Systematic Evaluation of Single-Use Systems Using Process Simulation Tools - Simulation tools can reveal whether disposables will be economical even after scale-up. - BioPharm International

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Systematic Evaluation of Single-Use Systems Using Process Simulation Tools
Simulation tools can reveal whether disposables will be economical even after scale-up.


BioPharm International Supplements


Abstract

The choice of single-use versus stainless-steel systems depends on a variety of process and other parameters such as bioreactor scale, product titer, and product changeover frequency. Computer-aided process design and simulation tools facilitate analysis and evaluation of process alternatives and assist scientists and engineers in their decision-making process. This article describes the steps required to build a comprehensive model in a batch process simulator for a process that uses single-use systems for buffer preparation and storage. The process is subsequently compared to a traditional method using stainless-steel tanks. The impact of single-use systems on production costs, demand for cleaning materials and consumables, and the cycle time of the process is thoroughly evaluated.


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As the number of biopharmaceutical molecules entering clinical trials is rising, there is an increased demand for technologies that can expedite the commercialization process. Disposables or single-use systems constitute such an enabling technology. They are commonly used for inoculum expansion using Wave rocking bioreactors that are available for working volumes of up to 500 L.1 More recently, stirred-tank disposable bioreactors have become available with working volumes of 1,000 L and 2,000 L, aimed at replacing small- to medium-scale stainless-steel bioreactors.2 Preparation and storage of cell-culture media and product purification buffers in disposable bags is another common application.3 The use of disposable bags greatly reduces the need for piping, clean-in-place (CIP) and steam-in-place (SIP) infrastructure, and the consumption of cleaning materials.1 This reduces the requirements for upfront capital investment and speeds up the commercialization process. These attributes of single-use systems make them particularly attractive to start-up companies that are short on capital and are under pressure to meet development milestones.

Single-use systems, however, result in increased cost of consumables and their application ceases to be advantageous beyond a certain scale of production. Detecting the turning-point scale is a challenging task that depends on process and other parameters. Process simulation and other modeling tools can play an important role in this task by facilitating the analysis and evaluation of alternatives at various scales. The focus of this article is on the role of such tools in the evaluation of process alternatives and, in particular, the evaluation and comparison of single-use versus the traditional stainless-steel systems.

The evaluation is done for a typical monoclonal antibody (MAb) facility at clinical manufacturing scale. Two process alternatives are evaluated in detail. In the first option, production buffers and media are prepared and stored in traditional stainless-steel tanks. In the second option, buffers and media are prepared and stored in single-use bags.

Process simulation tools can assist in the evaluation of process alternatives in all the stages of process development and product commercialization by facilitating the following and other related tasks:4–7

  • documentation and process understanding
  • calculation of material and energy balances
  • sizing of equipment and utilities
  • cost-of-goods analysis
  • process scheduling
  • cycle time analysis and debottlenecking
  • resource tracking as a function of time
  • environmental impact assessment.

The cost analysis and resource tracking capabilities of such tools are predominantly used in this case study. Capital and operating costs are used to compare the two alternatives at various production scales. The impact of single-use systems on the demand for cleaning materials, CIP skids, labor, and utilities are also considered.


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