IMPLEMENTING SUS AND SUPPLIER QUALIFICATION
Figure 1: Example of single-use system (SUS) implementation and process validation, including the application of FDA’s process
validation model and product lifecycle. As product development moves through the clinical phases to marketing of licensed
product, the complexity of the systems used and operations can increase. At the same time, process knowledge improves and
is eventually maintained in a state of control where the risk is controlled with the help of specific tools applied according
to a structured approach. (Adapted from FDA Process Validation guidance, Ref. 18.)
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As previously mentioned, the nature of SUT and their physical nature can give rise to complex issues. A structured approach
should be adopted for the implementation of SUS using "the QbD approach." Below are some of the practical issues involved.
First and foremost, end-users should have an appreciation of how the complexity and risks involved change over the product
lifecycle (see Figure 1). Below are a number of key points that should be addressed for a successful and structured approach to the implementation
and exploitation of SUS as the product lifecycle progresses:
- Manufacturing strategy
- Technology scoping
- Project plan
- Equipment and supplier selection
- Change management
- User requirements
- Non-GXP issues
- Procurement
- Commissioning and qualification
- Materials management during productive use
- Carbon footprint/sustainability
- Decommissioning/end of lifecycle
At all stages in the product lifecycle, an appropriate level of structure and documentation is essential.
Figure 2: Application of SUS during pharmaceutical development: the importance of a structured approach in SUS utilization
over the product lifecycle. Different types of SUS from various suppliers can be used over the product lifecycle, as illustrated
by the different coloured SUS symbols. Careful stakeholder management is essential across company functional areas to avoid
overruns of quality cost as product development advances to the marketing authorization. These costs may not have been apparent
in the early stage of the product lifecycle.
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The choice of SUS equipment and suppliers must not be allowed to become an ad-hoc process. This issue can be problematic for small–medium enterprises (SMEs) and large companies. Lack of control over this
decisional process at an early stage can lead to the selection of multiple equipment redundancies and the use of multiple
suppliers. Dealing with too many suppliers can significantly increase the resources, quality control, supplier qualification
effort required and costs at a later stage of implementation (see Figure 2).
Traditional validation app-roaches for SUS are not appliccable because these systems have a complex, integral, functional
performance and cannot be sampled and tested like a consumable (26).
The complex nature of SUS and their end-use implies that the starting materials (e.g., resins, films, and so forth) should
be treated as critical raw materials (27). Although the amount of resin needed for SUS is small compared to overall industry
requirements for polymers, the propensity for uncontrolled change can pose a significant risk. Equally, the diverse nature
and inherent variability of biotechnology based manufacturing processes, their design, equipment and facilities, the conditions
of preparation, and addition of buffers and reagents and training of the operators are key considerations, which illustrate
the importance of ensuring equipment compatibility for such processes (28).
As part of a quality audit process, an initial assessment called technical diligence extends beyond raw materials specification
and evaluation to include the SUS supplier's manufacturing process, quality systems, sourcing strategy and the compatibility
of the SUS with the end-user's process and facility (19, 29). This assessment provides a straightforward means of verifying
SUS product quality and compatibility with the end-user's operating environment.
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