In my opening editorial, I referred to an industry in transition. This is being driven by challenges that are by no means unique to biotech: all other industry sectors are experiencing similar pressures. We are seeing the impact in terms of factory design, manufacturing technologies, validation and business processes; these are all themes that have been addressed in this supplement. The big innovation in terms of manufacturing systems has been the wholesale acceptance of disposable manufacturing technologies during the last 10 years. As the industry moves to a strategically significant level of single-use technology integration, then we have to rethink our approach to manufacturing. Why? Well, for the stainless steel facility, the manufacturing assets are physical, owned and installed by the operator; however, in the case of the facility that is largely single-use, the operator is dependent on the suppliers and the whole supply chain delivering the manufacturing capacity when needed. If we go for a lean manufacturing approach, then that linkage is precise, with very little buffer in the system. This is in fact one of the key challenges discussed in the roundtable; that is, the impact of supplier base consolidation and its implications for manufacturing operations. Consolidation should be beneficial — as we want financially strong organizations in place that are keen to develop and nurture long-term partnerships. It is, however, dependent on a fair and equitable relationship between the supplier and the manufacturer and it is encouraging to see this topic being raised in Jennifer Maynard’s contribution (1). We need debate and the sharing of knowledge on what constitutes industry best practice. I would encourage sharing of information within the industry and the closer integration of the business processes such as procurement, engineering and validation (Figure 1) as soon as single use implementation is considered (2). Looking at other developments in materials management, the development of gamma-stable RFID tags for single-use components has great potential to help manage and secure the supply chain. It has benefits by ensuring that all single-use materials are tracked within the factory as well as in the supply chain.
As the industry and the supplier base gets more and more excited about the application of single-use technologies, the concept of the total disposable facility is regularly cited. My question is: what does this mean in terms of delivering value to the end-users? It is encouraging to see this complex issue being addressed here in the supplement (3). It is important to recognize that there is not one technology that, alone, will solve all our manufacturing issues: to get the right mix of technologies, it is important to understand the objectives and to have the right analytical tools to help optimize the design and understand the cost drivers. This will typically involve a mixture of formalized design processes, simulation and cost analysis tools. An example of an integrated approach to risk evaluation is given in Table 1. Implementation and the acceptance of single-use technologies requires that the supplier base matures alongside the user base, so that we can streamline implementation and reduce dependencies. This is particularly important in terms of achieving a common approach to the integration of different suppliers’ products, and the standardization of components, films and containers
Table 1. Understanding and managing the implementation of disposables.
In terms of disposable technologies, we have seen considerable developments in the last couple of years in single-use bioreactors, mixers, sensors and automation technologies, building on the more established technologies such as bags, connectors, filters, etc. It is interesting to note that where a technology is perceived to meet a specific need, then the take up is rapid: it seemed there was an unmet need for a stirred tank bioreactor and with the launch of the Thermofisher Single-Use bioreactor (SUB), we have seen a rapid uptake during the last 2 years (300 to 400 units sold). This has established a new single-use application as a production bioreactor in a relatively short period of time, which is unusual for our conservative industry. Bioreactor technology is an area wherein significant development is continuing both at the large-scale and at the small-scale, in the upstream area, we have the potential of storing our cells in a frozen format and of being able to expand our cells and produce our product in a closed system. The development of single-use systems is now extending into the microbial arena. In terms of single-use manufacturing technologies, there is still much to do regarding downstream systems, integrating operations, simplifying groups of disposables in terms of systems and looking at the whole issue of ergonomics and material handling. Finally, we cannot finish any discussion of single-use systems without considering waste management and sustainability. There is no doubt in my mind that the move from stainless steel to single-use systems has stimulated this whole discussion on the environmental impact of facilities, nowhere more so than in the US. This is a positive development in that we need to understand how these facilities impact on the environment. This is an area that BioPharm Services has been working on with our colleagues at Genentech, where we have been able to show that the implementation of single-use has the potential to reduce the carbon footprint of our facilities (4). Further work is needed, especially in terms of minimizing the amounts of single-use components used, the development of recycling approaches and waste treatment regimes.
We are witnessing an exciting period in biomanufacturing: the maturation of the industry, with its increasing pricing and competitive pressures, means that there are significant opportunities for all industry players. We are an industry in transition and, overall, no clear winners have emerged in terms of total portfolios of single-use technologies or business approaches. We are seeing a maturation of the supply base with the consolidation of suppliers; but, at the moment, innovation continues apace. This is good for our industry; it will deliver robust, cost-effective and high quality manufacturing, resulting in lower CoGs for new biological medicines, delivering better value to the patient. If we are to derive the full benefit from single-use technologies, the key challenge for our industry at this time is to come to terms with them in a way that integrates design, supply, quality and manufacturing perspectives.