A number of bioprocess analysts estimate that the entire single-use market has been growing at about 15–20% per year. Single-use bioreactors (SUB), in particular, are rapidly increasing in popularity and seem destined to stay. GEN polled a number of leading SUB biomanufacturers for their insights on this technology.
What are the biggest challenges for manufacturers of single-use bioreactors?
Mr. Abellan: Manufacturing disposable equipment having high-quality/high-tech control systems at the same time is a big challenge, since these manufacturing processes need different core competencies.
Single-use sensors still have a lack of performance and, therefore, sometimes do not meet the needs for high-performance process control. Also finding materials free from leachables/extractables is still a challenge.
Another challenge is to manufacture single-use bioreactors that encompass microbial culture with, for example, high oxygen demand or a larger pH range than is possible with single-use equipment at the moment. The limits here are clearly the higher requirements for material stability and higher performance sensors, similar to nondisposable solutions.
Dr. Arnold: Well, it’s a question of philosophy. What kind of solutions and technology do you want to rely on to serve the users of single-use bioreactors? As a manufacturer that aims to provide single-use bioprocess solutions that can be easily adapted to proven processes and workflows in each customer’s lab, we see only one main challenge: we believe we need to combine the advantages and features of both single-use and conventional bioreactor technologies to create products that allow users to gain the most reliable and scalable results.
For us, developing single-use bioreactors means transferring the geometry and control capabilities established in glass and stainless steel bioreactor technology to new materials in the form of advanced polymers.
Mr. Clapp: The first challenge is the realization that single-use bioreactors are not the same as their SIP counterparts. A single-use bioreactor is composed of two highly integrated elements: the equipment and the bag assembly. An appropriate amount of specification and review takes place (by the end-user, owner, etc.) for the bag assemblies—usually.
Quite often, however, more scrutiny is placed on the equipment element than is necessary. In so doing, the full value of single-use bioreactors has not been realized by the industry. And, it is not limited only to bioreactors.
The second challenge is that balancing standardization, intellectual property, and commercial success will be critical to the pace and extent of innovation and progress. There are many lessons to be learned from SIP bioreactors so that old mistakes are not repeated and new ones may be avoided
Mr. Giroux: The two main challenges are the inertia of the biopharmaceutical industry in embracing change. The high costs of implementing changes and the risks associated with making such changes result in slow adoption of technologies that may be ultimately beneficial to the end user’s bottom line.
Another issue revolves around educating the users about all of the benefits of single-use technologies. Much of the advantage of single-use systems comes from their flexibility, small footprint, and ease of use, but these benefits must be understood to be realized.
Dr. Golightly: Lack of standardization represents a challenge to both suppliers and consumers: end-users would prefer both the flexibility and potential cost benefits of interchangeability, but suppliers are presently determined to introduce value-adding differentiation.
The standardization dilemma involves nearly every key aspect of the single-use bioreactor system, from the consumable (bioreactor bag) to its holder (tote) to the control system employed to operate the system. As a supplier, we seek to add value by improving upon existing technologies and operator ease-of-use/workflow optimization, but we are also cautiously aware of not being too different’ given the potential cost of justifying new technologies to regulators.
The second biggest challenge is addressing the varied process needs of the myriad end-use applications in the most economical manner possible. For example, today many customers are interested in adapting single-use systems originally designed for traditional batch/fed batch operations to perfusion applications. End users would prefer a comprehensive design that can serve both applications; the single-use manufacturer has to address the complexity and cost of successfully designing systems capable of high performance in both applications.
Dr. Greller: One challenge is the required mindset change to align the stainless steel project world with a single-use product environment. In the past, users were accustomed to specifying to a large extent their specific stainless steel bioreactor solution. A great variability of designs have been realized for different customers and processes. After delivery, the customers would then qualify the system for their needs and use it. Given the ready-to-use, disposable character of single-use bioreactors, considerably increased responsibility regarding qualification and security of supply has become the job of suppliers of single-use bioreactors.
Secondly the integration of new sensor technologies, e.g., to enable implementation of process analytical technologies must be anticipated for different single-use bioreactor types.
While some of these smart sensor technologies are already mature, others are in an early development stage. In the latter case, a collaborative approach between the single-use bioreactor vendor and user is required. It involves a joint learning curve to bring the concept from the prototype stage to a reliable, robust industrial state.
Dr. Jagschies: One of the biggest challenges for manufacturers of single-use bioreactors is controlling the supply chain particularly at the start, and ensuring robust quality of the film and components in contact with cells. The start of the chain is normally a petrochemical company for whom biopharma is still a relatively small market and therefore not a top priority.
Then the initial film manufacturers are often reluctant to give the assurances of consistent and tracked manufacturing processes, which are required by the biopharma industry. Despite this, robust supply chains of plastics do exist.
Secondly, sensor technology and the availability of specifically designed single–use sensors is limiting. Having to use sensors designed for use in stainless steel systems immediately introduces the need for washing protocols and validation, negating some of the benefit of using single-use.
The ideal single-use bioreactor would contain single-use sensors of the same or superior quality to those currently available.