The Evolution of Single-Use Technologies in Aseptic Processing - Pharmaceutical Technology

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The Evolution of Single-Use Technologies in Aseptic Processing
The authors describe the origins of single-use components and explain their application to aseptic processes. They also show how disposable devices have changed over time and offer a glimpse of the future.

Pharmaceutical Technology
Volume 34, Issue 4, pp. 112-117

Future single-use processes

Figure 3
At first, single-use components were designed to be connected to a traditional unit operation. The newest advance in technology combines single-use components into a single-use unit operation. One day, these unit operations likely will be connected together to form a single-use process (see Figure 3).

Single-use unit operations currently are available for buffer and media preparations, ultra- and diafiltration, virus filtration, and bioreactors. Other process steps will follow soon, and low-volume streams inevitably will be processed within single-use designs in the near future. Large volumes probably will still need to be processed in hybrid solutions, which connect reusable and single-use process steps.

New disposable sensor technologies will ensure that process analytical technology needs are not neglected. Radio-frequency identification tags will enable the end user to connect systems safely and track systems during inventory-management or transfer activities.

Figure 4
Limitations such as mechanical instability at large volumes and cost factors within affinity chromatography will restrict the development of single-use processes (see Figure 4). Despite these limitations, the advantages of reduced setup times, the elimination of cleaning activities, and end-user protection justify converting even a small number of process steps to single-use technologies. Eliminating end-user intervention with presterilized, interconnected unit operations potentially can enhance safety within aseptic processing. Single-use technology inevitably will be an essential component within biopharmaceutical processes, even if the majority of components in a process is not single-use.

Validation and qualification needs

The validation requirements for a single-use aseptic process are the same as those for a traditional stainless-steel process. Because single-use systems are preassembled and presterilized by the vendor, the validation work requires a high level of vendor involvement. The end user works closely with the vendor to determine the specific validation and qualification parameters and activities needed to ensure the expected product performance for a given application. The vendor, therefore, must have an in-depth understanding of current regulatory requirements and good manufacturing practices. Moreover, the vendor must be able to adjust to the end user's needs. Every application and process stage has different specifications and critical aspects. These differences must be taken into consideration to avoid working too much or too little to satisfy validation requirements.

Table I: Common qualification tests performed by single-use equipment vendors.
Most single-use systems are gamma-irradiated at 25–50 kGy. The irradiation sterilization makes short- and long-term stability studies necessary to evaluate potential polymeric degradation, which could raise leachable levels or lower mechanical resistance. Irradiation commonly reduces the shelf life of polymeric devices, and personnel must determine the radiation limit that a given device can withstand. Qualification tests, defined by the vendor, are performed before any single-use unit or system is distributed to the industry. These qualification tests are manifold and are designed to meet regulatory requirements (see Table I). The end user can rely on the results of the vendor's qualification tests, but should consider process-specific validation requirements.

Process-validation studies would, for example, use a model solvent and simulate the process parameters within the end user's specifications. Leachable testing cannot always be performed with the product because the product would mask potential peaks. For this reason, model solvents that are similar to the solvent used within the product stream often are chosen. The possible influence of the environmental conditions within the end user's processes should be tested, however, to ensure that the disposable device performs to specifications. Process-validation steps vary according to disposable devices' purposes. Sterilizing-grade filters must undergo a product bacteria-challenge test under end users' process conditions. The influence of the process conditions and fluid on the challenge organisms or separation mechanisms should be determined. Product hold bags or mixing bags do not have to undergo bacteria-challenge tests, but possibly bacteria-ingress tests. Both filter and bag systems must be tested for leachables and extractables. As mentioned previously, the end user should request the vendor's assistance.


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