EXPLOITATION OF SUS

When Vivalis started to use disposables, like many companies engaging SUT for the first time, we saw it as a means for improving efficiency and quality of our research and biomanufacturing operations as part of a customer-driven focus. Subsequent experience drew out the nonconventional nature of SUS and three significant points were noted.

First, although it was thought that SUS would be qualified in the same manner as classical and reusable stainless-steel systems (referred here as multiple-use systems [MUS]), actual experience proved this assumption to be wrong. Second, key benefits such as rapidity of deployment and turnaround quickly became apparent such that the tendency was to think more along the lines of, "How many of these things can we deploy and how quickly"—a philosophy observed in many circumstances.

Beyond the advantages of SUT, as with any technology, there are some pitfalls. The implementation of SUS and their physical nature can bring forward complex issues such as the following:

• biocompatibility and extractables and leachables
• sterilization/irradiation
• SUS disposal
• compatibility and suitability for purpose of SUS
• potential lack of structure in implementing and exploiting SUS at a user level
• importance of a relationship with, or control of, the supplier
• potential inconsistency of the resins used for films, components and tubing
• importance of change management.

The topic of extractables and leachables is a frequently aired but often poorly discussed topic with many end-users having questions as to how to effectively address the subject. In practice, it depends on many issues such as product type, contact time and position in the product lifecycle. There is available guidance (see Refs. 12–15). The other points mentioned above illustrate the somewhat unconventional "out-of-the-box" nature of SUS compared with classical technology; these points are easily addressed as part of a structured implementation process based on current principles and practices and will be discussed in the following sections.

ADOPTING SUT AS PART OF A MANUFACTURING STRATEGY: A QBD APPROACH

A manufacturing strategy can be defined as a structured approach to the definition of the capability of a manufacturing system, specifying how it is organized and how it will operate, to meet objectives, which are consistent with the business objectives.

The development of a sound manufacturing strategy for the implementation of SUS in a biopharmaceutical context should be based on a quality-by-design (QbD) approach but what does this mean for the industry, and how can one relate to it?

In short, a QbD approach, which is based on the principles of International Conference on Harmonization (ICH) Q8, embraces the complementary concepts of quality risk management and pharmaceutical quality system management as detailed in ICH Q9 and Q10, process validation and verification and stakeholder management. These approaches have become part of the 21^st century manufacturing paradigm, laying the foundation for quality-driven processes (16–24).

Implementing SUS using a QbD approach implies the application of a thorough science and risk-based approach and understanding not only for the process for which the SUS will be used, but also the SUT that will be deployed. Such an approach will allow the identification and management of critical sources of variability. Control strategies can be used to maintain a state of control and facilitate continual improvement applied throughout the SUS product lifecycle. These strategies support patient safety and product availability. The forthcoming PDA technical report on SUS has adopted this philosophy and the approach required will be discussed in further detail (25).