What’s the current state of generic GH

[readalot]

This is pretty funny. So people here have been worried about aggregates and just didn’t realize that’s what they were worried about.

Rofl.

 

[Ateam2023]

Based on what Jano shared above (linked), yes. That is my understanding.

Nice overview of the methods...

Size-Exclusion Chromatography for the Analysis of Protein Biotherapeutics and their Aggregates - PMC

In recent years, the use and number of biotherapeutics has increased significantly. For these largely protein-based therapies, the quantitation of aggregates is of particular concern given their potential effect on efficacy and immunogenicity. This ...

pmc.ncbi.nlm.nih.gov

i read that, and i won't pretend i understand it, but i was able to grasp a portion of the idea, And will continue to follow along in the hopes it gets easier to understand, This is a very sensitive subject and may require more research and knowledge , I am glad there are a few "pioneers" leading the crusade, looking forward to the "end results" when they are presented,, Thanks ,,

 

[Ghoul]

i read that, and i won't pretend i understand it, but i was able to grasp a portion of the idea, And will continue to follow along in the hopes it gets easier to understand, This is a very sensitive subject and may require more research and knowledge , I am glad there are a few "pioneers" leading the crusade, looking forward to the "end results" when they are presented,, Thanks ,,

I don't think it'll ever end brother, nor should it.

But I encourage you to ask about anything that's unclear. Not only do those of us pursuing this in good faith not consider any question "stupid", but the questions force us to reevaluate what we think we already know, sometimes revealing an error or providing a new perspective that leads to information not previously considered.

We're all "citizen scientists" here and this is a group effort with room for everyone to contribute.

 

[readalot]

Have I missed any other questions related to filtration that we're seeking to answer with this proposed testing?

And kudos to you for fleshing out exactly what and how we would test. That was the big failure I made with the endotoxin testing for oils and challenge of trying to run an R&D project over a forum.

The method has to be properly qualified and calibrated prior to data generation. We may conclude we don't have the appropriate method to get accurate aggregate numbers. But at least everyone will learn something and we won't go down a rabbit hole needlessly this time.

Thank you.

 

[readalot]

It's not as if Dr. Winter didn't have access to SEC, but chose to use the MFI method (and a few others) to get a handle on how many particles were present and removed from the filtered GH.

Bump out of pure respect.

Good to know if we need a Porsche but only have access to a Yugo. No disrespect intended on the Yugo.

Flow Imaging Microscopy for Protein Particle Analysis—A Comparative Evaluation of Four Different Analytical Instruments - PMC

Flow imaging microscopy was introduced as a technique for protein particle analysis a few years ago and has strongly gained in importance ever since. The aim of the present study was a comparative evaluation of four of the most relevant flow imaging ...

pmc.ncbi.nlm.nih.gov

https://pmc.ncbi.nlm.nih.gov/articles/PMC3787219/figure/Fig4/

 

[Ghoul]

And kudos to you for fleshing out exactly what and how we would test. That was the big failure I made with the endotoxin testing for oils and challenge of trying to run an R&D project over a forum.

The method has to be properly qualified and calibrated prior to data generation. We may conclude we don't have the appropriate method to get accurate aggregate numbers. But at least everyone will learn something and we won't go down a rabbit hole needlessly this time.

Thank you.

Nothing needless about your efforts. Harm reduction seemed to stagnate for a long while here, and you stimulated a lot of people to start thinking about how to make things better than they currently are.

I love going back 15 years in the MESO archives and see how standards moved forward, in spurts, messy, argumentative, and always with resistance.

I like to keep in mind our best efforts are still going to look idiotic and dangerous compared to how harm reduction is practiced ten years from now.

 

[Ghoul]

Bump out of pure respect.

Good to know if we need a Porsche but only have access to a Yugo. No disrespect intended on the Yugo.

Flow Imaging Microscopy for Protein Particle Analysis—A Comparative Evaluation of Four Different Analytical Instruments - PMC

Flow imaging microscopy was introduced as a technique for protein particle analysis a few years ago and has strongly gained in importance ever since. The aim of the present study was a comparative evaluation of four of the most relevant flow imaging ...

pmc.ncbi.nlm.nih.gov

https://pmc.ncbi.nlm.nih.gov/articles/PMC3787219/figure/Fig4/

TBH micro flow inspection looks like child's play compared to what Jano does with chromatography.

MFI may not be a piece of gear Jano has, but he probobly has access to it.

 

[AlexDavis43]

Just to make sure everyone is on the same page (I need some reminding myself):

There is an actual study about GH aggregates (what we've been calling "dimer"), immunogenicity, and hGH therapy (summarized here) (Moore and Leppert, 1980).

Tl;dr: hGH with high aggregates (high "dimer") didn’t cause more immunogenicity than hGH with low dimer. And presence of GH antibodies didn’t affect hGH efficacy.

As mentioned above, some pharma GH has high dimer and plenty people here who use pharma GH say it has fewer side effects than low dimer UGL.

I'm sure that confused the shit out of some people. Perhaps someone else can do a better "Tl;dr:" to explain all the fuss with GH dimer (aggregates).

