Single-use bioreactors used to be limited in size and were only practical in lab setups ten years ago but today, manufacturers have launched 5,000 – 6,000 litre bioreactors that can be used everywhere. These new bioreactors have much higher titers than even multiuse equipment did ten years ago which allows industries to switch to single-use equipment which is designed specifically to achieve high titers in scalable environments. Due to the advancement in this reactors, single-use sensors have also been improved in parallel, making single-use skids ever more viable.
Single-use technologies have important advantages in terms of flexibility, scalability, and they 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 below questions will help to determine whether single-use bioreactors are appropriate for the processes in your lab. The words “stainless steel” and “reusable” are used interchangeably to describe multiuse bioprocessing equipment that must undergo CIP/SIP between batches.
Most often, it is not feasible to transition a GMP manufacturing process, producing quantities for commercial markets, from stainless steel to single-use equipment. For processes that may just be starting out or in the early development stages, it may be worthwhile to compare a single-use bioreactor to the reusable equipment. Continue asking these questions to determine which is more advantageous.
The majority single-use bioreactors have a maximum capacity of about 2,000 L with some exceptions. Due to recent advances in cell density and titer, single-use bioreactors are often capable of achieving yields equal to those of a larger traditional bioreactor. Recent calculations for monoclonal antibody (mAb) production indicate that stainless steel vessels are preferable as they are more economical, if you are looking to produce greater than two tons of antibodies per year. Single-use bioreactors are likely to be more advantageous for smaller volumes.
Modern drugs are typically only designed for small scale markets unlike vaccines such as the polio vaccine. Drugs for orphan diseases, targeted drugs for personalized medicines, cellular or genetic therapies, and powerful drugs requiring only low doses will not require 10,000 litre batches. The type of drug being produced along with its commercial usage and market will impact the appropriate batch sizes. This will determine whether it would be more appropriate to use a single-use bioreactor or reusable equipment.
There are different needs for the likes of labs, pilot facilities, and commercial production environments. Pilot facilities, whether they be GMP or non-GMP, scaling up and down is vital. Single-use bioreactors could be more beneficial in this case as they are significantly more scalable than reusable equipment. However, it would be important to consider whether it will appropriately model your larger-scale operating conditions. Single-use bioreactors are often preferable in labs as they have short-term scalability and can avoid the risk of cross contamination. It is important to make sure that you are able to appropriately model your critical process parameters in your small-scale system.
In reusable equipment, switching between batches of the same drug will take only 6-10 hours. However, uptime significantly drops for reusable equipment in a facility manufacturing different types of drugs. Full turnover of stainless-steel equipment from one batch to a different batch can take up to three weeks. Having a hybrid facility that contains single-use upstream equipment and stainless-steel downstream equipment, can shorten that to two weeks. When compared to a facility with just a single-use bioreactor, turn over between products can be as little as 48 hours which would save a lot of time in the work environment.
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. There is a downside to single-use equipment as sometimes customisation is necessary to get the optimal results from cultures. However, the benefit to having single-use prefabs is that they offer a high level of flexibility. This can allow you to use a facility for a wide variety of purposes whereas stainless-steel equipment can force you to design a highly customised facility that has a fixed infrastructure. This limits the abilities to produce multiple types of drugs in the facility.
Single-use bioreactors are superior when it comes to process intensification. These bioreactors can achieve higher titers and may be able to reach the same overall yields as larger, reusable equipment via scale-out. Overall facility footprint can be reduced as continuous manufacturing can be achieved on single-use bioreactors.
Operators will need to be retrained if transitioning to single-use bioreactors specifically when it comes to installing the vessels and sensors. While this is not a steep learning curve, it is a significant change. Single-use bioreactors generally require more manual handling which may present 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.
Single-use equipment presents a solution if you or your lab team are constantly waiting for validation and qualification of cleaning. This equipment can also be preferable if you have to wait for pieces of equipment to arrive as 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, switching to a single-use bioreactor is not for you. Stainless-steel bioreactors likely remain the best solution for your process.