April 30, 2020
Single-use technology & the way forward for pharmaceutical manufacturersReading time: 6 minutes
Not least since it was recommended by the FDA as a way to reduce the still-existing risk of contamination of bulk drug substance, single-use technology based on the application of disposable components has seen a rise in popularity in the pharmaceutical industry.
In light of this commendation it comes as no surprise that this relatively new technology, first employed in the 1990, has been and still is being adopted by an increasing number of players in this field – and is here to stay. As with most things in today’s society, manufacturer-independent flexibility rather than the utilization of rigid and sluggish technology is the way forward.
Single-use technologies (SUT) – the food industry as a role model
What started out as a novelty in the biotech field – due to the need to move ever increasing volumes of serum, biotech labs initially started using plastic bags common in the food industry – soon gained traction across the board. Once the serum arrived at the manufacturers’ labs packaged in plastic bags it didn’t take long for them to start imitating and adopting this type of container for their high-quality drug substance.
Of course, this brought with it the need for specific technologies geared towards single use that were both flexible and scalable. And while avoidance of tedious and costly cleaning and maintenance processes where the initial drivers for the development of technologies geared towards single use, they are now not only seen as more cost-effective but also as a safer alternative to traditional technologies.
Today, single-use systems challenge the established cycle of re-using stainless-steel equipment that entails complex cleaning processes to avoid risks such as cross-contamination or the failure to achieve sterility.
Main factors for the use of single-use technology
With the containers and the fluid pathways being preassembled and guaranteeing sterile handling of the pharmaceutical goods, the production-line process picks up speed and allows for an increased output in shorter intervals – thus adding another benefit. One of the key factors single-use technology, however, is that its employment provides for a streamlined process that is both monitored and scalable.
As the utilization of single-use technologies in the scope of labs and studies increases, so do the volumes produced using this relatively new and flexible method. This calls for innovative solutions, as the scaling up from miniscule amounts required in labs to blockbuster production of several thousand liters can prove difficult and problematic.
One and the same state-of-the art process and technology can be used in all areas, be it for lab production for testing or study purposes or blockbuster production of approved and certified compounds. In addition, single-use platforms allow for the optional integration of components such as filters where and as required.
Agility and scalability of single-use platforms vs. rigidity of established systems
While conventional stainless-steel systems have over decades been established as the basis of safe and reliable manufacturing processes for both classical pharmaceuticals and advanced biologics, they are not exactly flexible and agile – quite on the contrary.
However, the complex processes involved in the production of biopharmaceutical compounds require great flexibility while they should at the same time be cost-efficient. And this is where disposable single-use components come into play: Not only do they reduce the risk of (cross) contamination, they are also less expensive, easier to use and provide more flexibility than traditional processing technologies.
As a result, more and more leading players in the biopharmaceutical field are adopting single-use platforms that are both flexible and scalable.
The advantages that set them apart from the traditional and rather unwieldy stainless-steel systems and cryovessels speak for themselves, even at a glance:
- Increased flexibility: Tubing and filters are made of flexible materials such as plastic or silicone and can be modified easily and quickly as opposed to rigid stainless-steel pipes
- Reduced cleaning requirements: While steel components need to be cleaned after every batch, single-use equipment comes pre-sterilized and ready to use, leading to
- increased turnaround times and
- reduced risk of cross-contamination
- Decreased footprint and costs: Single-use technology requires less equipment to be stored on-site, plus the omission of cleaning and maintenance further reduces costs and storage requirements
Automated bulk filling systems for monitored single-use processes
The latter, namely a decreased footprint at better costs, is one of the key advantages to be considered when contemplating a change to single use systems: With their relative compact size automated filling systems for single use bags, both for bulk and lab purposes, are a space- but also cost-saving and time-efficient solution to handle the entire pharmaceutical logistics process, including filtration, filling as well as freezing and thawing – simply put, they are the way forward.
And single use bags, which are the initial cause for the emergence of and the basis for all single-use technologies, also score on several levels: When empty, single use bags are compact and require very little storage space, especially when compared to bulky cryovessels or bottles.
In addition, they are widely available in a range of sizes and capacities to cover different needs. Single-use technologies are generally compatible with bags of any brand and size without the need of complicated and tedious adaptations or adjustments.
Unlike stainless-steel systems that incorporate fixed components such as connectors, filters and pipes, single-use systems make use of pre-sterilized disposable part that require no cleaning at all.
Flexible Single Use Filtration Systems
In environments and industries where sterility is the norm, filtration becomes an important part in the handling of drug substances. A number of applications performed in clean rooms, such as the recovery of antibodies or the reduction of bioburden after cell harvest, require more or less large filtration areas.
And as different substances have different requirements, not every filter may be suitable for every substance – adding yet another challenge calling for a flexible solution.
As batch volumes increase from pilot to manufacturing scale, production processes become increasingly complex. This can require filter areas varying in size and covering more than 100 square feet as well as the incorporation of one or numerous filter capsules and connectors.
In terms of handling and efficiency, the ideal solution would be a flexible filtration system that can be integrated into existing filling, freezing and thawing platforms. SUSupport offers just that, and with filters coming not only in a choice of sizes but also for different pore sizes, this ready-to-use application not only minimizes time and effort but – above all – the risk of contamination.
Cold chain handling and storage
Single use bags have also proven to be the ideal approach for the entire cold-chain process including storage. They are a versatile and multilateral solution for a flexible – and above all scalable – freeze-thaw process, plus they add to the quality of the frozen goods.
Plate freezing allows for a speedy and at the same time controlled freezing of the valuable liquid solution contained in the single use bag: While the slow freezing rate of traditional freezers leads to the formation of large crystals that can cause friction and will increase cryoconcentration that impacts the quality of the medical substance, direct contact between freezing plates and bag leads to a more consistent freezing of the single use bag’s content at a higher velocity.
However, due to their sensitive nature, single use bags require some sort of protection, not least during shipping. Temperatures of up to -62 °F can cause materials to break and single use bags to rupture, which will invariably cause an excessive waste of valuable drug substance.
SUSupport has developed the stainless-steel RoSS shell to protect single use bags during the freezing process, the stainless steel not only acting as a protective buffer but also offering the best possible temperature transfer from freezer to bag to liquid.
On the inside the bag is further shielded by a layer of soft 3D foam. The shell is tamper-proof so the bag contained within cannot be accessed during the entire controlled freezing and logistics process.
The technical status of systems and service providers
Traditional systems that have been established over the years usually require all components from a single source; as a consequence, pharmaceutical manufacturers become dependent on their supplier.
Changes are near impossible or require a complete refit while modular single-use technologies are compatible with a range of brands, be it for single use bags or filters. They offer a versatile solution both for blockbuster production and lab purposes and can be modified and scaled as required but without the need of adapting entire processes or systems.
While single-use may not yet be as tried-and-tested and advanced as established traditional systems, it leaves room for constant improvement so it can be adjusted and customized to newly arising needs and requirements. It is the perfect basis for an agile and flexible technology that keeps up with the times.