Dr. Arnold: We see a steadily growing market for reliable, scalable, and fully functional single-use bioreactor solutions. There is tremendous demand, not only in conventional applications such as the cultivation of animal and human cells in the biopharmaceutical industry for instance, but also in traditional microbial biotechnology. Customers from all fields of bioprocessing are asking for advanced systems that meet their needs. That’s why we are focusing on the development of new solutions that satisfy their requirements.
Mr. Clapp: Adoption. That is an interesting word compared to, say, utilization or implementation or even accepted. Like other technologies, single-use and its application to bioprocess unit operations is following a fairly typical curve. Utilization or adoption continues to expand. There is a large body of knowledge now established: what works, what does not, the supplier playing field, etc. This began with the early adopters. Next was the move to process development activites. Biomolecules born from in single-use based process-development that have remained a viable market candidates are progressing through clinical trials; and even into production.
Areas of growth include microbial fermentation, cell therapy, personalized medicine, sensing technologies, and, of course, purification. With this in mind, single-use acceptance is a given. I would venture to say that our children’s children or their children will make routine use of single-use “bioreactors” as therapeutic aids—tools, at the hands of clinicians (physicians). These new bioreactors will not resemble what we know as bioreactors today, but the lineage will be undeniable. Looking back from that point in time, the era we are in now will be seen as the dawn of a medical treatment revolution.
Mr. Giroux: I do think that this technology has plateaued. Future growth in single-use can still be expected.
Future growth areas include:
1) Replacing equipment in existing markets. Even though the sunk cost of traditional systems may delay the adoption of single-use in manufacturing, the operational costs in these facilities are increasing yearly, which should lead to higher single-use adoption over time.
2) Taking a large share of emerging markets. We are now seeing the beginning of stem cell manufacturing, and we believe this field (and the next wave of cell-derived products) will predominantly adopt single-use, owing to its regulatory and cost-related benefits.
3) Creating new markets. Getting away from steam-in-place sterilization allows design flexibilities, which should lead to development of single-use bioreactors that could outperform traditional systems in some areas, resulting in market growth. Also, the lower capital outlays resulting from single-use adoption can also lead to the development of new markets.
Dr. Golightly: We do not believe the use has leveled. In fact, we believe it will continue to grow into the foreseeable future. As biopharmaceutical manufacturing groups continue to seek platform approaches and modularized unit operations, they are amenable to using single-use, ideally to its full extent, whereas today the vast majority employing single-use systems take a hybrid approach with some process equipment still being re-usable. Optimizing facilities, especially for multipurpose/product manufacturing, personalized medicine, e.g., cell therapy (T-Cell expansion), unique recombinant “eplacement enzymes or even unique mAbs requiring efficient smaller batch sizes (ideal for single-use), and the evolution of cell-based vaccine production (whether adherent cells on microcarriers or cells in suspension), all give rise to further employment of single-use bioreactors.
Dr. Greller: From our point of view the implementation of single-use solutions in upstream processing is still growing. While some solutions like the rocking motion-based single-use bioreactors have become the standard for cell expansion in the seed-train, there is still a lot of investment ongoing in stirred single-use bioreactor solutions not only for clinical manufacturing but also for commercial production. Especially due to the increased titers and smaller indications, the use of single-use bioreactors in commercial drug manufacturing will grow significantly.
Due to the integration of single-use sensor technologies in these workhorses they can now also support more advanced cell culture control approaches by using single-use pH, DO, and biomass in off-the-shelf bags. In the future, we expect to see more of these advanced control approaches in support of QbD-driven production approaches.
Moreover, biosimilars or biobetters will require a lean development and production approach implicating the use of off-the-shelf products. Also, in the diverse field of vaccines, the implementation of single-use bioreactors and process solutions is still on the upswing. While the user can select between different suppliers for mammalian cell culture single-use bioreactors, only a few of them just started the first steps into the field of microbial fermentation.
Dr. Jagschies: The adoption of single-use bioreactors and single-use equipment continues to grow as users are building new facilities with smaller capacities relative to traditional stainless steel. Also, companies are now bringing on line single-use plants, as recently announced by Shire, and are beginning to utilize bioreactors.
Geographically, we are seeing growth in all areas, especially where biologics are being produced. This increased use across the industry is resulting in double-digit growth figures for single-use technologies. New areas of use such as microbial fermentation and cell culture-based vaccines are also contributing to this growth.
