetic optimization procedure, also
emphasizing the procedural aspects concerning the encoding strat-
egy and the decoding algorithm as well. In addition, the specific
local search algorithm embedded within the proposed genetic
algorithm is examinated. The real-world benchmark according to
which the proposed HGA has been validated is reported in Section
4. The same section holds the comparison analysis affirming the
effectiveness of HGA in solving the specific batch-scheduling prob-
lem under investigation. Finally, conclusions are reported in Sec-
tion 5.
Perparaon Filling Lyophilizaon Sealing Packaging
Fig. 1. Process flow.
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 133

2. Description of the problem of lot i from lyophilizer j;

lcij lyophilizer CIP/SIP starting time after lot i is
Notations processed by lyophilizer j;
lc’ij (=lcij + lcs) lyophilizer CIP/SIP completing time
Indices after lot i is processed by lyophilizer j;
i=1, . . ., N; number of lots to be produced; lkij lyophilizer leak test starting time after lot i is
j = 1, . . ., M; lyophilizers; processed by lyophilizer j;
p = 1,2,..,P; product types; lk’ij (=lkij + lkt) lyophilizer leak test completing time
w = a, b; product categories; after lot i is processed by lyophilizer j;
d = 1, . . ., days of Time Horizon; cij change-over starting time before lot i is
TH; processed by lyophilizer j;
c’ij (=cij + cov) change-over completion time before
Parameters
lot i is processed by lyophilizer j;
pti lot i lyophilization process time;
cl(d) (=g(d)) aseptic area cleaning start time at day d;
fsu filling setup time;
h(x) hour clock time from 1 a.m. to 24 p.m. when
fll filling time;
variable x occurs (e.g. h(sij) = 21 means sij occurs
fcs filling CIP/SIP time;
at 21 p.m.)
lld lyophilizer load time;
d(x) day time from 1 to TH when variable x occurs
ltr allowable loading time reduction;
(e.g. d(sij) = 12 means that sij occurs at day 12);
lud lyophilizer unload time;
a_fill(j) allowable filling starting time for processing any
lcs lyophilizer CIP/SIP time;
lot through lyophilizer j within a given time
lkt lyophilizer leak test time;
limit;
cov changeover time ‘‘from lot p(i) to lot p(h)’’/
a_lyo(j) availability of lyophilizer j to start processing.
’’from lot p(h) to lot p(i)’’|p(i), p(h) = 4,
5 ^ p(i) – p(h);
cln aseptic area cleaning time;
prp preparation time limit; As described in the previous section, the proposed real-world
cfl time limit between two consecutive fillings; issue significantly differs from the theoretical scheduling models
cst complete sterilization time (including filling investigated by literature. The following paragraph aims to outline
machine CIP/SIP time); a formal as well as synthetic description of the problem.
sch shift change time; Assume N batches, also called lots, to be produced through M
Variables identical parallel machines. Each machine may process one lot at
p(i) product type corresponding to the i-th gene of a time. The provided N lots involve P|P < N different kinds of prod-
solution p; ucts; thus, each lot refers to a single product type. Lot processing
g(d) hour clock time corresponding to the d-th gene times connected to the different product types are a priori-known.
of solution g; Regardless of the multitude of constraints affecting the mentioned
w(i) category of product p(i); problem, it can be stated that both lot setup times and lot removal
p(i) = 1, 2, type of preparation for the i-th lot of p; times are sequence dependent. A number of time windows con-
3; forming to the planning time length have to be placed along the
r(i) = 1, . . ., number of preparation for i-th lot of p(i); planning time itself. During each time window neither setup nor
p(i); removal operations may occur. Neither preemptions nor machines’
sij setup filling starting time of lot i before being breakdowns are allowed. The whole set of lots is available at time
processed by lyophilizer j; zero.
s’ij (=sij + fsu) setup filling completing time of lot i The problem under investigation refers to a manufacturing pro-
before being processed by lyophilizer j; cess of pharmaceutical products. For the sake of privacy, neither
fij filling starting time of i-th lot before being the name of the company nor the specific kind of product may
processed by lyophilizer j; be discussed in this paper. As far as the material flow is concerned,
f’ij (=fij + fll) filling completing time of lot i before Fig. 1 shows the different production stages required to pass from
being processed by lyophilizer j; the raw material to the finished product. The first stage entails the
fcij filling machine CIP/SIP starting time of lot i preparation of the chemical solution, i.e. the semi-finished product
processed by lyophilizer j; that requires four more production stages before being delivered
fc’ij (=fcij + fcs) filling machine CIP/SIP completing and introduced through the market. According to what the com-
time of lot i processed by lyophilizer j; pany stated, no more than three lots of the same product may be
lij lyophilizer load starting time of lot i into contemporarily yielded by the preparation stage. In addition, once
lyophilizer j; batches involved within each preparation are completed, they can-
l’ij (=lij + lld) lyophilizer load completing time of lot not wait for more than a certain time period before being pro-
i into lyophilizer j; cessed at the subsequent stage. In fact, once the chemical
rij lyophilizer run starting time for lot i into solution for a given batch of product has been prepared, a set of fla-
lyophilizer j; cons needs to be filled at the filling stage. Actually, whenever a new
r’ij (=rij + pti) lyophilizer run completing time for lot preparation batch, hereinafter lot, has to be poured into the fla-
i into lyophilizer j; cons, a specific sterilization task is required and a setup of the fill-
uij lyophilizer unload starting time of lot i from ing machines is needed. Each lot comprises about 500 l of raw
lyophilizer j; product and its preparation may be executed in three ways,
u’ij (=uij + lud) lyophilizer unload completing time according to the quantity of lots it generates: single-, double- or
triple-lot preparation. A single-lot preparation implies just a single
lot of product; a double preparation fulfills two lots and a triple
134 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

preparation three lots. Since the production rate of the filling stage unload
depends on the specific kind of preparation, both preparation and load CIP /SIP
filling tasks are related and, as a consequence, preparation of lots leak test
must be planned along with the other tasks involved in the pro-
posed lot scheduling issue. Lyo 1
Whenever the filling of a given preparation is completed a
Cleaning-In-Place (CIP) and a Sterilization-In-Place (SIP) treatment,
namely CIP/SIP of the filling machine, has to be carried out.
Filling Lyo 2
Thereafter, flacons have to be loaded into the lyophilizer and
then lyophilization may start. Lyophilization is a process that
extracts the water from foods and other products so that the foods
or products remain stable and are easier to store at room temper- Lyo 3
ature (ambient air temperature). Lyophilization is a time consum-
ing process carried out using a simple principle of physics called CIP/SIP

sublimation. Sublimation is the transition of a substance from

the solid to the vapor state, without first passing through an inter-
mediate liquid phase.
After lyophilization is completed, flacons have to be unloaded
by the same operator employed for the loading task. Once all the
flacons have been unloaded, the lyophilizer has to be subject to a
twofold sterilization treatment named CIP/SIP and Leak test. How-
ever, the next paragraph discusses some cases in which such a
twofold treatment may be disregarded.
Then, bottles are closed at the sealing stage and, finally, they
pass through the packaging stage before being stored in the fin-
ished product inventory. It worth pointing out that both sealing
and packaging do not suffer any gap in terms of capacity; thus,
as indicated by the company managers, and through the numerous
empirical observations performed by authors, the first three man-
ufacturing stages strongly affect the performance of the process in
hand. Hence, the restricted capacity of the preparation stage along
with the numerous constraints affecting both filling and lyophiliza-
tion tasks significantly limit the production rate of the system in
hand. In particular, since a time-consuming cleaning/sterilization
phase is required on the filling equipment whenever an entire
preparation is processed, preparations that gather a high number
of lots (e.g. triple or double preparations) are preferred under the
makespan reduction perspective.
Nevertheless, as may be noticed in the next paragraphs, single
lot preparations may profitably be introduced in the time slots
generated by the numerous constraints affecting the problem in
hand.
In light of the aforementioned remarks, the overall process has
been modeled only on the basis of the lyophilization process while
filling has been managed as a preliminary task properly driven by
the type of preparation adopted for the lots to be processed (Fig. 2).
The observed lyophilization production stage entails three par-
allel identical lyophilizers, hereinafter called machines. Machines
are always available; thus no breakdowns may occur. Preemption
is not allowed. Since the preparation task should be planned
through a proper lot schedule, all the lots to be scheduled may
be considered as available at time zero. Descriptors of lots and
the other task times are known in advance. Since machines are
identical, allocation of lots to machines is based on the first avail-
able machine (FAM) policy. Filling may be anticipatory with
respect to lyophilization. Filled flacons may wait for a limited
amount of time before being loaded into a lyophilizer.
Both lyophilizer load and unload tasks are performed by the
same worker; thus, such a kind of tasks cannot be timely over-
lapped. Due to some international dispositions, the aseptic area
department must be cleaned every day during the third shift
and, in addition, the cleaning task should take 3 h; thus, the daily
cleaning phase cannot start before 22:00, or later than 03:00 a.m.
of the subsequent day. The time slot positioning of the department
cleaning plays a key role in the lot scheduling issue since no over-
lap between such a task and other manual activities (lyophilizer
Fig. 2. Filling and lyophilization within the aseptic area.
load/unload, filling) is allowed. In words, no risk of contamination
arising from the human presence is accepted during the cleaning
phase. Of course, lyophilizers may run when cleaning operations
are in progress.
2.1. Constraints of the problem
In light of what discussed in the previous section, the problem
under investigation has been modeled as a parallel machine sched-
uling problem, though the compulsory application of the GMP rules
for such a kind of company entails a significant distortion of the reg-
ular model usually studied by literature. The well-known Good
Manufacturing Practices (GMPs) are production and testing prac-
tices that helps to ensure a quality product. Many countries have
legislated that pharmaceutical and medical device companies must
follow GMP procedures, and have created their own GMP guide-
lines that correspond with their legislation. Basic concepts of all
of these guidelines remain more or less similar to the ultimate goals
of safeguarding the health of the patient as well as producing good
quality medicine, medical devices or active pharmaceutical prod-
ucts [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/
Manufacturing/ucm169105.htm].
The following list summarizes the constraints characterizing
the observed pharmaceutical manufacturing issue. For each con-
straint a mathematical description has been provided with the
aim of illustrating the relationships among the different variables.
It is worth pointing out as several constraints refer to the five prod-
uct types currently manufactured by the company.
1. Shop floor cleaning can be performed only during the third
shift (from 10:00 p.m. to 6:00 a.m.);
clðdÞ þ cln 6 24 þ 6 if ð22 6 clðdÞ 6 24Þ
ð1Þ
clðdÞ þ cln 6 6 if ðclðdÞ P 1Þ;
2. A triple lot preparation is allowed only for product type 3,
whether it is preceded by a single lot preparation of
product 1;
pðhÞ ¼ 3; rðiÞ ¼ 3 if pðhÞ ¼ 3 and pði  3Þ
h¼i;i1;i2 h¼i;i1;i2
¼ 1 and pði  3Þ ¼ 1 and i > 3; ð2Þ
3. Regardless of any kind of preparation, a proper setup opera-
tion of lot i on a lyophilizer j is required whenever the first
filling of any preparation occurs;

