Mark Kruszynski is Senior Principal Engineer, Technical Transfer at Baxter.

Mark Kruszynski

Single‑use solutions, such as bags, tank replacements and aseptic connection devices (ACDs) have revolutionised our industry, providing improved sterility assurance. The ease of use and time savings compared with conventional steam‑in‑place systems has improved our manufacturing process wherever ACDs have been used. Bag technology, from simple sampling systems to complex mixing systems, has changed how we design our manufacturing process and I would anticipate that the popularity of ACDs and single‑use systems will continue to increase over the next few years. 

 Mark Kruszynski. Senior Principal Engineer, Technical Transfer at Baxter.

More of our pharmaceutical clients are becoming familiar with single‑use technology and, if we take time early in our discussions to explain options and any potential benefits to them, clients will often be open to suggestions for its use. In projects that have particularly aggressive timelines, a single-use solution is one tool that our clients are beginning to consider more frequently, given that their use is generally associated with time savings.

Single‑use systems have the potential to provide significant cost advantages to both the contract manufacturer and the client, including:

reduced project initiation to manufacture lead time

reduced support system cost (i.e., WFI, clean steam, power, time).

The reduction in costs can be translated into increased efficiency for both parties; however, there does appear to be less benefit in switching once a product is commercialised — certainly after process validation has been completed. Therefore, our clients are naturally reluctant to switch at this stage unless there is a compelling reason to do so. The implementation of single‑use systems during the clinical manufacturing phase of a molecule’s development appears to provide the most intuitive benefit. As the technology evolves, other aspects may strengthen its suitability for all phases of manufacturing. 

One of our challenges is educating clients on the potential benefits versus risks of single‑use systems. Our clients are often more comfortable using traditional manufacturing systems because innovations can be perceived as introducing risk to a programme. 

If we believe that a client would benefit from the use of single‑use technology and they opt to implement it, the most important consideration that follows is product compatibility with the single-use system and evaluation of extractable/leachables from the equipment. It is critical to ask some specific questions. Does the product contact layer of the single‑use system affect the quality attributes of the drug product? What is the potential of protein aggregation? Will the bag absorb preservatives if part of the formulation? Will there be any impact on overall product stability? What is the cost of laboratory analysis to make these determinations?

Overall, single-use manufacturers have offered good definitions on what can be extracted out of their product, but an industry‑wide consensus to define the requirements of single‑use products in pharmaceutical manufacturing has yet to be established. I believe this is important because there are some key questions that remain unanswered. Are the biocompatibility requirements really appropriate for evaluating the suitability of a single-use system that will contact a drug product for a relatively short time (NMT 48 h)? What levels of extractables are unacceptable (is any level acceptable)? Should any kind of stress testing be performed to define compatibility, and what would be the relationship between stress conditions and actual storage use conditions?

One suggestion would be to have a standard published that sets out the minimal requirements for established product compatibility using single‑use systems, based on an agreement between single-use technology manufacturers and pharmaceutical manufacturers. 

Innovations of any kind that potentially enhance speed to market for our clients need to be evaluated to ensure product quality and safety. Single‑use solutions can potentially increase a CMO’s flexibility and responsiveness and, thus, the potential benefits seem to align the CMO and the client’s goals. I would anticipate that contract manufacturers will continue to embrace single‑use systems, as the capital equipment cost savings and manufacturing efficiency savings will push the industry toward greater use of the technology. Contract manufacturers who do not offer a single‑use alternative to traditional dedicated product equipment may be increasingly challenged to compete in the marketplace. 

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Single?use solutions, such as bags, tank replacements and aseptic connection devices (ACDs) have revolutionised our industry, providing improved sterility assurance.