Mr. Lamproye: It is obvious that the disposable equipment market will increase in the coming years: a fourfold increase in the next four years, according to experts. We at Novasep are even more inclined to believe that single-use solutions have a great future when we look at the adoption rate of our Sius® single-use solution for tangential flow filtration by both CMOs and biopharmaceutical companies. This future growth has to also be associated with the growth of biopharmaceutical and biotech markets by around 15% a year.
Another parameter is that in emerging countries, it is often not possible to register a drug without a local production plant. This stimulates the use of disposable solutions as it is necessary to limit investments and transfer issues. To conclude, most of the single-use technologies are not yet fully mature but they will meet the user needs more and more. In biomanufacturing especially, it is quite probable that disposable systems will outclass traditional steel reactors for a specific ranges of applications.
Mr. Marner: I don’t think we’ve seen a plateau, but I do think we are seeing an evaluation period of the systems that have quickly moved into the field. CMOs have quickly recognized the economic value of single-use systems for their flexible facility needs. Now, they are evaluating the performance of the manufacturing processes to decide whether to press the single-use concept down through the smaller platforms used in development and discovery.
Noncontract manufacturers will likely follow the path that CMOs have taken. Cell-line productivities continue to increase, permitting smaller bioreactor batches. So, traditional manufacturers are at the tipping point where the increased materials cost of single-use technology greatly outweighs the capital, cleaning, and contamination risk costs of sticking with traditional bioreactors. I think we’ll see continued single-use adoption at all scales.
Mr. Phillips: Adoption is far from plateauing. As mentioned before, the market is still young—it has only really been around for 10 to 12 years and still growing at a rate of about 20% or more. At ATMI LifeSciences, we believe this will continue to grow.
The fastest growing segments right now are single-use mixing and bioreactors. While single-use bag adoption has seen a bit of a plateau, the overall adoption of these technologies will continue to grow as companies are seeing the process and cost efficiencies of implementing these technologies in the new flexible facility model. Adoption will also grow as companies innovate new ways to apply the technologies to the needs of the market.
Dr. Rapiejko: The full potential of single-use bioreactors has yet to be realized. As the biopharmaceutical industry expands towards the development of a new generation of therapeutics, the single-use bioreactor will be leveraged to its fullest potential.
Start-up companies bringing their first molecules to clinic as well as CMOs will be the drivers of continued growth of single use bioreactors now that they have become accepted as a proven manufacturing platform.
Vaccine manufacturers that are moving from traditional, egg-based production methodologies to microcarrier-based bioreactor production are evaluating single-use bioreactors for their needs, as are researchers developing therapies based on stem cells. Other growth areas include personalized medicine, local flex-factory manufacturing sites, and/or biomolecules developed to treat orphan diseases.
These applications require smaller production batches as compared to blockbuster mABs and single-use bioreactor are ideally suited to meet the need versus traditional stainless steel systems. These growth areas, coupled with the manufacturer’s focus on quality, economy, and reliability insure that the best days of single use bioreactors remain ahead of us.
Mr. Whitford: We don’t see the adoption of single-use plateauting at all. On the contrary, we see interest accelerating in existing product types as innovations increase volumetric productivities and push required bioreactor working volumes to those supported by SUBs.
Furthermore, we see the industry moving to newer product types and manufacturing platforms that are well-supported and even synergized by SUBs. Initiatives toward such products as personalized medicine, cell culture manufactured vaccines of all types (including VLPs) and targeted therapies also demand SUB features at the production scale they support.
Manufacturing trends that continue to require SUB features include the renewed interest in transient transfection in process development, and continuous processing at the manufacturing scale through enhanced perfusion culture. Finally, the trend toward globalization and outsourcing is feeding the demand for low entry cost and flexible manufacturing facilities—characteristics that are hallmarks of SUBs!
Dr. Zoro: For small-scale bioreactors, it seems that incremental time savings (vs. glass reactors) have been insufficient to drive widespread adoption of single-use vessels alone. With the future in bioprocessing looking towards high-throughput parallel bioreactors and DoE applications, single-use technology must be combined with a major step change in productivity.
This can be realized through full bioreactor automation, delivering attendent benefits in experimental consistency and enabling larger and ever more powerful experimental studies, delivering ever faster and more efficient bioprocess development programs.