Research methodology
Preparing pharmaceutical required materials, manufacturing, and distributing medicines are significant matters in societies. Unfortunately, the pharmaceutical industry in Iran faces hardships originated from many reasons; sometimes some problems exist in the companies causing delays in supplying required medicines. All these reasons influence the performance of each element involving in pharmaceutical supply chain. Furthermore, changes occurred on the performance of each element affect the performance of the other ones and the whole of supply chain too because they interact with each other. These interactions encouraged us to choose agent based simulation approach. According to this approach, we can comprehend complex systems and remark that simple and also complex phenomena can be the result of interactions between autonomous and independent entities like agents operating within communities having different interaction modes (
29). It is innovative because you can investigate the changes occurring in the behavior of a specific agent as a result of changes happening in other agents’ behavior or environment. For example, if manufacturing agent could produce more quantities, the sale agent would be able to accept more requests and the lost sales would be reduced. The aim of this study is simulating the manufacturing behavior, sale, and receiving order behaviors pertinent to manufacturing and sale agents acting across a pharmaceutical supply chain of an Iranian manufacturing medicine as a case study. These two agents are considered because after interviews done with the company’s chief executive manager and strategic planning manager in order to get general information of the supply chain, it was founded that the sale and manufacturing departments have some problems affecting the entire supply chain unfavorably. Additionally, three medicines which each of them are related to each group of medicines produced by the company were selected by the chief executive mangers in order to be studied. The research has been done in two main phases: 1) modeling and 2) simulation.
To accomplish the first phase, mangers of those two related departments were interviewed in order to gather the general data of their performance. After that, the information of daily quantities related to produced medicines were gathered. Then, the mathematical and computer modeling were done. In some parts, regression modeling was used while in the other parts the system was modeled mathematically based on information gathered. More information is described about regression and modeling phase during the next parts.
The term computer simulation is pertinent to the application of a computational model to improve the understanding of a system›s behavior and/or to evaluate strategies for its operation, in explanatory or predictive schemes (
29). In the simulation phase, the computer simulation was done and the results were analyzed based on lean, agile, and green paradigm.
Modeling phase
A model represents the construction and working of some systems. A model is similar to the considered system but it is not as complex as it (
30). As it was mentioned above, regression modeling is a way done during some parts of the research. This method is a mathematical approach describing a process in terms of a set of associated variables. The values of one variable frequently depend on the levels of several others (
31). The single linear regression model and its parameters’ formulas are mentioned in the following (
32):
Karl Pearson developed a quantity called linear correlation coefficient measuring the strength and the direction of a linear relationship between two variables. Pearson’s r can range from -1 to 1. An r of -1 indicates a perfect negative linear relationship between variables, an r of 0 indicates no linear relationship between variables, and an r of 1 indicates a perfect positive linear relationship between variables. With real data, you would not expect to get values of r of exactly -1, 0, or 1. The mathematical formula for computing r is (33):
There is another quantity known as coefficient of determination (r
2) calculated based on correlation coefficient and defined as the proportion of variance explained by the regression model applied as a measure of success of predicting the dependent variable from the independent variables. It is applied in classical regression analysis; in fact, it is indicating how well the regression line represents the data (
34).
Mathematical modeling for sale agent
In this company, the sale manager provides a report related to periods of every three months containing the information of all orders received and all medicines sold during the periods as well as the calculated quantities which are equivalent to daily received orders and medicines sold. To model cumulative quantities of received orders (Rx), medicines sold (Sx), and lost sales (LSx) for each medicine during t days, the mentioned information was gathered and the cumulative quantities were calculated. The models are mentioned on
Table 2.
| The equation of received orders (Rx) | The equation of sold medicines (Sx) | The equation of lost sale (LSx) |
|---|
| Medicine related to non- antibiotic group | | | |
| Medicine related to antibiotic group | | | |
| Medicine related to semi-solid group | | | |
Mathematical modeling for manufacturing agents
To model the production capacity of manufacturing agents mathematically, the daily production information of each agent were gathered during 90 days and the cumulative quantities of gross production for each manufacturing agent were calculated. After that, the pertinent charts were drawn.
Figure 1 depicts an example of them. Then, regression modeling was applied.
Table 3 includes the result of the modeling. GPx is the abbreviation of cumulative gross production of the medicine x. Because the coefficient of determination (r
2) for each equivalent is near to 1, all equivalents model the related behaviors in the best manner.
Cumulative quantities of gross production for medicine manufactured by semi-solid manufacturing agent.
| The regression model of cumulative gross production (GPx) | r | r2 |
|---|
| The non-antibiotic agent | 19717.660 | 0.994 | 0.988 |
| Antibiotic manufacturing agent | | 0.992 | 0.984 |
| Semi-solid manufacturing agent | | 0.995 | 0.99 |
To model manufacturing agents’ producing waste behavior two parameters (mx) and (nx) calculated by the company management representative for each medicine considered; (mx) is portion of waste produced daily, and (nx) is portion of daily net production too. Therefore,the cumulative produced waste (Wx) and the cumulative net production of x (NPx) during t days can be calculated as follow:
Wx=mx×GPx (5)
NPx=nx×GPx (6)
Nx=1-mx (7)
Table 4 contains the Wx and NPx models related to each considered medicine.
