Single-use technology (SUT) in biopharmaceutical manufacture offloads many risks associated with upstream cell culture farther upstream—to media suppliers etc. A producer with a full-SUT process does not even carry the risk of cleaning and maintaining their own equipment. The purported economic and environmental benefits of SUT are related to the elimination of sterilization steam (because everything is gamma-sterilized before shipping) and the elimination of cleaning chemicals (because the bags are not cleaned for reuse).
The size limit of 2,000 L arises from the mode of sterilization—the penetration depth of gamma radiation from a cobalt-60 source is about 30 cm. In a stirred-tank configuration, this means that the rigid impeller inside the bag can be no larger than ~50 cm in diameter when the bag is folded up and irradiated from two sides. Following typical bioreactor geometry rules for animal cell culture (vessel height/diameter ratio and vessel/impeller diameter ratio), a 50-cm impeller indeed limits the scale to 2,000 L. For typical microbial bioreactor guidelines (very high OUR), the SUT limit is rather closer to 1,000 L. The 6,000 L bags are meant for very low cell density processes (very low OUR), like vaccine production in Vero cells on microcarriers. An alternate SUT configuration is the wave bag; the largest out there today is also 2,000 L (looks like a queen-size water bed) with a 50% working volume.
From my perspective, the SUT argument got too tortured between the small maximum size, the amount of waste generated (including daily media-prep bags, filters, and hoses), the observation that large stirred bags still need to sit in a permanent stainless-steel shell, and some discussion I found in “the trades” which said that SUT automation is suboptimal, apparently because the best single-use sensors (pH, temperature, etc) are not good enough for fully automatic operation. Combined with 100% manual unpacking, setting, connect/disconnect, and teardown of bags, the single-use idea seemed very much at odds with the fully automatic plant that many propose.
Finally, the gamma sterilization industry is extremely strained right now—the cobalt supply is tapped, or at least promised to EV-makers. New production of Co-60 is barely keeping pace with attrition at existing sterilization facilities, and the industry is already in triage mode with respect to what healthcare/biotech equipment gets to go through gamma sterilization versus what can go through an alternate sterilization, like ethylene oxide. So a significant expansion in the supply chain of SUT would be out of the question today.
(Aside: yes, ATFs are incredibly expensive today and their price could be expected to come down with market volume, but it doesn’t matter in the terms of my analysis. In my perfusion analysis, the perfusion devices contribute $10 out of $50/kg, and I assert an affordability threshold of $25.)
Given recent events, it is perhaps relevant to note that half of the nuclear facilities capable of turning Co-59 into Co-60 are in Russia. Cobalt supply issues are not easing up anytime soon.
I appreciate the response here and want to clarify my argument a bit. I totally understand that currently available SUT isn’t sufficient to make cultured meat cost-effective. I’m mostly arguing against the notion that these problems are intractable. To your point about the difficulties with gamma irradiation, it seems likely that there could be a reasonable alternative to gamma irradiation for SUT sterilization. At the moment, pharma companies get by just fine using stainless steel for processes > 2kL, so there isn’t much pressure to improve from that angle. If single-use is truly enabling for cultured meat, then that provides an impetus for more investment in improved sterilization technologies.
The purported economic and environmental benefits of SUT are related to the elimination of sterilization steam (because everything is gamma-sterilized before shipping) and the elimination of cleaning chemicals (because the bags are not cleaned for reuse).
The major cost savings I see for a cultured meat plant would be in a reduction in the requirements for air quality. A fully single use plant with completely aseptic connections can (in-theory) be run aseptically without a clean room. There would just be a small clean room for media and solution prep. Existing pharma plants using SUT tend to still need high quality air as there are some steps in the process that require manual manipulation. I’ve seen it suggested though that future biopharma processes which use fully integrated and continuous systems can be run in clean rooms with drastically lower air quality than existing plants.
Combined with 100% manual unpacking, setting, connect/disconnect, and teardown of bags, the single-use idea seemed very much at odds with the fully automatic plant that many propose.
