Extractables Protocol for Single-Use Disc-Stack Separators

Peer-reviewed

Article Submitted: January 30, 2024.
Article Accepted: April 8, 2024.

Abstract

Single-use biomanufacturing is a rapidly growing industry. In recent years, single-use centrifuges have become viable alternatives to traditional filters, promising 90% reductions in waste materials and improvements in process time and yield. However, these systems often have several fluid paths with different materials, complicating extractable studies. This case study describes how the risk assessment of the first-to-market single-use disc-stack centrifuge was conducted. This study shows how a dramatic modification of the surface-area-to-volume extraction ratio was required for the single-use system and how this was considered during interpretation of the results respecting industry best practice. Furthermore, it’s demonstrated how the detection of volatiles can vary depending on the approach of analysis, surface coatings, and where analytical study design should be considered to mitigate missing volatile extractables.

Single-use systems (SUS) have revolutionized biomanufacturing and often replace traditional stainless-steel equipment. Presterilized SUS are considered “safer, greener, cheaper, and faster” compared to traditional biomanufacturing systems (1) due to the reduction of water, man-hours, and chemicals. However, the waste handling of large SUS is an environmental challenge, and, therefore, there is a growing interest for single-use (SU) centrifugal separators, which could reduce the waste of SU filters by 60–80% (2–4).

SU centrifuges are used to separate host cell materials from target proteins following fermentation. In a SU production line, the only available options for cell separation are filtration and/or tubular centrifuges (5, 6). Advances in biomanufacturing have greatly increased the cell concentration and batch sizes upstream, which have caused challenges for filtering systems downstream. The performance of depth filters is largely dependent on the colloid content flow-through, and, at higher cell concentrations, the separation becomes increasingly difficult and costly as more filters are needed and exchanged more frequently.

In 2020, a first SU disc-stack centrifugal separator (Alfa Laval) (7) was introduced that offered continuous low-shear separation of cell batches 100–1000 L, without manual replacement of filters and with a limited footprint in the laboratory (see Figure 1). Yields up to 98% and <5% additional lysis could be obtained due to the low-shear design and the large surface area (SA) of the disc-stack inside the disposable separator insert (7).

Since 2020, other and larger SU disc-stack separators have reached the market (3,8), which all need validation and testing.

About the authors

Martin Kellerer Wåhlander is senior specialist–Materials and Coatings at Alfa Laval Technologies. Michael Creese is director of Chemical Analysis at Smithers MDT Limited. Pontus Linderholm is R&D manager at Alfa Laval Technologies.

Article details

BioPharm International®
Vol. 37, No. 8
September 2024
Pages: 17–22

Citation

When referring to this article, please cite it as Wåhlander, M.K.; Creese, M.; Linderholm, P. Extractables Protocol for Single-Use Disc-Stack Separators. BioPharm International 2024 37 (9).