By Nick Hutchinson
More than ever before, biopharmaceutical companies are able to establish their own in-house biomanufacturing capabilities. The adoption of single-use technology has reduced the need for expensive utilities systems and large manufacturing footprints. The inherent flexibility of this technology is allowing firms to connect steps in the production process with relative ease and without the need for fixed stainless steel pipework. Upfront capital costs have diminished and although operating costs remain, they are incurred only when the success of a drug candidate or licensed product warrants further production. Thus, single-use technologies provide a means to mitigate the risk of wasting large capital expenditures in the event a molecule is unsuccessful in the clinic or on the market.
Good engineering practices are key
Single-use technology is available for nearly every step in a biopharmaceutical manufacturing process below a certain scale of production. Biologics such as monoclonal antibodies and viral vaccines can be produced using processes in which the entire product, media and buffer flow-paths are disposable. However, companies attempting to install or expand new biomanufacturing capacity should be mindful that they should follow good engineering practices to maximize the probability of success. Despite the ease with which firms can install single-use capacity, relative to traditional stainless steel projects, this can nevertheless lead to an insufficient consideration of how firms should integrate single-use equipment with other steps in the process chain. The overlooking of proper integration can lead to incorrect equipment sizing, poor equipment design or an incomplete solution being developed. This can result in process failures, delays and the need to perform costly engineering rework.
A six step process for successful installing single-use bioproduction capacity
It can be useful for engineering teams to breakdown the execution of single-use engineering projects into six steps that start with a pre-conceptual design phase and end with commissioning and qualification. While this is especially important for larger projects, having this disciplined approach can pay dividends even on smaller projects. Each phase contains distinct but linked activities and outputs that ensure that processing steps will be integrated with one another. Teams can display the different phases on a project plan with the end of each phase representing a project milestone. The six phases can be described as follows:
1. Pre-Conceptual Design: The user requirement specification (URS) begins to be defined and process simulations can be run based upon information from the process description or a platform process. Process simulations allow engineers to calculate mass balances, buffer demands and process schedules. Equipment lists can be created and room layouts designed that will allow initial process flows to be described. During the pre-conceptual design phase, an evaluation of the process economics can generate estimates for equipment and consumable costs.
2. Conceptual Design: The engineering team will have develop the URS and take it towards completion. The results of applications and feasibility studies allow the process equipment to be defined. Utility requirements should be considered at this stage, as should the equipment automation strategy. Companies increasingly require the integration of equipment used for commercial manufacturing into distributed control systems.
3. Basic Engineering: Teams now add an additional level of detail to equipment descriptions and the process flow diagrams are finalized. The structure of the automation architecture is developed and the qualification strategy determined. A project quality plan needs to be written that will describe the project team, the roles and responsibilities of all the stakeholders and define the execution plan with milestones.
4. Detailed Engineering: Equipment specifications and detailed P&ID drawings are created before stakeholders approve the project for construction. 2-D and 3-D CAD drawing help the project team understand the equipment designs and space requirements within the facility.
5. Manufacturing: Standard equipment can be assembled and custom or configured equipment constructed.
6. Commissioning and Qualification: Factory acceptance testing is performed before the equipment is shipped to the facility in which it will be installed. Execution of site acceptance testing occurs at the recipient facility prior to the start of performance qualification testing.
Single-use technologies offer many benefits and are having a significant impact on the ability of even small companies to install their own production assets. Yet, although it is somewhat easier to purchase and install single-use systems than their stainless steel equivalent, engineers should still consider how the equipment will function within the overall context of the bioprocess. Adopting a structured approach to projects will ensure the seamless integration of bioprocess systems into the facility and avoid the need for unnecessary delays and rework.
Acknowledgments: Nick Hutchinson gratefully acknowledges the expert insight of Ganesh Kumar and Michael Koch from the Sartorius Stedim Biotech Integration Solutions Engineering Team
About the author: Nick Hutchinson is a Technical Content Marketing Manager at Sartorius Stedim Biotech.