FDA CPAC Meeting Dec 24 - Peptide focus continues

[Ghoul]

The December 2024 FDA meeting of the Compounding Pharmacy Advisory Committee is once again sounding the alarm on peptide immunogenicity risk, this time focusing in on aggregates as the primary factor, and the failure of non-pharma produced peptide formulations to prevent their development. They suggest aggregation control is the primary means by which to reduce risk of immunogenicity.*

CJC-1295, all forms, banned from compounding use by a majority vote due to concerned over genetic mutations, immunogenicity risk, and safer GH secretagogue availability,

AOD-9604, both forms, banned from compounding use by a majority vote due to immunogenicity risk, lack of safety and efficacy data.

Both may be reconsidered in the future if a manufacturer sponsors normal pharmaceutical clinical trial so safety and efficacy can be fully evaluated.



Full set of meeting slides available here:

https://www.fda.gov/media/184045/download

* I suggest UGL peptide users exercise aggregate control through proper reconstitution, handling, and filtration.

 

[readalot]

The December 2024 FDA meeting of the Compounding Pharmacy Advisory Committee is once again sounding the alarm on peptide immunogenicity risk, this time focusing in on aggregates as the primary factor, and the failure of non-pharma produced peptide formulations to prevent their development. They suggest aggregation control is the primary means by which to reduce risk of immunogenicity.*

CJC-1295, all forms, banned from compounding use by a majority vote due to concerned over genetic mutations, immunogenicity risk, and safer GH secretagogue availability,

AOD-9604, both forms, banned from compounding use by a majority vote due to immunogenicity risk, lack of safety and efficacy data.

Both may be reconsidered in the future if a manufacturer sponsors normal pharmaceutical clinical trial so safety and efficacy can be fully evaluated.

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Full set of meeting slides available here:

https://www.fda.gov/media/184045/download

* I suggest UGL peptide users exercise aggregate control through proper reconstitution, handling, and filtration.

Great work posting this. Thank you.

 

[Ghoul]

Great work posting this. Thank you.

I think the #1 thing tripping up otherwise safety and science conscious guys in the AAS community is seeing all the pharma peptides we use as having "no clinically significant" immunogenicity documented in the published pharma trials.

What's not immediately apparent is that is the end result of wringing immunogenicity out of the product during development, and only applicable to the specific pharma formulation up for approval, not one manufactured in any other manner by anyone else, and with no deviation from the protocol they specify, ie, once a week. Even the container it's supplied in plays a role.

It certainly doesn't apply to UGL, and the many unique forms of contaminants they may contain, inducing unique immune reactions, which the FDA points out are very difficult to characterize through testing, since they so closely resemble the original drug peptide.

I think they did their best to point this out by putting this text into one of the slides:

"For most peptides capable of inducing an immune response, impurities can change the quantity and the quality of the immune response"

The next level of peptide testing might be "contaminant characterization", which is advertised as available from specialist labs, but I have no idea how costly that would be.

One really interesting possibility, besides discovering that good results like "99% purity" may be a mirage caused by "close but not quite" "mutant peptides" that give false results, but those characterized impurities can be run through a simulator that would give us an idea of just how strongly the immune system would react to them, and even predict the chance of them cross reacting with natural peptides, and therefore the long term danger they present to health.

Talk about being fully informed...

 

[songsofpyramids]

CJC-1295, all forms, banned from compounding use by a majority vote due to concerned over genetic mutations, immunogenicity risk

I developed an “allergy” to cjc1295/grf 1-29 after 6-9 months of use. I now worry it was this and hope I didn’t do serious damage. Consequently, this is also why I now encourage people not to fuck with untested on humans research chems. Really hope I didn’t do lasting damage…

 

[Ghoul]

I developed an “allergy” to cjc1295/grf 1-29 after 6-9 months of use. I now worry it was this and hope I didn’t do serious damage. Consequently, this is also why I now encourage people not to fuck with untested on humans research chems. Really hope I didn’t do lasting damage…

The good and bad news regarding immunogenic effects is this.

Even in cases of immunogenicity that causes the effectiveness of the drug to weaken, often, but not always, a higher dose can overcome this immunity without inducing stronger immunogenicity.

Some forms of immunogenicity wear off over time, like vaccines that lose effectiveness.

However, like some immunizations, in certain cases they can last a lifetime, so you can definitely become "allergic" to a peptide, forever. Even worse, since we're talking about unknown peptide sequences being part of the impurity "soup", we don't know if they look similar enough to a natural peptide they're mimicking(like GLP or GH), that they can induce an allergy to them, perhaps permanently. This is what the FDA means by "catastrophic" effects to "healthy volunteers". After this happened a few times, the FDA required pharma to use computer models that not only assess the potential immune reaction to the peptide before injecting any into humans, but all the possible ways the peptide could break down into impurities, and what types of impurities could be created in manufacturing, and ensure none of them could, even worst case scenario, create these "catastrophic" outcomes.

UGL does none of this.

The only way to protect ourselves is to minimize the amount of "attention" the peptide gets from the immune system. This way, even if there's some random doom molecule present, if the immune system isn't on high alert because of large aggregates, unnecessarily frequent exposure (injecting more often than necessary), too concentrated of a solution, and other immunogenicity inducing factors, the likelihood of that worst case scenario is reduced, and that fucked up peptide chain goes unnoticed and gets metabolized out the system before any harm is caused.