The safe transportation of drug substances to sites for final formulation, fill and finish is critical. Especially considering the COVID-19 pandemic, there is increasing demand for effective cryopreservation solutions.
Many limitations for bottles
Traditionally drug substances have been frozen in bottles, mostly glass but also plastic. These bottles require sterilization prior to use and must be filled under a laminar flow to maintain sterility. Before reuse, they must be cleaned, and that cleaning must be validated. In addition, scaling of the freezing process is not always straightforward with bottles. Some plastic bottles are limited regarding the lowest temperatures at which they can be used. Furthermore, bottles require significant space for storage prior to use and during shipment.
Numerous advantages for biocontainer bags
Plastic biocontainer bags avoid the various limitations faced by bottles. They are single-use and come pre-sterilized with pre-installed sterile connectors and disconnectors, enabling a closed system with reduced setup times for filling and draining.
As with all single-use systems, there is no need for cleaning or cleaning validation of biocontainers for cryopreservation applications, which saves time and energy. In addition, filling and freezing of Allegro™ biocontainer bags is easily scaled from 50 mL to 20 L and underpinned by validation testing for use at temperatures as low as -80 °C.
Finally, biocontainer bags have a smaller footprint than bottles. Prior to use they are flat and can be easily stacked. Once filled, they can also be stacked during storage and shipment.
The flexibility and rapid setup offered by biocontainer bags are leading to their rapid adoption for cryopreservation and shipment of biologic drug substances from the manufacturing plant to the location where final formulation and fill and finish operations will be performed. Today single use biocontainer bags account for at least 50% of the market, and they will soon hold the greater share.
Fast freezing with plate freezer technology
The method of freezing can have a direct impact on the quality of the cryopreserved drug substance. Cytiva has partnered with Single-Use Support (SUS) to provide Robust Storage and Shipping (RoSS) technologies that include the RoSS plate freeze-thaw systems.
With this technology, faster and more homogeneous freezing is possible than can be achieved with conventional blast (or static) freezers, reducing the likelihood of cryoconcentration and the formation of unstable environments. Freezing with this platform is also scalable from lab to commercial quantities, allowing a single technology to be used from early phase development through launch.
The right protection is critical
Just like glass and plastic bottles, biocontainer bags do become brittle when exposed to low temperatures. The right protection is therefore essential to ensuring the integrity of the biocontainer bag during freezing, shipment, and thawing.
The RoSS technology addresses this critical need with its specially designed robust shell with foam inserts that protect the biocontainer against shocks and vibrations during freezing, storage, shipment, and thawing. The carefully frozen shell and biocontainer can be transported globally in RoSS shipping containers which are passive temperature-controlled container systems that are thermally insulated with expanded polypropylene. Using dry ice as the cooling agent, temperatures ≤ -60 °C can be reached.
Furthermore, studies have been able to validate the entire shipping cycle using our Allegro biocontainer bags combined with RoSS technology.