¼ 0 if rðiÞ > 1
sij ð3Þ
>0 if rðiÞ ¼ 1
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 135

4. A product size changeover (cij) is required whenever a lot i of 14. Once an a-category lot product completes the lyophilization
product type 4 (or 5) must be processed on a lyophilizer j phase, both CIPSIP and Leak test must be performed before
before/after a lot of any other type of product. processing another a-category lot on the same lyophilizer.
8
< > 0 if ðpðiÞ ¼ 4ð5Þ and pði  1Þ–4ð5ÞÞ
> lcij ; lkij > 0 if wðiÞ ¼ a; wðhÞ ¼ ajh > i;
cij or ðpðiÞ ¼ 4ð5Þ and pði þ 1Þ–4ð5ÞÞ ð4Þ pðhÞ is processed by j after p ðiÞ; ð14Þ
>
:
¼ 0 otherwise
15. Once an a-category lot product completes the lyophilization
5. Time overlap between the product size changeover and the phase, neither Leak test nor CIPSIP must be performed before
following activities is not allowed: filling and CIP/SIP. processing a b-category lot on the same lyophilizer.
0 0
cij P maxðfchk ; f hk Þ; ð5Þ lcij ; lkij0 if wðiÞ ¼ a; wðhÞ ¼ bjh > i;
h<i
k–j
pðhÞ is processed by j after pðiÞ; ð15Þ
6. During the department cleaning time any human related
task (lyophilizer load/unload lij/uij, setup sij and filling fij) 16. No shop floor cleaning may occur between the filling com-
cannot be carried out. The following relation refers to a gen- pletion time and the load start time of lot i on lyophilizer j;
eric task named gij. 0
clðdÞ P lij or clðdÞ þ cln < maxfsij ; f ij g ð16Þ
g ij clðdÞ þ cln if ðg ij < clðdÞ þ cln and
g 0ij P clðdÞ þ clnÞ or ðg ij 6 clðdÞ and g 0ij > clðdÞÞ ð6Þ 17. The time interval between the filling setup starting time sij
and the filling CIP/SIP starting time fci1,j⁄ of the previous
7. If any filling activity (setup included) occurs during the shift lot on another machine must be greater than or equal to
changeover (06:00, 14:00, 22:00) then it requires an addi- cst time;
tional time (aft) to be completed.
sij  fci1;j P cst ð17Þ
f ij
0 0
f ij þ aft;  and
if ðhðf ij Þ 6 h
0  h
hðf ij Þ P hÞj  ¼ 6; 14; 22

ð7Þ An illustrative example will be presented in order to demonstrate

8. In case of double-lot preparation, the time interval how such constraints influences the proposed scheduling problem.
between the filling completion time (f’i1,j⁄) of the previous
lot in the precedent machine (j⁄) and the filling starting 2.2. An illustrative example
time of lot i in machine j (fij) must be lower than or equal
to cfl time; In order to better depict how the mentioned constraints
0
increase the complexity of the proposed scheduling problem, the
f ij  f i1;j 6 cfl; if pði  1Þ ¼ pðiÞ ¼ 2; rði  1Þ ¼ 1; rðiÞ ¼ 2; following example may be analyzed. Seven lots (i = 1, . . ., 7) con-
ð8Þ nected to four product types (p = 1, . . ., 4) are considered. For sake
of clarity, hereinafter those four product types will be denoted by
9. Time interval between the filling starting time fij (or sij if p = A, B, C, D. Products belong to two categories (a and b) and lot
r(i) = 1) and the lyophilization starting time rij must be specifications are reported in Table 1.
lower than or equal to prp time; Let us suppose that the following sequence of lots p = (A-A-C-C-
rij  sij 6 prp; ðrðiÞ ¼ 1Þ or r ij  f ij 6 prp; ðrðiÞ > 1Þ; ð9Þ D-D-B) should be scheduled through the provided M = 3 lyophiliz-
ers, as to satisfy the mentioned constraints. Fig. 3 shows the Gantt
10. Whether a triple lot may be processed, the third lot filling diagram involving both filling and lyophilization phases for each
requires an additional time (aft) to be completed. lot and for each machine. Both filling and lyophilization related
0 tasks were reported into the same Gantt diagram with the aim of
f ij f ij þ fll þ aft; if pðiÞ ¼ 3 and rðiÞ ¼ 3; ð10Þ
explaining the way most constraints should be managed. The pro-
11. Lyophilizer loading and unloading tasks concerning two duction supervisor usually adopts the same approach to plan the
distinct lyophilizers have not to be overlapped. Loading short-term production scheduling. Shop floor cleaning time inter-
has priority with respect to unloading; vals (light blue areas) are located respecting both constraints 1
0 and 6. The lower time axis refers to the clock time of each day,
uhk lij ; if ðuhk þ lud P lij and uhk þ lud while the upper time axis holds the progressive time. Setup filling
0 0
6 lij Þ or ðuhk P lij and uhk 6 lij Þji–h; j–k ð11Þ and the filling task itself must precede the load task of the first lot
into the first lyophilizer (constr. 3). Once all the flacons have been
12. Loading tasks concerning two different lyophilizers have not loaded, lyophilization may start and the filling task for the second
to be overlapped in time, due to a limited workforce lot may start. To do that, a double-lot preparation should be
availability. provided for the two lots of product A. After the second filling is
0 completed a CIP/SIP task is required on the filling stage and any
lij lhk þ lld; if ðlhk þ lld P lij and lhk þ lld 6 lij Þji–h; j–k
subsequent filling setup may not start before a time interval
lhk lij þ lld; if ðlhk P lij and lhk 6 lij þ lldÞji–h; j–k equal to cst (constr. 18). Filling tasks executed during the shift
ð12Þ

