This article is part of a special feature on single-use systems that was published in the October issue of PTE Digital, available
There are a number of validation approaches that can be adopted — all of which incorporate the established approach of user
requirement specification (URS), design qualification (DQ), installation qualification (IQ), operational qualification (OQ)
and performance qualification (PQ). Validating singleuse systems, however, requires a few changes of emphasis with respect
to these specific steps.
For singleuse systems in general, validation can be performed in three areas. The first relates to the actual process operation
itself. This will be dependent on the intended use, e.g., aseptic operations, short or longterm product hold, levels of process
closure, the stage of clinical development and whether or not the product being produced is for commercial supply. A riskbased
approach will determine the validation programme based on the end use and process requirements. Secondly, it may be necessary
to validate the manufacturing process for the singleuse components and the quality assurance systems applied by the supplier.
Finally, the actual supply chain process of the singleuse system and the stability of the supply chain must be evaluated.
The validation approaches will also very much depend on whether the system is standard or customised. Suppliers are now developing
a range of standard packages for both components and control systems and, in such instances, validation packages can be obtained
from the supplier, which offer significant cost and time savings.
Key points to consider
The key consideration for the validation of single-use systems is the recognition that much of the ownership of the quality
systems will lie with the selected system's vendor. Additionally, as stated above, if the systems are part of standard packages
then this also needs to be factored into the validation approach. Companies are developing increasingly detailed packages
on leachables and extractables based on USP Class VI and European Pharmacopoeia requirements, as well as recommendations by
user groups, such as the BioProcess Systems Alliance. A casebycase assessment is required to determine, for example, if the
proposed process fits within the range of process fluids and operational conditions previously assessed by the vendor.
It should also be recognised that the use of the systems places much greater emphasis on the operators responsible for conducting
system assembly procedures. In most cases, there will be a reduced capacity to verify systems ahead of manufacturing operations.
Under these circumstances, IQ is required every time a system is used and the validation approach needs to take this into
consideration. Assessment of OP and staff training is also required to accommodate the change in process risk.
The risks lie not only in the formation of secure connections between items, such as sterile welds and connectors, but also
in connecting the various components correctly to form the intended assemblies. The impact of this is that in the initial
design phases, thorough URS generation and DQ emphasis needs to be placed on how the system is to be used and how operations
personnel will interface with the system, rather than assessing purely functional aspects. This, in turn, means that the process
will require a high level of input from the operational team throughout the design and validation process.
Over and above validating the fixed plant and the process, the programme will involve reviewing operational procedures — many
of which will be performed at a remote, third-party site. As such, the validation process will need to be more extensive with
respect to vendor audits where the entire operational and QA systems of the selected supplier will be appraised. A much closer
relationship between the supplier and end users will need to be established. One approach is to identify a limited number
of preferred suppliers — based as much on quality systems and supply chain stability as price — and then to look at the procurement
of new systems solely from pre-selected vendors. In addition, detailed assessments of operational procedures, including system
assembly and the training of associated procedures will be required. This is where the highest risks are likely to lie in
terms of operational errors and failed batches.