1

Single-use and Re-usable bioreactor plants in the

Bio-manufacturing Sector

Introduction

Bio-manufacturing is the significant part of the

developed economies. The ability of the bio-

manufacturers in introducing rapid, innovative

products has been the foundation of the

manufacturing sector to increase its market share

and result in worldwide competitiveness. Large-

scale availability of performance based, high quality

products within the sector in cost-effective manner

is due to the technological advances and processes.

 2

Bio-manufacturing is the science of using living

microorganisms and cells to produce commercially

feasible products which includes vaccines, drugs,

antibiotics, and proteins for medical purposes. The

industrial application of bio-manufacturing products

includes bio-fuels, industrial enzymes, and bio-

chemicals. A bio-reactor is the main tool of the bio-

manufacturing industry. It is the piece of equipment

used for cultivating the microorganisms, in a

contained system and under required temperatures,

to produce the desired products. It is designed to

trigger the metabolic activity of organism for

optimal growth.

There are many types of Bioreactors available in

the market depending on the process i.e. aerobic or

 3

anaerobic. They also differ in shape and size and

are mostly made of stainless steel. However,

recently, there has been a growing trend in the use

of single-use or disposable bioreactors. Disposable

bioreactor plants are being looked upon as key

change agent in bio-manufacturing sector. The new

technology presents its case as the ideal solution

which is both time and cost effective.

Single-use/disposable Bioreactor

There most common type of single-use bioreactor

is the stirred-tank reactor. The single-use is made up

a disposable bag. The disposable system consumes

only 32 mega joules of energy from the

 4

consumption of gamma irradiation. The single-use

bioreactor system consists of an outer support

container consisting of water jacketed heating

systems. In addition it has single-use bioreactor

process container, consisting of flexible bio-

container, disposable capsule filter, and a disposable

membrane absorb capsule. Some unit operations

involve hybrid systems with a combination of

single-use and cleanable components: e.g., capture

chromatography and concentration (Rawlings &

Pora 2009). It also consists of control system for

agitation and temperature.

 5

In text: Wilde, D., Noack, U., Kahlert, W.,

Barbaroux, M. and Greller, G. (2009).

 6

Multi-use/ Reusable Bioreactor

Mostly known as the stainless steel bioreactor, is

the traditional reusable bioreactor. It is a

combination of stainless steel and some reusable,

cleanable plastic components. It consists of stainless

steel buffer and storage tanks, liquid filters,

exhaust-gas filters, and capture and ion-exchanging

polishing chromatography columns and resins. The

process uses standard cleaning chemicals such as

sodium hydroxide and phosphoric acid along with

pyrogen-free water for product compounding,

buffers, cleaning agents, and rinsing. Moreover, for

 7

sterilizing purposes the steam is used at 130 C

(Sandstrome, 2009).

In Text: (stainless steel bioreactor s.b.)

Case for Single-use against reusable plant

The comparison basis for single-use and stainless

steel equipment, requires an evaluation of costs and

 8

benefits of both single-use and reusable bioreactors.

There is a strong case for single-use bioreactor as it

is best suited for small-scale manufacturing. Budget

cuts in research and development and health care

system has altered the production requirements.

Target-specific treatments demands quick and

innovative changes in product development. The

present demand for improved bio-manufactured

products especially in the case of personalized

treatments has resulted in production of smaller,

higher yielding batches. The scalability to increase

and decrease the output is higher in disposable

reactors as it is only viable to manufacture several

hundred litres. However, for commercial purposes

scalability is being modified to support up to 1000L

for future use.

 9

On the financial front the difference between

disposable and reusable bioreactor is further

widened. The operating expenses are less in

disposable as compare to stainless steel where the

latter later use the more consumables with huge

cleaning and sterilizing costs. Cleaning costs are

particularly huge and time-consuming. Disposable

eliminates the clean-in-place (CIP) and steam-in-

place (SIP) sterilizing procedures required between

the batches in the stainless steel. The stainless steel

reactors require the change over process between

each new batch and needs to be sterilized. This

sterilized testing is costly, and if not done can create

issues of cross-contamination. Cross contamination

means that there is a possibility of chemical based

contamination as well as biological contamination

 10

in fluid pathways in reusable reactor. In the case of

disposable reactors, the cross contamination is

eliminated because of single-use filters and

unidirectional disposable valves. The use of new

bags for each runs not only results in decreased

operating costs but also results in cost savings from

reduced cleaning. Furthermore, the disposable

reactor lowers down the labor costs as skilled labor

force is required for sterilizing testing and cleaning

in the case of stainless steel reactors. Moreover, the

disposable system is less complex; hence, it

eliminates the validation requirement that is needed

before each new batch. This makes installation easy

and lowers down the start-up costs and initial

capital investments. The heat calculation may add

up to the overall cost of stainless steel reactor

 11

because of high cost of steam generation and the

heat capacity of stainless steel hardware.

Lastly, the environmental cost associated with

disposable reactors includes the use of disposable

plastic bags. Although this cost maybe offset

cleaning water and chemicals used in reusable

reactors for cleaning and sterilization process.

Conclusion

The traditional, reusable stainless steel reactors are

high performing and since they have been in use for

so many years so the knowledge base about the

design and control base is wide, although they are

outdated and inefficient in comparison to efficient

disposable reactors. The latter not only speed up the

production process but also drive down the costs.

 12

Besides continual change and uncertainty in

demand for bio manufactures products has

incorporated a wider acceptance for bio process

bags in the sector. However there may be some

delimitation of disposable reactors. Firstly, there is a

potential risk for the puncture of disposable bag.

The variable costs of each new batch may vary a

little and the plastic fluid pathways can be pressure

and temperature sensitive.

Bio-manufactures can incorporate the disposable

components in the already existing stainless steel

reactors with little modification such as replacing

the disposable fluid path systems. This will speed

up the process needed in cleaning and validating the

reactor and make it ready for the next batch in short

 13

time. The addition of disposable components will

provide flexibility and efficiency. It will also enable

versatility in manufacturing infrastructure and will

provide product diversification.

 14

Bibliography

Craig Sandstrom (2009) Disposable vs. Traditional

Equipment- A Facility-Wide View: Society for

Biological Engineering, pp. 30-35.

Rawlings, B. and Pora, H. (2009) Environmental

Impact of Single-Use and Reusable Bioprocess

Systems, : Bio Process International , pp. 18-25.

Stainless steel Bioreactor, s.b. photograph,

viewed 2 April 2016,

<http://www.genengnews.com/Media/images

/Article/block_9296.jpg>

Wilde, D., Noack, U., Kahlert, W., Barbaroux,

M. and Greller, G. (2009). Bridging the Gap

from Reusable to Single-Use Manufacturing

with Stirred, Single-Use Bioreactors A

 15

Development Approach Based on the Gold

Standard. Bio Process International, pp. 36-

41. [Online] Available at:

https://www.researchgate.net/publication/24

2601404_Bridging_the_Gap_from_Reusable_t

o_Single-

Use_Manufacturing_with_Stirred_Single-

Use_Bioreactors_A_Development_Approach_B

ased_on_the_Gold_Standard [Accessed 2 Apr.

2016].