Perhaps there is no definitive case for which type of bioreactor is superior. The decision-making process is based on the requirements such as products, market demand and timeline, and capital budget.
Although there are now many single-use (SU) bioreactors on the market, and these seem to be the preferred choice for most new installations, stainless-steel (SS) bioreactors are still being used for many current manufacturing processes of licensed therapeutics.
The key differences are:
| Description | Single-Use | Stainless-Steel |
| Vessel shape | Cylindrical and cubical shapes | Cylindrical shape |
| Clean-in-place/Steam-in-place (CIP/SIP) | Minimal | Required |
| Cost of goods (CoGs) | Reduced in maintenance, but high in consumables | High in maintenance |
| Plant footprint | Flexible infrastructure | Fixed infrastructure |
| Scales | 20 L to 5000 L | Up to 20 000 L |
| Operational friendly | Yes, fast turnover rate | Slow turnover rate |
| Quality validation | Extractables and leachables | Product and microbial contamination |
| Environment | Plastic waste | Water and chemical discharge waste |
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Vessel shape: SS bioreactors are cylindrical to accommodate high pressure steam sterilization and cleaning during CIP/SIP. Most SU bioreactors are cylindrical as they were adopted from the design of their SS counterpart. However, there are also some cube shape SU bioreactors on the market which were designed to mitigate the vortexing effect at high agitation rate.
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CIP/SIP: These are part of the general operational process for SS bioreactors and are required both at the start and the end of a biological run. CIP/SIP are not usually necessary when using SU bioreactors.
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Cost of goods (CoGs): Routine CIP/SIP uses a large amount of caustic substances, which results in increased utility costs with SS bioreactors. High maintenance requirements of SS bioreactors and the associated facilities also results in increasing CoGs. The high expense of SU bioreactors derives mainly from the ongoing consumables.
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Plant footprint: The plant footprint in SS systems consists of fixed structures which lead to inflexibility and longer construction time. On the other hand, the SU facility can be constructed in a much shorter timeline and there is more flexibility to change the infrastructure for future development.
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Scales: SS bioreactors can range from small-scale up to 20 000 L to facilitate large-scale manufacturing demand. SU bioreactors are limited by scales as the current largest size general system is 2000 L. Larger scales up to 5000 L are currently in development.
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Operational friendly: SS bioreactors require a longer turnaround time between batches as they require CIP/SIP in place. SU bioreactors have a faster turnaround time which can facilitate more production batches.
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Quality validation: SU bioreactors would require a validation process to determine extractables and leachables. SS 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 process and finding alternative production sites.
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Environment: Both systems produce waste. SU bioreactors result in accumulation of plastic waste, whereas SS bioreactors produce a large quantity of caustic liquid waste.
Perhaps there is no definitive case for which type of bioreactor is more superior. The decision-making process is usually based on the requirements such as products, market demand and timeline, and capital budget.
Currently, many start-up companies such as Contract Development and Manufacturing Organizations (CDMO) tend prefer SU bioreactors as they have a faster construction time as well as high turnaround time between batches. This allows them to forecast more manufacturing batches. Most importantly, they can change between products without the concerns for product contamination. SU consumables may be costly, but this can be incorporated into the cost at the customer’s end. On the other hand, some biopharmaceuticals are adopting both SU and SS bioreactors as both types of bioreactors would give them the flexibility for change as well as capability for large-scale manufacturing.