Disposable culture systems are becoming increasingly prevalent compared to 10 years ago when it was used as a one-off production. Although, “classic” fermenters made from steel are still used everywhere, as they continue to equip their production facilities. Especially, due to their reliability and durability, alongside the main standard technological characteristics in design and processes.
Disposable consumables have also been used in laboratories for over a recent period of time, as it is very convenient and reasonably commercially. Moreover, when taken into consideration, the cost of research and concern of inaccurate results is many times likely than the cost of error. This is due to the lack of following proper cleaning and sterilisation regulations.
If you are faced with the option of scaling a process where there is always some shortage of input data, it can be difficult to consider all other options on the market (in terms of balancing valuable equipment and process requirements).
We want to share many years of experience connecting with our customers, analysing their satisfaction with the results of choosing different types of fermenters, based on the resources and information at their disposal.
In the next section (below), we will discuss and explore the main features of certain designs and compare their main advantages and disadvantages.
Comparison of disposable and classical bioreactors.
Comparative characteristics
Disposable bioreactor
Bioreactor in metal design
Designation
Culturing animal cells
Bacteria, yeast, filamentous fungi, animal and plant cells
Basic equipment
Comparatively lower (from the same manufacturer), but no more than 15-20%. For some manufacturers, the cost is even higher than for a line in a non-“disposable” version
Comparatively higher (from the same manufacturer), but no more than 15-20%. For some manufacturers, the cost is sometimes lower than for a line in a “disposable” version
Consumables for the process
Purchase, in addition to the standard set, additional consumables for each cycle of the process, it is necessary to consider both the supply chain and delivery time
Standard set of consumables
Energy consumption
The stage of sterilization of the bioreactor is excluded
Higher than when using disposable systems, because bioreactor cleaning and sterilization required
Time spent on the technological process
It is impossible to completely eliminate the stage of equipment cleaning between product batches, but it is significantly shorter
Depends on the degree of system automation (CIP, SIP)
Qualification
Slightly simplified, no cleaning qualifications required
Full procedure required
Injury of culture cells during stirring and bubbling (relevant only for animal cells)
Weakly expressed
Weakly expressed with the correct selection of equipment parameters
Extraction of unwanted substances from the reactor walls
The materials of the disposable systems should be carefully selected. Ideally, one should conduct additional research on the influence of this factor on a specific process
It is necessary to choose the right material for making the bioreactor. Additional research is not required due to their wide applicability
Mass transfer characteristics
They strongly depend on the design of the bioreactor, disposable bags do not have rigid walls and therefore their shape “floats” a little until they are completely filled, folds may form.
Mass transfer characteristics are well modelled at the equipment design stage
Potential for contamination
Low, with proper personnel training
Low, with proper equipment maintenance and personnel training
Recycling
With the scale of production from pilot and higher, it is necessary to solve the problem of disinfection of large one-time volumes of disposable materials, considering compliance with biological safety requirements
It happens according to the standard scheme. Disinfection is performed directly in the reactor without requiring additional equipment (autoclaves, etc.)
Length of the process
Disposable bioreactor in metal design have different characteristics. Choice of the bioreactor depends a lot on the process and culture. For instance, animal cells usually require a longer rearing period. The longer the process, the higher the risks of contamination of the final product. Therefore, when correlating the final cost of the product and the risks of contaminating the crop, manufacturers often prefer to use disposable systems. But with a competent organisation of the production process, using a “classic” bioreactor, the risks of infection are reduced to very low levels.
Cleaning
It should also be noted that the stage of cleaning the reactor itself when using disposable systems is minimised, but the issue of waste disposal after cultivation is more acute.
Capital cost
Manufacturers of disposable systems claim that they are cheaper in terms of capital cost. This statement is sometimes true when comparing prices for steel and “disposable” bioreactors from the same manufacturer (i.e. for a steel frame, for a bag with a jacket and a control unit), but the price difference (if any) is insignificant as it would cost roughly between 15-20 % of the price.
At the same time, in terms of current process costs, disposable systems are much more expensive, since only a few companies have sufficient technical equipment and design potential to produce quality disposable cultivation systems. When using disposable systems, there is always the possibility of extracting unwanted substances into the nutrient medium during cultivation, which means additional risks of reducing the productivity of the process.
Thus, separate requirements for materials arise. The quality of the disposable systems is high. However, the production of a disposable working part of the bioreactor is costly. It turns out that purchasing a disposable bioreactor with each new production cycle has to incur significant costs. In addition, on its main working part, which justifies itself if the cost of this “consumable” is lower than other current costs of fermentation or loss of production from its cycle.
Among other “pitfalls” in the operation of disposable systems are:
- unforeseen downtime in the production process due to cargo delays at customs;
- a “disposable” bioreactor cannot be operated without a disposable culture bag;
- if there is an unforeseen downtime in production for various reasons, then the previously purchased materials may expire, and with it the quality guarantee from the manufacturer.
For the convenience of risk assessment, we summarized these and other factors in the table below:
Considering all of the above, it can be concluded that for classical fermentation processes, steel reactors will be more cost effective. Moreover, for the cultivation of animal cells, it is necessary carefully approach the planning of the process, assessing and considering all the risks and production potential.
