• Makes cGMP process easier, eliminating validation issues because cleaning step is removed

• Shorter downtime and turnaround time due to elimination of cleaning steps

• Lower risk of batch contamination and cross-contamination

• Decreased operating cost and capital (initial) investment, savings on utilities, space, cleaning chemicals, and labor

• Quick adoption and modularity of single technologies

• Potentially increased production (quick turnover/less downtime)

Disadvantages

• Non-customizable: Difficult to adapt to different molecules.

• Scale-up: Challenges in maintaining quality at large volumes (up to 2000 L).

• Scale-down: High lower limits hinder effective studies.

• Mixing: Limited by rocking movement, suitable only for simple applications.

• Disposal: Environmental concerns due to plastic derivatives.

• Oxygen transfer: Low rates limit use to mammalian cell cultivation.

References

1. Advantages of Single Use Bioreactors | Lab Unlimited. www.labunlimited.com/advantages-of-single-use-bioreactors

2. “The Pros And Cons Of Single-Use Bioreactors.” PharmTech, 15 Nov. 2020, www.pharmtech.com/view/pros-and-cons-single-use-bioreactors

• Made of stainless steel or glass

• Has a cylindrical shape

  • To allow for high-pressure steam sterilization and efficient cleaning during the cleaning-in-place process.

• Holds up to 20 000L of media

  • Can handle a wide range of volumes, from small batches to large-scale productions.

• Has a slow turnover rate

  • The time needed for cleaning and sterilization takes longer.

• Cleaning-in-place is needed

  • Critical steps that must be carried out at the start and end of every production cycle.

• Has a fixed infrastructure

  • Less flexible and take longer to construct compared to other systems.

• High maintenance

  • large amounts of chemicals required for cleaning processes, as well as maintenance costs for the bioreactor and its associated infrastructure.

• Produces water and chemical waste.

Product and microbial contamination can occur.

• Inadequate CIP/SIP can cause contamination, leading to downtime of production.

Reference

https://www.cytivalifesciences.com/en/us/news-center/single-use-or-stainless-steel-bioreactors-10001?srsltid=AfmBOop0QS6hSSze5XrXYkngd7MOZFtYHJz7L5sRQVX1D8AXP39TO6M0

-Nadra

Disposable bioreactors are also known as single use bioreactors. Disposable bioreactors are used as they are convenient and cost-effective [1]. They reduce the risk of any cross-contamination occurring between different batches, reduce cleaning costs and lower turnaround time [2]. There are different types of single use bioreactors such as:

Airlift Bioreactors: A bioreactor (suitable for large scale production) which stirs the culture using gas. Gas is fed through the sparger ring from the bottom which directs air bubbles and liquid circulation. Air bubble flow upwards within the tube. [3]

Wave-Induced Motion Bioreactors (also known are rocking bioreactors): A bioreactor (suitable for small-scale production) which used wave movements to mix and aerate the culture medium. It is usually made up of a disposable flexible plastic bag that has been sterilized and filled with culture which is suspended in a outer container. The waves are generated by a rocking motion creating a mixing effect which allows the cells to be supplied with nutrients and sufficient oxygen. [1]

Stirred-tank bioreactors: A bioreactor with a simple cylindrical vessel with a stirrer. This bioreactor can be used for microbial fermentation or yeast fermentation. [4]

References

1) https://cellexus.com/blog/single-use-bioreactors/#:~:text=Single%2Duse%20bioreactors%20have%20become,in%20a%20rigid%20outer%20container.

2)https://www.sciencedirect.com/topics/engineering/disposable-bioreactors#:~:text=Disposable%20bioreactors%2C%20buffer%20make%2Dup,costs%2C%20and%20easing%20validation%20restrictions.

3) https://www.lab1st.com/airlift-bioreactors

4)https://www.sciencedirect.com/topics/engineering/stirred-tank-bioreactors#:~:text=The%20stirred%20tank%20bioreactor%20is,the%20brewing%20industry%20for%20centuries.

• Advantages

  -Well established and well understood

  -Available in large capacities and is space efficient since it is integrated into laboratory setups

  -More advanced measurement and controls

  -Reduced risk of contaminations as it is in a fixed place and is not moving in and out the room

• Disadvantages

  -Inflexible infrastructure

  -High utility cost

  -High maintenance requirements

  -Complex cleaning and sterilization requirements

References

https://www.cytivalifesciences.com/en/us/news-center/single-use-or-stainless-steel-bioreactors-10001?srsltid=AfmBOoqpoSEgYTh7tDiNgVtAKZlFf-7D_dmcfmB29LhPlrsbBj9q_i-u

Fixed-in-placed bioreactor

Fixed-in-placed bioreactors are a well established and widely understood technology. It uses glass vessels or stainless-steel tanks and pilot scales for process and development and prodcution of research-grade materials, toxicology studies, and Phase 1 clinical trail materials. For large-scale manufacturing (1000–25,000 L) of biotherapeutics, stainless-steel tanks are the industry standard.

Due to their robust construction and advanced control system, fixed-in-placed bioreactors are suitable for high-volume biologics production. They will be used for long term scalability as it effectively supports the process optimization despite being high cost and require operational efforts like Cleaning-in-Place (CIP) and Sterilization-in-Place (SIP) to minimize contamination and support the growth of cells/biologic material for drug manufacturing. This ensure consistency and reliability of the purity of drugs, batch integrity and regulatory compliance.

Disposable bioreactor

However, if the objective is to achieve small-scale production or rapid prototyping, disposable technologies will be considered in biopharmaceutical process to save time and reduce costs. Since only minimal training of personnel, fewer utilities and installation is required, disposable bioreactor can be implemented quickly into the laboratory. There is no need for CIP and SIP operation like fixed-in-placed bioreactor as the product contact portions provided are clean and presterilised.

Advanced in cell line engineering and process development have significantly increased productivity in cell culture. Example over the past 15 years, cell culture titers in fed-batch operation have risen from 0.05 to more than 10gL^-1. The use of disposables technologies support the efficient production of gram-scale quantities of research-grade material, allowing scale-up and the handling of multiple products. Disposable bioreactor are well-suited for use in Good Laboratory Practice (GLP) or Goof Manufacturing Practice (GMP) facility for the manufacturing of toxicology or even phase 1 and phase 2 material.

However, it is important to acknowledge that this system will still carries certerin risks like the potential for stockouts due to reliance on a single supplier which happens less common in traditional systems. Furthermore, most disposable products are patent-protected, making it challenging or even impossible to secure dual sourcing.

Therefore, both systems have a "double-edged sword" nature, the choice depends on the its specific objectives and scale and phase of the biopharmaceuticals process.

Reference

• https://sci-hub.se/https://doi.org/10.1016/B978-0-08-088504-9.00098-2

• https://www.beckman.com/resources/product-applications/quality-control-for-gmp-manufacturing/clean-in-place-cip-processes