Achieving Process Intensification by Scheduling and Debottlenecking Biotech Processes

An approach to reduce batch time, increase productivity, and decrease costs.
Feb 01, 2011
Volume 24, Issue 2


Process intensification is the new catchphrase in biotech processing. It includes concepts such as reducing the process time of a particular unit operation, decreasing the overall process time by improved alignment of various unit operations, and reducing plant idle time by improved equipment utilization. Biotech manufacturers are realizing that cost savings from such efforts, which result in improved productivity for a facility, far exceed those from the traditional focus area of raw materials. This article presents an approach for performing process scheduling and debottlenecking.

The combination of rising costs for discovery, development, and commercialization of biotech drugs, and ever increasing pressure on product pricing from the government and insurance agencies has put renewed focus on containing manufacturing costs in the biotech industry. Process intensification is emerging as one way to achieve this desired objective and includes concepts such as reducing the process time of a particular unit operation, decreasing the overall process time by improved alignment of various unit operations, and reducing idle plant time by improved equipment utilization. Individual unit operations (or process stages) and their relationships within the overall process are identified, including an assessment of resource and utility requirements from the host facility. After process models have been constructed, we can investigate complex and integrated biochemical processes and unit operations without the need for extensive experimentation or disruption to existing operations. The method can be used at all stages of process development from conceptual design to process scheduling and optimization.1

Anurag S. Rathore
The above-mentioned activities require process scheduling and debottlenecking using platforms such as Microsoft Excel or commercially available software.2–6 Some of the most widely used commercial software include, Aspen Technology's Aspen Batch Plus, Hyprotech Ltd's Batch Design Kit, and Intelligen's SuperPro and SchedulePro. These tools can optimize a manufacturing facility's capacity by scheduling the process to decrease batch cycle time and reduce the amount of equipment used, which will ultimately decrease pr2oduction costs.

Several questions arise when performing process scheduling and debottlenecking. How much would it cost to make a fixed amount of the product? How can I reduce the operational cost of the process? How much product can I make in this plant in a fixed time? What are the bottlenecks in my current process and plant? What is the relationship between capital investment and the resulting capacity expansion? How can I relate the scheduling of a process to changes in priorities or production demand?

In this twenty-first article in the Elements of Biopharmaceutical Production series, we introduce some of the key concepts of process scheduling and debottlenecking, and present an approach for performing these activities. Two case studies—one for a single- product biotech facility and another for a multiproduct biotech facility—illustrate our approach.


Process Scheduling

Process scheduling for a production facility is performed to minimize production time and costs by making decisions about what to make, when to make, with which staff, and on which equipment. The overall aim is to maximize operational efficiency and reduce costs. Commercially available scheduling tools provide the production scheduler with powerful graphical interfaces that can be used to visually optimize real-time workloads in various stages of production, while pattern recognition enables the software to automatically create scheduling opportunities, which may not be otherwise apparent without this analysis.5–6 Manual scheduling, using available platforms such as Microsoft Excel, also can be effective because the user has the advantage of customizing the tool as required, compared with commercial software that are more rigid. Manually developed approaches, however, may lack the user-friendliness of commercial software.

Process scheduling can be conducted by backward or forward scheduling methods and can help allocate plants, machinery, and human resources, plan production processes, and purchase raw materials. Forward scheduling involves planning tasks from the date resources become available to determine the shipping date or due date. Backward scheduling is planning the tasks from the due date or required-by date to determine the start date or any required changes in capacity. The benefits of scheduling include a decrease in process changeovers, reduction in inventory, increase in production efficiency, leveling of labor load, accurate delivery of milestones, and ability to gather real-time information.

Process Debottlenecking

Process debottlenecking generally includes identifying and removing bottlenecks in equipment and resources. Equipment-based bottlenecks can be eased or eliminated by adding or removing equipment. Resource-based bottlenecks, however, may be unavoidable and may limit the net productivity of the plant. Feed throughput for a production facility is directly proportional to the batch size and inversely proportional to the cycle time; thus, for constant batch sizes we can reduce the cycle time by extensive scheduling, which will subsequently increase throughput. To increase a batch size, we will need to increase the process efficiency or perform scale-up of the process.3

Economic Evaluation

Economic evaluation is necessary when deciding between in-house production and outsourcing. Building a new production facility to manufacture a biotech product is not only a major capital expenditure, but also a lengthy process. To make this decision, information regarding the required capital investment and time to complete the facility is necessary. Even if the decision is made to outsource production, the above-mentioned cost analysis will still be useful as a basis for negotiating with contract manufacturers.4 Irrespective of the decision on where to manufacture, further scheduling and optimization is always useful for maximizing profitability. In a recent publication, the authors illustrated how process scheduling and optimization for a monoclonal antibody product made in a multiproduct biotech facility was used for performing material and energy balances, sizing equipment and utilities, estimating capital and operating costs, and analyzing cycle times.1

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