(2) re working at scale, is it really necessary to be 100% sterile? I’ve noticed in our commercial scale batches at cmos there is actually sometimes a bit of contamination, but it does not necessarily impact production. Has anyone calculated what is an acceptable level of contamination in terms of how many initially contaminating microbes? I.e. is one contaminating bacillus cell in your initial seed enough to screw up the whole batch or does it need to be like 1000 initial bacillus cells in order for their exponential curve to cross the exponential growth curve of your production organism in time for the bacillus to impact productivity - who is modelling this, what margin of error does it give you for UV sterilisation?
we have gone for 100% sterility as a baseline to build our systems, but you are right that perfect sterility may not be needed for many processes. I haven't seen data here but it would be quite interest to explore - I know some probiotic plants are not perfectly clean, they just test for contaminants / pathogens at the end and say they're good to go. This is a topic worth exploring.
are there any limitations on which organisms can be grown in airlift, and are the cell densities the same as what is achievable with stirred tanks? ie is there any reason to think that this will not eventually be applicable for all processes, or is it only applicable for some processes? Would love to see you do 2 posts: (1) If/when you can share on how much this tech reduces facility build costs vs conventional SIP respect to different reactor sizes (I imagine it is hard to get the UV sterilisation to work for very large reactors?).
there isn't technically a limit but there are many tradeoffs. viscosity and cell density being the main one, but there is literature out there where people grew filamentous fungi in airlifts... it just might take obscene amounts of energy to bubble enough gas through the broth. and yes, more insights and data coming soon!
Plans to compete with or integrate with single use systems? What in-line monitoring software providers do you integrate with? I think cell-free is a better paradigm changer than more efficient sterilization, but I'm sure UV will be viable for cell free environment as well.
Congrats on the launch!
have you thought about calling it RIP? 🦠🪦 Radiating in place
love this
(2) re working at scale, is it really necessary to be 100% sterile? I’ve noticed in our commercial scale batches at cmos there is actually sometimes a bit of contamination, but it does not necessarily impact production. Has anyone calculated what is an acceptable level of contamination in terms of how many initially contaminating microbes? I.e. is one contaminating bacillus cell in your initial seed enough to screw up the whole batch or does it need to be like 1000 initial bacillus cells in order for their exponential curve to cross the exponential growth curve of your production organism in time for the bacillus to impact productivity - who is modelling this, what margin of error does it give you for UV sterilisation?
we have gone for 100% sterility as a baseline to build our systems, but you are right that perfect sterility may not be needed for many processes. I haven't seen data here but it would be quite interest to explore - I know some probiotic plants are not perfectly clean, they just test for contaminants / pathogens at the end and say they're good to go. This is a topic worth exploring.
are there any limitations on which organisms can be grown in airlift, and are the cell densities the same as what is achievable with stirred tanks? ie is there any reason to think that this will not eventually be applicable for all processes, or is it only applicable for some processes? Would love to see you do 2 posts: (1) If/when you can share on how much this tech reduces facility build costs vs conventional SIP respect to different reactor sizes (I imagine it is hard to get the UV sterilisation to work for very large reactors?).
there isn't technically a limit but there are many tradeoffs. viscosity and cell density being the main one, but there is literature out there where people grew filamentous fungi in airlifts... it just might take obscene amounts of energy to bubble enough gas through the broth. and yes, more insights and data coming soon!
Incredible! Congratulations!
thanks Eshan, love your newsletter !
🙏🏾
Plans to compete with or integrate with single use systems? What in-line monitoring software providers do you integrate with? I think cell-free is a better paradigm changer than more efficient sterilization, but I'm sure UV will be viable for cell free environment as well.