Should I switch to single-use bioreactors?
Ten years ago, single-use bioreactor (SUB) vessels were limited in size, making them only practical for lab setups. However, Thermo Scientific is launching a 5,000 L single-use bioreactor and BioInno is already using a 6,000 L reactor. These reactors have much higher titers than even multiuse equipment did ten years ago – enabling switches to single-use equipment which is designed specifically to achieve high titers in scalable environments. Single-use sensors have improved in parallel with the reactors, making single-use skids ever more viable.
Single-use technologies provide serious advantages in terms of flexibility and scalability, and have largely eliminated purity concerns. However, stainless steel is often still advantageous if custom designs are necessary or if batch sizes are very large (capacity can be up to 10x higher than SUBs).
The following is a set of questions to consider when determining whether single-use bioreactors are appropriate for your process. We use “stainless steel” and “reusable” interchangeably to describe multiuse bioprocessing equipment that must undergo CIP/SIP between batches.
Does the process exist already?
Most often, it is not feasible to transition a GMP manufacturing process, producing quantities for commercial markets, from stainless steel to single-use equipment. However, for processes in the early stages of development which are not yet well characterized, it is worthwhile to compare single-use and reusable equipment. Continue asking these questions to determine which is more advantageous.
What size batches will you be running?
Most single-use bioreactors have a maximum capacity of about 2,000 L (although, as indicated by the examples above, significant headway has been made in increasing that batch size). Due to recent advances in cell density and titer, smaller bioreactors are often capable of achieving yields equal to those of a 10-year-old larger reactor. Recent calculations for monoclonal antibody (mAb) production indicate that stainless steel vessels are preferable (more economical) if you are looking to produce greater than two tons of antibodies per year. For smaller volumes, single-use systems are likely to be more advantageous.
What type of drug are you manufacturing?
Many modern biologic drugs are designed for significantly smaller markets than, say, the polio vaccine. Drugs for orphan diseases, targeted drugs for personalized medicines, cellular or genetic therapies, and powerful drugs requiring only low doses – none of these scenarios will require 10,000 L batches. The type of drug and its commercial usage and market will directly impact the appropriate batch sizes, which will inform whether it makes more sense to use single-use or reusable equipment (see previous question).
What type of facility are you designing?
Labs, pilot facilities, and commercial production environments all have different needs. In pilot facilities (GMP or non-GMP), scaling up and down is critical. While single-use equipment is significantly more scalable than stainless steel, it is important to consider whether it will appropriately model your larger-scale operating conditions. In labs, short-term scalability and avoiding risk of cross contamination generally make single-use preferable. Make sure that you are able to appropriately model your critical process parameters in your small-scale system.
Will the facility produce a single drug, or switch between various types?
Switching between batches of the same drug, even on reusable equipment, will only take 6-10 hours. However, uptime drops dramatically for reusable equipment in a facility manufacturing different types of drugs: a full turnover of stainless steel equipment from one batch to the next can take up to three weeks. A hybrid facility, with single-use upstream equipment and stainless steel downstream equipment, can shorten that to two weeks. In contrast, a facility with single-use equipment can be turned over between products in as little as 48 hours.
How much customization does your process require?
Single-use prefabs have the powerful capability to quickly develop and scale biologics manufacturing – and they provide a sharp contrast to the highly customized stainless steel skids to which many manufacturers are accustomed. The biggest downside of these prefabs is that customization is sometimes necessary to get optimal results from cultures. The upside is that single-use prefabs offer a surprisingly high level of flexibility in allowing you to use a facility for a wide variety of purposes. While using stainless steel equipment often forces you to design a highly customized facility with a fixed infrastructure – limiting the types of drugs which can be produced there – prefabs are not highly specialized to a single process.
Is process intensification a high priority?
If yes, single-use facilities are far superior. Single-use equipment can achieve higher titers and may be able to reach the same overall yields as larger, reusable equipment via scale-out. Continuous manufacturing can also be achieved on single-use systems, further reducing the overall facility footprint.
How strong is your operator training program?
Transitioning to single-use systems will require retraining operators, specifically to install the vessels and sensors. While this is not a steep learning curve, it is a significant change. Further, SUBs generally require more manual handling, presenting risks to operators that must be mitigated through comprehensive training. Alternatively, if you have experienced purity issues due to improper equipment sterilization, then new training programs on single-use equipment may be able to address both shortcomings of training and purity concerns.
What are your operational bottlenecks?
If you are constantly waiting for validation and qualification of your cleaning processes (or if your lab team is constantly waiting for the autoclave cycle to complete), single-use equipment presents a simple solution. If you are often waiting for pieces of equipment to arrive, single-use is also preferable: customized stainless steel reactors often have lead times of over a year, and then require several months for qualification. However, if you are unable to meet production demands and need to scale up and produce larger batches, don’t switch to single-use – stainless steel bioreactors likely remain the best solution for your process.