This article is part of a special feature on single-use systems that was published in the October issue of PTE Digital, available at http://www.pharmtech.com/ptedigital1010.

Tony Hitchcock

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.

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.