Radspinner: I think the first barrier is the investment in stainless steel that occurred quite extensively over the last five to ten years. There was undercapacity for a while, so then there was tremendous investment in stainless. And now as titers have gone up, we have excess capacity in stainless, and it's hard to invest in single-use when we have that outstanding commitment and outstanding investment.
I think the second barrier, as more and more people engage in single-use technologies, is that they are concerned about extractables and leachables. They are not necessarily quite sure where to start, so they begin asking questions, and that sort of slows down the process.The third barrier, I think, is doubts about the integrity of containers. If people are storing very valuable product in those containers, they're obviously concerned about the risks.
Lastly, in some areas of single use there is an extensive number of products that meet users' needs, however the portfolio in its entirety is not always complete. There are some gaps.
BioPharm: There is some debate about rinsing disposable equipment before use. Do disposables need to be rinsed before use?
Radspinner: No. Most are clean manufactured, using very clean materials, and sterilized prior to use, for example with gamma irradiation, and then stored in outer containers that are also sealed. So there is no rinsing requirement for the vast majority of single-use technologies.
BioPharm: By using disposable equipment one can delay a lot of capital expenditures. But are there convincing arguments that disposables can save companies money overall—throughout the product lifecycle?
Radspinner: Yes, there are many examples. We have put together a complex economic and strategic modeling initiative to look at strategic advantages, operational advantages, and economic advantages. It really depends, obviously, on the cost of electricity, the cost of clean steam, what investment you have in stainless, how much room you have (single use routinely takes less square footage than fixed equipment). All these factor in. It's a complex model and it's something that really needs to be looked at in detail. But there have been presentations at various conferences that show tremendous long-term advantage.
BioPharm: What is the environmental impact of disposables?
Radspinner: When I look at environmental impact, I look at net environmental impact. Clearly, as most disposables or single-use technologies are based on polymers or various plastics, they can be incinerated or landfilled. But when you look at net impact—the reduction in cleaning materials and cleaning liquids, which are potentially caustic chemicals, and the reduction in energy use for steam, etc.—in many cases there are net benefits.
The Bioprocess Systems Alliance, which is a consortium of various groups involved in single-use technologies, has looked into this net benefit, at least from an initial review point of view. You can find those studies at http://bpsalliance.org/.
BioPharm: Do you think there is any need for increased standardization, for example in terms of materials of construction, or in the way extractables and leachables testing is conducted?
Radspinner: Clearly, standards would help. BPSA has begun to look into standards. I'm engaged on the ASTM E-55 committee on pharmaceutical manufacturing, and that's another avenue, through global consensus standards. The process has just begun, but there's clearly a need and it would be a benefit to the entire community.
BioPharm: Are there still limitations of scale in disposables?
Radspinner: It's relative. If you look at bioreactors, they are around 1,000–2,000 L on the high end. That's very reasonable, depending on whether it's fed batch or perfusion. If you look at product storage, you're looking at around 2,500 L or so, and mixing as high as 3,000. This may be smaller than typical 10,000 or 20,000 L reactors, however, titers have gone up tremendously over the last decade. So the amount of drug being produced is so much greater that people are rethinking whether they need these very large reactors. There are limitations downstream, around chromatography, where the single-use area is more restrictive in scale.
This conversation has been edited for clarity and length.
David Radspinner, PhD, is director of global marketing & customer applications, bioprocess production at Thermo Fisher Scientific