@Ghoul
Trying to wrap my head around backfilling process that you described earlier in this thread. I've read the post multiple time, but I feel like I'm misunderstanding something.
It's not you, I'm just not that motivated to write up a clear step by step process tbh,
In the steps above, you mention that you draw the entire vial into a 3ml syringe with a filter,
Draw the reconstituted peptide only using a needle, remove needle, then install filter (and needle).
and then you backfill it into an insulin syringe. Afterward, you store that 3ml syringe with the filter in your refrigerator. If I'm understanding it properly, you have the entire contents of the vial in the 3ml syringe. Wouldn't that contaminate the compound, since the back of the 3ml syringe and the needle even if you cap it, is considered non-sterile?
If you're referring to my point that the barrel of every syringe is exposed to a non sterile environment, even without removing the plunger, yes, you're correct.
This of course means it's a risk with any user prefilled syringe, a common practice even among nurses (but the FDA explicitly advises against it).
However in this case it's moot. Not only because of the demonstrably low incidence of issues with prefilled syringes, especially those filled with a bacteriostatic solution, but the simple fact that .22um filtration sterilizes the peptide solution as you push it through the filter.
In other words, you're filtering as you're filling whatever the receptacle is, a vial, a backfilled syringe, or a coupled syringe. In theory, if you could exercise perfect control, you could just inject directly, changing the needle attached to the filter each time, using it like a manual multi-dose injection pen, I haven't had to guts to try that. I might sneeze and easily overdose myself,
Wouldn't it be better to keep the peptide in the vial and then only filter out the amount you need with the 3ml syringe that you then backfill, according to your suggestion?
I fail to see how this is better than using a new insulin syringe to pierce the vial and extracting the amount you need. Following you filter the peptide after reconstituting into a new sterile vial.
You also mentioned that filtering a peptide twice is unwarranted. Wouldn't there be some benefit from filtering a peptide once after reconstituting into a new sterile syringe. Then perhaps using a setup like the above where you use a 3ml syringe to filter per dose before injection. Is there a potential that aggregates in an unsterile peptide vial might damage a peptide if you don't filter.
I think you should avoid double filtration for this reason: Aggregation consumes viable peptide. There is a saturation point where all things being equal, aggregation development slows, then presumably stops, When you filter out aggregates, you've created "space" for more aggregation. This takes time, it's not instant, but if you're going to filter, I think you're better off just waiting until the last possible moment, whether it's an entire vial or per dose. Perhaps if a vial sits around longer than you expected a second filtration would be warranted, just before you start using it again. Pharma knows exactly how their peptide will behave because they control almost all variables, If anything's changed, in manufacturing or even the material of the plunger in a prefilled syringe, they're required to demonstrate to the FDAs satisfaction this won't increase aggregation and immunogenicity. This just happened with a 1 year delay imposed by the FDA to an updated Egrifta (Tesamorelin) formulation. They demanded proof aggregation wouldn't increase as a result of the change. We're working completely in the dark here.
Speaking of tesamorelin, because that compound is renown for painful site reactions, it's uniquely suited to demonstrate the impact of filtration. I challenge anyone to use an unfiltered dose, then a filtered dose, and fail to notice the reduction in discomfort, QSCs only excipient is mannitol, the pharma formula uses unknown excipients (I haven't found them anyway), so this reduced reaction can't be explained by the removal of excipients, and the most obvious explanation would be the reduction of aggregates,
For example, take the two following scenarios:
1) Inject BAC water into the same vial the peptide came in without filtering it. Then filter per injection.
Would that have the same risk as
2) Filtering a peptide into a new sterile vial after reconstituting and then filtering per injection?
As mentioned above, I think "making room" for more aggregate development may result in more loss than just letting aggregate homeostasis develop, then filtering once. But again, this is where the limitations of not being able to analyze aggregate development in all sorts of scenarios leaves us having to make our best guess. Maybe filtering just after reconstitution, removing the contaminant "seed" particles like glass and silicon droplets that also foster aggregation, then again just before
use, would on balance lead to less aggregation than only filtering once immediately before use. There's no way to tell. This is something pharma, and therefore researchers need not concern themselves with, because they're not using particle contaminated vials like we are.
Look at the FDA applications for peptides. Tests are required to ensure "leachables and extractables" from their containers aren't transferring anything harmful into the solution. I've seen tests showing the compounds you'd associate with a dirty tire manufacturing plant easily leach from cheap unregulated bromobutyl stoppers into solutions in trace amounts, Maybe not big deal with a once a year shot, but 300ml injected annually, 5% of your total blood volume, could add up to be a problem.
I fully concede I could be misunderstanding what you said, and if so I look forward to your clarification. I appreciate all the work you do in trying to protect people in this forum. Even though some consider it overkill. I want to fully understand the precautions you take along with the rationale behind them so that I may incorporate the best practices into my own.
I welcome questions and challenges presented with intellectual integrity. I continuously revisit and revise my practices based on the best conclusions I can draw from available information. I challenge myself, taking the opposite position , becoming my own adversary to measure potential new harms being introduced while trying to reduce others. That's why I was prepared to mention the "making space" issue post filtration. Very few things are pure "harm reduction" with no novel risks being introduced.
I'm simply sharing my thoughts based on what I've discovered, and leave it to the individual, without judgement, to decide what, if anything they feel they want to do about it.
