Is the future of bioreactors stainless, or is it single-use? That's a trick question: it's both. As single-use technology improves, it's tempting to think of single-use bioreactors as replacements for their reusable stainless-steel predecessors. The reality is more nuanced. Here we'll cover some basic differences between these two types of bioreactors.
Although there are now many single-use bioreactors on the market, and these seem to be the preferred choice for most new installations, stainless-steel bioreactors are still being used for many current manufacturing processes of licensed therapeutics. However, as bioprocess intensification and higher cell culture titers improve, and as more small-batch therapeutics are developed, some manufacturers are opting to scale out (with multiple smaller single-use bioreactors) rather than scale up to the volumes available only in stainless steel systems. We'll dive into the reasons below—but first, the main differences.
Key differences between single-use and stainless-steel bioreactors
|
Single use |
Stainless steel |
|
|
Vessel shape |
Cylindrical and cubical shapes |
Cylindrical shape |
|
Clean-in-place/steam-in-place (CIP/SIP) |
Minimal |
Required |
|
Costs |
Higher for consumables, lower for maintenance and startup |
Lower for consumables, higher for maintenance and startup |
|
Facility use |
Flexible infrastructure, smaller footprint |
Fixed infrastructure, larger footprint |
|
Production volumes |
20 L to 5000 L |
Up to 20 000 L |
|
Operational impacts |
Faster turnover rates |
Slower turnover rates |
|
Quality validation |
Extractables and leachables |
Product and microbial contamination |
Vessel shape: Stainless-steel bioreactors are cylindrical to accommodate high pressure steam sterilization and cleaning during CIP/SIP. The first single-use bioreactors were cylindrical, as they were adopted from the design of their stainless-steel counterparts. However, cube-shaped single-use bioreactors are now available, which helps to mitigate the vortexing effect at high agitation rates.
CIP/SIP: These are part of the general operational process for stainless-steel bioreactors and are required both at the start and the end of a biological run. CIP/SIP are not usually necessary when using single-use bioreactors.
Cost: Initial investments are generally higher for stainless-steel bioreactors than for single-use bioreactors, owing to the infrastructure required for stainless-steel systems. Routine CIP/SIP uses a large amount of caustic substances, which results in increased utility costs with stainless-steel bioreactors. High maintenance requirements of stainless-steel bioreactors and the associated facilities also increase cost of goods. The expense of single-use bioreactors derives mainly from the ongoing consumables. At very large scales (i.e., in commercial mAb production) it's still generally more cost-effective to produce mAbs in stainless steel systems despite the substantial upfront investments required.
Facility use: The plant footprint in stainless-steel systems consists of fixed structures, which can lead to longer construction times and less overall flexibility in the use of a facility. They also tend to have a larger footprint than single-use systems of comparable size. Single-use bioreactors can usually be installed on a shorter timeline (especially when used with standardized bioreactor bags), and they permit more flexibility to change the infrastructure for future development.
Volumes: Stainless-steel bioreactors can range from 500 mL up to 20 000 L. The largest single-use bioreactor on the market at present is 6000 L.
Operational impacts: Stainless-steel bioreactors require a longer turnaround time between batches as they require CIP/SIP. Single-use bioreactors have a faster turnaround time, which can facilitate more production batches.
Quality validation: Single-use bioreactor bags require a validation process to determine extractables and leachables. Stainless-steel bioreactors do not have this issue, but if CIP/SIP is inadequate, there could be issues with contamination. The impact can be substantial as it could result in downtime, long investigation processes, and finding alternative production sites.
Perhaps there is no definitive case for which type of bioreactor is superior. The best option for a given situation is based on a huge range of factors, including the products to be made, market demand and timeline, and capital budget.
Currently, many start-up companies such as contract development and manufacturing organizations (CDMOs) tend prefer single-use bioreactors, as they have a faster construction time as well as short turnaround time between batches. This allows them to forecast more manufacturing batches. Most importantly, single-use systems minimize the risk of cross-contamination, which makes them better suited for facilities manufacturing multiple products.
FAQs
Is a single-use bioreactor better than a stainless-steel bioreactor?
Neither option is objectively better. In general, single-use bioreactors offer more operational agility and flexibility. Stainless-steel bioreactors have a longer history of use and are available in volumes up to 20 000 L, which is preferable in some cases (such as manufacturing of blockbuster mAbs in a dedicated facility).
Which bioreactor type is more cost-effective: single-use or stainless steel?
At commercial production volumes such as the tens of thousands of liters needed for blockbuster mAbs, stainless-steel systems cost less per unit of product than single-use systems. However, for facilities producing pre-commercial therapeutics in smaller batches, the initial investments required for stainless-steel systems can make them less cost-effective overall.
How does maintenance differ between single-use and stainless-steel bioreactors?
The main difference is that stainless-steel bioreactors require regular cleaning in place to ensure sterility, whereas single-use bioreactors rely on pre-sterilized consumables that are used once and discarded, which eliminates the time and facility space that would otherwise be required for a reusable system.
Explore other articles in the series
What are the different types of bioreactors?