Over the last year have the market drivers for single-use/disposable technologies changed at all? What have you observed?
Joseph Prado, Director, cGMP Biomanufacturing Operations, Catalent Biologics: I have not seen a major change in the actual market drivers for single-use or disposable technologies. It has been relatively consistent over the last year or so, except for a few of our competitors adding this capability for their customers, and others who may have already had single-use are offering different films or bag sizes. Catalent Biologics on the other hand, has offered single-use and disposable options to our partners since 2013.
Eric S. Langer, Managing Partner, BioPlan Associates, Inc.: The Covid-19 pandemic is affecting purchases of non-essential inventory (some R&D, etc), and this includes single-use technologies. But the exact impact of the crisis has not been evaluated yet. In our 17th Annual Report and Survey of Biomanufacturing, however, we collected global data just before the crisis, and assuming the mid- and long-term trends will remain consistent, we are seeing a consistent up-take in adoption of single-use technologies. This is shown in various data points, for example, when asked about “New Expenditures: Facility’s top 3 NEW bioprocessing expenditures in the past year.” We found that the top new expenditures are going to be in single-use technologies (62% for basic bags, connectors, etc, and 49% are indicating they will spend more on single-use bioreactors). The third biggest new expenditure will be on cell culture media, optimization, etc.
Don Young, Sr. Product Manager, BioProcess Containers, Thermo Fisher Scientific: Yes. We have seen a significant increase in demand coupled with some profound component supply challenges, resulting in a shift in end-user stocking patterns and strategies. End-users are holding more stock of finished SUT products as well as some specific SUT components.
Next, the concept of interchangeability is now a common discussion topic amongst end-users as well as between SUT suppliers and end-users. Interchangeability differs from equivalence. Proprietary value is driving this shift. Many critical SUT component suppliers have chosen to keep key information proprietary, regarding the formulation of their SUT components. Without that formulation information, interchangeability is the best way to overcome that information gap. Interchangeability, if thoughtfully considered, offers SUT end-users with a variety of benefits, but only if these end-users are willing to invest the time and eff ort to demonstrate that certain SUT components are interchangeable in certain production workflow steps. Interchangeability is best suited for those unit operations that are nondrug product contact unit operations. Conversely, interchangeability may be more difficult or even out-of-scope for those unit operations where the SUT products come into direct contact with the end-users bulk drugs, precursors or intermediates.
What are the top five features or benefits companies are seeking when they look at singleuse/disposable technologies?
Prado: In my experience, companies are looking for three main benefits when using single-use or disposable technologies – lower cost, time savings, and flexibility. Single-use options usually need less capital investments, and there is a quicker turnaround time between batches since cleaning validation is not required, consequently increasing productivity. Single-use and disposables can reduce, or altogether eliminate product cross contamination, de-risking a company’s project and invested resources. They can also allow CDMOs such as Catalent to provide large scale capacity, as well as continue serving customers with small and mid-scale production needs.
Langer: In our study, we found over the past 10 years that SUS technologies are being adopted for a very wide variety of reasons. However, the top reasons (in order) include:
- Decrease risk of product cross-contamination
- Eliminate cleaning requirements
- Reduce time to get facility up and running
- Faster campaign turnaround time
- Reduce capital investment in facility & equipment
These factors have shifted in order of importance over time, but they have remained the primary drivers. Just a few of the other reasons include:
- Flexibility of a ‘modular’ approach
- Improve scheduling ability
- Greater assurance of sterility
- Ability to sterile-sample
Young: Supply assurance – As mentioned earlier, product availability and SUT suppliers’ ability to reliably and consistently supply end-users is the most critical concern. As SUT is adopted in cGMP processes, supply assurance becomes even more critical.
Product quality – Quality is closely related to reliability of supply, but worthy of additional attention for this discussion. Particles, especially the non-embedded variety, must be minimized, especially in the wetted/fluid-contact surface. “Zero” particulates remain a desired requirement by end-users, but so far has been unattainable by suppliers.