13. If before any lyophilizer load there is not any in-progress

activity with exception of filling (e.g. CIPSIP, Leak test, Table 1
Unload), then the loading task time may be reduced by ltr Features of the products to be scheduled.
time.
Lots to be scheduled 1 2 3 4 5 6 7
0 0 0
lij lij þ lld  ltr; if lij  maxflchj ; u0hj ; lkhj g > 1 ð13Þ Product type – p A A B C C D D
h<i Product category – w a a b a a b b
136 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147
Fig. 3. Gantt diagram concerning filling and lyophilization phases.
changeover have a longer duration (aft time increment), as con-
firmed by the different length of the green blocks (constr. 7). Also
in this case the two lots of product C should be arranged as a dou-
ble preparation lot. Due to both CIP/SIP and Leak test in machine
one, the lyophilizer load starting time of lot 4 is delayed with
respect to the filling completing time provided for the same lot.
Anyway, constraint 9 is satisfied as the time interval between the
filling starting time and the lyophilization starting time is lower
than prp. Because of the change from a product of type F to a prod-
uct of type B, a changeover task conforming to constraint 4 and 5
must be arranged (look at the black block separating products type
F from products type B). The difference of length between the
lyophilizer loading task of lot 4 and the others is justified by con-
straint 13. CIP/SIP and leak test between lot 1 and lot 4 in machine
1 is due to what constraint 14 states, while the same tasks are
missing when lot category b must be processed after a product of
category a, e.g. see lot 5 and 6 after lot 2 and 3 respectively (constr.
16). The positioning of the cleaning time interval plays a key role
for the feasibility of a given schedule. It can be emphasized by
Fig. 3 when the second filling, preliminary to lot 6, must be delayed
due to the incompatibility of such task with the cleaning phase of
day 3, which starts at 1 a.m. and finishes at 4 a.m. of day four. How-
ever, such a delay is lower than cfl and constraint 8 is not violated.
Finally, as exhibited by Fig. 3, the unloading task of lot 5 in
machine 2 is delayed in order to satisfy constraint 11. Lot 7, which
belongs to product type B, is handled by a single-lot preparation, as
confirmed by the presence of the CIP/SIP in the filling machine. The
schedule of preparations for each product, which arises from the
Gantt diagram, is reported in Table 2.
Regardless of product type B, all the products to be produced have
to be prepared through a double-lot (p(i) = 2) preparation, as to
reduce the number of filling machine’s setups and, to increase the
production rate of the manufacturing system. The number of prepa-
ration r(i) denotes if a given lot is the first or the second lot to be
filled. In fact, for each kind of preparation, just the first lot needs a
preliminary setup of the filling machine before being processed.
3. The proposed optimization procedure
3.1. General principles
A GA is a metaheuristic optimization procedure that simulates
the natural evolution. Firstly, a set of solutions is generated (the
Table 2
Preparation schedule.
Lot to be scheduled – i 1 2 3 4 5 6 7
Product type – p A A C C D D B
Type of preparation – p(i) 2 2 1 2 2 2 2
Number of preparation – r(i) 1 2 1 1 2 1 2
initial population) and then such population is replaced by a new
one due to a mechanism that preserves the most promising solu-
tions. Indeed, the population evolution proceeds by means of a
reproduction mechanism called crossover, which selects one or more
couples of chromosomes (the parents) and recombines them to
generate the children (two new chromosomes). Children replace
parents in the new population. Search towards unexplored areas
of the solutions domain is assured by means of a mutation opera-
tor, which can randomly alter one or more chromosomes within
the current population. A termination condition allows the gener-
ational process to be stopped within a finite computational time.
One of the key issues for enhancing the performance of metaheu-
ristics regards the problem encoding as well as the related decod-
ing procedure. The problem encoding is the way a given problem
may be represented by a string of numbers. On the other hand,
decoding consists of a proper procedure assessing the performance
of a given solution, with respect to the provided set of constraints
to be observed. Usually, for a constrained problem to be optimized,
a twofold approach may be taken into account. The former uses a
set of constraint repairing procedures as to ensure the feasibility
of a decoded solution; the latter makes full use of a penalty func-
tion, which increases the objective function value whenever a con-
straint is violated. Due to the high number of constraints included
in the problem under investigation, a few areas of feasible solu-
tions, whose investigation may result quite tricky, should charac-
terize the space of solution. For the same reason, a regular
metaheuristics addressing a so constrained scheduling issue, likely
may remain trapped into a local optimum; thus, a proper local
search mechanism has been adopted to improve the searching per-
formance of the proposed optimization algorithm. In particular,
since the problem at hand is strongly influenced by the time posi-
tioning of the cleaning shifts, a proper local search algorithm focus-
ing on the cleaning shift starting times has been implemented.
Such a Focused Local Search (FLS) has been applied to the initial
population of the proposed GA, thus increasing the quality of
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147
solutions at the initial stage. Then, the same search mechanism
solely to the best solution is applied once a given number of
genetic iterations has been achieved. A detailed description of
the proposed HGA is reported in the following paragraphs.
3.2. Encoding a chromosome
Due to the particular structure of the problem under investiga-
tion, the adopted encoding approach is based on a two-stage chro-
mosome (hereinafter defined as x = p + g), as reported in Table 3.
The first stage (p) holds the sequence of lots to be processed, while
the second one, denoted by g, includes the department cleaning
starting time for each day of the provided time horizon TH. Thus,
as for example, p(3) = A means that a lot of product A is the third
job to be processed, while g(2) = 3 denotes that cleaning task of
the aseptic area at day 2 should start at 3 a.m., since cleaning time
intervals starting from 24:00 p.m. to 3:00 a.m. always refer to the
previous day.
3.3. Decoding procedure and fitness evaluation
A specific decoding procedure has been developed with the aim
of keeping as much as possible the feasibility of a certain chromo-
some x, and driving the genetic exploration just towards areas of
feasible solutions as well. For that reason, such decoding algorithm
has been equipped with several repair instructions, aiming to over-
come most constraint violations. In order to balance exploration
and exploitation of the proposed metaheuristics, a proper violation
function has been provided for a set of specific constraints. In fact,
an excessive number of repairing actions may convert the decoding
procedure into a constructive algorithm, thus raising the risk of
being trapped into a local near-optimal solution.
The time positioning of cleaning time intervals along the pro-
vided time horizon is a crucial aspect of the entire decoding proce-
dure, and it may strongly affect the feasibility of a given solution. In
order to properly manage the time variables included within the g
sub-chromosome, the time horizon has been arranged conforming
to a discrete time representation. So, the overall planning time,
whose length should be preliminary tuned according to the num-
ber of lots to be scheduled, is divided into a defined number of
identical time units. Conforming to the standard processing times
provided by the company, in the present research a time unit equal
to 1 h has been adopted.
According to Section 2.2, the filling stage decoding has been
included in the overall decoding procedure, which involves the
lyophilization phase as well. Remembering that the filling task
depends on the kind of lot preparation and its efficacy can be
enhanced whether triple-lot and double-lot preparations are max-
imized, the kind of preparation for each lot is managed by a proper
automatic procedure whose aim is reducing the required number
of single-lot preparations, thus giving priority to triple- and dou-
ble-lot preparations.
Table 4 shows an example about how the automatic procedure
concerning the lot preparation issue works. The first lot (p(1) = B)
to be processed must be prepared as a single-lot since it is followed
by a different type of product (A). Both second and third lot to be
Table 3
Outline of chromosome encoding.
x 5. Of course, once the mentioned actions have been applied to
p g
1 2 3 ... i ... N 1 2 3 ... d ...
B A A ... p(i) ... D 22 3 24 ... g(d) ...
137
Table 4
Example of lot preparation management.
i 1 2 3 4 5 6 7 8 9 10 11 12
p(i) B A A C C C B B D D D A
p(i) 1 2 2 2 2 1 2 2 2 2 2 1
r(i) 1 1 2 1 2 1 1 2 1 2 1 1
w(i) b a a a a a b b a a a a
scheduled are the same products (p(2) = A, p(3) = A); thus, a dou-
ble-lot preparation should be arranged: p(2) = A is the first lot to
be worked (r(2) = 1), while p(3) = A is the second prepared lot
(r(3) = 2) to be poured into the flacons. Although three C lots have
to be processed after product A, they cannot be prepared as triple-
lots because of constraint 2. Hence, fourth and fifth lot should be
managed by a double-lot preparation (p(4) = p(5) = 2), while the
remaining C lot (p(6)) is handled by a single-lot preparation
(p(6) = 1). Preparation of the downstream lots should be arranged
according to the same fashion (see Table 4). It worth pointing
out that triple-lot preparations according to constraint 2 are han-
dled by the same automatic procedure.
In short, five different leading blocks may denote the structure
of the implemented decoding algorithm:
1. First block initializes the input data defined by the user, which
also depend on the time length characterizing the planning per-
iod. However, TH depends on the number of lots to be sched-
uled. Then, for a given chromosome x to be decoded: (a)
cleaning time intervals are allocated along the provided time
horizon, according to the starting times within the g sub-chro-
mosome; (b) a kind of preparation related to the sub-chromo-
some p is assigned to each lot of the sequence by means of
the mentioned automatic procedure.
2. Second block runs the filling task related to the first lot of any
preparation to be processed. As a consequence, setup tasks
(constraint 3) and product size changeovers (constraint 4) are
managed in this block. Further, such a block of decoding proce-
dure includes two ad-hoc repair instructions addressing any
possible time overlap arising from violation of either con-
straints 5 or 6.
3. Third block is able to manage the filling task concerning the sec-
ond/third lot of any double/triple lot preparation. In case of tri-
ple-lot preparation (constraint 2), the same block is able to
schedule the filling task pertaining to both second and third
lot of such a triple preparation. Similarly to block two, this por-
tion of decoding algorithm is equipped with the same repair
instructions able to cope with any unfeasibility arising from
violation of constraints 6 and 5. In addition, in order to fulfill
the time gap required by constraint 9, such block holds a spe-
cific repair algorithm (denoted as EFL), whose role will be clar-
ified in the next sections.
4. Fourth block handles the lyophilization phase of each lot, also
including complementary tasks like loading, unloading and,
when required, CIP/SIP and leak test. It runs any possible time
overlap both constraints 11 and 12 refer to. In addition, this part
of decoding algorithm has a twofold role: reducing the loading
time in case constraint 13 occurs and tackling the task schedul-
ing affected by the product category issue (see constraints 14,
and 15). Finally, constraint 16 violation, concerning the time
overlap between the activities supporting lyophilization and
the shop cleaning, is properly faced by this block.
decode a certain schedule, a number of constraint violations
may be generated. Fifth block assigns penalties whenever con-
TH
straints 8,16 and 17 are violated and, additionally, it computes
22
the fitness function as follows:
138 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

0
fitness ¼ max flkNj g  intðv iol  J  N1:07 Þ ð1Þ endif
j¼1;:::;J
if (constraint 9 is violated, i.e. the time interval
It is a combination of two parts. The former consists of the total between fij and the expected rij > prp) then
completion time of the whole mix of lots, which coincides with the EFL repair procedure: solution is repaired by
Leak test completion time of the last processed lot. The latter is the converting the
violation function that raises the makespan value whenever a vio- second/third preparation lot into a single
lation (viol) of some aforementioned constraint occurs. The struc- preparation lot.
ture of the proposed objective function is the result of an See Appendix A.
extended tuning analysis performed at varying number of lots. endif
The following paragraph reports the pseudo-code of the whole if r(i) = 3 then
decoding procedure where each step represents one of the afore- f’ij f’ij + aft (constraint 10);
mentioned blocks. Thereafter, the pseudo-code of the EFL repairing endif
algorithm is reported. a_fill(j) f’ij;
Decoding pseudo-code endif
Step 4: Lyophilization
Input: solution chromosome x = p + g;
lij max(a_lyo(j); f’ij);
TH: provided Time Horizon in days;
l’ij lij + lld;
a_fill(j), a_lyo(j) "j e 1, . . ., J;
rij l’ij;
Step 1: Initialization
r’ij rij + pti;
- Allocation of daily cleaning starting times g(d) "d e 1,
uij r’ij;
. . ., TH to the provided time horizon:
u’ij uij + lud;
- Assignation of the kind of preparation p(i) e {1, 2, 3}
flag = 0;
"i e 1, ..., N.
if category of p(i  1) = a and category of p(i) = b
Step 1.1: i=1, select the first lot to be scheduled;
then
Step 1.2: select first available machine j e {1, ..., M};
flag = 1; neither CIPSIP nor Leak test are required
r(i) = 1, first lot to be processed must be the first lot of
(constr. 15);
preparation;
endif
Step 2: First preparation-lot filling (constr. 3)
if (time overlap between load lyophilizer and
if r(i) = 1 then
department cleaning (constr.6) = true) then
sij a_fill(j);
viol = viol + oti; where oti is the overlap time
if p(i) = D or p (i) = E then
interval between the two mentioned tasks;
product size changeover time cov is required before
endif
the filling setup may start (constr. 4);
if (time overlap between load and unload (constr.11)
changeover task may not be overlapped with either
on a lyophilizer z e {1, . . ., J}|z – j = true) then
CIP/SIP or filling tasks (constr. 5);
uzk lij + lld; where k is the lot assigned to
sij sij + cov;
lyophilizer z: k e {1, . . ., N}|k – i;
endif
u’zk uzk + lud;
s’ij sij + fsu;
a_lyo(k) u’zk;
fij s’ij;
if (both leak test and CIP/SIP for lot k and
f’ij fij + fll;
lyophilizer z = true) then
if (time overlap between setup/filling and shop floor
lczk u’zk;
cleaning = true) then
lc’zk lczk + lcs;
sij g(d) + cln: setup starting time is shifted to the
lkzk lc’zk;
cleaning completion time;
lk’zk lkzk + lkt;
endif
a_lyo(k) lk’zk;
if (time overlap between setup/filling and shift
endif
change = true) then
endif
f’ij f’ij + aft (constraint 7);
if (time overlap between load and load (constr. 12)
endif
on a lyophilizer z e {1, . . ., J}|z – j = true) then
a_fill(i) f’ij; update start filling availability time;
lij l’zk+lld; where k is the lot assigned to
goto Step 4;
lyophilizer z: k e {1, . . ., N}|k – i;
endif
endif
Step 3: Second/third preparation-lot filling
if (load time reduction is allowed according to
if r(i) > 1 then
constraint 13) then
fij f’i1,j⁄; where j⁄ is the previous machine a lot has
l’ij=l’ij-ltr;
been assigned to;
if (time overlap between unload and shop floor
if (time overlap between filling and shop floor
cleaning (constr.6) = true) then
cleaning = true) then
uij g(d) + cln;
fij g(d) + cln: setup starting time is shifted to the
endif
cleaning completion time;
if flag = 0 (constr. 14) then
endif
csij u’ij;
if (time overlap between setup/filling and shift
cs’ij csij;
change = true) then
lkij csij;
f’ij f’ij + aft (constraint 7);
lk’ij lkij;
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 139

