Qingdao Sigma Chemical Co., Ltd (International, US, EU, Canada and Australia domestic

[readalot]

More...

For SVPs ranging in size from 10 µm to the visible threshold, the limits are harmonized in the USP, EP, and JP at 6,000 and 600 per container for ≥10 µm and ≥25 µm particles, respectively, in 100 mL containers. For containers larger than 100 mL, limits are 25 per mL and 3 per mL for particles of ≥10 µm and ≥25 µm, respectively (Ishii-Watabe et al., 2015, Perez et al., 2016). For particles <10 µm, no compendial limits would be applicable, presumably this correlates to the approximate size of a human erythrocyte suggesting that particles smaller than an erythrocyte are of less concern because they are unlikely to embolize.

 

[readalot]

A whole section with refs...

5.2. Proteinaceous particles
Proteinaceous particles may be present in therapeutic proteins at release or form during

 

[AlexDavis43]

Wow this is quite interesting! Because I have read just as your quoted study states, that there are higher amounts of immunogenicity in Tesa, I suppose I haven't seen the latter of your comment on the affect on efficacy, but if this is true then that is pretty remarkable.

Where was this study? Thanks man

It may or may not be applicable. Then again the paients trialed on Egrifta weren't healthy either. There is a Tesamorelin study on healthy individuals but they did not assess for immunogenicity

 

[readalot]

https://www.thermofisher.com/at/en/home/industrial/pharma-biopharma/pharma-biopharma-learning-center/biopharmaceutical-characterization-information/protein-aggregate-subvisible-particles-analysis-information.html

Enjoy:

https://www.pharmout.net/wp-content/uploads/2018/02/NGVF-2016-D2.T2.2.2-Roy-Cherris-Particle-Determination-Guidance-for-Parenteral-Products.pdf

 

[Middus]

View attachment 316445

Yep. I don't usually like posting things like this, so as not to make people slack up on their precautions regarding filtering. not all immunogenicity is the same. Not all users of peptides are the same. Not all therapeutic proteins are the same.

 

[Trailmixed]

Yep. I don't usually like posting things like this, so as not to make people slack up on their precautions regarding filtering. not all immunogenicity is the same. Not all users of peptides are the same. Not all therapeutic proteins are the same.

Very true. Safe side is definitely filtering. Each filter is only $0.50 anyways haha, just a minute more in the grand scheme of the reconstitution process. Not too bad IMO

 

[Middus]

Like when you consider that a rate of grievous immune reaction of 0.5 in 10,000 will absolutely cause a drug to be discarded.. It puts a lot of things into perspective. You don't wanna be that 0.5 group, but that rate means if 7 people are going through something on a forum like meso for example, it is unlikely to be that thing. Hence my common things occur commonly mantra.

 

[Ghoul]

It may or may not be applicable. Then again the paients trialed on Egrifta weren't healthy either. There is a Tesamorelin study on healthy individuals but they did not assess for immunogenicity

This is common "knuckle dragger" logic and reveals the sheer ignorance on the topic.

"This immunogenicity stuff impacts the sick and weak, not us strong healthy bodybuilders."

Immunogenicity is more pronounced in healthy people with a vigorous immune system.

Read that again and think about it.

A healthy immune system reacts, and develops immunity to neutralize perceived "threats" far more strongly and effectively than those with a weakened immune system.

Who's going to have a stronger immune response? A healthy person, or the fucking immunocompromised AIDS patients in the Egrifta trial?

Again, I need to emphasize this because it's the point where any rational person would determine anyone with such a lack of basic understanding has no credibility on this topic. None. How could they?

The greatest risk from severe immunogenic reactions. the ones that go beyond merely reducing efficacy of a drug into life threatening reactions are HEALTHY VOLUNTEERS in clinical trials. Several of these incidents prompted the FDA to require far more immunogenicity testing before a peptide could be injected into any human volunteers.

 

[Middus]

This is common "knuckle dragger" logic and reveals the sheer ignorance on the topic.

"This immunogenicity stuff impacts the sick and weak, not us strong healthy bodybuilders."

Immunogenicity is more pronounced in healthy people with a vigorous immune system.

Read that again and think about it.

A healthy immune system reacts, and develops immunity to neutralize perceived "threats" far more strongly and effectively than those with a weakened immune system.

Who's going to have a stronger immune response? A healthy person, or the fucking immunocompromised AIDS patients in the Egrifta trial?

Again, I need to emphasize this because it's the point where any rational person would determine anyone with such a lack of basic understanding has no credibility on this topic. None. How could they?

The greatest risk from severe immunogenic reactions. the ones that go beyond merely reducing efficacy of a drug into life threatening reactions are HEALTHY VOLUNTEERS in clinical trials. Several of these incidents prompted the FDA to require far more immunogenicity testing before a peptide could be injected into any human volunteers.

View attachment 316447

Bruh.. Because i restrained myself from calling out the exagerration and fiction you posted about Erythropoetin alpha the other day..

You just went and googled up stuff without doing proper research and winged it. I let it be because It was of no value to that discussion, but you overestimate your grasp of some of these things and grossly underestimate the competence of others.

