Production planning of biopharmaceutical manufacture.

Multiproduct manufacturing facilities running on a campaign basis are increasingly becoming the norm for biopharmaceuticals, owing to high risks of clinical failure, regulatory pressures and the increasing number of therapeutics in clinical evaluation. The need for such flexible plants and cost-effective manufacture pose significant challenges for planning and scheduling, which are compounded by long production lead times, intermediate product stability issues and the high cost - low volume nature of biopharmaceutical manufacture. Scheduling and planning decisions are often made in the presence of variable product titres, campaign durations, contamination rates and product demands. Hence this thesis applies mathematical programming techniques to the planning of biopharmaceutical manufacture in order to identify more optimal production plans under different manufacturing scenarios. A deterministic mixed integer linear programming (MILP) medium term planning model which explicitly accounts for upstream and downstream processing is presented. A multiscenario MILP model for the medium term planning of biopharmaceutical manufacture under uncertainty is presented and solved using an iterative solution procedure. An alternative stochastic formulation for the medium term planning of biomanufacture under uncertainty based on the principles of chance constrained programming is also presented. To help manage the risks of long term capacity planning in the biopharmaceutical industry, a goal programming extension is presented which accounts for multiple objectives including cost, risk and customer service level satisfaction. The model is applied to long term capacity analysis of a mix of contractors and owned biopharmaceutical manufacturing facilities. In the final sections of this thesis an example of a commercial application of this work is presented, followed by a discussion on related validation issues in the biopharmaceutical industry. The work in this thesis highlighted the benefits of applying mathematical programming techniques for production planning of biopharmaceutical manufacturing facilities, so as to enhance the biopharmaceutical industry's strategic and operational decision-making towards achieving more cost-effective manufacture

A Multiperiod Supply Chain Network Design Considering Carbon Emissions

This paper introduces a mixed integer linear programming formulation for modeling and solving a multiperiod one-stage supply chain distribution network design problem. The model is aimed to minimize two objectives, the total supply chain cost and the greenhouse gas emissions generated mainly by transportation and warehousing operations. The demand forecast is known for the planning horizon and shortage of demand is allowed at a penalty cost. This scenario must satisfy a minimum service level. Two carbon emission regulatory policies are investigated, the tax or carbon credit and the carbon emission cap. Computational experiments are performed to analyze the trade-offs between the total cost of the supply chain, the carbon emission quantity, and both carbon emission regulatory policies. Results demonstrate that for a certain range the carbon credit price incentivizes the reduction of carbon emissions to the environment. On the other hand, modifying the carbon emission cap inside a certain range could lead to significant reductions of carbon emission while not significantly compromising the total cost of the supply chain

Operations Management of Logistics and Supply Chain: Issues and Directions

There has been consensus that logistics as well as supply chain management is a vital research field, yet with few literature reviews on this topic. This paper sets out to propose some hot issues in the current research, through a review of related literature from the perspective of operations management. In addition, we generate some insights and future research directions in this field

Supply chain management for the process industry

This thesis investigates some important problems in the supply chain management (SCM) for the process industry to fill the gap in the literature work, covering production planning and scheduling, production, distribution planning under uncertainty, multiobjective supply chain optimisation and water resources management in the water supply chain planning. To solve these problems, models and solution approaches are developed using mathematical programming, especially mixed-integer linear programming (MILP), techniques. First, the medium-term planning of continuous multiproduct plants with sequence-dependent changeovers is addressed. An MILP model is developed using Travelling Salesman Problem (TSP) classic formulation. A rolling horizon approach is also proposed for large instances. Compared with several literature models, the proposed models and approaches show significant computational advantage. Then, the short-term scheduling of batch multiproduct plants is considered. TSP-based formulation is adapted to model the sequence-dependent changeovers between product groups. An edible-oil deodoriser case study is investigated. Later, the proposed TSP-based formulation is incorporated into the supply chain planning with sequence-dependent changeovers and demand elasticity of price. Model predictive control (MPC) is applied to the production, distribution and inventory planning of supply chains under demand uncertainty. A multiobjective optimisation problem for the production, distribution and capacity planning of a global supply chain of agrochemicals is also addressed, considering cost, responsiveness and customer service level as objectives simultaneously. Both ε- constraint method and lexicographic minimax method are used to find the Pareto-optimal solutions Finally, the integrated water resources management in the water supply chain management is addressed, considering desalinated water, wastewater and reclaimed water, simultaneously. The optimal production, distribution and storage systems are determined by the proposed MILP model. Real cases of two Greek islands are studied

Petroleum Refining and Petrochemical Industry Integration and Coordination under Uncertainty

Petroleum refining and the petrochemical industry account for a major share in the world energy and industrial market. In many situations, they represent the economy back-bone of industrial countries. Today, the volatile environment of the market and the continuous change in customer requirements lead to constant pressure to seek opportunities that properly align and coordinate the different components of the industry. In particular, petroleum refining and petrochemical industry coordination and integration is gaining a great deal of interest. However, previous research in the field either studied the two systems in isolation or assumed limited interactions between them. The aim of this thesis is to provide a framework for the planning, integration and coordination of multisite refinery and petrochemical networks using proper deterministic, stochastic and robust optimization techniques. The contributions of this dissertation fall into three categories; namely, a) Multisite refinery planning, b) Petrochemical industry planning, and c) Integration and coordination of multisite refinery and petrochemical networks. The first part of this thesis tackles the integration and coordination of a multisite refinery network. We first address the design and analysis of multisite integration and coordination strategies within a network of petroleum refineries through a mixed-integer linear programming (MILP) technique. The integrated network design specifically addresses intermediate material transfer between processing units at each site. The proposed model is then extended to account for model uncertainty by means of two-stage stochastic programming. Parameter uncertainty was considered and included coefficients of the objective function and right-hand-side parameters in the inequality constraints. Robustness is analyzed based on both model robustness and solution robustness, where each measure is assigned a scaling factor to analyze the sensitivity of the refinery plan and the integration network due to variations. The proposed technique makes use of the sample average approximation (SAA) method with statistical bounding techniques to give an insight on the sample size required to give adequate approximation of the problem. The second part of the thesis addresses the strategic planning, design and optimization of a network of petrochemical processes. We first set up and give an overview of the deterministic version of the petrochemical industry planning model adopted in this thesis. Then we extend the model to address the strategic planning, design and optimization of a network of petrochemical processes under uncertainty and robust considerations. Similar to the previous part, robustness is analyzed based on both model robustness and solution robustness. Parameter uncertainty considered in this part includes process yield, raw material and product prices, and lower product market demand. The Expected Value of Perfect Information (EVPI) and Value of the Stochastic Solution (VSS) are also investigated to numerically illustrate the value of including the randomness of the different model parameters. The final part of this dissertation addresses the integration between the multisite refinery system and the petrochemical industry. We first develop a framework for the design and analysis of possible integration and coordination strategies of multisite refinery and petrochemical networks to satisfy given petroleum and chemical product demand. The main feature of the work is the development of a methodology for the simultaneous analysis of process network integration within a multisite refinery and petrochemical system. Then we extend the petroleum refinery and petrochemical industry integration problem to consider different sources of uncertainties in model parameters. Parameter uncertainty considered includes imported crude oil price, refinery product price, petrochemical product price, refinery market demand, and petrochemical lower level product demand. We apply the sample average approximation (SAA) method within an iterative scheme to generate the required scenarios and provide solution quality by measuring the optimality gap of the final solution

Interactive Multicriteria Approach to Facility Location-Allocation Models Under Stochastic Demand

Industrial Engineering and Managemen