i = i + 1; ing problems. For example, Azzaro-Pantel, Bernal-Haro, Baudet,

if i + 1 > N then goto Step 5 Domenech, and Pibouleau (1998) developed a two-stage methodol-
if r(i) = 1 then goto Step 2 ogy for the short-term batch scheduling problem. The first step
if r(i) > 1 then goto Step 3 involves the discrete-event simulation (DES) to model the produc-
Step 5: Compute constraint violation and fitness tion system behavior. In the second step they used genetic algo-
The overall schedule is analyzed rithms (GAs) for minimizing the average residence time to
for (any overlap time interval (oti) arising from produce a set of batches. Mönch, Balasubramanian, Fowler, and
constraint 8, 16 and 17 violation) Pfund (2005) studied the diffusion and oxidation areas of semicon-
viol = viol + oti; ductor wafer fabrication, where the machines can be modeled as
next parallel batch processors. They attempted to minimize total
Step 5.1: Fitness function weighted tardiness on parallel batch machines with incompatible
0
fitness ¼ maxj¼1;...;J flkNj g int(viol  J  N1.07); job families and unequal jobs ready times through a Genetic algo-
rithm combined with a decomposition method. Motivated by sched-
uling of diffusion operations in the wafer fabrication facility, Chiang,
EFL repairing procedure pseudo-code Cheng, and Fu (2010) attempted to minimize the total weighted tar-
diness on parallel batch machines with incompatible job families
Step 1: Identification of day d⁄ corresponding to lyophilizer j and dynamic job arrival. They proposed a memetic algorithm with
availability time: a new genome encoding scheme to search for the optimal or near-
if cl(d⁄) 6 a_lyo(j) 6 cl(d⁄) + cln then optimal batch formation and batch sequence simultaneously.
a_lyo(j) cl(d⁄) + cln; Machine assignment is resolved in the proposed decoding scheme.
endif Recently, Behnamian, Fatemi Ghomi, Jolai, and Amirtaheri (2012)
Step 2: Check if a forward shifting equal to cfl of the filling studied the minimization of makespan in a three-machine flowshop
start time fij may satisfy constraint 2 violation, scheduling problem in which a batch processing machine is located
otherwise, to ensure the feasibility of solution, lot i must between two single processing machines on first and third stages.
be treated as a single lot: Since the problem under study is NP-hard, a genetic algorithm is also
if a_lyo(j) + lld  fij > prp and a_lyo(j) + lld  fij 6 prp + fll proposed to minimize makespan. Finally, both efficacy and effi-
then ciency of a genetic algorithms with a novel chromosome representa-
fij a_lyo(j) + lld-prp; tion has been recently exploited for the multi-objective order
elseif a_lyo(j) + lld-fij > prp + fll then scheduling problem in a complicated production environment
if a_lyo(j) + lld-prp P f’i1,j⁄ + cst then (constr. 17) (Guo, Wong, Li, & Ren, 2013).
sij a_lyo(j) + lld-prp; The main motivation behind the hybridization of different algo-
goto step 3 rithms is to exploit the complementary character of different opti-
elseif a_lyo(j) + lld-cst P f’i1,j⁄ + cst then (constr. 17) mization strategies, that is, hybrids are believed to benefit from
sij a_lyo(j) + lld-cst; synergy. In fact, choosing an adequate combination of complemen-
goto step 3 tary algorithmic concepts can be the key for achieving top perfor-
else mance in solving many hard optimization problems (Blum,
sij f’i1,j⁄ + cst; Puchinger, Raidl, & Roli, 2011). Recently, Liao, Chang, Kuo, and
endif Liao (2014) strengthened the effectiveness of hybrid metaheuris-
Step 3: tics for solving the unrelated parallel machine scheduling and
s’ij sij + fsu; inbound truck sequencing in a multi-door cross docking system
fij s’ij; in consideration of sequence dependent setup, and both zero and
f’ij fij + fll; nonzero release time. Finally, further noteworthy research contri-
if (time overlap between setup/filling and shift butions in the field of the parallel machine scheduling problem
change = true) then were endorsed by Cheraghi, Vishwaram, & Krishnan, 2003;
f’ij f’ij + aft; Huang & Guo, 2004; Wang, Wang, Zhao, Zhang, and Xu (2013).
endif
update lot preparation schedule: p(i), r(i), "i = 1, . . ., N;
inserting the CIP/SIP task before the previous lot filling: 3.5. Structure of the proposed hybrid genetic algorithm
lci1,j⁄ f’i1,j⁄; The proposed genetic algorithm has been developed according
lc’i1,j⁄ lci1,j⁄ + cst; exit to the specific features of the industrial problem under investiga-
tion. The high number of constraints, the double encoding, the
presence of lots of the same products to be scheduled, as well as
3.4. Genetic algorithms and hybridization the need of keeping unchanged some groups of lots related to some
product types, led to the development of ad-hoc genetic operators.
Since most scheduling problems in batch processing belong to In addition, because of the numerous constraints, a local search
the family of problems classified as NP-complete, genetic algorithms focusing on the selection of the daily cleaning starting times has
and, in general, metaheuristic optimization algorithms represent a been embedded, as to improve the exploitation of the metaheuris-
good alternative for solving large-scale combinatorial problems. As tics around a certain local minimum.
for the parallel machines scheduling problems, in the last decades The initial population generation has been arranged in the fol-
numerous literary contributions emphasized the effectiveness of lowing way. Regardless of the large number of constraints to be
genetic algorithms (Balin, 2011; Costa, Cappadonna, & Fichera, managed and of the filling stage, the problem may be assimilated
2013; Vallada & Ruiz, 2011; Wang & Chou, 2010) and simulated to an identical parallel machines scheduling problem. Since the
annealing (Celano, Costa, & Fichera, 2008; Damodaran & Vélez- LPT schedule is demonstrated to be very effective for the makespan
Gallego, 2012; Kim, Kim, Jang, & Chen, 2002; Li, Ng, et al., 2011; Li, minimization in identical parallel machines scheduling problems
Yang, & Ma, 2011; Low, 2005) Further, a variety of research contribu- (Baker & Trietsch, 2009), just one chromosome of the initial
tions employed genetic algorithms for approaching batch schedul- population is generated by the LPT dispatching rule, as for the per-
140 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

constraints interact with the cleaning interval issue, the local

search operates only on the g sub-chromosome and it cyclically
is employed to investigate an extended neighborhood of the cur-
rent best solution. After a variety of trial-and-error test runs on
both small- and large-sized problems, a cyclic threshold of 50 iter-
ations has been identified as a good compromise between explora-
tion and exploitation for the proposed hybrid evolutionary
algorithm (Crepinsek, Liu, & Mernik, 2013).
Fig. 4 shows the flow chart of the proposed metaheuristic opti-
mization algorithm, whereas the following sub-sections deal with
the implemented FLS and with the adopted genetic operators.
The exit criterion of the proposed optimization technique is the
total number of iterations, hereinafter denoted as Niter.

3.5.1. Focused Local Search

The aim of the focused local search is finding a new near opti-
mal solution by keeping unchanged the permutation sub-chromo-
some p and by varying just the cleaning shift starting time for each
day, i.e. each gene of the provided g sub-chromosome. Once a new
cleaning time yields a makespan reduction of the current solution,
such a modified solution will represent the new seed chromosome
to be investigated. In detail, the search mechanism replaces each
gene of the g sub-chromosome with an integer number included
in the range [22–27], where values 25, 26, 27 correspond to
01:00 a.m., 02:00 a.m., 03:00 a.m. cleaning starting times. Once
all genes pertaining to g have been varied through the mentioned
time range, the best solution will be saved and introduced within
the genetic population. The pseudo-code exhibiting the proposed
focused local search is reported in the following paragraph.
Pseudo code of FLS

Input: chromosome solution x = p + g

Step 0: Initialization
x0 x, p0 p, g0 g, gopt g, best_mk = a big number;
Step 1: Second-stage h chromosome perturbation
g1 g0;
for d = 1 to TH
for h = 22–27
if h > 24 then
h’ = h  24;
else
Fig. 4. Flow chart of the proposed HGA.
h’ = h
endif
g1(d) = h’
mutation sub-chromosome. On the other hand, the corresponding Compute makespan:
integer sub-chromosome g is randomly generated. Starting from Makespan(x1) = Makespan(p0+g1)
the LPT-based sub-chromosome (wherein lots to be scheduled if C(x1) < best_mk then
are grouped in G groups corresponding to the types of product to g0(d) g1(d)
be processed), a neighborhood of G  1 permutation sub-chromo- gopt(d) g1(d)
somes is built to populate the remaining G  1 locations of the ini- goto Step 2
tial population. For instance, if a number of lots pertaining to three else
product types (A, B, C) has to be produced, and the LPT schedule is g1(d) g0(d)
(A, B, C), then the corresponding last insertion-based neighborhood endif
should consist in the following G  1 permutation schedules: (C, A, next h
B), (B, C, A). Also for these chromosomes, genes provided by their Step 2: perturbation of another gene
respective g sub-chromosomes are drawn from a uniform distri- next d
bution U[22 p.m., 3 a.m.]. Then, if POP is the genetic population
size, the remaining POP-G permutation sub-chromosomes are ran- 3.5.2. Crossover
domly copied from the already devised G chromosomes, whereas Whenever a pair of parent chromosomes is selected by a regular
their corresponding integer sub-chromosomes are again randomly roulette wheel criterion, a proper crossover operator is carried out
generated. with probability pcross. It combines both a Position Based Crossover
Once the initial population has been arranged, a proper focused (PBC) (Michalewicz, 1994) to be applied to p (the permutation sub-
local search FLS is applied on the integer part of each chromosome chromosome), and a proper uniform crossover to be used for g (i.e.
as to improve the quality of solutions of the initial population. In the integer coded sub-chromosome). Indeed, the adopted PBC
words, it aims to depurate each individual of the unfeasibility operator differs from the regular one, as its recombination
caused by the provided daily cleaning time intervals. Since most mechanism has to respect the provided number of lots per product
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 141

type. In addition, lots of product D and E cannot be separated, as
mentioned in the earlier sections.
Fig. 5 shows how a regular PBC procedure may be applied to a
couple of parent chromosomes P1 and P2, which handle the fol-
lowing amount of products: 3 units of product type A, four units
of product type B and three units of product type C. Selected posi-
tions are those corresponding to Npc = 5 bold lines between the two
parents. Genes (alleles) related to the unselected positions (locus)
are copied into their corresponding parents. Whereas, for a given
child, genes related to the selected positions assume a new value
conforming to the order they are reported into the other parent.
The number of units per product type must be unchanged after
the crossover is performed. Children arising from the PBC are
denoted in Fig. 5 with C1 and C2, respectively.
In case the two selected parents have the same fitness, a regular
Shift Insertion (SI) operator is applied with probability pSI to their
permutation chromosomes, thus rejecting the risk that the PBC
operator yields two children identical to their parents. In that case,
two positions are randomly selected for each parent and the corre-
sponding child is generated according to a regular shift-insertion
mechanism. Fig. 6 shows the application of a SI crossover between
positions 3 and 7 of parent P1.
As far as the second part of chromosome g is concerned, a reg-
ular Uniform Crossover (UC) has been implemented. According to a
coin toss probability criterion, a regular exchange of genetic mate-
rial is performed between two parents as to create two distinct
children. Fig. 7 reports an example of the UC operator.
3.5.3. Mutation and elitism
Mutation operator plays a key role to enhance the exploitation
phase of a genetic algorithm. It consists of a small perturbation to a
chromosome, on the basis of a specific probability pmut. The pro-
posed metaheuristic algorithm has been equipped by a pairwise
interchange operator, which randomly exchanges two genes
belonging to the same chromosome. After both crossover and
mutation are carried out, in order to avoid any loss of the best per-
forming individual from the current population, an elitism strategy
has been embedded in the proposed GA. Thus, whenever any new
population is missing of the best solution, it is inserted again in a
randomly chosen position of the new population.
4. Computational test and comparisons
This section deals with the comparison of a set of metaheuris-
tics, as to select the most suitable method for approaching the
industrial scheduling issue under investigation. First of all the
way the computational tests have been designed is discussed.
Then, a set of numerical results will be exhibited with the aim of
motivating the outperformance of the proposed HGA. Finally,
HGA will be tested and empirically validated with respect to the
schedules recently adopted by the company supervisor for a real
production plan.
All the methods were implemented in Visual Basic for Applica-
tion (VBA) language, within a MS Excel spread sheet installed in a
personal computer with a 2.7 GHz Intel Core i5 and 6 GB of RAM.