 

[AlexDavis43]

Yep. I don't usually like posting things like this, so as not to make people slack up on their precautions regarding filtering. not all immunogenicity is the same. Not all users of peptides are the same. Not all therapeutic proteins are the same.

It's always good to have other sides of the argument and alternate opinions presented.

Otherwise some might see the implications relating filtering peptides to preventing mad cow disease or autoimmunity. When the end point can simply be no change in efficacy.

 

[egruberman]

My cheap ass hates that I have to include LH and FSH test.

I get this thing:



For that price I get test total and free, comprehensive metabolic panel, FSH, LH, CBC, SHBG, and Estradiol.

I can't find anything like that for anywhere near that price on their site now.

 

[Middus]

Another famous (among the pharma peptide community) case was Erythropoietin.

People developed immunity to proteins critical to production of red blood
cells, resulting in severe, life threatening immunity,

This wasn't discovered until they'd been using it for years, because at the clinical level, no one can check for antibodies like this. Only the trials were monitoring for immunogenicity, since it's expensive and complex.

It took over a decade to figure out what happened. The manufacturer of prefilled syringes started using tungsten pins to make holes in the syringe. This left behind atomic level traces of tungsten particles. The particles caused the protein to aggregate, and the immune system responded to these aggregates, developing an immunity to them, which unfortunately, looked very similar to the natural protein critical to red blood cell production.

View attachment 316046

Those are your outstanding rates bro.
1.4 cases/year for ever 10,000 persons using it.
the peak was 4.5 people for ever 10,000 people with chronic kidney disease.

of course this is a disaster. Drugs are not supposed to worsen a disease, but come on bro!

Common things occur commonly!!!



Should we worry about immunogenicity, of course. This is a harm reduction forum, but please, some of us know what the fuck we are talking about.
191 cases world wide. 59 cases since 2002-2009 (world wide)

 

[AlexDavis43]

Bruh.. Because i restrained myself from calling out the exagerration and fiction you posted about Erythropoetin alpha the other day..

You just went and googled up stuff without doing proper research and winged it. I let it be because It was of no value to that discussion, but you overestimate your grasp of some of these things and grossly underestimate the competence of others.

You can't have a healthy discussion or disagreement with some people. He calls people low IQ retards all the time (eg, 1 & 2).

Microsoft Study Finds AI Makes Human Cognition “Atrophied and Unprepared”

 

[jung]

I use Call-on-Doc for bloodwork. Literally copy and paste all the labcorp labs I want; like 33 tests I think; hand over those lab codes to Call-on-Doc; give some very vague list of symptoms (poor sleep, hormonal support, low sex drive, etc.) to tie to the labs requested, pay the $39 consultation fee; Call-on-Doc then submits the request to my insurance. My insurance barely covers anything for preventative blood work, but they cover 100% of diagnostic based bloodwork. They don't say a word or push back on anything I submit; just need it to be relevant to the diagnostic code/symptoms.

So I end up getting about $500-$600 of super fancy panels and labs for $39. I do this multiple times a year. Granted not everyone's insurance may do that, so you have to call your insurance up and ask how they deal with diagnostic vs preventative labs. FYI, I just have an average BCBS PPO plan. It does not go against my deductible. It's just covered.

$39 for over $500 worth of labs if I was cash pay? I haven't seen any deal beat that yet.

 

[Middus]

It's always good to have other sides of the argument and alternate opinions presented.

Otherwise some might see the implications relating filtering peptides to preventing mad cow disease or autoimmunity. When the end point can simply be no change in efficacy.

Healthy people will react differently. They may have stronger immunity, but they may also have better clearance of the tesamorelin antibody. My specific mention of Healthy people is that we don't know if healthy people will have cross reactivity with growth hormone releasing hormone. But the study have performed on healthy individuals showed efficacy of Tesa in healthy people over a year. I just figured that if immunogenicity and neutralizing antibody was stronger, efficacy will be affected and this will skew results between AD and Placebo groups or at least affect P values regarding efficacy? That of course is extrapolation on my part, but reasonable. Which is why added no immunologic tests were performed on that group

 

[AlexDavis43]

View attachment 316450
Those are your outstanding rates bro.
1.4 cases/year for ever 10,000 persons using it.
the peak was 4.5 people for ever 10,000 people with chronic kidney disease.

of course this is a disaster. Drugs are not supposed to worsen a disease, but come on bro!

Common things occur commonly!!!

View attachment 316452

Should we worry about immunogenicity, of course. This is a harm reduction forum, but please, some of us know what the fuck we are talking about.
191 cases world wide. 59 cases since 2002-2009 (world wide)

But you can't say there's no chance

 

[aljowa]

So I only have a undergrad biochem degree, and I don't claim to be an expert at all but I am seeing some possible glaring flaws in your theories of aggregation esp with suggesting filtering as a solution. If aggregates are readily forming from peptides or peptide blends they should be interfering with any optical based analytic technique unless said aggregates just so happen to have the same absorbances of the targeted substances(incredibly unlikely). This should be very easy for some one like Jano to test for. Love to hear him chime in on this.

