No, it's not separate from the issue of fibril formation. But you are correct that even if fibril formation isn't an issue, it could still be unsafe for other reasons.Respectfully, I feel like you (and others) are conflating issues that have nothing to do with each other and creating heightened risks where they simply don't exist.
Whether or not Cagrilinitide is safe for long term use is completely separate from the issue of fibril formation. There may be 0 practical risk of fibril formation happening, but it could be proven unsafe for other reasons. In that regard we should treat it just like any other unapproved drug.
There is a huge difference between "pH you need to formulate a specific compound" and reconstitution pH. It is very normal that compounds only form at a certain pH, temperature, pressure, concentration, and are then perfectly stable after. Pretty much all of the inorganic substances we interact with on a daily basis operate this way.
It's possible that the Cagrilinitide we buy from grey sources experiences more "stress", but it doesn't matter if that stress isn't comparable to the stress needed for fibril formation - 41 hrs, 98°, in a centrifuge.
But we know that fibril formation is a health risk that NN considers important enough to have selected for formulations that minimize them.
The NN patent also specifies that Cagrilintide should be stored at that PH until injection time when it is mixed with Semaglutide in their patent. They mention that acetic acid is used to keep the pH stable post formulation, and that the concentration of buffer must keep it at 4.0 in the medical device. They're explicit all over the patent about it needing to be right around that pH all the way until delivery, even though it means having to store it separately in the device to the semaglutide. It does not seem like it's just a matter of needing to be at that pH only during the original formulation.
The centrifuge experiment is meant just to speed up the process - it's quite possible that 2 weeks sitting in a warehouse and then being transported by <truck/train/plane> before being lyophilized ultimately has the same result - and lyophilization won't do anything to the fibrils besides also turning them to powder, and then they'll reconstitute just like the peptide. It's like how they'll "age" whisky by putting the barrels on a boat - 6 months there produces similar results to sitting in a barrel house for a decade or so.
NN might be doing all of this out of an overabundance of caution and it's all fine regardless, but I'm a pretty firm believer that unless we really know that the fibrils are a nonissue that confidently telling people it's a nonissue is a mistake.
For example, this is all I would feel comfortable saying about the potential safety of cagri:
"We do not know what pH the original Cagrilintide raw material was formulated at and what the conditions were prior to lyophilization. Novo Nordisk believes that cagrilintide must be kept stable at around 3.5 - 4.5 pH, favoring 4.0, due to concerns around fibril formation. There are potential concerns around health risks from fibrils. We know that under relatively extreme conditions that cagrilintide at a 7.5 pH will form fibrils. We do not know how closely those conditions match the process for what we have available for purchase or how transferable that information is to other conditions. You can use acetic acid to get the pH for your cagrilintide down to 4 after the fact. You can use a filter to potentially remove any fibrils that have aggregated together, but singular fibrils that did not aggregate or ones that did not aggregate to larger than the filter's size will not be caught. There are of course also the general risks of unknown long-term side effects even unrelated to fibril formation. Choose whether these concern you enough to skip cagrilintide or not based on your own risk tolerance."