4.1. Test cases design

The goal of the first phase was identifying a set of instances in

P1 B A A C C C B B A B terms of product mixes necessary to compare the different optimi-

P2 A A B B B A B C C C Table 5
Class I – 25 lots problems.

C1 A A B B C C C B A B Product type Scenario problem

1 2 3 4 5 6 7 8 9 10

C2 B A A A B B B C C C A 3 4 7 0 1 6 10 7 10 5
B 2 5 0 6 5 3 4 5 8 5
C 14 7 9 14 11 6 8 2 4 5
Fig. 5. Position based cross-over for permutation stage p. D 6 0 9 0 7 0 3 11 0 5
E 0 9 0 5 0 10 0 0 3 5

P1 B A A C C C B B A B
Table 6
Class I – 50 lots problems.

Product type Scenario problem

C1 B A C C C B A B A B 1 2 3 4 5 6 7 8 9 10
A 6 8 14 0 2 12 20 14 20 10
Fig. 6. Shift insertion for permutation stage p. B 4 10 0 12 10 6 8 10 16 10
C 28 14 18 28 22 12 16 4 8 10
D 12 0 18 0 16 0 6 22 0 10
E 0 18 0 10 0 20 0 0 6 10

P1 22 23 22 3 2 22 1

Table 7
P2 23 24 22 23 2 2 3 Genetic parameters.

Parameter Value
C1 23 23 22 23 2 2 3 POP 50 (if N 6 25); 100 (otherwise)
Niter 400 (if N 6 25); 800 (otherwise)
pcr 0.9
C2 22 24 22 3 2 22 1 Npc dN=15e þ 1
pSI 0.50
pmut 0.05
Fig. 7. Modified uniform crossover for permutation stage g.
142 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

zation methods. On the basis of the industrial practice, the com-
pany supervisor supported the present research by providing us
with two classes of real-world problems with two levels of lots
to be scheduled. Class I holds 25 lots, while class II is based on
50 lots. Then, S = 10 different production scenarios (s = 1, . . ., S)
have been supplied by the company for each class. Tables 5 and
6 thoroughly report the number of lots per product type required
by each scenario, for class I and II respectively. Once the overall
set of scenario problems has been arranged, the provided four opti-
mization methods (namely Local Search (FLS), Simulated Anneal-
ing (SA), Genetic Algorithm (GA) and HGA) have been compared.
A summary of the main features concerning the aforementioned
optimization methods is reported in the following sub-section.
4.2. Remarks about the implemented methods
The aim of the present sub-section is to inform the reader about
the main aspects and the setting parameters characterizing the
tested algorithms, with exception of HGA.

Table 8
RPD based comparison among the proposed metaheuristics: 25 lots.

ME r Problems
1 2 3 4 5 6 7 8 9 10
LS 1 0.058 0.063 0.030 0.064 0.040 0.023 0.073 0.045 0.063 0.045
2 0.112 0.020 0.030 0.059 0.045 0.026 0.006 0.040 0.063 0.074
3 0.049 0.086 0.030 0.056 0.088 0.017 0.006 0.028 0.057 0.040
4 0.112 0.029 0.030 0.067 0.074 0.086 0.062 0.045 0.063 0.068
5 0.101 0.057 0.030 0.056 0.054 0.026 0.006 0.017 0.075 0.074
6 0.049 0.086 0.030 0.056 0.088 0.017 0.006 0.028 0.057 0.040
7 0.047 0.086 0.041 0.070 0.048 0.029 0.006 0.045 0.075 0.040
8 0.058 0.029 0.030 0.067 0.017 0.026 0.006 0.045 0.057 0.040
9 0.038 0.029 0.030 0.056 0.000 0.026 0.006 0.045 0.063 0.045
10 0.036 0.017 0.030 0.011 0.074 0.026 0.028 0.040 0.063 0.074
AVE 0.066 0.050 0.031 0.056 0.053 0.030 0.020 0.038 0.064 0.054
ST.DEV 0.030 0.029 0.003 0.017 0.029 0.020 0.026 0.010 0.007 0.016
MIN 0.036 0.017 0.030 0.011 0.000 0.017 0.006 0.017 0.057 0.040
MAX 0.112 0.086 0.041 0.070 0.088 0.086 0.073 0.045 0.075 0.074
SA 1 0.134 0.032 0.033 0.078 0.051 0.032 0.185 0.082 0.141 0.088
2 0.096 0.040 0.049 0.056 0.051 0.098 0.076 0.074 0.132 0.091
3 0.115 0.057 0.044 0.070 0.051 0.049 0.017 0.074 0.084 0.077
4 0.090 0.086 0.074 0.081 0.051 0.103 0.101 0.068 0.060 0.085
5 0.099 0.080 0.041 0.067 0.051 0.032 0.020 0.077 0.123 0.088
6 0.115 0.057 0.044 0.070 0.097 0.049 0.017 0.074 0.084 0.077
7 0.068 0.092 0.063 0.070 0.051 0.034 0.132 0.077 0.138 0.071
8 0.074 0.060 0.038 0.073 0.040 0.057 0.093 0.068 0.159 0.094
9 0.112 0.103 0.099 0.067 0.054 0.026 0.020 0.071 0.078 0.077
10 0.093 0.103 0.077 0.075 0.085 0.040 0.118 0.071 0.069 0.071
AVE 0.100 0.071 0.056 0.071 0.058 0.052 0.078 0.074 0.107 0.082
ST.DEV 0.020 0.025 0.021 0.007 0.018 0.027 0.059 0.004 0.035 0.008
MIN 0.068 0.032 0.033 0.056 0.040 0.026 0.017 0.068 0.060 0.071
MAX 0.134 0.103 0.099 0.081 0.097 0.103 0.185 0.082 0.159 0.094
GA 1 0.025 0.063 0.011 0.059 0.051 0.000 0.076 0.088 0.060 0.091
2 0.079 0.052 0.000 0.059 0.063 0.032 0.008 0.017 0.060 0.085
3 0.055 0.032 0.033 0.070 0.071 0.017 0.008 0.017 0.003 0.085
4 0.049 0.026 0.063 0.089 0.037 0.023 0.008 0.071 0.075 0.085
5 0.038 0.023 0.044 0.067 0.060 0.032 0.017 0.071 0.060 0.071
6 0.055 0.032 0.033 0.070 0.071 0.017 0.008 0.017 0.003 0.085
7 0.077 0.037 0.014 0.059 0.026 0.023 0.017 0.091 0.036 0.088
8 0.033 0.000 0.000 0.067 0.037 0.040 0.017 0.088 0.078 0.071
9 0.058 0.069 0.033 0.011 0.017 0.020 0.008 0.063 0.072 0.088
10 0.055 0.055 0.049 0.067 0.028 0.020 0.000 0.000 0.075 0.014
AVE 0.052 0.039 0.028 0.062 0.046 0.022 0.017 0.052 0.052 0.076
ST.DEV 0.017 0.021 0.021 0.020 0.020 0.011 0.021 0.035 0.029 0.023
MIN 0.025 0.000 0.000 0.011 0.017 0.000 0.000 0.000 0.003 0.014
MAX 0.079 0.069 0.063 0.089 0.071 0.040 0.076 0.091 0.078 0.091
HGA 1 0.030 0.017 0.047 0.011 0.017 0.026 0.006 0.043 0.006 0.068
2 0.033 0.011 0.011 0.011 0.000 0.020 0.006 0.017 0.036 0.068
3 0.030 0.026 0.041 0.064 0.034 0.040 0.006 0.063 0.000 0.023
4 0.038 0.032 0.025 0.008 0.060 0.026 0.006 0.003 0.000 0.068
5 0.000 0.017 0.038 0.064 0.031 0.011 0.006 0.034 0.072 0.068
6 0.030 0.011 0.014 0.056 0.043 0.020 0.006 0.040 0.006 0.020
7 0.044 0.020 0.030 0.056 0.034 0.052 0.006 0.068 0.072 0.000
8 0.019 0.034 0.011 0.000 0.048 0.029 0.006 0.060 0.072 0.020
9 0.030 0.023 0.011 0.011 0.040 0.052 0.006 0.040 0.009 0.082
10 0.047 0.034 0.038 0.064 0.034 0.029 0.006 0.040 0.057 0.085
AVE 0.030 0.023 0.027 0.035 0.035 0.030 0.006 0.041 0.033 0.050
ST.DEV 0.013 0.009 0.014 0.028 0.015 0.013 0.000 0.020 0.032 0.031
MIN 0.000 0.011 0.011 0.000 0.000 0.011 0.006 0.003 0.000 0.000
MAX 0.047 0.034 0.047 0.064 0.060 0.052 0.006 0.068 0.072 0.085

Underline identifies the lowest AVE values among the four groups of data. Bold highlights the lowest values of MIN and MAX, for each column, among the provided four
groups.
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 143

Table 9
RPD based comparison among the proposed metaheuristics: 50 lots.