Secondly, If these aggregates are large enough that filtering them would be remotely effective then you should also be able to "see" them visually with the naked eye by shinning a laser through the solution and looking for observable light scattering. We used this technique in a lab course to detect the presence of nanoparticles.

food for thought.

It's in the Egrifta document itself on page 8

[

You will certainly make friends among the know-nothings here who'll latch onto your post, They're not arguing based on facts. have done no research, and have a personal beef with me.

I'll dismantle your commentary piece by piece. In individual posts.

Let me start by saying aggregates inducing immunogenicity is not my "theory". That claim alone demonstrates the lack of effort on your part.

I'll document everything I say. Will you?

View attachment 316431View attachment 316432

I have a lot of respect for @Ghoul for the invaluable information they've contributed to this site, and I know that I have personally found many of their posts incredibly interesting; they've helped to further my understanding of PEDs and related medicines, and I admire the intellectual drive that must support uncovering this knowledge. I don't think anyone who is approaching the topic of immunogicity in good faith is doubting the factuality of the issue. Having said that, I see nothing wrong with questioning aspects of immunogicity and provoking open discussion about the practical scale of the issue. A basic, foundational tenet of philosophy of science is the aim of discovering truths about the physical world via various means and methods that are testable and falsifiable. Healthy scientific practice involves questioning the basis of established scientific theories, as well as their perceived logical consequences, regardless of how well-supported they may be. If a theory cannot withstand honest critique, it needs to be re-evaluated in order for it to align itself closer to the truth of the subject matter being investigated.

This is all to say that there is no need for dismissive and hostile rhetoric when engaging in a discussion, and it only serves to detract from the argument of the person utilizing such tactics. If we can agree that we all want the same thing, finding answers that move us closer to the truth, then there is no need for personal insults or to interpret another person's questions as an attack on one's character. This type of behavior gives off the impression that one is attaching themselves in a dogmatic fashion to a specific claim, and that any question regarding the claim's validity is attacking the belief system of the individual. This is more indicative of a religious belief and has no place in a discussion regarding scientific claims. We are all in the same boat trying to get to the same destination, and there is nothing wrong with someone questioning the route the ship should take, provided they can argue their conclusion with a strong argument that cannot be rebutted. If a theory is so obviously well-established and empirically supported, then it should make it that much easier to defeat any argument against it, which will only strengthen the validity and soundness of the theory. In this sense, questioning the theory actually ends up benefitting the theory in the long run. All of this can proceed without passive aggressiveness and insults, which only distract from the discussion, and is far better for the quality of the dialogue and those reading from the sidelines, so to speak.

My apologies for the text wall, but it's disheartening to see such an interesting discussion get bogged down with unnecessary and irrelevant rhetoric.


P.S.
love y'all

 

[Middus]

You can't have a healthy discussion or disagreement with some people. He calls people low IQ retards all the time (eg, 1 & 2).

Microsoft Study Finds AI Makes Human Cognition “Atrophied and Unprepared”

I generally shy away from topics I know nothing about, so I don't like comments I put out being dismissed as knuckle dragging, especially when I feel His contributions are valuable in regard to said topic.

There is no point in me countering warnings, but I mean, calling that suggestion knuckle dragging? Its merely a comment borne out of tolerance limits/preference.

Plus another good thing about the Erythropoietin mishap is that it was due to the rubber stoppers contaminating the peptide. This is one thing he has been campaigning about so that's great!! However, he attributed it to Tungsten which prompted my fiction comment.

Now I need to go fix my computer. Seemed to have wiped my desktop by syncing one drive

 

[Ghoul]

Bruh.. Because i restrained myself from calling out the exagerration and fiction you posted about Erythropoetin alpha the other day..

You just went and googled up stuff without doing proper research and winged it. I let it be because It was of no value to that discussion, but you overestimate your grasp of some of these things and grossly underestimate the competence of others.

Give it your best shot.

Let's stick to one point at a time though. I have more than enough to counter your points in turn.

You've implied that immunogenicity is only relevant to the sick and not the healthy. It's something you share with @AlexDavis43.

Make that make sense. It's been brought up by you and Alex repeatedly.

How is an ill, weakened person more likely to have a potent immunogenic reaction than a healthy person?

 

[AlexDavis43]

Healthy people will react differently. They may have stronger immunity, but they may also have better clearance of the tesamorelin antibody. My specific mention of Healthy people is that we don't know if healthy people will have cross reactivity with growth hormone releasing hormone. But the study have performed on healthy individuals showed efficacy of Tesa in healthy people over a year. I just figured that if immunogenicity and neutralizing antibody was stronger, efficacy will be affected and this will skew results between AD and Placebo groups or at least affect P values regarding efficacy? That of course is extrapolation on my part, but reasonable. Which is why added no immunologic tests were performed on that group

So people can get GH antibodies measured, but they aren't necessarily the ones that interfere with GH function. So we still wouldn't know.

And if efficacy was unaffected in those with & without antibodies, what's the point?

We have antibodies to loads of things. Not a boogie monster.