Increasing Patient Safety: Risk assessement in filling process of small volumes

Autologous therapies are therapies that are derived from the patient and as such they exhibit certain specific requirements. The scope of such therapies differs greatly from what we usually see in the biopharma industry, and they require special handling and care.

The quantities are much smaller than usual, but nonetheless they need to be shipped in a highly sterile and protected manner.

Both logistics as well as the compliance that come with the manufacturing process of such therapies currently still pose certain problems that need to be solved. One of those aspects that cannot be handled with traditional methods is the filling process.

The filling process for autologous therapies poses a variety of challenges, according to experts.¹ It requires one batch for one patient, which gives a completely new meaning to the term “small batch filling”. The filling process on such a level is comparable with clinical phase-1 studies or even pre-clinical trials. 

Even though some of these challenges can be tackled with established processes. But as autologous therapies are becoming increasingly commercialized, best practices need to be developed for automated filling. 

Single-use technology to improve the filling process of autologous therapies

In most autologous therapies cells are collected from the patient and filled into a primary packaging, such as single-use bags or vials for further processing.

Along with experts recommendations to use "a closed and pump-driven system that constantly checks the bags’ weight" during the filling process, manual processes often fail to maintain consistency and accuracy of performing a standardized aliquotation into single-use bags. Moreover, the open architecture of manual filling procedures bear increased risk of contamination, whereas a closed automated system prevents such occurences. 

Single Use Support has established a fully automated and fully scalable filling and draining system for single use bags of various sizes and of all established manufacturers. The system ensures highest filling accuracy thanks to different technologies, gravimetric and flowmeter. Depending on the filling volume this can be down to few mL.

Protecting ATMP in small single-use bags

The filled bags are advised to be protected in a robust secondary packaging to prevent leakages during freezing, storage and shipping processes, such as Single Use Support’s RoSS.KSET, the small version of the RoSS shell. ¹

The RoSS shell and RoSS.KSET are protective shells for 2D single-use bags that prevents product loss through breakages to <0.001%. The secondary packaging is vendor-agnostic which means that all types of bags from multiple vendors can be accommodated safely.

It is suitable for small volumes in clinical studies, clinical trials, but also for commercial production of viral vectors, plasmid DNA, autologous cell therapies and more.

 The 3D foam inside the shell offers optimum bag protection against external forces. The frame is made of high-quality plastic and stainless-steel that withstands extremely cold temperatures. Its design even enables to advance the freezing process with plate-based freezers to ensure advanced methods to cool the valuable liquids to -80°C and less.

Patient safety thanks to bag protection

RoSS.KSET boasts an innovative and intuitive locking mechanism, allowing for full tamper-evident single-use bag protection This is a non-negotiable requirement for autologous therapies such as the CAR-T cell therapy. If the liquids are not protected and are damaged in transit, the vital therapy is rendered useless. 

Volumes for traditional therapies consist of several hundred bags, whereas autologous therapies may only require a handful of containers. But scale-up can be earlier than expected and the transfer from clinical to commercial production must be prepared. Planning automation and scalable technologies help immensely to ramp up production once it is needed. It also supports the process consistency throughout different scales. When handling of small volumes is already automated in an early stage, it is a way more straightforward path to commercialization of the drug product. The benefit of a closed systems with automated solutions add value by offering a higher degree of sterility, safety, and process flexibility.