ME r Problems
1 2 3 4 5 6 7 8 9 10
LS 1 0.022 0.024 0.013 0.063 0.048 0.023 0.031 0.030 0.000 0.010
2 0.060 0.027 0.067 0.029 0.047 0.027 0.022 0.036 0.000 0.065
3 0.101 0.023 0.038 0.040 0.085 0.056 0.061 0.001 0.031 0.030
4 0.073 0.053 0.039 0.035 0.041 0.020 0.073 0.001 0.031 0.061
5 0.101 0.061 0.001 0.029 0.047 0.021 0.061 0.036 0.037 0.033
6 0.101 0.023 0.038 0.040 0.085 0.056 0.061 0.001 0.031 0.030
7 0.101 0.055 0.034 0.039 0.041 0.021 0.036 0.036 0.039 0.000
8 0.039 0.027 0.034 0.004 0.075 0.020 0.031 0.001 0.000 0.031
9 0.035 0.053 0.067 0.040 0.075 0.052 0.061 0.036 0.031 0.062
10 0.064 0.060 0.046 0.076 0.076 0.050 0.031 0.031 0.000 0.036
AVE 0.070 0.041 0.038 0.040 0.062 0.035 0.047 0.021 0.020 0.036
ST.DEV 0.031 0.017 0.021 0.020 0.019 0.017 0.018 0.017 0.017 0.022
MIN 0.022 0.023 0.001 0.004 0.041 0.020 0.022 0.001 0.000 0.000
MAX 0.101 0.061 0.067 0.076 0.085 0.056 0.073 0.036 0.039 0.065
SA 1 0.408 0.197 0.324 0.134 0.052 0.130 0.098 0.072 0.215 0.144
2 0.699 0.162 0.322 0.210 0.185 0.206 0.071 0.178 0.080 0.104
3 0.395 0.176 0.447 0.105 0.385 0.125 0.242 0.112 0.271 0.175
4 0.176 0.147 0.357 0.146 0.429 0.145 0.426 0.079 0.068 0.172
5 0.417 0.128 0.421 0.140 0.355 0.172 0.248 0.139 0.152 0.141
6 0.395 0.176 0.447 0.105 0.385 0.125 0.242 0.112 0.271 0.175
7 0.419 0.066 0.388 0.105 0.116 0.114 0.065 0.170 0.073 0.172
8 0.632 0.130 0.355 0.174 0.085 0.096 0.223 0.187 0.217 0.144
9 0.627 0.130 0.121 0.121 0.111 0.168 0.248 0.110 0.192 0.135
10 0.419 0.089 0.125 0.071 0.120 0.063 0.178 0.154 0.218 0.180
AVE 0.459 0.140 0.331 0.131 0.222 0.134 0.204 0.131 0.176 0.154
ST.DEV 0.153 0.041 0.118 0.040 0.148 0.041 0.108 0.040 0.078 0.025
MIN 0.176 0.066 0.121 0.071 0.052 0.063 0.065 0.072 0.068 0.104
MAX 0.699 0.197 0.447 0.210 0.429 0.206 0.426 0.187 0.271 0.180
GA 1 0.060 0.096 0.044 0.068 0.051 0.043 0.039 0.037 0.012 0.034
2 0.059 0.052 0.014 0.065 0.058 0.030 0.074 0.042 0.037 0.042
3 0.071 0.061 0.015 0.046 0.085 0.058 0.037 0.075 0.017 0.073
4 0.066 0.037 0.052 0.040 0.076 0.034 0.095 0.073 0.014 0.095
5 0.064 0.081 0.034 0.048 0.073 0.070 0.076 0.024 0.039 0.068
6 0.071 0.061 0.015 0.046 0.085 0.058 0.037 0.075 0.017 0.073
7 0.036 0.038 0.046 0.048 0.069 0.088 0.040 0.042 0.037 0.095
8 0.066 0.066 0.018 0.048 0.071 0.064 0.091 0.040 0.039 0.042
9 0.056 0.038 0.052 0.065 0.037 0.023 0.080 0.073 0.014 0.065
10 0.028 0.040 0.031 0.056 0.044 0.090 0.059 0.067 0.014 0.037
AVE 0.058 0.057 0.032 0.053 0.065 0.056 0.063 0.055 0.024 0.062
ST.DEV 0.015 0.020 0.016 0.010 0.017 0.023 0.023 0.019 0.012 0.023
MIN 0.028 0.037 0.014 0.040 0.037 0.023 0.037 0.024 0.012 0.034
MAX 0.071 0.096 0.052 0.068 0.085 0.090 0.095 0.075 0.039 0.095
HGA 1 0.014 0.035 0.008 0.035 0.014 0.049 0.000 0.000 0.002 0.010
2 0.000 0.038 0.010 0.003 0.041 0.000 0.022 0.027 0.011 0.010
3 0.029 0.038 0.000 0.004 0.047 0.021 0.036 0.036 0.011 0.010
4 0.018 0.037 0.008 0.013 0.047 0.002 0.031 0.000 0.000 0.036
5 0.039 0.029 0.000 0.039 0.018 0.024 0.019 0.022 0.014 0.010
6 0.029 0.038 0.000 0.004 0.047 0.021 0.036 0.036 0.011 0.010
7 0.011 0.000 0.008 0.000 0.011 0.037 0.018 0.040 0.012 0.010
8 0.032 0.026 0.008 0.001 0.011 0.038 0.031 0.022 0.011 0.025
9 0.039 0.038 0.008 0.001 0.000 0.037 0.031 0.010 0.014 0.036
10 0.015 0.035 0.010 0.035 0.024 0.027 0.031 0.001 0.000 0.036
AVE 0.023 0.031 0.006 0.014 0.026 0.026 0.026 0.020 0.009 0.019
ST.DEV 0.013 0.012 0.004 0.016 0.018 0.016 0.011 0.016 0.006 0.012
MIN 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.010
MAX 0.039 0.038 0.010 0.039 0.047 0.049 0.036 0.040 0.014 0.036

Underline identifies the lowest AVE values among the four groups of data. Bold highlights the lowest values of MIN and MAX, for each column, among the provided four
groups.

4.2.1. Local search

It may be defined as a regular local search, which carries out a
search in the neighborhood of a temporary seed solution. Once the
search mechanism finds a better solution, it will represent the new
seed solution and, on the same fashion, the search procedure starts
again until an exit criterion based on the number of iterations is
satisfied. The p sub-chromosome pertaining to each seed solution
may be perturbed by means of two operators: shift insertion (SI)
and pairwise interchange (PI). Probability of perturbation for the
p sub-chromosome is 50%, and both SI and PI have a coin toss prob-
ability to be selected, as well. As concerns the g-stage solution,
each gene may be randomly modified with probability 0.05 within
the range [22:00; 03:00]. Perturbation of the g sub-chromosome is
always performed for a given seed solution.
4.2.2. Genetic algorithm
The structure of the tested Genetic Algorithm is identical to that
developed for the proposed HGA, as described in Section 3. In
words, the proposed GA may be considered as a HGA without the
contribution of the focused local search. Table 7 reports the genetic
parameters adopted for both the proposed GA and HGA.
144 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

4.2.3. Simulated annealing
It consists of a regular Simulated Annealing (Kirkpatrick, Gelatt,
& Vecchi, 1983), which starts with a randomly generated seed solu-
tion. The perturbation operators adopted for both the p-stage and
the g-stage solution are the same as those used by the aforemen-
tioned local search method. Thus, a coin toss probability drives
the selection of either SI or PI operator. Similarly, the probability
of perturbing the p sub-chromosome is equal to 50%, while each
gene of the g sub-chromosome is modified through a 5% probabil-
ity. The cooling constant has been set to a = 0.992 while the initial
temperature is equal to 1000 or 500, conforming to the class of
problem to be optimized and to the number of evaluations to be
ensured.
4.3. Numerical results
In order to reduce the variability of performance due to the ran-
dom seed driving evolutionary methods, R = 10 replicates (r = 1, . . .,
R) with different seeds have been taken into account for each sce-
nario problem s (s = 1, . . ., 10) and for each optimization method m
(m = 1, . . ., 4). As a consequence, 4  10  10  2 = 800 runs have
been exploited to test the proposed optimization procedures.
Tables 8 and 9 show the relative performance deviations (RPDs)
for each replicate of a given scenario where RPD is computed as
follows:
current r  bestMK s
RPDr;s ¼   100; 8r ¼ 1; . . . ; R;
bestMK s
where currentr is the makespan obtained by a certain metaheuris-
tics for the r-th replicate pertaining to a specific scenario problem
s, and bestMKs is the best makespan achieved among the tested
metaheuristics over the 10 replicates for the s-th scenario problem:
quite clear as the Simulate Annealing is never able to compete with
the alternative optimization procedures.
The effectiveness of the proposed HGA with respect to the other
methods may be better observed by Table 9. In fact, large-sized
instances usually involve a wider space of solutions and, as a con-
sequence, they should emphasize the ability of a certain optimiza-
tion method in searching the most promising solutions. HGA
ensures the lower average RPI values (AVE) for each investigated
scenario problem. Looking at the bold type values, HGA reaches
the minimum makespan for nine scenario problems out of ten
and, in addition, it is able to minimize the maximum RPD in nine
cases out of ten. Finally, numerical results in terms of standard
deviation highlight the robustness of the proposed HGA in solving
large-sized problems. Regardless of the SA, which reveals again a
lack of performance, Fig. 9 outlines the average RPD behavior as
both the replicate and the meta-heuristics change.
The effectiveness of metaheuristic algorithms should be evalu-
ated not only under the quality of solutions viewpoint but also in
terms of computational time efficiency. Table 10 reports the aver-
age computational times required by each metaheuristic algorithm
for each class of problem. Although the number of evaluations for
each metaheuristics is approximately the same, a slight difference
of computational performance can be observed. As concerns Class I
scenario problems both LS, SA and HGA need a smaller computa-
tional time on the average with respect to GA, respectively. Nota-
bly, the rapidity of LS and SA is justified by their simple
algorithm structure, which manages a single seed solution instead
ð2Þ of a population of chromosomes; on the other hand, the lower
computational times required by HGA confirm the effectiveness
0.120

bestMK s ¼ min MK s;r;m 8s ¼ 1; . . . ; 10; ð3Þ 0.100

r¼1;...;R
m¼1;...;4

0.080
The exit criterion used for each metaheuristics algorithm is the
total number of fitness evaluations. In particular, scenario prob- HGA
RPD

lems included in Class I were investigated on the basis of about 0.060

LS
30,000 evaluations while, as concerns larger size problems in Class
SA
II, about 60,000 solution evaluations have been taken into account. 0.040
GA
Conforming to the employed computational equipment, class I
problems took about 6 min to converge, while problems involving 0.020
50 lots needed about 15 min to achieve the provided exit criterion.
The genetic parameters as well as the other parameters required 0.000
by the other optimization methods have been selected by an 0 1 2 3 4 5 6 7 8 9 10
ANOVA analysis that, for sake of brevity, was not reported in this scenario
paper.
Table 8 refers to a customer demand of 25 lots. By looking at the Fig. 8. Average RPD diagram for Class I problems.

Average RPI values (AVE) is it possible to notice as HGA outper-

forms the other meta-heuristics (ME), with exception of scenarios
six and eight where GA and FLS achieve the best results. Whether 0.080
the minimum value of RPD (MIN) is considered as performance
0.070
indicator, a substantial equilibrium exists between GA and HGA,
while values related to the maximum RPD confirm again the effec- 0.060
tiveness of HGA with respect to the other techniques. Furthermore, 0.050
the standard deviation results put in evidence the robustness of the
RPD

0.040 HGA
proposed HGA, as confirmed by the results obtained for the sev-
0.030 LS
enth scenario problem (ST.DEV = 0). In addition, the maximum
GA
standard deviation due to scenario nine is just equal to 0.032. 0.020
Finally, it is worth noting as the quality of solutions of SA is quite 0.010
poor, as the percentage gap in terms of average RPD goes from 5.2%
0.000
to 10.7%. Fig. 8 shows the average RPD variation diagram as both
0 2 4 6 8 10 12
the scenario problem and the metaheuristic algorithm changes.
Scenario
Again, it highlights the significance performance of HGA that
mostly lies below the other competitors related curves. Also, it is Fig. 9. Average RPD diagram for Class II problems.
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147 145

Table 10
Computational times analysis.

