Future single-use processes
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
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.
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
Table I: Common qualification tests performed by single-use equipment vendors.
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.