Global presence – SUT suppliers should have a global presence since many SUT end-users are multi-national corporations with manufacturing sites (hence demand) spread across the globe. Smaller biotechs are willing to evaluate smaller regional suppliers early on, but are often limited because of poor choices made early on as they try to scale up and grow their business.
Technical data – SUT end-users are employing the products across their production work-streams. In those unit operations where the SUT products contact bulk drug products, precursors or drug intermediates – the SUT products must not be additive, adsorptive or reactive. SUT suppliers must supply their customers with in-depth data based on the most recent industry standards or recommendations. The BioPhorum Operations Group (BPOG) and the Product Quality Research Institute (PQRI) guidance documents are two of the more prominent examples of industry recommendations.
Reliability – No failures, no leaks. Reliability continues to be the most important feature. It’s a lofty goal that drives suppliers’ process improvement strategies and tactics.
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“Green” initiatives are a very hot topic globally. What resources or programs do you have in place to reduce the environmental impact of disposable plastic processing equipment?
Langer: What is currently being done with disposal of SUS products is almost inverse to what the industry respondents think SHOULD be done. In our study, we found over 10 different options being done currently.
But of these, relatively few are what respondents feel is right. Just a few examples:
What function or process in a biopharm facility provides the most “bang for the buck” when implementing a single-use/disposable system?
Prado: When biopharma companies are looking to lower cost, while also saving time, they find that implementing single-use or disposable systems does just that. By eliminating the cleaning process, companies are having quicker turnaround times between batches, which also translates to an increase in productivity with less downtime between batches.
Langer: Single use systems are ubiquitous in bioprocessing, so suggesting a single top area is difficult. Areas where there would be a lot of bang-for-buck include single use chromatography (cheaper Protein-A) for example. Single use downstream operations are in high demand, including harvest steps, and various continuous bioprocessing downstream steps. There are areas, according to our study, where innovation would be very welcome from the industry suppliers.
Young: For hybrid production facilities that use a combination of stainless steel and single-use system it’s reducing process equipment off-line time intervals due to specific rate-limiting unit operations. Single-use systems can significantly increase process velocity. Historically, these rate-limiting unit operations are most common in biologics purification processes.
For purely single-use production facilities it’s the reduction of the clean-in-place and steam-in-place infrastructure – which can account for up to 80% of a facility’s water consumption. This can benefit both upstream and downstream processes.
The time and cost savings can be significant, depending on the number of process runs per year.
Do you think the market for these technologies has reached a saturation point? Are there areas/functions that can still benefit from disposable technologies that are untouched?
Prado: I do not believe that single-use or disposable technology have reached a saturation point. There are still plenty of other areas which could benefit from these technologies - recombinant proteins, monoclonal antibodies, gene therapy, cell therapy - both in small- and large-scale manufacturing. Availability of single-use instrumentation is still growing, and the availability of different film types (for larger vessels) still needs to expand. By having more options available, some recombinant proteins, monoclonal antibodies and cell therapy can be adapted to single-use technology.
Langer: Absolutely not saturated…in fact, we are still at an inflection point, where relatively few SUS systems are used in commercial-scale operations (most are in clinical manufacturing scale). So as these clinical projects move into larger commercial scale, the market will increase significantly.
In terms of areas left untouched - there is still much work to be done. Our study shows a large number of areas where more innovation is being demanded. Just a few of these include: SUS control systems, probes, sensors, bioreactors, and mixing systems. In addition, automation systems for SUS technologies tops many facilities’ ‘wish list’ for improved technologies.
Young: No. We have not reached the saturation point. There are thousands of new molecular entities actively being researched and developed. More than 1000 biosimilars, 500 biobetters and nearly 2000 next-generation biologics in development, about 300 new vaccines in development, and about the same number of cell or gene therapies in development. Single-use systems will be the primary production platform for many of those and it’s likely that all will use single-use systems in some way.
Not sure about ‘untouched’, but for sure the production workflows for cell and gene therapies have yet to achieve the level of single-use system optimization realized in biologics production and in this way under-utilize single-use systems.