April 9, 2019

How to avoid mistakes during the filling process for cell and gene therapies and make sure that no human life is at risk

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.

Bioprocessonline.com recently published an article that dealt with that issue. The authors acknowledged that the filling process for autologous therapies poses a variety of challenges. 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. However, some of these challenges can be tackled with established processes.

As autologous therapies are becoming increasingly commercialized, best practices need to be developed. Until such time it is advisable to combine established methods and technologies from all scientific and developmental fields.

Using single use technology for the filling process of autologous therapies

Most commonly, autologous therapies are filled using single use bags or vials. As those therapies are usually infused, single use bags directly attachable to the infusion set are the best choice.

The authors of above-mentioned article recommend a closed  and pump-driven system that constantly checks the bags’ weight.

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 measures the weight with an accuracy rate of +/- 10 ml for every 10l.

Usually, the filled bags are packed into cassettes to guarantee an even consistency and texture prior to freezing and thus making sure they won’t break or burst. The authors use Single Use Support’s RoSS_KSET as an example:

RoSS.KSET - Single Use Support

RoSS.KSET is a 100 % stable shell, specifically for CAR-T therapy bag protection which means single-use bioprocess containers with a volume of 50 ml to 0.5 L. The 3D foam on the inside offers optimum protection against external shocks. The frame is made of high-quality plastic that can withstand extremely cold temperatures.

Additionally, RoSS.KSET boasts an innovative and intuitive locking mechanism, allowing for full single-use bag protection, which is a non-negotiable requirement for autologous therapies such as the CAR-T cell therapy. If the content is not protected and gets damaged during shipping, the vital therapy is rendered useless.

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According to Herman F. Bozenhardt and Erich H. Bozenhardt, vials are another method for the handling of autologous therapies. Established solutions for vials already exist, however, they have to be newly defined for personalized therapies. Clinical volumes for traditional therapies consist of several hundred vials, whereas autologous therapies may only require a handful of vials.

Thus, if you only need – for example – five vials, the most logical approach would be to fill those five vials manually by using a pipette. This process however poses risks regarding sterility and consistency. Closed vials offer more flexibility for manual filling and guarantee a higher degree of sterility.

Mistakes during filling process for cell and gene therapies

Michael Eder

Senior Marketing Manager