| Wx | NPx |
|---|
| Mathematical model of non-antibiotic manufacturing agent’s behavior | Wn = 0.005600682 × GPn | NPn = 0.994399318 × GPn |
| mathematical model of antibiotic manufacturing agent’s behavior | Wa = 0.003054849 × GPa | NPa = 0.996945 × GPa |
| Mathematical model of semi-solid Manufacturing agent’s behavior | Ws = 0.0044090946 × GPs | NPs = 0.995909054 × GPs |
Computer modeling
The simulation program was composed on MATLAB based on the information gathered. Simulation time (T), order quantity (oq), portion of waste pertinent to each medicine produced daily (mx), and portion of net production relevant to each medicine (nx), as well as coefficient of production capacity (A) are considered as parameters can be adjusted by users. In addition, users can determine that the material is provided by foreign or domestic suppliers. Based on the interview done with the company chief executive manager, when needed material is provided by domestic suppliers, lead time is 90 days; it is considered 180 days when suppliers are foreign. The lead time is applied for comparing total needed time for manufacturing received orders (nt) and Simulation time. For computer modeling, the mathematical models were used. For example, you can follow the logic behind a part of computer modeling when the aim is to investigate production feasibility for the specified order quantities during a determined period by means of simulation.
The general format for the formula of all GPx is mentioned in following:
Based on the formula, the required time for process of producing received orders (pt) is formulated as follow:
During writing the program, the codes were supervised, tested, and confirmed by two experts who are university professors teaching simulation courses and having at least three years experience of teaching MATLAB too. Finally, when the simulation program was written entirely, it was tested by experts several times; the results were based on the reality. For example, when the program was run for the antibiotic medicine, we came in conclusion the supply chain is not agile according to charts and numeric data derived. In the real world, the company’s supply chain pertinent to each medicine is not agile too.
Simulation phase
Simulation is the imitation of a real world process or system; gathering artificial history of a system reached by simulation and observing them propel us to apprehend operating characteristic of the real system modeled (
35). Simulation is applied in different situation. For example, it is used before altering an existing system or building a new one to reduce the chances of failure, meet specifications, eliminate unforeseen bottlenecks, prevent under or over-utilization of resources, and optimize system performance (
30). Many scenarios can be considered to be simulated; in this paper, four scenarios are considered for simulating the supply chain. They are mentioned during next parts.
Scenario 1
In order to investigate the production capacity, received orders, sales, and lost sales during the 350 days, which is equivalent to one working year, the program was run for each medicine. Parameters considered for simulation were those calculated according to data gathered therefore the real situation is simulated based on this scenario.
Table 5 embraces the simulation parameters.
Figures 2-
4 manifest the charts derived from simulation.
T = 350
|
|---|
mx
| nx
|
|---|
| The non-antibiotic medicine | The antibiotic medicine | The semi-solid medicine | The non-antibiotic medicine | The antibiotic medicine | The semi-solid medicine |
|---|
| 0.005600682 | 0.003054849 | 0.0044090946 | 0.994399318 | 0.996945 | 0.995909054 |
The non-antibiotic medicine’s charts resulted from running the simulation program based on scenario 1
The antibiotic medicine’s charts resulted from running the simulation program based on scenario 1
The semi-solid medicine’s charts resulted from running the simulation program based on scenario 1
Scenario 2
It was decided to investigate what would happen to the production capacity of non-antibiotic medicine manufacturing agent if the parameter (mx) was decreased to half?
Table 6 contains the results.
The non-antibiotic medicine
|
|---|
T = 350 days
|
|---|
m = 0.005600682
| m = 0.002800341
|
|---|
| Variable name | The simulation result | Variable name | The simulation result |
|---|
| Wn | 30445.298 | Wn | 15222.649 |
| NPn | 5405553.042 | NPn | 5420775.691 |
Scenario 3
Based on a research have been done in the company by a team that is responsible to improve the processes and their performance, it was not clarified correctly how long the processes last; otherwise, the speed of production processes at some stages can be increased. Poor maintenance is another reason which has an impact on the production capacity because it causes the production line stops working. The new scenario for simulation is increasing the production capacity 1.2 times as a result of solving the noted problems. The results of simulating the non-antibiotic medicine’s supply chain under the new condition are mentioned on
Table 7 and
Figure 5.
The non-antibiotic medicine
|
|---|
T = 350 daysm = 0.005600682
|
|---|
Before increasing production capacity (A = 1)
| After increasing production capacity (A = 1.2)
|
|---|
| Variable name | The result of simulation | Variable name | The result of simulation for T days |
|---|
| GPn | 5435998.34 | GPn | 6523198 |
| NPn | 5405553.042 | Npn | 6486663.65 |
The charts resulted from running the simulation program based on scenario 1 before and after increasing production capacity
Scenario 4
According to this scenario, the possibility of receiving 145000 units’ orders for the non-antibiotic medicine which should be prepared during next 70 days while the company confronts lack of raw material and the suppliers are domestic was investigated.
Table 8 embraces the results.
The Non-Antibiotic Medicine
|
|---|
T = 70 daysm = 0.005600682oq = 145000Lead time = 90
|
|---|
| GPn | NPn | Nt |
|---|
| 1071425.54 | 1065424.8263 | 100.56 |