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Great question, but not a simple answer!
I’m not a QA/CMC/manufacturing expert but I oversee those groups. You can’t separate QA from manufacturing, so first some general background on vaccine manufacturing from @IFPMA 1/
@smc90 @a16z @JorgeCondeBio
https://www.ifpma.org/wp-content/uploads/2014/01/IFPMA-ComplexJourney-Part_One_2016.pdf https://twitter.com/gkossakowski/status/1296250586682155014
I’m not a QA/CMC/manufacturing expert but I oversee those groups. You can’t separate QA from manufacturing, so first some general background on vaccine manufacturing from @IFPMA 1/
@smc90 @a16z @JorgeCondeBio
https://www.ifpma.org/wp-content/uploads/2014/01/IFPMA-ComplexJourney-Part_One_2016.pdf https://twitter.com/gkossakowski/status/1296250586682155014
Influenza is a good place to start when discussing benefits of newer technologies, and also because @JorgeCondeBio asked about eggs on the @a16z podcast. Here’s a brief summary of benefits of recombinants vs cells vs eggs for flu vaccines from @CDCgov 2/
https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm
https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm
Traditional vaccines are complex biologics that are difficult to characterize the way we do drugs. So it's essential that the manufacturing process and all reagents be tightly controlled to ensure consistency of the end-product (which is also carefully characterized). 3/
We like to say “the process is the product,” and QA plays a key role throughout. Here’s a WHO paper from 2000 that gives a sense for the complexity of traditional vaccine manufacturing and QA, much of which hasn't changed, courtesy of @rahulsinghvi. 4/
https://pdfs.semanticscholar.org/6e48/9aaf5a5f7646679a5cf925466083b4aa188b.pdf?_ga=2.260656141.1425419210.1597941071-154229862.1597941071
https://pdfs.semanticscholar.org/6e48/9aaf5a5f7646679a5cf925466083b4aa188b.pdf?_ga=2.260656141.1425419210.1597941071-154229862.1597941071
Recombinant vaccines are attractive because the product is more consistent and easy to characterize. But they still require biological systems (eg, bacteria, yeast, cells, plants) which creates complexity from a production consistency and QA standpoint. 5/
Here’s an overview of recombinant platforms and Table 2 captures a few of the things that need to be controlled in manufacturing. 6/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106376/
In general, complexity of the process and QA is reduced as we move from biology to chemistry. mRNA vaccines can be produced in a cell-free system and characterized much more easily than traditional vaccines. Here’s a summary of manufacturing benefits. 7/ https://www.nature.com/articles/s41541-020-0159-8
Finally, here’s a comparison of a range of platforms that can be used for low-cost, rapid vaccine manufacturing with process flows and pros/cons. 8/ https://onlinelibrary.wiley.com/doi/full/10.1002/biot.201800376
Irrespective of the platform, the complexity and importance of quality assurance in vaccine manufacturing can’t be overstated.
Unfortunately there are just too many QA parameters to summarize in a thread, even one this long! 9/
Unfortunately there are just too many QA parameters to summarize in a thread, even one this long! 9/
Safety and quality are the dominant drivers of time and expense in the development and manufacturing of any vaccine. But nothing is more important. 10/