Moving to long duration perfusion (> 30 days) reduces the need for unpacking / teardown. There have been biopharma companies which have demonstrated the ability to run stable perfusion for up to 60 days. For the most part, companies haven’t gone longer than that mostly because it’s not really necessary.
Single-use technology (SUT) in biopharmaceutical manufacture offloads many risks associated with upstream cell culture farther upstream—to media suppliers etc. A producer with a full-SUT process does not even carry the risk of cleaning and maintaining their own equipment. The purported economic and environmental benefits of SUT are related to the elimination of sterilization steam (because everything is gamma-sterilized before shipping) and the elimination of cleaning chemicals (because the bags are not cleaned for reuse).
The size limit of 2,000 L arises from the mode of sterilization—the penetration depth of gamma radiation from a cobalt-60 source is about 30 cm. In a stirred-tank configuration, this means that the rigid impeller inside the bag can be no larger than ~50 cm in diameter when the bag is folded up and irradiated from two sides. Following typical bioreactor geometry rules for animal cell culture (vessel height/diameter ratio and vessel/impeller diameter ratio), a 50-cm impeller indeed limits the scale to 2,000 L. For typical microbial bioreactor guidelines (very high OUR), the SUT limit is rather closer to 1,000 L. The 6,000 L bags are meant for very low cell density processes (very low OUR), like vaccine production in Vero cells on microcarriers. An alternate SUT configuration is the wave bag; the largest out there today is also 2,000 L (looks like a queen-size water bed) with a 50% working volume.
From my perspective, the SUT argument got too tortured between the small maximum size, the amount of waste generated (including daily media-prep bags, filters, and hoses), the observation that large stirred bags still need to sit in a permanent stainless-steel shell, and some discussion I found in “the trades” which said that SUT automation is suboptimal, apparently because the best single-use sensors (pH, temperature, etc) are not good enough for fully automatic operation. Combined with 100% manual unpacking, setting, connect/disconnect, and teardown of bags, the single-use idea seemed very much at odds with the fully automatic plant that many propose.
Finally, the gamma sterilization industry is extremely strained right now—the cobalt supply is tapped, or at least promised to EV-makers. New production of Co-60 is barely keeping pace with attrition at existing sterilization facilities, and the industry is already in triage mode with respect to what healthcare/biotech equipment gets to go through gamma sterilization versus what can go through an alternate sterilization, like ethylene oxide. So a significant expansion in the supply chain of SUT would be out of the question today.
(Aside: yes, ATFs are incredibly expensive today and their price could be expected to come down with market volume, but it doesn’t matter in the terms of my analysis. In my perfusion analysis, the perfusion devices contribute $10 out of $50/kg, and I assert an affordability threshold of $25.)
Given recent events, it is perhaps relevant to note that half of the nuclear facilities capable of turning Co-59 into Co-60 are in Russia. Cobalt supply issues are not easing up anytime soon.
I appreciate the response here and want to clarify my argument a bit. I totally understand that currently available SUT isn’t sufficient to make cultured meat cost-effective. I’m mostly arguing against the notion that these problems are intractable. To your point about the difficulties with gamma irradiation, it seems likely that there could be a reasonable alternative to gamma irradiation for SUT sterilization. At the moment, pharma companies get by just fine using stainless steel for processes > 2kL, so there isn’t much pressure to improve from that angle. If single-use is truly enabling for cultured meat, then that provides an impetus for more investment in improved sterilization technologies.
The major cost savings I see for a cultured meat plant would be in a reduction in the requirements for air quality. A fully single use plant with completely aseptic connections can (in-theory) be run aseptically without a clean room. There would just be a small clean room for media and solution prep. Existing pharma plants using SUT tend to still need high quality air as there are some steps in the process that require manual manipulation. I’ve seen it suggested though that future biopharma processes which use fully integrated and continuous systems can be run in clean rooms with drastically lower air quality than existing plants.
Moving to long duration perfusion (> 30 days) reduces the need for unpacking / teardown. There have been biopharma companies which have demonstrated the ability to run stable perfusion for up to 60 days. For the most part, companies haven’t gone longer than that mostly because it’s not really necessary.