The Challenges of Adopting Single-Use Technology - Insights on single-use systems implementation and exploitation in biopharmaceutical manufacturing and processing, based on a QbD approach. - BioPharm


The Challenges of Adopting Single-Use Technology
Insights on single-use systems implementation and exploitation in biopharmaceutical manufacturing and processing, based on a QbD approach.

BioPharm International Supplements
Volume 25, Issue 11, pp. s4-s8


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.)
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.
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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