Modularization of manufacturing for increased process flexibility

CMOs and CDMOs must be flexible in their technologies and business models. ​

Process flexibility allows contract development and manufacturing organizations to adapt to the needs of the pharmaceutical industry. The requirements for fluid management and cold chain logistics are volatile and depend on different parameters, such as areas of application, drug substance production processes, volumes and preferred primary packaging.

Therefore, CMOs are embracing flexible process solutions that allow for catering to different needs. On the other hand, cost-efficiency and limited risks are yet to be fulfilled in order to achieve profitable business arrangements with biotech companies. Balancing out different variables whilst ensuring uninterrupted market supply of finished drug products might impact affordability, especially when considering consistent capacities and production quality as well as the potential of scaling up production quantities.

Figure 1: RoSS.FILL, the best-in-class aseptic filling platform, to be attached modularly to different filling racks​​

Single-use technology to drive process flexibility

Single-use fluid management systems help CMOs improve their freedom of process. They are modular by nature, thus facilitating customization according to customer requests. With cell and gene therapies playing an increasingly important role in the industry, the advancement of single-use systems will further drive the trend towards flexibility. Overall, adaptive systems are already in great demand.

Additionally, the supply of single-use systems needed for cold chain logistics is increasingly important, especially for autologous cell and gene therapies. With their short turnaround times and need to prevent product loss – in particular for personalized therapies – the single-use system supply chain requires reliable partners that can guarantee availability and short lead times.

Modern manufacturing facilities follow different approaches to meet requirements for scaled-up production, with modular processes promoting agility in production and support.

Augmenting manufacturing of drug substances with the implementation of single-use systems​
Customers willing to repurpose available stainless-steel bioreactor tanks connect these with a variety of single-use assemblies. This setup improves flexibility and meets the demands of different biomanufacturing processes. It reduces capital investments by augmenting available equipment with single-use solutions instead of building a new stainless-steel facility, including durable piping.¹​

Replacing stainless-steel by single-use equipment​
Single-use bioreactor bags can replace stainless-steel tanks completely. Bioreactor bags in different sizes already include state-of-the-art sensor technology to go even further and implement cGMP process monitoring.

Overall, both acquisition and operating costs can be minimized with single-use systems: facilities no longer require cleaning and sterilization procedures and have a reduced need of human and time resources, which in turn leads to an average decline of 46% in total water & energy consumption, and hence a further reduction of total cost of ownership.²​ In addition, single-use technologies are more sustainable than equipment based on stainless-steel, with a CO2 footprint decreased by 35%.²​ 

Customizing aseptic filling solutions for CMOs/CDMOs

CMOs and CDMOs aspire to have increased levels of flexibility for multiple applications. There is a myriad of options available, and efficient filling solutions that are easy to plug and play prove to be the way forward.

The process step of aliquoting liquids into single-use bioprocess containers in an automated manner holds many options. Only modular – and hence flexible – single-use systems like Single Use Support’s automated filling platform system RoSS.FILL​ can keep up with process versatility as it is widely compatible.³​

Figure 2: Modularity of single-use technologies to provide process flexibility in fluid management.​​

Primary packaging

While well-established rigid containers (bottles or carboys) are still widely used, single-use bioprocess containers will be the primary packaging for pharmaceutical liquids of the future. Hybrid platform solutions​ are compatible with both, single-use bags and bottles, in one.

RoSS.FILL is an aseptic dispensing platform to fill drug products into 2D and 3D single-use containers. The control unit can be attached to different filling racks; it can therefore be applied universally for filling of single-use bags and bottles of all available sizes and manufacturers. The platform can be scaled up and out by attaching multiple racks to increase batch volumes for commercialized production or even perform continuous filling by utilizing alternating filling racks.

Sterile connection and disconnection

Most established products for the connection and disconnection of tubings for liquid transfer in biopharmaceutical manufacturing are sterile tube welding and aseptic connectors, the latter being more cutting-edge. Aseptic connectors are compatible with all types and sizes of tubing and can be placed at any time or any place. There are multiple options with regards to single-use assembly components​, which can all be considered for modular aliquotation into single-use bioprocess containers.

Process Simplification with Integrated Valves

The stepper valve is integrated in RoSS.FILL to dispense liquids into single-use bags and bottles while allowing full process control. The innovative valve regulates filling throughput with the option of accelerating filling speed with a controlled flow rate. The sealer valve is integrated in the automated filling platform system RoSS.FILL to perform aseptic closing of tubings right after the filling process.

This revolutionary automated process step​ replaces the need for other sealing technologies that are complex and time-consuming to perform. The lack of human intervention will reduce resources in terms of workforce, time, training and validation, and also human operational errors.  With smart valves, it is possible to achieve unprecedented productivity gains in biopharma fluid management by filling & sealing in a single operation. 

Modular or modular

In modern bioproduction, it will be inevitable to resort to modular systems, in particular with regards to the process of fluid management. There are too many risks of getting lost in the variety and complexity of options, depending on a single supplier of single-use systems, or being limited in compatibility and scalability. There’s a reason why CMOs are striving for process versatility and process control. In order to keep playing a role in the volatile and ever-evolving biopharmaceutical industry, CMOs will need to rely even more on innovation.  It can be argued that only single-use technologies that promote automation, vendor independence, modularity and, as a result, process flexibility are of real value to the industry.

Figure 3: RoSS.FILL CGT, the single-use technology for modular and automated filling into small single-use bags.​​

References​

1.​ ​Wieland, M. Single-use bioprocessing: Why it pays off to switch to single-use systems now​ (2022). 
2. ​Ken Davis. Single-Use Systems – Show Me the Green!​ ISPE San Francisco/Bay Area Chapter Newsletter Vol 19/2, 18 (2014).
3.​ Single Use Support GmbH: Process Flexibility Guide​ (2022).