How to confirm that single-use manufacturing is feasible for mAb processes at a 1,000-liter plus scale? Pall helped Rentschler to find the answers.
Rentschler Biotechnologie GmbH, is a contract development and manufacturing organization offering full services in development and production of biopharmaceuticals. Subsequent investments have led to a facility with bioreactor capacities up to 2,500 L and nine state-of-the-art suites for GMP production as well as three GMP filling lines and more than 600 fully trained employees.
Those facilities have been successfully used for manufacture of various recombinant biotechnology proteins as well as antibody products for many clients. But Rentschler recognized that introducing single-use SU systems could potentially offer significant benefits over our stainless steel upstream and hybrid systems downstream. Rentschler therefore embarked on a concept study to assess the suitability of its processes for conversion to a complete SU system. Afterward, the company prepared and proceeded with a project plan for implementing a single-use upstream and downstream process for generic antibody manufacture.
Rentschler’s concept study focused on development of two 1,000-L manufacturing lines in an existing building with fully disposable upstream and downstream unit operations. In 2010, the company successfully implemented a single-use bioprocessing line as part of its development plan. The concept study identified several beneficial features, as listed in the “Single-Use Benefits” box.
The concept study showed that many restrictions inherent to stainless steel systems could be removed by replacing them with SU technology. Results also suggested that successful implementation would require reconstructing part of an existing building. Also, many of Rentschler’s clients were specifying disposable technologies. So, it was clear that SU manufacturing systems should be a fundamental part of Rentschler’s business strategy for the future.
Existing Process for mAb Manufacture
Rentschler’s SU development program was based on the process diagrammed in Figure 1. With a working capacity of ≤3,000 L, the process was based on a hybrid system using mainly stainless steel, cleanable equipment typically associated with MAb production but some SU components in downstream processing. As a contract manufacturer, Rentschler’s requirement for multiproduct capabilities for each line demand thorough and fully validated CIP/SIP procedures. Those were especially important to eliminate cross-contamination and the need for dedicated lines when processes use media containing animal components in their seed trains.
Additional checks were needed for performance and integrity after repeated cleaning and regeneration of reusable components such as ultrafiltration (UF) cassettes, ion- exchange chromatography resins, and virus filters. All these and other factors were important drivers in evaluating SU technology.