Solutions for automated aseptic filling of monoclonal antibodies

The growing request for monoclonal antibodies in scientific research and clinical applications also results in the need for professional aseptic filling solutions for mAb manufacturing. Be it in cancer therapy or the treatment of autoimmune disorders: The field of applications for mAbs is continuously growing – all the more reason for manufacturers to be concerned about safe and effective mAb handling and transfer.

Hence, this article will address the complexity of aseptic aliquoting within the production process of monoclonal antibodies, with a particular emphasis on factors that contribute to its success. Subsequently, solutions shall be presented that allow not just for modern but future-proof monoclonal antibody filling.

Monoclonal antibody filling – one step among others

Looking at the entire mAb production process, the filling step emerges as a crucial act within a broader narrative. It marks the finalization of an antibody product as it is prepared for its application. However, fluid management is a dimension that is reflected in every step of monoclonal antibody production, rather than only in the final stages.

Consider the preceding movements: from identifying and isolating antibody-producing cells to their cultivation and subsequent purification, fluids are transferred several times both in upstream and downstream settings. Ensuring an aseptic environment is essential throughout the whole production line in order to avoid contamination. However, it is in the final step of mAb filling when the success of the entire manufacturing process is at stake once more.

What determines success in mAb filling?

Success in monoclonal antibody filling – of course – is first and foremost determined by the quality of the product itself. But even the most innovative biologics may be ruined when dispensing processes do not meet the high standards set by regulatory authorities, the pharmaceutical market, and particular characteristics of the products themselves.

Antibodies are fragile proteins, requiring precision in meeting stringent temperature parameters while avoiding exuberant physical stress. Additionally, aseptic conditions have to be maintained during the entire filling process, as monoclonal antibodies cannot be subjected to heating or other means of terminal sterilization.¹ Therefore, all the components of a mAb filling process – all the way down to bioprocess tubing solutions – have to be sterile, but also free from impurities like extractables or leachables.

Safety is another critical consideration in mAb production. This is especially true when manufacturing products like ADCs (antibody drug conjugates): They are in parts composed of substances that are potentially hazardous for both staff and the environment. As a consequence, safe handling of monoclonal antibodies, bioconjugates as well as production intermediates is crucial.

Even though automation is being increasingly adopted in monoclonal antibody filling, this does not per se guarantee maximum batch-to-batch consistency. Thus, solutions to homogenize filled monoclonal antibody products are often implemented to optimize the outcome of their production process, the progress of which is further determined by pecuniary aspects.

To keep the costs in monoclonal antibody production low in order to ensure that these products remain broadly accessible, optimization of every manufacturing step is advised. This also affects fluid management in mAb production, which requires scalable and adjustable systems that reduce the risk of product loss while being efficient and reliable.¹ 

Automated filling solutions for homogeneous mAb aliquotation

Single Use Support has developed automated process solutions for safe and efficient fluid management in monoclonal antibody production. The resulting end-to-end processes are designed to provide maximum scalability and flexibility while avoiding bottlenecks within production cycles.

This holistic approach in mAb handling not only covers innovative cold chain solutions, but also dedicated, high-performing fluid management systems for monoclonal antibody filling.

RoSS.PADL – homogenizing monoclonals at ease

Engineered for standardized cooling and gentle kneading of single-use bags, Single Use Support’s RoSS.PADL ensures a seamless and consistent mixture of therapeutic substances. Compared to manual interventions, this automated system can enhance efficiency and minimize the risk of product quality variations.

Bag-agnostic and scalable, RoSS.PADL accommodates single-use bags from various bag manufacturers, employing an adjustable massaging mechanism and optional cooling for fluid homogenization within a set temperature range. Integrated into Single Use Support's end-to-end solutions, RoSS.PADL represents a cutting-edge, adaptable tool for standardized bag-to-bag consistency during monoclonal antibody filling.

Aseptic mAb filling with RoSS.FILL

Depending on the specific solution, systems within the RoSS.FILL platform are able to operate at an impressive pace of up to 300 liters per hour. This automated single-use system places a premium on process safety, being designed for aseptic filling processes based on single-use systems. And in addition to the remarkable speed, RoSS.FILL also stands out in terms of precision, flexibility, and scalability.

The platform caters to an additional rack and diverse filters while also allowing optional PUPSIT (pre-use post sterilization integrity testing), providing a nuanced and tailored approach in mAb manufacturing. The capability for seamless manifold changes adds a strategic layer, allowing for swift and precise adjustments to evolving production processes.

Packaging for mAbs – neat and tidy with IRIS and RoSS®

To ensure the safe packaging of monoclonal antibodies, Single Use Support relies on the effective pairing of IRIS single-use bioprocess containers and RoSS® Shell.

IRIS (Innovative. Robust. Individual. Single-use) single-use bioprocess containers are qualified across a temperature range between -196°C and +50°C. Characterized by a low extractables and leachables profile, these versatile vessels facilitate the secure storage, shipping, and freezing of monoclonal antibodies and other pharmaceutical liquids.

Complementing IRIS single-use bioprocess containers, the RoSS® Shell is a robust secondary packaging with a staggering <0.001% product loss rate. Using 3D foam and a robust PE frame, single-use bags can be immobilized and protected during transport, freeze, and thaw processes. Additionally, RoSS® shell is stackable, thus supporting manufacturers in saving valuable space during cold storage and shipping. Together, IRIS single-use bioprocess containers and the RoSS® Shell represent the centerpiece in the mAb filling process framed by Single Use Support.