 

[readalot]

Just to give you a little taste of how complex all this is just for the pharma products aka "biosimilars":

Required reading before you consider UG GH just so you have an appreciation.

And this was just part of the story getting Omnitrope approved vs Genotropin.

https://www.tandfonline.com/doi/abs/10.1185/03007991003719642

Biosimilars: controversies as illustrated by rhGH

In 2006, the first two biosimilar rhGH formulations were granted marketing authorisation in the European Union Omnitrope26zz and Valtropin27xx, based on com- parison with the reference rhGH products Genotropin and Humatrope, respectively. Both products met the criteria for regulatory approval of biosimilars containing rhGH, as stipulated by the EMA (Table 2). The clinical studies sub- mitted for regulatory approval of both products are sum- marised in Table 3.

Omnitrope is a rhGH variant produced in an Escherichia
coli(E. coli) host strain. The marketed formulation is soma- tropin Sandoz powder for solution for injection produced by API Sandoz GmbH. However, during clinical develop- ment two other formulations were also used: somatropin Sandoz powder for solution for injection produced by API Covance Biotechnology Service Inc., and somatropin Sandoz liquid produced by API Sandoz GmbH. Three sup- portive pharmacokinetic/pharmacodynamic studies in healthy volunteers, one efficacy study and one pivotal tol- erability study were submitted to obtain regulatory approval for this product (Table 3)26.

The pivotal efficacy study (EP2K-99-PhIII/EP2K- 00-PhIII-Fo)26,28 was a multi-centre, randomised, con- trolled, open-label, nine-month phase III study comparing the effects of somatropin Sandoz powder (API Covance) and the approved reference product Genotropin which is also produced in E.coli in 89 treatment-naı¨ve children
(2–14 years) with idiopathic growth hormone deficiency
(GHD).

The four primary efficacy endpoints were body height,
height standard deviation score (HSDS), HV and HVSDS.
No statistically significant differences were observed for
these efficacy parameters between both treatment groups
during the nine-month comparative period, indicating
comparable therapeutic efficacy between Genotropin and somatropin Sandoz powder (API Covance). In a sup- portive six-month follow-up trial (EP2K-00-PhIII-AQ) in the same patient group28, comparable therapeutic efficacy was also shown between somatropin Sandoz powder (API
Sandoz) and somatropin Sandoz liquid (API Sandoz).

During the primary nine-month study, almost 60% of patients treated with somatropin Sandoz powder (API Covance) developed anti-GH antibodies and all patients developed antibodies against E. coli proteins (HCPs), versus only about 2% and 0% of patients treated with Genotropin. This observation could be attributed to high concentrations of HCPs in the powder produced by API Covance, which enhance the development of anti-GH
antibodies. Therefore, additional purification steps were introduced in the manufacturing process.

Consequently, the HCP concentrations in the subsequent formulations
(somatropin Sandoz powder and somatropin Sandoz liquid
produced by API Covance) were within the range known
from other approved rhGH-containing formulations.
Indeed, in the pivotal tolerability study (EP2K- 02-PhIII-Lyo)26,28 a multi-centre, open-label phase III trial evaluating the effects of somatropin Sandoz powder
(API Sandoz) in 51 treatment-naı¨ve children with idio-
pathic GHD no anti-GH antibodies were detected after 12 months, while only one patient developed anti-HCP antibodies. Therefore, Omnitrope was considered to be comparable to Genotropin in terms of tolerability and immunogenicity, and it was granted marketing authorisa-
tion by EMA for all six therapeutic indications of the ref-erence product Genotropin (Table 3).

Ask your UG vendor about his or her HCPs' testing and QC program today. It ain't all just aggregates of somatropin monomer. Get familiar with your UG lab's downstream purification process.

 

[readalot]

HCPs? Glad you asked...

Monitoring process-related impurities in biologics–host cell protein analysis - PMC

During biologics development, manufacturers must demonstrate clearance of host cell impurities and contaminants to ensure drug purity, manufacturing process consistency, and patient safety. Host cell proteins (HCPs) are a major class of ...

pmc.ncbi.nlm.nih.gov

The problematic HCPs typically fall into the categories of enzymes such as serine protease, disulfide isomerase and phospholipase affecting the stability of the drug product, immunogenic proteins and stimulants of patient immune responses, or abundant hitchhiker proteins binding to the drug protein. Specific HCPs in the drug product may impact drug quality, formulation, biological function, or immunogenicity [40]

ref 40

Host-Cell Protein Measurement and Control

This article reviews the definition of HCPs, risks posed by HCPs, regulatory concerns, commonly accepted ELISA methods for HCP measurement and their limitations, and orthogonal methods available for HCP characterization.

www.biopharminternational.com

Risks Associated with HCPs

HCPs constitute a major group of process-related impurities in a drug product. The risks associated with HCPs are primarily immunogenicity. HCPs are complex mixtures with diverse physiochemical and immunological properties (2). Almost all HCPs carry clinical safety risks as foreign proteins due to the potential to elicit immune response in humans. In addition, some HCPs can also act as adjuvants to enhance immune response to a drug product (1, 3). Certain HCPs with proteolytic activity can also affect drug product stability and efficacy if not adequately removed or inactivated (4). HCPs have the potential to affect both the safety and efficacy aspects of a given drug product.