Class rr I II
1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
LS 1 204 206 204 204 182 205 205 204 203 204 976 977 992 992 973 970 963 969 970 931
2 203 205 205 204 181 204 203 204 203 203 973 978 996 996 971 970 965 968 972 933
3 205 205 203 205 181 205 204 204 203 205 974 991 993 994 971 970 965 970 983 934
4 204 205 204 205 181 205 203 204 204 204 973 980 992 994 965 968 962 967 971 932
5 206 205 203 205 182 206 203 203 203 204 972 981 994 997 967 965 960 968 977 938
6 206 205 204 206 181 206 203 204 203 205 972 981 993 996 969 970 957 967 952 943
7 205 205 204 204 182 205 202 204 203 203 972 978 993 992 967 969 964 968 935 933
8 205 205 205 204 182 205 202 203 204 204 971 978 991 972 966 969 963 977 933 934
9 205 205 204 205 181 205 202 204 203 204 898 980 992 974 968 968 966 968 932 931
10 205 206 205 204 181 205 202 203 203 205 978 997 991 976 970 971 964 970 929 935
ave 205.0 205.4 204.1 204.7 181.7 205.3 202.7 203.6 203.0 204.1 965.9 982.1 992.7 988.3 968.7 969.0 962.9 969.2 955.4 934.4
g_ave 202.0 968.9
st.dev 6.9 19.2
SA 1 191 202 185 185 186 186 185 186 186 186 777 786 799 813 785 821 775 781 809 795
2 191 203 185 186 187 186 186 186 187 186 765 820 760 806 826 837 763 827 781 838
3 191 205 185 187 186 187 186 186 186 189 771 792 767 782 820 877 765 814 779 763
4 192 207 185 186 185 186 185 186 186 187 782 827 754 793 775 835 777 782 770 817
5 194 207 185 187 185 187 185 186 186 186 768 859 809 786 813 830 803 819 771 775
6 194 208 185 186 186 187 186 186 186 186 817 802 788 792 798 819 774 803 812 824
7 197 209 185 186 187 187 186 187 186 186 760 810 806 814 828 869 782 803 782 786
8 197 209 185 187 189 186 186 186 185 186 802 824 788 799 838 838 750 817 800 807
9 200 195 186 186 189 187 185 186 187 186 806 828 803 796 789 831 737 814 799 823
10 201 187 185 186 189 187 186 186 186 186 763 813 791 827 796 814 786 816 782 807
ave 194.8 203.2 185.1 186.2 186.9 186.6 185.6 186.1 186.1 186.4 558.2 583.4 562.5 572.1 576.7 598.8 551.2 577.2 563.5 574.3
g_ave 188.7 800.4
st.dev 6.1 25.8
GA 1 267 335 328 351 322 378 285 319 292 319 1157 1157 1158 1160 1154 1164 1155 1157 1152 1155
2 292 347 338 356 340 358 292 331 325 369 1161 1167 1157 1161 1157 1173 1157 1157 1150 1156
3 268 339 330 350 337 363 313 371 307 343 1161 1161 1160 1162 1159 1170 1153 1156 1154 1158
4 251 347 294 351 339 353 307 372 319 352 1161 1161 1157 1164 1159 1166 1155 1156 1146 1163
5 286 343 326 333 325 346 308 372 319 333 1157 1161 1154 1160 1157 1165 1157 1163 1152 1159
6 290 324 329 340 346 355 316 371 329 330 1164 1158 1157 1165 1159 1170 1157 1177 1146 1154
7 287 340 352 345 331 342 292 371 325 338 1161 1163 1155 1157 1157 1166 1154 1156 1150 1154
8 279 266 319 328 337 371 302 367 313 331 1156 1160 1157 1161 1160 1167 1151 1156 1151 1158
9 285 399 347 368 336 371 301 371 329 331 1158 1157 1153 1157 1155 1174 1153 1157 1151 1163
10 271 317 326 348 281 352 314 371 341 314 1159 1160 1157 1161 1156 1170 1148 1157 1153 1164
ave 277.6 335.7 328.9 347.0 329.4 358.9 303 361.6 319.9 336 1159.6 1160.4 1156.6 1160.8 1157.3 1168.7 1154.1 1159.2 1150.5 1158.4
g_ave 329.8 1158.6
st.dev 29.3 5.6
HGA 1 170 172 170 170 152 171 171 170 169 170 1063 1058 1058 1059 1066 1061 1049 1051 1050 1059
2 169 171 171 170 151 170 169 170 169 169 1060 1058 1055 1064 1056 1062 1051 1050 1047 1050
3 171 171 169 171 151 171 170 170 169 171 1059 1061 1064 1061 1062 1060 1052 1055 1048 1052
4 170 171 170 171 151 171 169 170 170 170 1062 1059 1057 1063 1061 1060 1046 1055 1049 1054
5 172 171 169 171 152 172 169 169 169 170 1061 1055 1057 1060 1063 1064 1048 1054 1045 1052
6 172 171 170 172 151 172 169 170 169 171 1062 1060 1055 1062 1059 1060 1049 1053 1047 1054
7 171 171 170 170 152 171 168 170 169 169 1062 1060 1058 1061 1059 1061 1034 1055 1044 1053
8 171 171 171 170 152 171 168 169 170 170 1062 1062 1059 1060 1061 1058 1046 1054 1048 1055
9 171 171 170 171 151 171 168 170 169 170 1063 1059 1058 1062 1061 1061 1047 1054 1047 1054
10 171 172 171 170 151 171 168 169 169 171 1063 1054 1060 1062 1063 1061 1046 1052 1043 1056
ave 170.8 171.2 170.1 170.6 151.4 171.1 168.9 169.7 169.2 170.1 1061.7 1058.6 1058.1 1061.4 1061.1 1060.8 1046.8 1053.3 1046.8 1053.9
g_ave 168.3 1056.3
st.dev 5.7 6.0

Bold data refer to g_ave and st.dev results.

of the focused local search in reducing the computational times Table 11

and improving the quality of solutions. Standard deviations con- Scenario problems for the validation analysis.
firms the robustness of HGA under the computational viewpoint. Product type Problem
The computational time analysis connected to Class II shows
1 2 3 4 5 6 7 8
how the problem size affects the time to convergence. SA and GA
A 3 7 0 2 6 5 0 2
are the shortest and the longest algorithm respectively, while
B 0 0 4 3 0 0 7 8
HGA seem to be negatively influenced by the problem size. Never- C 12 15 14 13 25 33 27 23
theless, the average computational performance of HGA is still D 11 7 0 0 14 13 0 0
comparable to LS and SA. E 0 0 6 5 0 0 17 15

4.4. Empirical validation of proposed HGA

namely HGA. To this aim, a set of eight schedules manually per-
The final step of the proposed numerical analysis entails the formed by the production supervisor and recently used by the
experimental validation of the proposed scheduling method, company, have been compared with the corresponding optimal
146 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147

Table 12
Comparison in terms of makespan RPD and NAL to validate HGA.

Problem Replicate RPD NAL

1 2 3 4 5 Ave Min Max Ave Min Max
1 10.6 9.9 9.9 12.4 10.1 10.6 12.4 9.9 2.00 2.00 3.00
2 9.1 10.7 10.1 13.6 10.9 10.9 13.6 9.1 3.00 2.00 3.00
3 10.7 8.3 10.7 12.0 7.0 9.7 12.0 7.0 2.00 1.00 2.00
4 7.2 4.7 7.2 8.5 3.4 6.2 8.5 3.4 2.00 2.00 2.00
5 10.4 8.3 11.8 10.4 10.4 10.3 11.8 8.3 4.00 3.00 4.00
6 4.6 7.6 8.7 5.3 7.1 6.7 8.7 4.6 3.00 2.00 3.00
7 6.3 3.7 6.8 7.1 7.6 6.3 7.6 3.7 3.00 2.00 3.00
8 7.1 10.3 6.9 7.1 6.7 7.6 10.3 6.7 3.00 2.00 4.00
Ave 8.6 10.7 6.8 2.75 2.00 3.00