Search for the term HCPs on MESO. What do you find?

 

[Toaster]

Sounds like you guys are on the right track.

As someone mentioned above. No matter the outcome everyone in the community will learn something from your efforts.

Later people can reference your results when this topic comes back up. If they have concerns or new ideas they can use your data to build on that by refining their own testing parameters.

 

[iris]

Sounds like you guys are on the right track.

As someone mentioned above. No matter the outcome everyone in the community will learn something from your efforts.

Later people can reference your results when this topic comes back up. If they have concerns or new ideas they can use your data to build on that by refining their own testing parameters.

I think your advocating measurable outcomes, in real terms, is reasonable.
Looking not only for theoretical data but also practical verifiability for one's own purposes is fair, if the means to carry that out are available.

This test will be very interesting.

 

[readalot]

@Ghoul

Have you started your fan club and monthly newsletter yet? You got some big fans at SST and especially AlexDavis. AD43 for Fan Club President?

Practical knowledge.

https://steroidsourcetalk.cc/index.php?threads/meso.19181/post-197882

 

[Ghoul]

@Ghoul

Have you started your fan club and monthly newsletter yet? You got some big fans at SST and especially AlexDavis. AD43 for Fan Club President?

Practical knowledge.

https://steroidsourcetalk.cc/index.php?threads/meso.19181/post-197882

Going to SST to find validation for their hatred of me is reminiscent of loser drunks whining from the safety of a dive bar that no one at work appreciates their brilliance.

Revealing their cowardice, afraid to be held accountable for their words on the forum the target of their crying actually is.

 

[Rakusa]

What's the reason for some people to report HGH #1 gives them good sleep, while HGH #2 wrecks their sleep? Considering both are sitting around near the same exact purity of lets say 98%.

 

[Sampei]

What's the reason for some people to report HGH #1 gives them good sleep, while HGH #2 wrecks their sleep? Considering both are sitting around near the same exact purity of lets say 98%.

Different reaction to it.
Dose is important too, at high dosage GH during the night doesn't give me that rock sleep feel plus it depends on what other substance you are on.

Reta wreck my sleep so I could attribute the issue to the GH when in reality it's not.

 

[Ghoul]

What's the reason for some people to report HGH #1 gives them good sleep, while HGH #2 wrecks their sleep? Considering both are sitting around near the same exact purity of lets say 98%.

The latest guidelines recommend doctors monitor for disordered breathing during sleep after GH treatment is started.

Based on this, the only plausible theory I can think of is:

1: There's a lot more going on with the HGH being injected by the user than the purity level, usually taken months ago by the vendor.

TLDR for any number of reasons using the "same" dose of HGH, each testing 99% purity, potency can still vary from one product to the next. One might have rapid drop off in purity, so 99% becomes 90% by the time it's in the syringe, or another causes a high level of immunogenic reaction lowering the effectiveness due to aggregates or contaminants in a cheap, unwashed dirty vial.

2. We know HGH improves lung function. Unfortunately deeper breathing can trigger obstructive apnea in vulnerable individuals, disrupting sleep.

So ironically, it could be that one vendor's "good" HGH, where a 5iu dose is working like 5iu, is improving lung function to the point an existing vulnerability to sleep apnea is triggered by the change in breathing, while 5ius of the "crap" HGH is weaker, working more like 3ius, enough to improve sleep, but not boosting lung function to the point apnea is triggered.

 

[Trenbolonetax]

Just received a portion of my lobster order. I submitted payment on 3/4. Received tracking numbers 3/5. 2 china, 1 intl express (upgraded free; ty).

Some of the most prompt communication I've encountered with a vendor. Opened package today and was delighted. Some of the best looking believable stealth I've seen. You can tell he takes a lot of pride in his product and work, and I can really appreciate that. It really shows.

I have been notified of tracking updates and generally kept in the loop with what was happening.

This experience with the peps (reta, tirz, sema) has me now really considering a GH purchase. Also eyeing those geno pens for $160...is generic GH the same as pharma? I have my opinion on that.

Does pharma GH improve my sleep whereas generic does not? I don't know...I'd have to try it...

 

[AlexDavis43]

Just received a portion of my lobster order. I submitted payment on 3/4. Received tracking numbers 3/5. 2 china, 1 intl express (upgraded free; ty).

Some of the most prompt communication I've encountered with a vendor. Opened package today and was delighted. Some of the best looking believable stealth I've seen. You can tell he takes a lot of pride in his product and work, and I can really appreciate that. It really shows.

I have been notified of tracking updates and generally kept in the loop with what was happening.

This experience with the peps (reta, tirz, sema) has me now really considering a GH purchase. Also eyeing those geno pens for $160...is generic GH the same as pharma? I have my opinion on that.

Does pharma GH improve my sleep whereas generic does not? I don't know...I'd have to try it...

Ask ChatGPT xD

 

[Ateam2023]

Is Lobster still doing the 10 kits deal? Does anybody know?