schedules provided by the developed scheduling tool. The adopted
key performance indicator is the total completion time of the
whole mix of lots and the main goal consists of evaluating the
expected number of additional lots that the proposed intelligent
tool may lead to. Table 11 exhibits both the type and the number
of lots that characterize each scenario problem involved in the val-
idation analysis. Table 12 makes the reader able to compare the
schedules performed by the company with those yielded by the
HGA. In particular, five replicates with different seeds have been
carried out for each scenario problem and the corresponding RPD
comparing the performance arising from each replicate with that
manually reached by the company has been reported in Table 12.
Numerical results confirm that HGA is able, on the average, to
ensure a makespan reduction equal about to 8.6%. According to
an optimistic viewpoint, the average makespan reduction could
achieve the 10.7%, while the worse expected result should entail
a 6.8% makespan reduction with respect to the company approach
based on the supervisor’s experience. Basically, the most signifi-
cance makespan improvement (13.6%) pertains replicate four of
problem two, whereas the worst result (3.4%) is ascribable to the
fifth replicate of problem four. However, it worth pointing out as
the HGA-based scheduler is able to assure a makespan reduction
as well as a production rate improvement in all the investigated
tested cases. As far as the Number of Additional Lots (NAL) indica-
tor, numerical results are reported in Table 12 too. NAL is equal to
the number of additional lots that may be started within the time
window between the makespan reached by the company schedule
and that yielded by HGA. Since the scenario problems provided by
the company should embrace a time horizon equal about to one
month, the results in terms of NAL highlight as HGA may generate
an average NAL increase, which goes from a minimum of two to a
maximum of three lots. Without loss of generality, it could be sta-
ted that the average annual benefit gained from the proposed
scheduling method is equal about to 33 lots.
5. Conclusion
In this paper a real-life batch scheduling problem from the
pharmaceutical industry has been addressed. The scheduling prob-
lem under investigation is characterized by several constraints and
process features, most of which due to a series of compulsory dis-
positions that firms working in the pharmaceutical environment
have to respect. Since the mentioned constraints strongly increase
the degree of complexity of the problem under investigation, no
mathematical modeling has been developed and, as a result, any
chance of optimally solving the proposed scheduling problem has
been disregarded. Thus, a dedicated hybrid genetic algorithm has
been developed in order to fulfill the firm’s requirements. Since
most constraints refer to the time overlap between different tasks,
a proper two-stage encoding has been designed. In particular, the
first-stage chromosome is arrange as a permutation string aiming
to run the lot sequencing, while the second stage-stage chromo-
some drives the time allocation of the cleaning shifts along the pro-
vided time horizon. In fact, since the more restrictive constraint
concerns the compulsory execution of a daily cleaning shift, a spe-
cific portion of the chromosome has been committed to the time
allocation of the cleaning shifts. Then, in order to properly manage
the mentioned constraints, a specific decoding algorithm has been
embedded within the proposed metaheuristics. Basically, it com-
putes the fitness function of a given chromosome by adopting a
twofold constraint management procedure. Most constraint viola-
tions are repaired during the decoding procedure, while the
amount of violations concerning the remaining constraints feed a
proper penalty function connected to the makespan computation.
In light of what stated before about the influence of the cleaning
shifts time location, the proposed HGA integrates a regular GA
framework and a proper local search whose purpose is evaluating
the neighborhood of a specific solution, just by varying the integer
sub-chromosome holding the cleaning schedule.
The quality of solutions as well as the robustness of the pro-
posed HGA was tested with respect to a set of alternative metaheu-
ristics, namely a Simulated Annealing, a regular genetic algorithms
and a specific local search. The test benchmark was generated
through a set of real-world data supplied by the company and
the obtained numerical results confirmed the effectiveness of the
proposed HGA under the quality of solution viewpoint. Further-
more, a set of schedules performed by the company supervisor
have been utilized as a benchmark to validate the proposed HGA
and to evaluate the average difference of performance between
the empirical approach used by the company to date and the pre-
sented optimized expert system. The proposed genetic optimiza-
tion engine has been embedded within a customized production
scheduler that is currently used by the company supervisor.
Though the scheduler is mainly oriented to the short-term produc-
tion planning, often it used by the management of the company for
approaching medium-term forecast analyses, whose objective is to
provide the expected number of lots the system is able to produce
within a specific time window.
References
Azzaro-Pantel, C., Bernal-Haro, L., Baudet, P., Domenech, S., & Pibouleau, L. (1998). A
two-stage methodology for short-term batch plant scheduling: discrete event
simulation and genetic algorithms. Computers & Chemical Engineering, 22(10),
1461–1481.
Balin, S. (2011). Non-identical parallel machine scheduling using genetic algorithm.
Expert Systems with Applications, 38(6), 6814–6821.
Baker, K. R., & Trietsch, D. (2009). Principles of sequencing and scheduling. NJ: Wiley &
Sons Inc.
Behnamian, J., Fatemi Ghomi, S. M. T., Jolai, F., & Amirtaheri, O. (2012). Minimizing
makespan on a three-machine flowshop batch scheduling problem with
transportation using genetic algorithm. Applied Soft Computing, 12, 768–777.
Blum, C., Puchinger, J., Raidl, G. R., & Roli, A. (2011). Hybrid metaheuristics in
combinatorial optimization: A survey. Applied Soft Computing, 11, 4135–4151.
 A. Costa / Computers & Industrial Engineering 79 (2015) 130–147
Celano, G., Costa, A., & Fichera, S. (2008). Scheduling of unrelated parallel
manufacturing cells with limited human resources. International Journal of
Production Research, 46, 405–427.
Chen, Y.-Y., Cheng, C.-Y., Wang, L.-C., & Chen, T.-L. (2013). A hybrid approach based
on the variable neighborhood search and particle swarm optimization for
parallel machine scheduling problems – A case study for solar cell industry.
International Journal of Production Economics, 141, 66–78.
Cheng, B., Cai, J., Yang, S., & Hu, X. (2014). Algorithms for scheduling incompatible
job families on single batching machine with limited capacity. Computers and
Industrial Engineering. http://dx.doi.org/10.1016/j.cie.2014.06.014.
Cheraghi, S. H., Vishwaram, V., & Krishnan, K. K. (2003). A hybrid genetic algorithm
for scheduling of a single batch-processing machine. International Journal of
Industrial Engineering: Theory Applications and Practice, 10(2), 175–187.
Chiang, T.-C., Cheng, H.-C., & Fu, L.-C. (2010). A memetic algorithm for minimizing
total weighted tardiness on parallel batch machines with incompatible job
families and dynamic job arrival. Computers & Operations Research, 37,
2257–2269.
Costa, A., Cappadonna, F. A., & Fichera, S. (2013). A hybrid genetic algorithm for job
sequencing and worker allocation in parallel unrelated machines with
sequence-dependent setup times. International Journal of Advanced
Manufacturing Technology, 69, 2799–2817.
Crepinsek, M., Liu, S.-H., & Mernik, M. (2013). Exploration and exploitation in
evolutionary algorithms: A survey. ACM Computing Surveys, 45(3). Art. 35.
Damodaran, P., & Vélez-Gallego, M. C. (2012). A simulated annealing algorithm to
minimize makespan of parallel batch processing machines with unequal job
ready times. Expert Systems with Applications, 39(1), 1451–1458.
Fu, R., Cheng, T. C. E., Ng, C. T., & Yuan, J. (2013). An optimal online algorithm for
single parallel-batch machine scheduling with incompatible job families to
minimize makespan. Operations Research Letters, 41, 216–219.
Guo, Z. X., Wong, W. K., Leung, S. Y. S., Fan, J. T., & Chan, S. F. (2006). Mathematical
model and genetic algorithm for the job shop scheduling problem in mixed- and
multi- product assembly environment: A case study based on the apparel
industry. Computers & Industrial Engineering, 50, 202–219.
Guo, Z. X., Wong, W. K., Li, Z., & Ren, P. (2013). Modeling and Pareto optimization of
multi-objective order scheduling problems in production planning. Computers
& Industrial Engineering, 64, 972–986.
He, Y., & Hui, C.-W. (2010). A binary coding genetic algorithm for multi-purpose
process scheduling: A case study. Chemical Engineering Science, 65, 4816–4828.
Hermann, J. (2006). Handbook of production scheduling. New York, NY 10013, USA:
Springer+Science+Business Media, Inc.
Huang, D. C., & Guo, H. D. (2004). Hybrid genetic algorithm for solving job
scheduling problem on non-identical parallel machines based on JIT technique.
Computer Integrated Manufacturing Systems, 10(3), 298–302.
Huang, S., Cai, L., & Zhang, X. (2010). Parallel dedicated machine scheduling problem
with sequence-dependent setups and a single server. Computers & Industrial
Engineering, 58, 165–174.
Jia, J., & Mason, S. J. (2009). Semiconductor manufacturing scheduling of jobs
containing multiple orders on identical parallel machines. International Journal
of Production Research, 47(10), 2565–2585.
Kim, D. W., Kim, K. H., Jang, W., & Chen, F. F. (2002). Unrelated parallel machine
scheduling with setup times using simulated annealing. Robotics and Computer-
Integrated Manufacturing, 18(3–4), 223–231.
Kirkpatrick, S., Gelatt, C. D., & Vecchi, M. P. (1983). Optimization by simulated
annealing. Science, 220, 671–680.
Kopanos, G. M., Mendez, C. A., & Puigjaner, L. (2010). MIP-based decomposition
strategies for large-scale scheduling problems in multiproduct multistage batch
plants: A benchmark scheduling problem of the pharmaceutical industry.
European Journal of Operational Research, 207, 644–655.
Li, K., Yang, S.-L., & Ma, H.-W. (2011a). A simulated annealing approach to minimize
the maximum lateness on uniform parallel machines. Mathematical and
Computer Modeling, 53(5–6), 854–860.
Li, S., Ng, C. T., Cheng, T. C. E., & Jinjiang, Yuan (2011b). Parallel-batch scheduling of
deteriorating jobs with release dates to minimize the makespan. European
Journal of Operational Research, 210, 482–488.
147
Li, X. L., Huang, Y. L., Tan, Q., & Chen, H. P. (2013). Scheduling unrelated parallel
batch processing machines with non-identical job sizes. Computers & Operations
Research, 40, 2983–2990.
Liao, T. W., Chang, P. C., Kuo, R. J., & Liao, C.-J. (2014). A comparison of five hybrid
metaheuristic algorithms for unrelated parallel-machine scheduling and
inbound trucks sequencing in multi-door cross docking systems. Applied Soft
Computing, 21, 180–193.
Lin, R., & Liao, C.-J. (2012). A case study of batch scheduling for an assembly shop.
International Journal of Production Economics, 139, 473–483.
Liu, L. L., Ng, C. T., & Cheng, T. C. E. (2009). Scheduling jobs with release dates on
parallel batch processing machines. Discrete Applied Mathematics, 157,
1825–1830.
Low, C. (2005). Simulated annealing heuristic for flow shop scheduling problems
with unrelated parallel machines. Computers & Operations Research, 32(8),
2013–2025.
Loukil, T., Teghem, J., & Fortemps, P. (2007). A multi-objective production
scheduling case study solved by simulated annealing. European Journal of
Operational Research, 179, 709–722.
Meeran, S., & Morshed, M. S. (2012). A hybrid genetic tabu search algorithm for
solving job shop scheduling problems: A case study. Journal of Intelligent
Manufacturing, 23, 1063–1078.
Michalewicz, Z. (1994). Genetic algorithms + data structures = evolution programs
(2nd ed.). Springe-Verlag.
Missbaurer, H., Hauber, W., & Stadler, W. (2009). A scheduling system for the
steelmaking-continuous casting process. A case study from the steel-making
industry. International Journal of Production Economics, 47(15), 4147–4172.
Mönch, L., Balasubramanian, H., Fowler, J. W., & Pfund, M. E. (2005). Heuristic
scheduling of jobs on parallel batch machines with incompatible job families
and unequal ready times. Computers & Operations Research, 32, 2731–2750.
Pearn, W. L., Chung, S. H., Chen, A. Y., & Yang, M. H. (2004). A case study on the
multistage IC final testing scheduling problem with reentry. International
Journal of Production Economics, 88, 257–267.
Sand, G., Till, J., Tometzki, T., Urselmann, M., Engell, S., & Emmerich, M. (2008).
Engineered versus standard evolutionary algorithms: A case study in batch
scheduling with resources. Computers & Chemical Engineering, 32(11),
2706–2722.
Soman, C. A., Van Donk, D. P., & Gaalman, G. J. C. (2007). Capacitated planning and
scheduling for combined make-to-order and make-to-stock production in the
food industry: An illustrative example. International Journal of Production
Economics, 108, 191–199.
Soyuer, H., Kocamaz, M., & Kazancoglu, Y. (2007). Scheduling jobs through multiple
parallel channels using an expert system. Production Planning and Control, 18(1),
35–43.
Stefansson, H., Sigmarsdottir, S., Jensson, P., & Shah, N. (2011). Discrete and
continuous time representations and mathematical models for large production
scheduling problems: A case study from the pharmaceutical industry. European
Journal of Operational Research, 215, 383–392.
Vallada, E., & Ruiz, R. (2011). A genetic algorithm for the unrelated parallel machine
scheduling problem with sequence dependent setup times. European Journal of
Operational Research, 211(3), 612–622.
Venditti, L., Pacciarelli, D., & Meloni, C. (2010). A tabu search algorithm for
scheduling pharmaceutical packaging operations. European Journal of
Operational Research, 202, 538–546.
Yang, T. (2009). An evolutionary simulation-optimization approach in solving
parallel-machine scheduling problems – A case study. Computers and Industrial
Engineering, 56, 1126–1136.
Wang, W.-L., Wang, H.-Y., Zhao, Y.-W., Zhang, L.-P., & Xu, X.-L. (2013). Parallel
machine scheduling with splitting jobs by a hybrid differential evolution
algorithm. Computers & Operations Research, 40, 1196–1206.
Wang, H. M., & Chou, F. D. (2010). Solving the parallel batch-processing machines
with different release times, job sizes, and capacity limits by metaheuristics.
Expert Systems with Applications, 37(2), 1510–1521.